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Bipolar Disorder - Multiple Languages: MedlinePlus
Management of Ophthalmologic Disorders, Including Macular Degeneration.
National Technical Information Service (NTIS)
A drug may be used in the preparation of a medicament for the treatment or prevention of an ophthalmologic disorder, wherein the drug inihibits, antagonizes, or short-circuits the visual cycle at a step of the visual cycle that occurs outside a disc of a ...
R. R. Rando
Multiple personality disorder in criminal law.
The authors review the recent literature on multiple personality disorder (MPD), the most severe and chronic of the dissociative disorders, in relation to court cases of competence to stand trial, the insanity defense, and research on malingerers feigning MPD. Issues relevant in the assessment of competency and insanity are described. Features characteristic of MPD, including amnesia and alterations in consciousness and personality, have varying degrees of influence over the criminal behavior of an individual with MPD. As in other psychiatric disorders, the influence of MPD on an individual's competence to stand trial, and sanity, can be evaluated systematically. This article discusses a specific diagnostic tool, the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D), an extensively field tested instrument that is potentially quite useful in forensic assessment of suspects manifesting dissociative symptoms and disorders. The particular advantages of the SCID-D will be reviewed in the context of some well known criminal cases involving MPD. Further research using diagnostic interviews for the systematic assessment of dissociative symptoms and MPD in criminal cases will continue to clarify the influence of these symptoms in a forensic context. PMID:8148515
Steinberg, M; Bancroft, J; Buchanan, J
Multiple presentation of mitochondrial disorders
PubMed Central
The aim of this study was to assess the heterogeneous clinical presentations of children with mitochondrial disorders evaluated at a metabolic neurogenetic clinic. The charts of 36 children with highly suspected mitochondrial disorders were reviewed. Thirty one children were diagnosed as having a mitochondrial disorder, based on a suggestive clinical presentation and at least one of the accepted laboratory criteria; however, in five children with no laboratory criteria the diagnosis remained probable. All of the patients had nervous system involvement. Twenty seven patients also had dysfunction of other systems: sensory organs in 15 patients, cardiovascular system in five, gastrointestinal system in 20,urinary system in four, haematopoietic system in four, and endocrine system in nine. The clinical presentation was compatible with an established syndrome in only 15 children. Severe lactic acidosis or ragged red muscle fibres were encountered in very few patients. These results suggest that mitochondrial disorders should be evaluated in children presenting with a complex neurological picture or multisystem involvement.?
Nissenkorn, A.; Zeharia, A.; Lev, D.; Fatal-Valevski, A.; Barash, V.; Gutman, A.; Harel, S.; Lerman-Sagie, T.
An additional monogenic disorder that masquerades as multiple sclerosis
Microsoft Academic Search
In their comprehensive differential diagnosis of monogenic diseases that can mimic multiple sclerosis, Natowicz and Bejjani did not include a newly recognized monogenic disorder known under the acronym of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy); this disorder can mimic MS clinically and radiologically to a remarkable extent. The underlying histopathological lesion of CADASIL is a non-atherosclerotic,
K. Vahedi; E. Tournier-Lasserve
Emotional Disorders in People with Multiple Sclerosis
... and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on ... manage their MS • Lead to suicide What is MS? MS is thought to be an autoimmune disease ...
Multiple Peroxisomal Enzymatic Deficiency Disorders
Biologic, morphologic, and biochemical investigations performed in 2 patients demonstrate multiple peroxisomal deficiencies in the cerebrohepatorenal syndrome of Zellweger (CHRS) and neonatal adrenoleukodystrophy (NALD). Very long chain fatty acids, abnormal bile acids, including bile acid precursors (di- and trihydroxycoprostanoic acids), and C29-dicarboxylic acid accumulated in plasma in both patients. Generalized hyperaminoaciduria was also present. Peroxisomes could not be detected in CHRS liver and kidney; however, in the NALD patient, small and sparse cytoplasmic bodies resembling altered peroxisomes were found in hepatocytes. Hepatocellular and Kupffer cell lysosomes were engorged with ferritin and contained clefts and trilaminar structures believed to represent very long chain fatty acids. Enzymatic deficiencies reflected the peroxisomal defects. Hepatic glycolate oxidase and palmitoyl-CoA oxidase activities were deficient. No particle-bound catalase was found in cultured fibroblasts, and ether glycerolipid (plasmalogen) biosynthesis was markedly reduced. Administration of phenobarbital and clofibrate, an agent that induces peroxisomal proliferation and enzymatic activities, to the NALD patient did not bring about any changes in plasma metabolites, liver peroxisome population, or oxidizing activities. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5
Vamecq, Joseph; Draye, Jean-Pierre; Van Hoof, Francois; Misson, Jean-Paul; Evrard, Philippe; Verellen, Gaston; Eyssen, Hendrik J.; Van Eldere, Johan; Schutgens, Ruud B. H.; Wanders, Ronald J. A.; Roels, Frank; Goldfischer, Sidney L.
Similarities between near-death experiences and multiple personality disorder
In this paper I compare the phenomenology of near-death experiences to that of multiple personality disorder. The comparison reveals a number of similarities, including out-of-body experiences, the transcendental environment, encounter with the higher self, possible temporal lobe involvement, and antecedent child abuse. Rather than being disparate and unrelated experiences, I suggest that the near-death experience and multiple personality disorder may
William J. Serdahely
Genetic disorders that masquerade as multiple sclerosis.
There are many genetic disorders that have signs and symptoms suggestive of multiple sclerosis and that may easily be overlooked in the evaluation of both adult and pediatric multiple sclerosis patients. The recognition of a genetic disorder as the cause of a patient's "multiple sclerosis" phenotype has important implications not only for the patient, but often also for others in the patient's family who may be at risk for the same disease. We present here a review of single gene disorders that can masquerade as multiple sclerosis. For each disorder, the major clinical and biochemical characteristics are discussed, together with the appropriate testing to screen for and confirm the diagnosis. In addition, guidelines are presented for when to suspect an underlying genetic condition in a patient with a diagnosis of definite or probable multiple sclerosis. The great variety of genetic disorders that can masquerade as multiple sclerosis and the many implications of a genetic diagnosis underscore the importance of recognizing genocopies of multiple sclerosis. PMID:8116663
Natowicz, M R; Bejjani, B
[Ocular motor disorders in multiple sclerosis].
Multiple sclerosis is the most common disabling neurological disease in young people. Many neuro-ophthalmological manifestations can occur during the course of the illness, and optic neuritis is both the most frequent and the best known. However, some ocular motility disorders can also occur, but since there may be no symptoms, they often remain underdiagnosed. These eye movement disorders are mostly related to brain-stem and cerebellum lesions. They can be acute, indicating a spatial dissemination of the demyelinating disease, and consequently may indicate the need for systemic treatment of multiple sclerosis. More often, they evolve slowly, progressing with the multiple sclerosis. In this case, they could provide a clue to the prognosis of the disease. In this survey, we discuss the two major symptoms of ocular motor disorders likely to occur during multiple sclerosis: oscillopsia and diplopia. PMID:18971858
Rougier, M-B; Tilikete, C
Multiple Object Tracking in Autism Spectrum Disorders
ERIC Educational Resources Information Center
Difficulties in visual attention are often implicated in autism spectrum disorders (ASD) but it remains unclear which aspects of attention are affected. Here, we used a multiple object tracking (MOT) task to quantitatively characterize dynamic attentional function in children with ASD aged 5-12. While the ASD group performed significantly worse…
Koldewyn, Kami; Weigelt, Sarah; Kanwisher, Nancy; Jiang, Yuhong
Finding a simple path with multiple must-include nodes
This paper presents an algorithm to find a simple path in the given network with multiple must-include nodes in the path. The problem of finding a path with must-include node(s) can be easily found in some special cases. However, in general, including multiple nodes in the simple path has been shown to be NP-Complete. This problem may arise in network
Hars Vardhan; Shreejith Billenahalli; Wanjun Huang; Miguel Razo; Arularasi Sivasankaran; Limin Tang; Paolo Monti; Marco Tacca; Andrea Fumagalli
Unusual cases of multiple symmetrical lipomatosis with neurological disorders.
Multiple symmetrical lipomatosis (MSL) is a rare disorder of unknown etiology defined as the presence of multiple and symmetrical fatty accumulations, usually involving the upper trunk, neck and head. Frequently associated findings include diabetes mellitus, hyperlipidemia, liver disease, hypothyroidism and polyneuropathy of unknown origin, but nevertheless, there are published reports of cognitive disorders in patients with MSL. We describe two unusual cases (38-year-old and 45-year-old Greek men) of MSL who presented with polyneuropathy and memory disorders. This is the first description of memory disorders in patients with MSL. We propose that Mini-Mental State Examination and assessment of cognitive functions should be performed for all patients with MSL. The underlying mechanism in our patients remains unknown, and this question should be the subject of a future study. PMID:20048140
Triantafyllou, Nikolaos I; Zalonis, Ioannis; Kararizos, Grigoris; Gkiatas, Konstantinos; Christidi, Fotini; Kararizou, Evangelia
Pharmacotherapy of vestibular and ocular motor disorders, including nystagmus.
We review current pharmacological treatments for peripheral and central vestibular disorders, and ocular motor disorders that impair vision, especially pathological nystagmus. The prerequisites for successful pharmacotherapy of vertigo, dizziness, and abnormal eye movements are the "4 D's": correct diagnosis, correct drug, appropriate dosage, and sufficient duration. There are seven groups of drugs (the "7 A's") that can be used: antiemetics; anti-inflammatory, anti-Méničre's, and anti-migrainous medications; anti-depressants, anti-convulsants, and aminopyridines. A recovery from acute vestibular neuritis can be promoted by treatment with oral corticosteroids. Betahistine may reduce the frequency of attacks of Méničre's disease. The aminopyridines constitute a novel treatment approach for downbeat and upbeat nystagmus, as well as episodic ataxia type 2 (EA 2); these drugs may restore normal "pacemaker" activity to the Purkinje cells that govern vestibular and cerebellar nuclei. A limited number of trials indicate that baclofen improves periodic alternating nystagmus, and that gabapentin and memantine improve acquired pendular and infantile (congenital) nystagmus. Preliminary reports suggest suppression of square-wave saccadic intrusions by memantine, and ocular flutter by beta-blockers. Thus, although progress has been made in the treatment of vestibular neuritis, some forms of pathological nystagmus, and EA 2, controlled, masked trials are still needed to evaluate treatments for many vestibular and ocular motor disorders, including betahistine for Méničre's disease, oxcarbazepine for vestibular paroxysmia, or metoprolol for vestibular migraine. PMID:21461686
Strupp, Michael; Thurtell, Matthew J; Shaikh, Aasef G; Brandt, Thomas; Zee, David S; Leigh, R John
Extending a clinical repository to include multiple sites.
With the consolidation of health care organizations and services, a clinical repository comprising data from a single site is no longer sufficient. Individual patient data are now spread across multiple sites comprising a single enterprise. Users require an integrated view, or at least a common view, of these clinical data across multiple sites. Many issues arise when one tries to merge data from multiple, distinct organizations into an existing schema. We have addressed these issues while extending our clinical repository for Barnes Hospital with data from Jewish Hospital, both of which are members of the recently formed BJC Health System. We describe the architecture of our existing repository, approaches and issues in extending this repository to include multiple sites, and the specific issues we addressed in our system. PMID:8563308
Marrs, K A; Kahn, M G
Multiple neuroendocrine disorder in Salla disease.
Salla disease represents the slowly progressive adult form of the sialic acid storage diseases, a group of autosomal-recessive neurodegenerative disorders in which psychomotor development, ataxia, axial hypotonia, and spasticity in the lower limbs occur. No skeletal dysostosis or organomegaly is present, and life expectancy is normal. Short stature can also be observed. Progressive cerebral and cerebellar atrophy associated with dysmyelination and corpus callosum hypoplasia have been shown by magnetic resonance imaging studies. We report the first patient with Salla disease in whom combined growth hormone and gonadotropin deficiencies, hypothalamic pituitary in origin, have been demonstrated by neuroendocrine studies. We believe that the multiple neuroendocrine disorder may be the consequence of the abnormalities of common neuronal pathways regulating growth hormone and gonadotropin synthesis or secretion related to the brain storage of free sialic acid and/or to the neurodegenerative process occurring in Salla disease. Therefore, a complete endocrinologic evaluation of these patients is both warranted and useful. PMID:11669356
Grosso, S; Berardi, R; Farnetani, M A; Margollicci, M; Mancini, M G; Morgese, G; Balestri, P
Difficulties in visual attention are often implicated in autism spectrum disorders (ASD) but it remains unclear which aspects of attention are affected. Here, we used a multiple object tracking (MOT) task to quantitatively characterize dynamic attentional function in children with ASD aged 5–12. While the ASD group performed significantly worse overall, the group difference did not increase with increased object speed. This finding suggests that decreased MOT performance is not due to deficits in dynamic attention but instead to a diminished capacity to select and maintain attention on multiple targets. Further, MOT performance improved from 5–10 years in both typical and ASD groups with similar developmental trajectories. These results argue against a specific deficit in dynamic attention in ASD.
A hybrid system for diagnosing multiple disorders.
This paper investigates the advantages of introducing feedback between the processes of automated medical diagnosis and automated diagnostic-knowledge acquisition. Experimental results show that a diagnostic system with such feedback is capable of an efficiency/accuracy trade-off when applied to the problem of diagnosing multiple disorders. A primary feature of this work is a new mechanism, called the "diagnostic-unit" representation, for remembering results of previous diagnoses. The diagnostic-unit representation is explicitly tailored to capture the most likely relationships between disorders and clusters of findings. Unlike typical bipartite "If-Then" representations, the diagnostic-unit representation uses a general graph representation to efficiently represent complex causal relationships between disorders and clusters of findings. In addition to the basic diagnostic-unit concept, this paper presents experience-based strategies for incrementally deriving and updating diagnostic units and the various relationships between them. Techniques for selecting diagnostic units relevant to a given problem and then combining them to generate solutions are also described.
Jang, Y.
Post-Traumatic Stress Disorder - Multiple Languages: MedlinePlus
... Stress Disorder - Multiple Languages Arabic (???????) Bosnian (Bosanski) Burmese (myanmasa) Kirundi (Rundi) Russian (???????) Somali (af Soomaali) ... Stvarna bolest - Bosanski (Bosnian) Multimedia Healthy Roads Media Burmese (myanmasa) Post-Traumatic Stress Disorder (PTSD) English myanmasa ( ...
Immune-mediated extrapyramidal movement disorders, including Sydenham chorea.
Immune-mediated extrapyramidal movement disorders typically occur in previously healthy children. Immune-mediated movement disorders may occur as a postinfectious, paraneoplastic, or idiopathic process. Sydenham chorea (SC) is the classical poststreptococcal movement and psychiatric disorder, and may be associated with other features of rheumatic fever. The outcome is typically good, although residual chorea, psychiatric disturbance, and relapses are possible. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a syndrome of streptococcal-induced tics and obsessive-compulsive disorder. Although a number of investigators have reported an association between streptococcal infection and neuropsychiatric syndromes, the PANDAS hypothesis is controversial. Encephalitis lethargica is an encephalitic illness with parkinsonism, dyskinesias, and psychiatric disturbance as dominant features. The exact disease mechanism is not understood, although an autoimmune process is suspected. NMDA-R encephalitis is a new entity characterized by encephalitis with dramatic psychiatric disturbance, dyskinesias, cognitive alteration, and seizures. Patients have autoantibodies against the NMDA-R that appear to be pathogenic: immune therapies appear warranted to minimize disability. Movement disorders are also described associated with systemic lupus erythematosus and antiphospholipid syndrome. The differential diagnosis and investigation approach of acute-onset movement disorders are also discussed. PMID:23622334
Dale, Russell C
Neck Injuries and Disorders - Multiple Languages: MedlinePlus
Biomechanical disorders of foot in multiple sclerosis.
Multiple sclerosis (MS) has a multifactorial etiology located at the interaction point of environmental factors--nutritional, geographic, infectious, etc.--with genetic factors, which confers susceptibility to disease or alters its development. This research presents a case study focused on complex assessment of a patient using clinical and functional assessment, biomechanical gait evaluation using RSScan force plate. Biomechanical parameters (contact area, load, impulse, force, pressure, foot balance) are the parameters that we obtain after force plate measurements. Analyzing the results of the functional assessment, it is found an anatomical functional abnormality with a tendency to increase. Biomechanical tests show an asymmetric gait due to the impact of neurological disorders generated in the proprioceptive system. Global analysis of values (surface contact, pressure, force, load, impulse, active contact area) indicates the fact that there is a tendency to develop a higher pressure in the anterior-medial region of the plant in an attempt to maintain balance. It is a tendency to increase the active contact area in the forefoot region; this increase is explained by the body tendency to develop compensatory mechanisms to maintain balance. PMID:23188451
Neam?u, M C; Rusu, Ligia; Rusu, P F; Marin, M; Neam?u, Oana Maria
Academic Choice for Included Students with Emotional and Behavioral Disorders
Students with emotional disturbances present with behavioral and academic deficits that often limit their participation in general education settings. As an antecedent intervention, academic choice provides multiple choices surrounding academic work promoting academic and behavioral gains. The authors examined the effects of assignment choice with…
Skerbetz, Mandi Davis; Kostewicz, Douglas E.
Clinical and urodynamic evaluations of urinary disorders in multiple sclerosis.
Urinary dysfunction is a major clinical problem and a significant cause of disability in multiple sclerosis (MS) patients. Indeed, the bothersome symptom of urinary dysfunction may adversely affect social relationships and activities in MS patients. Since many causes of urinary dysfunction are described, a thorough evaluation including history, clinical examination and evaluation of quality of life is necessary. Generally, diagnosis of urinary disorders is complex with intricated pathophysiologic factors. In these cases, urodynamic investigations are necessary to better understand symptoms pathophysiology and choose the best treatment. PMID:24980885
Amarenco, G; de Sčze, M; Ruffion, A; Sheikh Ismael, S
Multiple Neuroendocrine Disorder in Salla Disease
Salla disease represents the slowly progressive adult form of the sialic acid storage diseases, a group of autosomal-recessive neurodegenerative disorders in which psychomotor development, ataxia, axial hypotonia, and spasticity in the lower limbs occur. No skeletal dysostosis or organomegaly is present, and life expectancy is normal. Short stature can also be observed. Progressive cerebral and cerebellar atrophy associated with dysmyelination
Salvatore Grosso; Rosario Berardi; Maria Angela Farnetani; Maria Margollicci; Maria Grazia Mancini; Guido Morgese; Paolo Balestri
Multiple Myeloma: Presenting as a Neurological Disorder
A case is reported of multiple myeloma presenting with signs and symptoms of paraplegia in a patient with a history of hypertension and remote cerebral vascular accident. The laboratory findings of hyperproteinemia and uricemia suggest a protein synthesizing abnormality. This case emphasizes that most patients with protein abnormality should be investigated by protein electrophoresis and immunoelectrophoresis. Unusual clinical presentation of multiple myeloma may result in an erroneous diagnosis unless proper investigation in the appropriate line is made. ImagesFigure 1Figure 2
Sen, Sisir Kumar; Hunter, Samuel B.; Dent, Carl A.; Green, Louis D.
Immunophenotyping in multiple myeloma and related plasma cell disorders
SUMMARY Plasma cell disorders form a spectrum ranging from the asymptomatic presence of small monoclonal populations of plasma cells to conditions like plasma cell leukemia and multiple myeloma, in which the bone marrow can be replaced by the accumulation of neoplastic plasma cells. Immunophenotyping has become an invaluable tool in the management of hematological malignancies and is increasingly finding a role in the diagnosis and monitoring of plasma cell disorders. Multiparameter flow cytometry has evolved considerably during the past decade with an increasing ability to screen large numbers of events and to detect multiple antigens at the same time. This, along with a better understanding of the phenotypic heterogeneity of the clonal plasma cells in different disorders, has made immunophenotyping an indispensible tool in the diagnosis, prognostic classification and management of plasma cell disorders. This book chapter addresses the approaches taken to evaluate monoclonal plasma cell disorders, and the different markers and techniques that are important for the study of these diseases.
Kumar, Shaji; Kimlinger, Teresa; Morice, William
Including Students with Severe, Multiple Disabilities in General Physical Education
Many children with severe disabilities never have the opportunity to try general physical education (GPE) because their Individualized Education Program (IEP) team feels that they will not be successful, will not benefit, or will not be safe. However, there are ways to safely, successfully, and meaningfully include children with severe…
Block, Martin E.; Klavina, Aija; Flint, Wayne
Movement disorders in multiple sclerosis and other demyelinating diseases.
Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system characterized by dissemination of the lesions in time and space. While tremor is frequently seen in patients with multiple sclerosis, other movement disorders such as parkinsonism, dystonia, chorea, ballism, paroxysmal dystonia, paroxysmal chorea, myoclonus, tourettism, restless leg syndrome and hemifacial spasm are less frequently reported. In this systematic review of the literature, we describe the different movement disorders reported in patients with multiple sclerosis and attempt to characterize their relation with the underlying demyelinating process. We also summarize the reports of movement disorders described in other demyelinating diseases such as neuromyelitis optica, acute disseminated encephalomyelitis and central pontine myelinolysis. PMID:23522528
Mehanna, Raja; Jankovic, Joseph
42 CFR 137.327 - May multiple projects be included in a single construction project agreement?
Code of Federal Regulations, 2012 CFR
...multiple projects be included in a single construction project agreement? 137.327 Section...SERVICES TRIBAL SELF-GOVERNANCE Construction Project Assumption Process § 137...multiple projects be included in a single construction project agreement? Yes, a...
Satanism, Ritual Abuse, and Multiple Personality Disorder: A Sociohistorical Perspective
During the past decade in North America, a growing number of mental health professionals have reported that between 25% and 50% of their patients in treatment for multiple personality disorder (MPD) have recovered early childhood traumatic memories of ritual torture, incestuous rape, sexual debauchery, sacrificial murder, infanticide, and cannibalism perpetrated by members of clandestine satanic cults. Although hundreds of local
Sherrill Mulhern
Multiple Traumatic Experiences and the Development of Posttraumatic Stress Disorder
This study assesses the differential and combined impacts of multiple lifetime stressors in the development and severity of posttraumatic stress disorder (PTSD) symptoms. One hundred and four clinical and 64 nonclinical participants were assessed for their exposure to four types of interpersonal trauma: physical and sexual abuse in childhood,…
Scott, Sheryn T.
Rapidly evolving hypopituitarism in a boy with multiple autoimmune disorders.
A 10-year-old boy with acute onset cranial diabetes insipidus and multiple autoimmune disorders had evolving panhypopituitarism, thought to be due to autoimmune hypophysitis. Over 18 months, a dramatic clinical course with progressive hypopituitarism and development of type 1 diabetes mellitus was evident. Serial brain imaging showed changes suggestive of germinoma. PMID:23586429
Jevalikar, Ganesh; Wong, Sze Choong; Zacharin, Margaret
Should an obsessive-compulsive spectrum grouping of disorders be included in DSM-V?
The obsessive-compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive-compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or "chapter") in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive-Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of "Anxiety and Obsessive-Compulsive Spectrum Disorders." These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V. PMID:20533367
Phillips, Katharine A; Stein, Dan J; Rauch, Scott L; Hollander, Eric; Fallon, Brian A; Barsky, Arthur; Fineberg, Naomi; Mataix-Cols, David; Ferrăo, Ygor Arzeno; Saxena, Sanjaya; Wilhelm, Sabine; Kelly, Megan M; Clark, Lee Anna; Pinto, Anthony; Bienvenu, O Joseph; Farrow, Joanne; Leckman, James
Hitting Closer to Home: A Multiple Family Prevention Group for Adolescent Disordered Eating
This article presents an innovative multiple family psychoeducational group for the prevention of disordered eating among adolescent females. An overview of the concerns facing adolescents today is presented, including sociocultural norms, body dissatisfaction associated with pubertal changes, teasing regarding weight and shape, and family influences. Evidence regarding past prevention efforts are cited, indicating the need for the development of psychoeducational
Colleen E. Clemency; Andrea Dixon Rayle
Effects of structural disorders on sequential tunneling in multiple quantum wells
NASA Astrophysics Data System (ADS)
Based on an isotropic random distribution model, the effects of structural disorders embedded in the barriers on the sequential electron tunneling in multiple quantum wells were studied at low temperatures. By using a sequential tunneling model [Stievenard et al., Appl. Phys. Lett. 61 (1992) 1582], the transmission coefficient through a single barrier was calculated using a finite-difference method and averaged over random configurations of disorders. To compute the tunneling current, a self-consistent calculation for the electronic states was performed, including the Hartree and exchange interactions and non-parabolic energy dispersion. Both disorder-assisted and disorder-impeded electron tunneling phenomena were found as a function of the activation energy. The effects of electric field, barrier width, and temperature were also studied. The predicted resonant disorder-assisted electron tunneling should be large enough to be observable at low temperatures in an experiment.
Huang, Danhong; Singh, Anjali; Cardimona, D. A.
Should Sluggish Cognitive Tempo Symptoms Be Included in the Diagnosis of Attention-Deficit/hyperactivity Disorder?
Objective: To determine the impact of including sluggish cognitive tempo items on the factor and latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in boys and girls. Method: Parent report of two sluggish cognitive tempo items on a population-based sample of 1,430 female twins and 1,414 male twins were analyzed…
Todd, Richard D.; Rasmussen, Erik R.; Wood, Catherine; Levy, Florence; Hay, David A.
Non-reversible multiple-refrigeration-cycle solar apparatus including a variable directing valve mechanism
SciTech Connect
A non-reversible multiple-refrigeration-cycle solar apparatus, including a variable directing valve mechanism for conditioning a medium, defrosting the apparatus, and absorbing, storing and using solar energy.
Cramer Sr., C. V.
Unified description for hopping transport in organic semiconductors including both energetic disorder and polaronic contributions
We developed an analytical model to describe hopping transport in organic semiconductors including both energetic disorder and polaronic contributions due to geometric relaxation. The model is based on a Marcus jump rate in terms of the small-polaron concept with a Gaussian energetic disorder, and it is premised upon a generalized effective medium approach yet avoids shortcomings involved in the effective transport energy or percolation concepts. It is superior to our previous treatment [Phys. Rev. B1098-012110.1103/PhysRevB.76.045210 76, 045210 (2007)] since it is applicable at arbitrary polaron activation energy Ea with respect to the energy disorder parameter ?. It can be adapted to describe both charge-carrier mobility and triplet exciton diffusion. The model is compared with results from Monte Carlo simulations. We show (i) that the activation energy of the thermally activated hopping transport can be decoupled into disorder and polaron contributions whose relative weight depend nonlinearly on the ?/Ea ratio, and (ii) that the choice of the density of occupied and empty states considered in configurational averaging has a profound effect on the results of calculations of the Marcus hopping transport. The ?/Ea ratio governs also the carrier-concentration dependence of the charge-carrier mobility in the large-carrier-concentration transport regime as realized in organic field-effect transistors. The carrier-concentration dependence becomes considerably weaker when the polaron energy increases relative to the disorder energy, indicating the absence of universality. This model bridges a gap between disorder and polaron hopping concepts.
Fishchuk, I. I.; Kadashchuk, A.; Hoffmann, S. T.; Athanasopoulos, S.; Genoe, J.; Bässler, H.; Köhler, A.
Anxiety Symptoms in Boys with Autism Spectrum Disorder, Attention-Deficit Hyperactivity Disorder, or Chronic Multiple Tic Disorder and Community Controls
We compared symptoms of generalized anxiety disorder (GAD) and separation anxiety disorder (SAD) in 5 groups of boys with\\u000a neurobehavioral syndromes: attention-deficit\\/hyperactivity disorder (ADHD) plus autism spectrum disorder (ASD), ADHD plus\\u000a chronic multiple tic disorder (CMTD), ASD only, ADHD only, and community Controls. Anxiety symptoms were assessed using parent\\u000a and teacher versions of a DSM-IV-referenced rating scale. All three groups
Sarit Guttmann-SteinmetzKenneth; Kenneth D. Gadow; Carla J. DeVincent; Judy Crowell
Ca V1.2 Calcium Channel Dysfunction Causes a Multisystem Disorder Including Arrhythmia and Autism
CaV1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from
Igor Splawski; Katherine W. Timothy; Leah M. Sharpe; Niels Decher; Pradeep Kumar; Raffaella Bloise; Carlo Napolitano; Peter J. Schwartz; Robert M. Joseph; Karen Condouris; Helen Tager-Flusberg; Silvia G. Priori; Michael C. Sanguinetti; Mark T. Keating
Somatization disorder
Opinion statement There are many new developments regarding somatization disorder, which is among the most difficult and cumbersome of the psychiatric\\u000a disorders encountered in neurology practice. Diagnostic criteria have been revised to facilitate clinical care and research.\\u000a The differential diagnosis includes neurologic disorders (eg, multiple sclerosis, epilepsy), systemic medical disorders, and other psychiatric disorders (eg, mood and anxiety disorders, conversion disorder,
Donald M. Hilty; James A. Bourgeois; Celia H. Chang; Mark E. Servis
Microvascular decompression for trigeminal neuralgia: comments on a series of 250 cases, including 10 patients with multiple sclerosis
OBJECTIVE—To examine surgical findings and results of microvascular decompression (MVD) for trigeminal neuralgia (TN), including patients with multiple sclerosis, to bring new insight about the role of microvascular compression in the pathogenesis of the disorder and the role of MVD in its treatment.?METHODS—Between 1990 and 1998, 250 patients affected by trigeminal neuralgia underwent MVD in the Department of Neurosurgery of the "Istituto Nazionale Neurologico C Besta" in Milan. Limiting the review to the period 1991-6, to exclude the "learning period" (the first 50 cases) and patients with less than 1 year follow up, surgical findings and results were critically analysed in 148 consecutive cases, including 10 patients with multiple sclerosis.?RESULTS—Vascular compression of the trigeminal nerve was found in all cases. The recurrence rate was 15.3% (follow up 1-7 years, mean 38 months). In five of 10 patients with multiple sclerosis an excellent result was achieved (follow up 12-39 months, mean 24months). Patients with TN for more than 84 months did significantly worse than those with a shorter history (p<0.05). There was no mortality and most complications occurred in the learning period. Surgical complications were not related to age of the patients.?CONCLUSIONS—Aetiopathogenesis of trigeminal neuralgia remains a mystery. These findings suggest a common neuromodulatory role of microvascular compression in both patients with or without multiple sclerosis rather than a direct causal role. MVD was found to be a safe and effective procedure to relieve typical TN in patients of all ages. It should be proposed as first choice surgery to all patients affected by TN, even in selected cases with multiple sclerosis, to give them the opportunity of pain relief without sensory deficits. ??
Broggi, G.; Ferroli, P.; Franzini, A.; Servello, D.; Dones, I.
Extension of the ADC Charge-Collection Model to Include Multiple Junctions.
The ADC model is a charge-collection model derived for simple p-n junction silicon diodes having a single reverse-biased p-n junction at one end and an ideal substrate contact at the other end. The present paper extends the model to include multiple junct...
L. D. Edmonds
Annual Research Review: The neurobehavioral development of multiple memory systems - implications for childhood and adolescent psychiatric disorders.
Extensive evidence indicates that mammalian memory is organized into multiple brains systems, including a 'cognitive' memory system that depends on the hippocampus and a stimulus-response 'habit' memory system that depends on the dorsolateral striatum. Dorsal striatal-dependent habit memory may in part influence the development and expression of some human psychopathologies, particularly those characterized by strong habit-like behavioral features. The present review considers this hypothesis as it pertains to psychopathologies that typically emerge during childhood and adolescence. These disorders include Tourette syndrome, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, eating disorders, and autism spectrum disorders. Human and nonhuman animal research shows that the typical development of memory systems comprises the early maturation of striatal-dependent habit memory and the relatively late maturation of hippocampal-dependent cognitive memory. We speculate that the differing rates of development of these memory systems may in part contribute to the early emergence of habit-like symptoms in childhood and adolescence. In addition, abnormalities in hippocampal and striatal brain regions have been observed consistently in youth with these disorders, suggesting that the aberrant development of memory systems may also contribute to the emergence of habit-like symptoms as core pathological features of these illnesses. Considering these disorders within the context of multiple memory systems may help elucidate the pathogenesis of habit-like symptoms in childhood and adolescence, and lead to novel treatments that lessen the habit-like behavioral features of these disorders. PMID:24286520
Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S; Packard, Mark G
Pharmacotherapy in the Management of Voiding and Storage Disorders, Including Enuresis and Encopresis
Enuresis and encopresis are disorders of the bladder and rectum, and this article helps in understanding the neurobiology of lower urinary tract and anorectal function to help in the treatment of these disorders. Treatment for children with these disorders emphasizes either a psychological or pharmacological approach.
Reiner, William G.
Bipolar Disorder and Multiple Sclerosis: A Case Series
Background. The prevalence of psychiatric disturbance for patients with multiple sclerosis (MS) is higher than that observed in other chronic health conditions. We report three cases of MS and bipolar disorder and we discuss the possible etiological hypothesis and treatment options. Observations. All patients fulfilled the McDonald criteria for MS. Two patients were followed up in psychiatry for manic or depressive symptoms before developing MS. A third patient was diagnosed with MS and developed deferred psychotic symptoms. Some clinical and radiological features are highlighted in our patients: one manic episode induced by high dose corticosteroids and one case of a new orbitofrontal MRI lesion concomitant with the emergence of psychiatric symptoms. All patients needed antipsychotic treatment with almost good tolerance for high dose corticosteroids and interferon beta treatment. Conclusions. MRI lesions suggest the possible implication of local MS-related brain damage in development of pure "psychiatric fits" in MS. Genetic susceptibility is another hypothesis for this association. We have noticed that interferon beta treatments were well tolerated while high dose corticosteroids may induce manic fits.
Sidhom, Youssef; Ben Djebara, Mouna; Hizem, Yosr; Abdelkefi, Istabrak; Kacem, Imen; Gargouri, Amina; Gouider, Riadh
Bedside Tested Ocular Motor Disorders in Multiple Sclerosis Patients
Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated. Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (n = 150, 92%) or clinically isolated syndrome (n = 13, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed. Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability (P = 0.0005) and showed more frequently infratentorial MRI lesions (P = 0.004). Localization of previous relapses was not associated with presence of OMDs. Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.
Servillo, G.; Renard, D.; Taieb, G.; Labauge, P.; Bastide, S.; Zorzon, M.; Castelnovo, G.
Multiple electrolyte disorders in a neurosurgical patient: solving the rebus
Background It is important to ensure an adequate sodium and volume balance in neurosurgical patients in order to avoid the worsening of brain injury. Indeed, hyponatremia and polyuria, that are frequent in this patient population, are potentially harmful, especially if not promptly recognized. Differential diagnosis is often challenging, including disorders, which, in view of similar clinical pictures, present very different pathophysiological bases, such as syndrome of inappropriate antidiuresis, cerebral/renal salt wasting syndrome and diabetes insipidus. Case presentation Here we present the clinical report of a 67-year-old man with a recent episode of acute subarachnoid haemorrhage, admitted to our ward because of severe hyponatremia, hypokalemia and huge polyuria. We performed a complete workup to identify the underlying causes of these alterations and found a complex picture of salt wasting syndrome associated to primary polydipsia. The appropriate diagnosis allowed us to correct the patient hydro-electrolyte balance. Conclusion The comprehension of the pathophysiological mechanisms is essential to adequately recognize and treat hydro-electrolyte disorders, also solving the most complex clinical problems.
Extension of the ADC Charge-Collection Model to Include Multiple Junctions
NASA Technical Reports Server (NTRS)
The ADC model is a charge-collection model derived for simple p-n junction silicon diodes having a single reverse-biased p-n junction at one end and an ideal substrate contact at the other end. The present paper extends the model to include multiple junctions, and the goal is to estimate how collected charge is shared by the different junctions.
Edmonds, Larry D.
Nonlocal photopolymerization kinetics including multiple termination mechanisms and dark reactions. Part I. Modeling
The photochemical processes present during free-radical-based holographic grating formation are examined. A kinetic model is presented, which includes, in a more nearly complete and physically realistic way, most of the major photochemical and nonlocal photopolymerization-driven diffusion effects. These effects include: (i) non-steady-state kinetics (ii) spatially and temporally nonlocal polymer chain growth (iii) time varying photon absorption (iv) diffusion controlled viscosity effects (v) multiple termination mechanisms, and (vi) inhibition. The convergence of the predictions of the resulting model is then examined. Comparisons with experimental results are carried out in Part II of this series of papers [J. Opt. Soc. Am. B 26, 1746 (2009)].
Gleeson, Michael R.; Sheridan, John T. [UCD School of Electrical, Electronic and Mechanical Engineering, UCD Optoelectronic Research Centre, and The SFI-Strategic Research Cluster in Solar Energy Conversion, College of Engineering, Mathematical and Physical Sciences, University College Dublin, Belfield, Dublin 4 (Ireland)
[Hypersexual disorder will not be included in the DSM V : a contextual analysis].
Hypersexuality disorder has not been added to the list of psychiatric disorders for the Diagnostic and Statistical Manual of Mental Disorders (DSM) V, to be published in May 2013. The evolution of the concept of hypersexuality disorder and its series of different models call into question the controversial context within which its inclusion is considered for the DSM V. A brief contextual analysis makes clear that the creation of this concept follows moral norms and psychosocial values. The construction of hypersexuality disorder in terms of a diagnostic entity rests on the clash of social forces at play in the development process. This article lays the foundation to contemplate the manner in which entities for psychiatric disorders are constructed. PMID:23888588
Toussaint, I; Pitchot, W
Development of a versatile enrichment analysis tool reveals associations between the maternal brain and mental health disorders, including autism
Background A recent study of lateral septum (LS) suggested a large number of autism-related genes with altered expression in the postpartum state. However, formally testing the findings for enrichment of autism-associated genes proved to be problematic with existing software. Many gene-disease association databases have been curated which are not currently incorporated in popular, full-featured enrichment tools, and the use of custom gene lists in these programs can be difficult to perform and interpret. As a simple alternative, we have developed the Modular Single-set Enrichment Test (MSET), a minimal tool that enables one to easily evaluate expression data for enrichment of any conceivable gene list of interest. Results The MSET approach was validated by testing several publicly available expression data sets for expected enrichment in areas of autism, attention deficit hyperactivity disorder (ADHD), and arthritis. Using nine independent, unique autism gene lists extracted from association databases and two recent publications, a striking consensus of enrichment was detected within gene expression changes in LS of postpartum mice. A network of 160 autism-related genes was identified, representing developmental processes such as synaptic plasticity, neuronal morphogenesis, and differentiation. Additionally, maternal LS displayed enrichment for genes associated with bipolar disorder, schizophrenia, ADHD, and depression. Conclusions The transition to motherhood includes the most fundamental social bonding event in mammals and features naturally occurring changes in sociability. Some individuals with autism, schizophrenia, or other mental health disorders exhibit impaired social traits. Genes involved in these deficits may also contribute to elevated sociability in the maternal brain. To date, this is the first study to show a significant, quantitative link between the maternal brain and mental health disorders using large scale gene expression data. Thus, the postpartum brain may provide a novel and promising platform for understanding the complex genetics of improved sociability that may have direct relevance for multiple psychiatric illnesses. This study also provides an important new tool that fills a critical analysis gap and makes evaluation of enrichment using any database of interest possible with an emphasis on ease of use and methodological transparency.
The Effects of Including a Callous-Unemotional Specifier for the Diagnosis of Conduct Disorder
Background: "With Significant Callous-Unemotional Traits" has been proposed as a specifier for conduct disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The impact of this specifier on children diagnosed with CD should be considered. Methods: A multi-site cross-sectional design with…
Kahn, Rachel E.; Frick, Paul J.; Youngstrom, Eric; Findling, Robert L.; Youngstrom, Jennifer Kogos
Developmental trauma disorder: pros and cons of including formal criteria in the psychiatric diagnostic systems
Background This article reviews the current debate on developmental trauma disorder (DTD) with respect to formalizing its diagnostic criteria. Victims of abuse, neglect, and maltreatment in childhood often develop a wide range of age-dependent psychopathologies with various mental comorbidities. The supporters of a formal DTD diagnosis argue that post-traumatic stress disorder (PTSD) does not cover all consequences of severe and complex traumatization in childhood. Discussion Traumatized individuals are difficult to treat, but clinical experience has shown that they tend to benefit from specific trauma therapy. A main argument against inclusion of formal DTD criteria into existing diagnostic systems is that emphasis on the etiology of the disorder might force current diagnostic systems to deviate from their purely descriptive nature. Furthermore, comorbidities and biological aspects of the disorder may be underdiagnosed using the DTD criteria. Summary Here, we discuss arguments for and against the proposal of DTD criteria and address implications and consequences for the clinical practice.
Cancer Risk Among Infertile Women with Androgen Excess or Menstrual Disorders (including Polycystic Ovary Syndrome)
Objective To define relationships of androgen excesses to cancer risk. Design Retrospective cohort study. Patients Among 12,193 women evaluated for infertility between 1965-1988 and traced for cancer incidence through 1999, 2,560 had androgen excess or menstrual disorders; among these, 412 met established criteria for PCOS. Main Outcome Cancer incidence. Methods Derivation of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer risk comparisons with the general population and rate ratios (RRs) for comparisons with other infertility patients. Results Androgen excess/menstrual disorders patients showed significant SIRs for breast (1.31, 95% CIs 1.05-1.62) and uterine (2.02, 1.13-3.34) cancers and melanoma (1.96, 1.12-3.18). Significant associations for breast and uterine cancers were restricted to primary infertility patients (respective SIRs of 1.53 and 3.48). After adjustment for other cancer predictors, the only excess risk was for uterine cancer among primary infertility patients. Compared to women with secondary infertility and no androgen excess/menstrual disorder, those with primary infertility and a disorder had a RR of 1.88 (95% CI 0.82-4.32). Cancer risks among the women with PCOS or androgen excess disorders appeared similar to the more comprehensive group. Conclusions Previous findings linking androgen excess disorders to elevated uterine cancer risks may largely reflect underlying risk profiles.
Brinton, Louise A.; Moghissi, Kamran S.; Westhoff, Carolyn L.; Lamb, Emmet J.; Scoccia, Bert
Multiple Hits, Including Oxidative Stress, as Pathogenesis and Treatment Target in Non-Alcoholic Steatohepatitis (NASH)
Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.
Takaki, Akinobu; Kawai, Daisuke; Yamamoto, Kazuhide
?-Thalassaemia prototype of a single gene disorder with multiple phenotypes
As the defective genes for more and more genetic disorders become unravelled, it is clear that patients with the same genotype\\u000a can have many different clinical conditions even in monogenic disorders. The remarkable phenotypic diversity of the ?thalassaemias\\u000a is prototypical of how the wide spectrum in disease severity can be generated. The most reliable and predictive factor of\\u000a disease phenotype
Swee Lay Thein
Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up
In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build-up (thermalization transient) within the detector cannot be ignored. Another example where signal build-up might be observed is when a {sup 3}He based system is used to track the evolution of the time correlated signal created by a higher multiplying item within a reflective configuration such as the measurement of a spent fuel assembly. In this work we develop expressions for the GUFs which include signal build-up.
Croft, Stephen [Los Alamos National Laboratory; Evans, Louise G [Los Alamos National Laboratory; Schear, Melissa A [Los Alamos National Laboratory
Including Students with Attention-Deficit/Hyperactivity Disorder in Mainstream Schools
Around 80% of pupils with attention deficit disorders are educated in mainstream schools. The difficulties relating to inattention, impulsivity and hyperactivity experienced by such pupils present mainstream educators with a unique set of challenges and opportunities. In this article, Neil Humphrey, Senior Lecturer in the Psychology of Education…
Humphrey, Neil
School Factors Associated with Mainstream Progress in Secondary Education for Included Pupils with Autism Spectrum Disorders
This research examined the factors promoting inclusion of young people with Autism Spectrum Disorders (ASD) in mainstream secondary schools, and noted high levels of behavioral difficulties in these pupils. The size of the secondary school, and the class size, impacted positively on the pupils with Autism, and the number of other pupils with…
Osborne, Lisa A.; Reed, Phil
School factors associated with mainstream progress in secondary education for included pupils with Autism Spectrum Disorders
This research examined the factors promoting inclusion of young people with Autism Spectrum Disorders (ASD) in mainstream secondary schools, and noted high levels of behavioral difficulties in these pupils. The size of the secondary school, and the class size, impacted positively on the pupils with Autism, and the number of other pupils with Special Educational Needs (SEN) statements and the
Lisa A. Osborne; Phil Reed
Should binge eating disorder be included in the DSM-V? A critical review of the state of the evidence.
Binge eating disorder (BED) was introduced in 1994 as a provisional eating disorder diagnosis. The core symptom is recurrent binge eating in the absence of inappropriate compensatory behaviors and/or extreme dietary restraint. This review examines the status of the literature on BED according to five criteria that have been proposed to determine whether BED warrants inclusion in the psychiatric nosology as a distinct eating disorder. We conclude that each of these criteria was met. There is a commonly accepted definition of and assessment approach to BED. The clinical utility and validity of BED have been established, and BED is distinguishable from both bulimia nervosa and obesity. BED should be included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. PMID:18370619
Striegel-Moore, Ruth H; Franko, Debra L
Simultaneous measurement of adenosine triphosphate release and aggregation potentiates human platelet aggregation responses for some subjects, including persons with Quebec platelet disorder.
Platelet aggregometry and dense granule adenosine triphosphate (ATP) release assays are helpful to diagnose platelet disorders. Some laboratories simultaneously measure aggregation and ATP release using Chronolume® a commercial reagent containing D-luciferin, firefly luciferase and magnesium. Chronolume® can potentiate sub-maximal aggregation responses, normalising canine platelet disorder findings. We investigated if Chronolume® potentiates human platelet aggregation responses after observing discrepancies suspicious of potentiation. Among patients simultaneously tested by light transmission aggregometry (LTA) on two instruments, 18/43 (42%), including 14/24 (58%) with platelet disorders, showed full secondary aggregation with one or more agonists only in tests with Chronolume®. As subjects with Quebec platelet disorder (QPD) did not show the expected absent secondary aggregation responses to epinephrine in tests with Chronolume®, the reason for the discrepancy was investigated using samples from 10 QPD subjects. Like sub-threshold ADP (0.75 ?M), Chronolume® significantly increased QPD LTA responses to epinephrine (p<0.0001) and it increased both initial and secondary aggregation responses, leading to dense granule release. This potentiation was not restricted to QPD and it was mimicked adding 1-2 mM magnesium, but not D-luciferin or firefly luciferase, to LTA assays. Chronolume® potentiated the ADP aggregation responses of QPD subjects with a reduced response. Furthermore, it increased whole blood aggregation responses of healthy control samples to multiple agonists, tested at concentrations used for the diagnosis of platelet disorders (p values <0.05). Laboratories should be aware that measuring ATP release with Chronolume® can potentiate LTA and whole blood aggregation responses, which alters findings for some human platelet disorders, including QPD. PMID:22234747
Hayward, C P M; Moffat, K A; Castilloux, J-F; Liu, Y; Seecharan, J; Tasneem, S; Carlino, S; Cormier, A; Rivard, G E
Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure
A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.
Yang, Jihui (Lakeshore, CA); Shi, Xun (Troy, MI); Bai, Shengqiang (Shanghai, CN); Zhang, Wenqing (Shanghai, CN); Chen, Lidong (Shanghai, CN); Yang, Jiong (Shanghai, CN)
Rosai–Dorfman disease of multiple organs, including the epicardium: An unusual case with poor prognosis
Rosai–Dorfman disease (RDD) is a benign proliferative histiocytic disorder predominantly of the lymph nodes with extranodal involvement in some cases. However, serous membranes are seldom involved in the extranodal cases, and epicardial involvement is never reported. Most RDD cases show a self-limiting process with good prognosis and corticosteroid treatment in some patients exhibiting good effect. We recently observed a case
Jiquan Chen; Hao Tang; Bing Li; Qingyu Xiu
Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.
The field of science and medicine has experienced a flood of data and technology associated with the human genome project. Over 10,000 human diseases have been genetically defined, but little progress has been made with respect to the clinical application of this knowledge. A notable exception to this exists for pachyonychia congenita (PC), a rare, dominant-negative keratin disorder. The establishment of a non-profit organization, PC Project, has led to an unprecedented coalescence of patients, scientists, and physicians with a unified vision of developing novel therapeutics for PC. Utilizing the technological by-products of the human genome project, such as RNA interference (RNAi) and quantitative RT-PCR (qRT-PCR), physicians and scientists have collaborated to create a candidate siRNA therapeutic that selectively inhibits a mutant allele of KRT6A, the most commonly affected PC keratin. In vitro investigation of this siRNA demonstrates potent inhibition of the mutant allele and reversal of the cellular aggregation phenotype. In parallel, an allele-specific quantitative real-time RT-PCR assay has been developed and validated on patient callus samples in preparation for clinical trials. If clinical efficacy is ultimately demonstrated, this "first-in-skin" siRNA may herald a paradigm shift in the treatment of dominant-negative genetic disorders. PMID:18495438
Leachman, Sancy A; Hickerson, Robyn P; Hull, Peter R; Smith, Frances J D; Milstone, Leonard M; Lane, E Birgitte; Bale, Sherri J; Roop, Dennis R; McLean, W H Irwin; Kaspar, Roger L
Incorporating Interoperability Functionality for Increasing Patient Safety with PCA-Included Multiple Infusion Therapy
\\u000a Implementation of interoperability in an infusion therapy system intends to enhance safety, by allowing intercommunication\\u000a among medical devices connected to a patient. Some postoperative specific cases entail the patient with multiple drug delivery\\u000a devices. As adverse drug events (ADEs) can occur with the use of infusion pumps, the multiplication of those devices at the\\u000a patient's bedside establishes the need of
S. M. Krishnan; M. Vanicatte; I. Lee; J. M. Goldman
Multiple effects of repetitive transcranial magnetic stimulation on neuropsychiatric disorders.
Repetitive transcranial magnetic stimulation (rTMS) is a new tool that has been used for the treatment of patients with neuropsychiatric disorders. However, the mechanisms underlying the effects of rTMS are still unclear. We analyzed the changes in mRNA expression in mouse brain that occurred after rTMS with an Affymetrix GeneChip. Following 20days of rTMS, many genes were differentially expressed in the mouse brain. Downregulation of Period 2 and 3 mRNA expression levels and a subsequent decrease in food and water intake were observed. HSP70 mRNA expression levels were upregulated after transient and chronic rTMS. In N2A 150Q cells, an upregulation of HSP70 mRNA and protein levels and subsequent cell-protective effects were observed after chronic rTMS. In addition, dopamine receptor 2 mRNA expression levels were downregulated, and a subsequent decrease in the binding of [(3)H]raclopride was observed. These results indicated that the modulation of several genes may be involved in the therapeutic mechanisms of chronic rTMS for patients with neuropsychiatric disorders. PMID:23524259
Ikeda, Tetsurou; Kurosawa, Masaru; Morimoto, Chikao; Kitayama, Shigeo; Nukina, Nobuyuki
Long-term Methylphenidate Therapy in Children With Comorbid Attention-Deficit Hyperactivity Disorder and Chronic Multiple Tic Disorder
Background: This study examined changes in attention- deficit hyperactivity (ADHD) behaviors and motor and vo- cal tics during long-term treatment with methylphenidate. Methods: Thirty-four prepubertal children with ADHD and chronic multiple tic disorder (who had participated in an 8-week, double-blind, placebo-controlled methylphen- idate evaluation) were evaluated at 6-month intervals for 2 years as part of a prospective, nonblind, follow-up study.
Kenneth D. Gadow; Jeffrey Sverd; Joyce Sprafkin; Edith E. Nolan; Steven Grossman
Including Parent Training in the Early Childhood Special Education Curriculum for Children With Autism Spectrum Disorders
Parent training has been shown to be a very effective method for promoting gen- eralization and maintenance of skills in children with autism. However, despite its well- established benefits, few public school programs include parent training as part of the early childhood special education (ECSE) curriculum. Barriers to the provision of parent training include the need for parent education models
Brooke Ingersoll; Anna Dvortcsak
Metastatic calcinosis (including calcinosis cutis) in a young dog with multiple urinary tract abnormalities.
Metastatic calcinosis associated with chronic renal failure and multiple urinary tract abnormalities was diagnosed in a 6-month-old Brittany spaniel that was presented with calcinosis cutis. This case report highlights the importance of skin as an indicator of systemic disease. The aetiopathogenesis of the four main types of tissue calcification is defined and discussed with an emphasis on metastatic calcinosis. PMID:21410567
Muller, Arnaud; Degorce-Rubiales, Frédérique; Guagučre, Eric
A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder
The pleiotropic messenger molecule nitric oxide (NO) has been implicated in a variety of higher CNS functions, including learning, memory, and emotionality. In the human brain, NO is predominantly formed by neuronal NO synthase (NOS-I), while the so-called ' endothelial' isoform NOS-III also con- tributes to NO generation. We recently reported that NOS-III knockout mice display decreased adult neurogenesis and
Andreas Reif; Alexander Strobel; Christian P. Jacob; Sabine Herterich; Christine M. Freitag; Theresia Töpner; Rainald Mössner; Sabrina Fritzen; Angelika Schmitt; Klaus-Peter Lesch
Ampliative medicament allergy: concomitant sensitivity to multiple medicaments including yellow soft paraffin, white soft paraffin, gentian violet and Span 20.
A patient developed multiple rare medicament contact allergies including sensitivities to gentian violet, yellow and white soft paraffin, and Span 20 (sorbitan monolaurate). Nickel sensitivity antedated these medicament allergies. The possibility that nickel sensitivity is a marker of predilection to develop multiple medicament allergies was tested. We were unable to demonstrate an increased incidence of nickel sensitivity in a group of patients with 2 or more medicament allergies. PMID:7105686
Lawrence, C M; Smith, A G
In the context of studies on the psy chophysiological differences between alterpersonalities in patients with multiple personality disorder (MPD), a patient with diminished need for anesthetics, especially analgesics, during major surgery is described. Psychophysiologic study of MPD patients during anesthesia is recommended, as the relation between doses of medication and their effects can be directly assessed.
Nico Moleman; Jan B. F. Hulscher; Onno van der Hart; D. Nico Moleman; Gert L. Scheepstra
Disorder-induced incoherent scattering losses in photonic crystal waveguides: Bloch mode reshaping, multiple scattering, and breakdown of the Beer-Lambert law
Through a combined theoretical and experimental study of disorder-induced incoherent scattering losses in slow-light photonic crystal slab waveguides, we show the importance of Bloch mode reshaping and multiple scattering. We describe a convenient and fully three-dimensional theoretical treatment of disorder-induced extrinsic scattering, including the calculation of backscatter and out-of-plane losses per unit cell, and the extrapolation of the unit-cell loss
M. Patterson; S. Hughes; S. Schulz; D. M. Beggs; T. P. White; L. O'Faolain; T. F. Krauss
Deficits in adults with Autism Spectrum Disorders when processing multiple objects in dynamic scenes
Scientific Abstract People with autism spectrum disorder (ASD) process visual information in a manner that is distinct from typically developing individuals. They may be less sensitive to people's goals and, more generally, focus on visual details instead of the entire scene. To examine these differences, people with and without ASD were asked to detect changes in dynamic scenes with multiple elements. Participants viewed a brief video of a person or an inanimate object moving from one object to another; after a delay, they reported whether a second video was the same or different. Possible changes included the figure, the object the figure was moving from, or the object it was moving toward (the 'goal'). We hypothesized that individuals with ASD would be less sensitive to changes in scenes with people, particularly elements that might be the person's goal. Alternately, people with ASD might attend to fewer elements regardless of whether the scene included a person. Our results indicate that, like controls, people with ASD noticed a change in the 'goal' object at the end of a person's movement more often than the object at the start. However, the group with ASD did not undergo the developmental improvement when detecting changes in start and end objects that was evident typically. This led to deficits in adults with ASD that were not specific to scenes with people or to 'goals'. Improvements in visual processing that underlie mature representation of scenes may not occur in ASD, suggesting late developing brain processes are affected.
O'Hearn, Kirsten; Lakusta, Laura; Schroer, Elizabeth; Minshew, Nancy; Luna, Beatriz
Multiple Informant Agreement on the Anxiety Disorders Interview Schedule in Youth with Autism Spectrum Disorders
Abstract Objective The purpose of this study was to examine child, parent, and clinician's consensus agreement on the Anxiety Disorders Interview Schedule, Child and Parent versions (ADIS-C/P) in a sample of children and adolescents with autism spectrum disorders (ASD). Method Youth with ASD (n=85; age range=7–17 years) and their parents were each administered the ADIS-C/P by a trained clinician. Consensus diagnoses were determined in a clinical conference using best estimate procedures that incorporated all available information. Results Children and youth with ASD diagnoses generally showed poor diagnostic agreement with parents and clinical consensus, whereas parents showed good-to-excellent diagnostic agreement with clinical consensus diagnoses. Diagnostic agreement between parents and consensus was moderated by the specific ASD diagnosis. Otherwise, the pattern of relationships did not systematically differ as a function of age or externalizing comorbidity. Conclusions These data suggest that parent and youth agreement regarding the presence of clinical levels of anxiety is markedly poor among youth with ASD. Additionally, clinicians are likely to base their diagnostic impressions on parent report, placing minimal emphasis on child report.
Ehrenreich May, Jill; Wood, Jeffrey J.; Jones, Anna M.; De Nadai, Alessandro S.; Lewin, Adam B.; Arnold, Elysse B.; Murphy, Tanya K.
Importin-? negatively regulates multiple aspects of mitosis including RANGAP1 recruitment to kinetochores
Importin-? is the main vector for interphase nuclear protein import and plays roles after nuclear envelope breakdown. Here we show that importin-? regulates multiple aspects of mitosis via distinct domains that interact with different classes of proteins in human cells. The C-terminal region (which binds importin-?) inhibits mitotic spindle pole formation. The central region (harboring nucleoporin-binding sites) regulates microtubule dynamic functions and interaction with kinetochores. Importin-? interacts through this region with NUP358/RANBP2, which in turn binds SUMO-conjugated RANGAP1 in nuclear pores. We show that this interaction continues after nuclear pore disassembly. Overexpression of importin-?, or of the nucleoporin-binding region, inhibited RANGAP1 recruitment to mitotic kinetochores, an event that is known to require microtubule attachment and the exportin CRM1. Co-expressing either importin-?–interacting RANBP2 fragments, or CRM1, restored RANGAP1 to kinetochores and rescued importin-?–dependent mitotic dynamic defects. These results reveal previously unrecognized importin-? functions at kinetochores exerted via RANBP2 and opposed by CRM1.
Roscioli, Emanuele; Di Francesco, Laura; Bolognesi, Alessio; Giubettini, Maria; Orlando, Serena; Harel, Amnon; Schinina, Maria Eugenia
Experience of gratitude, awe and beauty in life among patients with multiple sclerosis and psychiatric disorders
Background Feelings of gratitude and awe facilitate perceptions and cognitions that go beyond the focus of illness and include positive aspects of one's personal and interpersonal reality, even in the face of disease. We intended to measure feelings of gratitude, awe, and experiences of beauty in life among patients with multiple sclerosis and psychiatric disorders, particularly with respect to their engagement in specific spiritual/religious practices and their life satisfaction. Methods We conducted a cross-sectional survey with standardized questionnaires to measure engagement in various spiritual practices (SpREUK-P) and their relation to experiences of Gratitude, Awe and Beauty in Life and life satisfaction (BMLSS-10). In total, 461 individuals (41?±?13 years; 68% women) with multiple sclerosis (46%) and depressive (22%) or other psychiatric disorders (32%) participated. Results Among participants, 23% never, 43% rarely, 24% often, and 10% frequently experienced Gratitude. In contrast, 41% never, 37% rarely, 17% often, and 6% frequently experienced Awe. Beauty in Life was never experienced by 8% of the sample, and 28% rarely, 46% often, and 18% frequently experienced it. Gratitude (F?=?9.2; p?=?.003) and Beauty in Life (F?=?6.0; p?=?.015) were experienced significantly more often by women than men. However, the experience of Awe did not differ between women and men (F?=?2.2; n.s.). In contrast to our hypothesis, Gratitude/Awe cannot explain any relevant variance in patients' life satisfaction (R2?=?.04). Regression analyses (R2?=?.42) revealed that Gratitude/Awe can be predicted best by a person's engagement in religious practices, followed by other forms of spiritual practices and life satisfaction. Female gender was a weak predictor and underlying disease showed no effect. Conclusions Gratitude/Awe could be regarded as a life orientation towards noticing and appreciating the positive in life - despite the symptoms of disease. Positive spirituality/religiosity seems to be a source of gratitude and appreciation in life, whereas patients with neither spiritual nor religious sentiments (R-S-) seem to have a lower awareness for these feelings.
Genetic Evidence Implicating Multiple Genes in the MET Receptor Tyrosine Kinase Pathway in Autism Spectrum Disorder
A functional promoter variant of the gene encoding the MET receptor tyrosine kinase alters SP1 and SUB1 transcription factor binding, and is associated with autism spectrum disorder (ASD). Recent analyses of postmortem cerebral cortex from ASD patients revealed altered expression of MET protein and three transcripts encoding proteins that regulate MET signaling, hepatocyte growth factor (HGF), urokinase plasminogen activator receptor (PLAUR) and plasminogen activator inhibitor-1 (SERPINE1). To address potential risk conferred by multiple genes in the MET signaling pathway, we screened all exons and 5? promoter regions for variants in the five genes encoding proteins that regulate MET expression and activity. Identified variants were genotyped in 664 families (2,712 individuals including 1,228 with ASD) and 312 unrelated controls. Replicating our initial findings, family-based association test (FBAT) analyses demonstrated that the MET promoter variant rs1858830 C allele was associated with ASD in 101 new families (P=0.033). Two other genes in the MET signaling pathway also may confer risk. A haplotype of the SERPINE1 gene exhibited significant association. In addition, the PLAUR promoter variant rs344781 T allele was associated with ASD by both FBAT (P=0.006) and case-control analyses (P=0.007). The PLAUR promoter rs344781 relative risk was 1.93 (95% Confidence Interval [CI]: 1.12?3.31) for genotype TT and 2.42 (95% CI: 1.38?4.25) for genotype CT compared to genotype CC. Gene-gene interaction analyses suggested a significant interaction between MET and PLAUR. These data further support our hypothesis that genetic susceptibility impacting multiple components of the MET signaling pathway contributes to ASD risk.
Campbell, Daniel B.; Li, Chun; Sutcliffe, James S.; Persico, Antonio M.; Levitt, Pat
Dubowitz Syndrome Is a Complex Comprised of Multiple, Genetically Distinct and Phenotypically Overlapping Disorders
Dubowitz syndrome is a rare disorder characterized by multiple congenital anomalies, cognitive delay, growth failure, an immune defect, and an increased risk of blood dyscrasia and malignancy. There is considerable phenotypic variability, suggesting genetic heterogeneity. We clinically characterized and performed exome sequencing and high-density array SNP genotyping on three individuals with Dubowitz syndrome, including a pair of previously-described siblings (Patients 1 and 2, brother and sister) and an unpublished patient (Patient 3). Given the siblings' history of bone marrow abnormalities, we also evaluated telomere length and performed radiosensitivity assays. In the siblings, exome sequencing identified compound heterozygosity for a known rare nonsense substitution in the nuclear ligase gene LIG4 (rs104894419, NM_002312.3:c.2440C>T) that predicts p.Arg814X (MAF:0.0002) and an NM_002312.3:c.613delT variant that predicts a p.Ser205Leufs*29 frameshift. The frameshift mutation has not been reported in 1000 Genomes, ESP, or ClinSeq. These LIG4 mutations were previously reported in the sibling sister; her brother had not been previously tested. Western blotting showed an absence of a ligase IV band in both siblings. In the third patient, array SNP genotyping revealed a de novo ?3.89 Mb interstitial deletion at chromosome 17q24.2 (chr 17:62,068,463–65,963,102, hg18), which spanned the known Carney complex gene PRKAR1A. In all three patients, a median lymphocyte telomere length of ?1st centile was observed and radiosensitivity assays showed increased sensitivity to ionizing radiation. Our work suggests that, in addition to dyskeratosis congenita, LIG4 and 17q24.2 syndromes also feature shortened telomeres; to confirm this, telomere length testing should be considered in both disorders. Taken together, our work and other reports on Dubowitz syndrome, as currently recognized, suggest that it is not a unitary entity but instead a collection of phenotypically similar disorders. As a clinical entity, Dubowitz syndrome will need continual re-evaluation and re-definition as its constituent phenotypes are determined.
Stewart, Douglas R.; Pemov, Alexander; Johnston, Jennifer J.; Sapp, Julie C.; Yeager, Meredith; He, Ji; Boland, Joseph F.; Burdett, Laurie; Brown, Christina; Gatti, Richard A.; Alter, Blanche P.; Biesecker, Leslie G.; Savage, Sharon A.
Rugulactone and its analogues exert antibacterial effects through multiple mechanisms including inhibition of thiamine biosynthesis.
Rugulactone is a dihydro-?-pyrone isolated from the plant Cryptocarya rugulosa in 2009. It has been reported to display IkB kinase (IKK) inhibitory activity, as well as antibiotic activity in several strains of pathogenic bacteria. However, its biological targets and mode of action in bacteria have not yet been explored. Here we present enantioselective syntheses of rugulactone and of some corresponding activity-based protein profiling (ABPP) probes. We found that the ABPP probes in this study are more potent than rugulactone against Staphyloccocus aureus NCTC 8325, S. aureus Mu50, Listeria welshimeri SLCC 5334 and Listeria monocytogenes EGD-e, and that molecules of this class probably exert their antibacterial effect through a combination of targets. These targets include covalent inhibition of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMPP) kinase (ThiD), which is an essential component of the thiamine biosynthesis pathway in bacteria. This represents the first example of a small-molecule inhibitor of ThiD. PMID:22653914
Nodwell, Matthew B; Menz, Helge; Kirsch, Stefan F; Sieber, Stephan A
Investigation of multiple roots of the resistive wall mode dispersion relation, including kinetic effects
The resistive wall mode instability in tokamak plasmas has a complex frequency which can be determined by a dispersion relation that is cubic, in general, leading to three distinct roots. A simplified model of the dispersion relation, including kinetic effects, is presented and used to explore the behavior of these roots. By changing the plasma rotation frequency, it is shown that one root has a slow mode rotation frequency (less than the inverse wall time) while the other two rotate more quickly, one leading and one lagging the plasma rotation frequency. When realistic experimental parameters from the National Spherical Torus Experiment [M. Ono et al., Nucl. Fusion 40, 557 (2000)] are used, however, only one slow rotating, near-marginal stability root is found, consistent with present experiments and more detailed calculations with the MISK code [B. Hu et al., Phys. Plasmas 12, 057301 (2005)]. Electron collisionality acts to stabilize one of the rotating roots, while ion collisionality can stabilize the other. In devices with low rotation and low collisionality, these two rotating roots may manifest themselves, but they are likely to remain stable.
Berkery, J. W.; Sabbagh, S. A. [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York 10027 (United States); Betti, R. [Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543 (United States)
An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders
This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.
Bell, I.R.; Miller, C.S.; Schwartz, G.E. (Univ. of Arizona Health Sciences Center, Tucson (United States))
The issue of satanic ritual abuse has gained widespread public and professional attention in. the past 10 years. During therapy, many adult AMPI) (multiple personality disorder) patients describe memo- ries of .such abuse beginning in childhood..Simultaneou.sly, there are pre-school children reporting cnrrent incidents of sexual and physical abuse involving salanism in day care settings. Professionals specifi- cally addressing the day
Susan C. Van Benschoten
Associations Between Multiple Types of Stress and Disordered Eating Among Girls and Boys in Middle School
Stress is common during adolescence, yet no known studies have linked particular types of stress (performance, relationship,\\u000a education, financial, and family) with disordered eating among adolescents in middle school. The present study investigated\\u000a sex differences in types of stress and how multiple types of stress were associated with girls' and boys' body dissatisfaction,\\u000a dieting behaviors, and bulimic symptoms. We found
Elizabeth H. Blodgett Salafia; Jessica L. Lemer
The Cost Savings of Expanding Medicaid Eligibility to Include Currently Uninsured Homeless Adults with Substance Use Disorders
Following the June 2012 Supreme Court ruling that states are no longer mandated to expand their Medicaid programs in 2014 as part of the Affordable Care Act, many states plan to opt out of the expansion, citing affordability as their primary concern. In response to this controversy, the present study evaluated the cost savings of expanding Medicaid coverage to include currently ineligible homeless adults with substance use disorders, a subset of the population that incurs some of the greatest societal costs and is disproportionately impacted by uninsurance. Using a time horizon of 7 years, separate analyses were conducted for state and federal governments, and then a final analysis evaluated the combined costs for the other two models. Results of the study demonstrate that, although the expansion will be associated with a net cost when combining state and federal expenses and savings, states will experience tremendous savings if they choose to participate.
Zur, Julia; Mojtabai, Ramin; Li, Suhui
The cost savings of expanding Medicaid eligibility to include currently uninsured homeless adults with substance use disorders.
Following the June 2012 Supreme Court ruling that states are no longer mandated to expand their Medicaid programs in 2014 as part of the Affordable Care Act, many states plan to opt out of the expansion, citing affordability as their primary concern. In response to this controversy, the present study evaluated the cost savings of expanding Medicaid coverage to include currently ineligible homeless adults with substance use disorders, a subset of the population that incurs some of the greatest societal costs and is disproportionately impacted by uninsurance. Using a time horizon of 7 years, separate analyses were conducted for state and federal governments, and then a final analysis evaluated the combined costs for the other two models. Results of the study demonstrate that, although the expansion will be associated with a net cost when combining state and federal expenses and savings, states will experience tremendous savings if they choose to participate. PMID:24198085
Psychiatric comorbidity including nicotine dependence among individuals with eating disorder criteria in an adult general population sample.
The goal was to analyze psychiatric disorders among individuals who satisfied at least one eating disorder criterion (EDC). The data derived from a cross-sectional survey study with a probability sample of residents of a northern German area with 4075 study participants, aged 18-64 years (participation rate 70.2%). Face-to-face in-home computer-aided interviews (Composite International Diagnostic Interview) were used to assess the diagnostic criteria of eating disorders and nicotine dependence, alcohol dependence, depressive, anxiety, and somatoform disorders according to the Diagnostic and Statistical Manual (DSM-IV). Former or current smokers had an odds ratio (OR) of 1.7 (95% confidence intervals, CI, 1.1-2.4 and 1.1-2.6, respectively) for one EDC compared with never smokers. Subjects with a lifetime psychiatric disorder were more likely to have two or more EDC than individuals who never had the respective disorder (nicotine dependence: OR 2.5, CI 1.5-4.2; alcohol dependence or abuse: OR 2.4, CI 1.2-4.7; depressive disorders: OR 2.2, CI 1.4-3.4; anxiety disorders: OR 2.9, CI 1.9-4.5). To conclude, nicotine dependence, alcohol dependence or abuse, depressive disorders, and anxiety disorders are related to two or more EDC in this adult general population sample. PMID:16364452
John, Ulrich; Meyer, Christian; Rumpf, Hans-Jürgen; Hapke, Ulfert
Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Anxiety in Children : A Multiple Baseline Design Analysis
Objective: The present study evaluated a 10-week psychosocial treatment designed specifically for children with attention-deficit/hyperactivity disorder (ADHD) and a comorbid anxiety disorder. Method: Using a nonconcurrent multiple baseline design, the authors treated 8 children ages 8-12 with ADHD, combined type, and at least 1 of 3 major anxiety…
Jarrett, Matthew A.; Ollendick, Thomas H.
AD synapses contain abundant A? monomer and multiple soluble oligomers, including a 56 kDa assembly
Much evidence indicates that soluble amyloid beta (A?) oligomers are key mediators of early cognitive loss, but the localization and key peptide species remain unclear. We have used flow cytometry analysis to demonstrate that surviving Alzheimer's disease (AD) synapses accumulate both A? and p-tau. The present experiments use peptide-specific xMAP assays and Western blotting to identify the A? peptide species in synaptosome-enriched samples from normal human subjects, neurologic controls, and AD cases. A?40 peptide levels did not vary, but both A?42 and A? oligomers were increased in soluble AD extracts, with oligomer levels 20-fold higher in aqueous compared to detergent extracts. In Western blots, a ladder of SDS-stable oligomers was observed in AD cases, varying in size from monomer, the major peptide observed, to larger assemblies up to about 200 kD and larger. Multiple oligomers, including monomer, small oligomers, a 56 kD assembly, and APP were correlated with the A? level measured in flow cytomety-purified synaptosomes. These results suggest that multiple APP processing pathways are active in AD synapses and multiple soluble oligomeric assemblies may contribute to synaptic dysfunction.
Sokolow, Sophie; Henkins, Kristen M.; Bilousova, Tina; Miller, Carol A.; Vinters, Harry V.; Poon, Wayne; Cole, Gregory M.; Gylys, Karen Hoppens
Overcoming the Diffraction Limit Using Multiple Light Scattering in a Highly Disordered Medium
We report that disordered media made of randomly distributed nanoparticles can be used to overcome the diffraction limit of a conventional imaging system. By developing a method to extract the original image information from the multiple scattering induced by the turbid media, we dramatically increase a numerical aperture of the imaging system. As a result, the the resolution is enhanced by more than five times over the diffraction limit and a field of view is extended over the physical area of the camera. Our technique lays the foundation to use a turbid medium as a far-field superlens.
Choi, Youngwoon; Yang, Taeseok Daniel; Fang-Yen, Christopher; Kang, Pilsung; Lee, Kyoung Jin; Dasari, Ramachandra R.; Feld, Michael S.; Choi, Wonshik
A nonlinear model for fluid flow in a multiple-zone composite reservoir including the quadratic gradient term
Based on material balance and Darcy's law, the governing equation with the quadratic pressure gradient term was deduced. Then the nonlinear model for fluid flow in a multiple-zone composite reservoir including the quadratic gradient term was established and solved using a Laplace transform. A series of standard log-log type curves of 1-zone (homogeneous), 2-zone and 3-zone reservoirs were plotted and nonlinear flow characteristics were analysed. The type curves governed by the coefficient of the quadratic gradient term (?) gradually deviate from those of a linear model with time elapsing. Qualitative and quantitative analyses were implemented to compare the solutions of the linear and nonlinear models. The results showed that differences of pressure transients between the linear and nonlinear models increase with elapsed time and ?. At the end, a successful application of the theoretical model data against the field data shows that the nonlinear model will be a good tool to evaluate formation parameters more accurately.
Wang, Xiao-Lu; Fan, Xiang-Yu; He, Yong-Ming; Nie, Ren-Shi; Huang, Quan-Hua
Relationship between Temporomandibular Disorders, Widespread Palpation Tenderness and Multiple Pain Conditions: A Case - Control Study
The multiple bodily pain conditions in temporomandibular disorders (TMD) have been associated with generalized alterations in pain processing. The purpose of this study was to examine the relationship between the presence of widespread body palpation tenderness (WPT) and the likelihood of multiple comorbid pain conditions in TMD patients and controls. This case-control study was conducted in 76 TMD subjects with WPT, 83 TMD subjects without WPT, and 181 non-TMD matched control subjects. The study population was also characterized for clinical pain, experimental pain sensitivity, and related psychological phenotypes. Results showed that (1) TMD subjects reported an average of 1.7 comorbid pain conditions compared to 0.3 reported by the control subjects (p<0.001); (2) Compared to control subjects, the odds ratio (OR) for multiple comorbid pain conditions is higher for TMD subjects with WPT [OR 8.4 (95% CI 3.1–22.8) for TMD with WPT versus OR 3.3 (95% CI 1.3–8.4) for TMD without WPT]; (3) TMD subjects with WPT presented with reduced pressure pain thresholds (PPTs) in both cranial and extra-cranial regions compared to TMD subjects without WPT; and (4) TMD subjects with WPT reported increased somatic symptoms. These findings suggest that pain assessment outside of the orofacial region may prove valuable for the classification, diagnosis, and management of TMD patients.
Chen, Hong; Slade, Gary; Lim, Pei Feng; Miller, Vanessa; Maixner, William; Diatchenko, Luda
Coexistence of Multiple Genotypes, Including Newly Identified Genotypes, in Outbreaks of Gastroenteritis Due to Norovirus in Japan
Norovirus (NV) (formerly called Norwalk-like virus) is the most common cause of acute nonbacterial gastroenteritis in humans. Recently, we reported an NV genotyping scheme based on variability in the capsid N-terminal/shell (N/S) domain gene (Katayama et al., Virology 299:225-239, 2002). We found 19 genotypes, including nine of genogroup I and 10 of genogroup II. In the present study, we investigated the molecular epidemiology of NV from 66 outbreaks that occurred in Saitama Prefecture, Japan, from 1997 to 2002. We screened 416 stool specimens by a real-time reverse transcription (RT)-PCR method (Kageyama et al., J. Clin. Microbiol. 41:1548-1557, 2003) and detected 156 NV-positive specimens, from which we amplified the capsid N/S domain gene by RT-PCR and then cloned the PCR products. After sequencing these clones, we obtained 368 sequence variants (strains). By applying our classification scheme to the strains from Saitama and other published strains, we identified a total of 31 genotypes, including an additional five genotypes for genogroup I and seven for genogroup II. Of the 31 genotypes, 26 were present in the Saitama area during that time period. These results provide additional evidence for the great diversity of human NV genotypes. Specimens from all shellfish-related infections contained multiple genotypes, including several new genotypes. On the other hand, single genotypes were observed mostly in outbreaks that originated in semiclosed communities. Thus, the number of NV genotypes in each outbreak depended on the route of transmission.
Kageyama, Tsutomu; Shinohara, Michiyo; Uchida, Kazue; Fukushi, Shuetsu; Hoshino, Fuminori B.; Kojima, Shigeyuki; Takai, Reiko; Oka, Tomoichiro; Takeda, Naokazu; Katayama, Kazuhiko
Joint source based analysis of multiple brain structures in studying major depressive disorder
We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.
Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang
The Presentation of Narcissistic Personality Disorder in an Octogenarian: Converging Evidence from Multiple Sources
Little is known about personality disorders (PDs) in later life. One reason for this dearth of knowledge is that many investigators believe that PDs soften with age. Recent anecdotal and empirical evidence, however, suggests that PDs are still very relevant in later life and may actually have unique presentations and consequences. The DSM-IV PD criteria seem to overlook these possibilities, perhaps because the personalities of older adults were not sufficiently understood when these criteria were written. But without age-appropriate criteria, clinicians and investigators who work with older adults may be unable to measure PDs adequately in their clients and research participants. A starting point for better understanding these disorders in older adults is the presentation of rich, empirical, clinical descriptions of symptoms and related behaviors using data from multiple instruments and sources. To this end, we describe in depth a case of narcissistic PD (NPD) in a woman in her mid 80s. This case study reveals that NPD is indeed relevant in the context of later life and impairs functioning in significant ways.
Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.
Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults. PMID:24723877
Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J
Manual for the psychotherapeutic treatment of acute and post-traumatic stress disorders following multiple shocks from implantable cardioverter defibrillator (ICD).
Background: In view of the increasing number of implanted cardioverter defibrillators (ICD), the number of people suffering from so-called "multiple ICD shocks" is also increasing. The delivery of more than five shocks (appropriate or inappropriate) in 12 months or three or more shocks (so called multiple shocks) in a short time period (24 hours) leads to an increasing number of patients suffering from severe psychological distress (anxiety disorder, panic disorder, adjustment disorder, post-traumatic stress disorder). Untreated persons show chronic disease processes and a low rate of spontaneous remission and have an increased morbidity and mortality. Few papers have been published concerning the psychotherapeutic treatment for these patients. Objective: The aim of this study is to develop a psychotherapeutic treatment for patients with a post-traumatic stress disorder or adjustment disorder after multiple ICD shocks. Design: Explorative feasibility study: Treatment of 22 patients as a natural design without randomisation and without control group. The period of recruitment was three years, from March 2007 to March 2010. The study consisted of two phases: in the first phase (pilot study) we tested different components and dosages of psychotherapeutic treatments. The final intervention programme is presented in this paper. In the second phase (follow-up study) we assessed the residual post-traumatic stress symptoms in these ICD patients. The time between treatment and follow-up measurement was 12 to 30 months. Population: Thirty-one patients were assigned to the Department of Psychocardiology after multiple shocks. The sample consisted of 22 patients who had a post-traumatic stress disorder or an adjustment disorder and were willing and able to participate. They were invited for psychological treatment. 18 of them could be included into the follow-up study. Methods: After the clinical assessment at the beginning and at the end of the inpatient treatment a post-treatment assessment with questionnaires followed. In this follow-up measurement, minimum 12 months after inpatient treatment, posttraumatic stress was assessed using the "Impact of Event Scale" (IES-R). Setting: Inpatient treatment in a large Heart and Thorax Centre with a Department of Psychocardiology (Kerckhoff Heart Centre). Results: From the 18 patients in the follow-up study no one reported complaints of PTSD. 15 of them reported a high or even a very high decrease of anxiety and avoidance behaviour. Conclusions: The fist step of the treatment development seems to be successful. It shows encouraging results with an acceptable dosage. The second step of our work is in process now: we evaluate the treatment manual within other clinical institutions and a higher number of psychotherapists. This leads in the consequence to a controlled and randomised comparison study. PMID:24403967
Jordan, Jochen; Titscher, Georg; Peregrinova, Ludmila; Kirsch, Holger
Multiple Channel Exposure Therapy: Combining Cognitive-Behavioral Therapies for the Treatment of Posttraumatic Stress Disorder with Panic Attacks
A large proportion of patients who present for treatment of posttraumatic stress disorder (PTSD) experience comorbid panic attacks, yet it is unclear to what extent currently available PTSD treatment programs address this problem. Here we describe a newly developed treatment, multiple-channel exposure therapy (M-CET), for comorbid PTSD and panic…
Falsetti, Sherry A.; Resnick, Heidi S.; Davis, Joanne
Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis
Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD.
Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.
Potential for Early-Life Immune Insult Including Developmental Immunotoxicity in Autism and Autism Spectrum Disorders: Focus on Critical Windows of Immune Vulnerability
Early-life immune insults (ELII) including xenobiotic-induced developmental immunotoxicity (DIT) are important factors in childhood and adult chronic diseases. However, prenatal and perinatal environmentally induced immune alterations have yet to be considered in depth in the context of autism and autism spectrum disorders (ASDs). Numerous factors produce early-life-induced immune dysfunction in offspring, including exposure to xenobiotics, maternal infections, and other prenatal–neonatal
Rodney R. Dietert; Janice M. Dietert
Plasmon losses in core-level photoemission spectra studied by the quantum Landau formula including full multiple scattering
We study the angular and energy dependence of surface and bulk plasmon losses accompanying deep core excitations in simple metals. Here full multiple scatterings of photoelectrons are taken into account before and after the plasmon losses within the quantum Landau formula, which can describe overall features of the photoemission bands. For example, multiple plasmon loss features can be calculated by use of the formula. Two simple metals, Al and Na, are studied here. The depth profiles of the plasmon losses are strongly influenced by the elastic scatterings. The model assuming single elastic scatterings overestimates the losses from deep emitters due to the forward focusing effects, whereas the model accounting for full multiple scatterings gives a much rapidly decaying function of the depth due to the defocusing effects and rich structures due to the photoelectron diffraction. The single elastic scattering approximation gives a poor result both for the depth profiles and for the loss spectra. The present multiple scattering calculations successfully explain the azimuthal dependence of the loss spectra, which reflect the local geometry around the emitters.
Kazama, Misato; Shinotsuka, Hiroshi; Ohori, Yusuke; Niki, Kaori; Fujikawa, Takashi; Kövér, László
Fatigue and Sleep-Disordered Breathing in Multiple Sclerosis: A Clinically Relevant Association?
Background. Fatigue in patients with multiple sclerosis (MS) is highly prevalent and severely impacts quality of life. Recent studies suggested that sleep-disordered breathing (SDB) significantly contributes to fatigue in MS. Study Objective. To evaluate the importance of routine respirography in MS patients with severe fatigue and to explore the effects of treatment with continuous positive airway pressure (CPAP). Patients and Methods. We prospectively assessed the presence of severe fatigue, as defined by a score of ?5.0 on the Fatigue Severity Scale (FSS), in 258 consecutive MS patients. Ninety-seven patients (38%) suffered from severe fatigue, whereof 69 underwent overnight respirography. Results. We diagnosed SDB in 28 patients (41%). Male sex was the only independent associate of SDB severity (P = 0.003). CPAP therapy in 6 patients was associated with a significant reduction of FSS scores (5.8 ± 0.5 versus 4.8 ± 0.6, P = 0.04), but the scores remained pathological (?4.0) in all patients. Conclusion. Respirography in MS patients with severe fatigue should be considered in daily medical practice, because SDB frequency is high and CPAP therapy reduces fatigue severity. However, future work is needed to understand the real impact of CPAP therapy on quality of life in this patient group.
Kallweit, Ulf; Baumann, Christian R.; Harzheim, Michael; Hidalgo, Hildegard; Pohlau, Dieter; Bassetti, Claudio L.; Linnebank, Michael; Valko, Philipp O.
Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel.
Light transmission aggregometry (LTA) is used worldwide for the investigation of heritable platelet function disorders (PFDs), but interpretation of results is complicated by the feedback effects of ADP and thromboxane A(2) (TxA(2)) and by the overlap with the response of healthy volunteers. Over 5 years, we have performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or ATP secretion test results were identified in 58% of participants. In 84% of these, the patterns of response were consistent with defects in Gi receptor signaling, the TxA(2) pathway, and dense granule secretion. Participants with defects in signaling to Gq-coupled receptor agonists and to collagen were also identified. Targeted genotyping identified 3 participants with function-disrupting mutations in the P2Y(12) ADP and TxA(2) receptors. The results of the present study illustrate that detailed phenotypic analysis using LTA and ATP secretion is a powerful tool for the diagnosis of PFDs. Our data also enable subdivision at the level of platelet-signaling pathways and in some cases to individual receptors. We further demonstrate that most PFDs can be reliably diagnosed using a streamlined panel of key platelet agonists and specified concentrations suitable for testing in most clinical diagnostic laboratories. PMID:23002116
Dawood, Ban B; Lowe, Gillian C; Lordkipanidzé, Marie; Bem, Danai; Daly, Martina E; Makris, Mike; Mumford, Andrew; Wilde, Jonathan T; Watson, Steve P
Evaluation of participants with suspected heritable platelet function disorders including recommendation and validation of a streamlined agonist panel
Light transmission aggregometry (LTA) is used worldwide for the investigation of heritable platelet function disorders (PFDs), but interpretation of results is complicated by the feedback effects of ADP and thromboxane A2 (TxA2) and by the overlap with the response of healthy volunteers. Over 5 years, we have performed lumi-aggregometry on 9 platelet agonists in 111 unrelated research participants with suspected PFDs and in 70 healthy volunteers. Abnormal LTA or ATP secretion test results were identified in 58% of participants. In 84% of these, the patterns of response were consistent with defects in Gi receptor signaling, the TxA2 pathway, and dense granule secretion. Participants with defects in signaling to Gq-coupled receptor agonists and to collagen were also identified. Targeted genotyping identified 3 participants with function-disrupting mutations in the P2Y12 ADP and TxA2 receptors. The results of the present study illustrate that detailed phenotypic analysis using LTA and ATP secretion is a powerful tool for the diagnosis of PFDs. Our data also enable subdivision at the level of platelet-signaling pathways and in some cases to individual receptors. We further demonstrate that most PFDs can be reliably diagnosed using a streamlined panel of key platelet agonists and specified concentrations suitable for testing in most clinical diagnostic laboratories.
Lowe, Gillian C.; Lordkipanidze, Marie; Bem, Danai; Daly, Martina E.; Makris, Mike; Mumford, Andrew; Wilde, Jonathan T.; Watson, Steve P.
Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias
BackgroundMutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias.Methodology\\/Principal FindingsWe evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either
Slimane Allali; Jean-Baptiste Muller; Raja Brauner; Diana Lourenço; Radia Boudjenah; Vasiliki Karageorgou; Christine Trivin; Henri Lottmann; Stephen Lortat-Jacob; Claire Nihoul-Fékété; Olivier de Dreuzy; Ken McElreavey; Anu Bashamboo; Joerg Gromoll
Ca analysis: An Excel based program for the analysis of intracellular calcium transients including multiple, simultaneous regression analysis?
Here I present an Excel based program for the analysis of intracellular Ca transients recorded using fluorescent indicators. The program can perform all the necessary steps which convert recorded raw voltage changes into meaningful physiological information. The program performs two fundamental processes. (1) It can prepare the raw signal by several methods. (2) It can then be used to analyze the prepared data to provide information such as absolute intracellular Ca levels. Also, the rates of change of Ca can be measured using multiple, simultaneous regression analysis. I demonstrate that this program performs equally well as commercially available software, but has numerous advantages, namely creating a simplified, self-contained analysis workflow.
Greensmith, David J.
P450 Oxidoreductase Deficiency: A Disorder of Steroidogenesis with Multiple Clinical Manifestations
NSDL National Science Digital Library
Cytochrome P450 enzymes catalyze the biosynthesis of steroid hormones and metabolize drugs. There are seven human type I P450 enzymes in mitochondria and 50 type II enzymes in endoplasmic reticulum. Type II enzymes, including both drug-metabolizing and some steroidogenic enzymes, require electron donation from a two-flavin protein, P450 oxidoreductase (POR). Although knockout of the POR gene causes embryonic lethality in mice, we discovered human POR deficiency as a disorder of steroidogenesis associated with the Antley-Bixler skeletal malformation syndrome and found mild POR mutations in phenotypically normal adults with infertility. Assay results of mutant forms of POR using the traditional but nonphysiologic assay (reduction of cytochrome c) did not correlate with patient phenotypes; assays based on the 17,20 lyase activity of P450c17 (CYP17) correlated with clinical phenotypes. The POR sequence in 842 normal individuals revealed many polymorphisms; amino acid sequence variant A503V is encoded by ~28% of human alleles. POR A503V has about 60% of wild-type activity in assays with CYP17, CYP2D6, and CYP3A4, but nearly wild-type activity with P450c21, CYP1A2, and CYP2C19. Activity of a particular POR variant with one P450 enzyme will not predict its activity with another P450 enzyme: Each POR-P450 combination must be studied individually. Human POR transcription, initiated from an untranslated exon, is regulated by Smad3/4, thyroid receptors, and the transcription factor AP-2. A promoter polymorphism reduces transcription to 60% in liver cells and to 35% in adrenal cells. POR deficiency is a newly described disorder of steroidogenesis, and POR variants may account for some genetic variation in drug metabolism.
Walter L. Miller (San Francisco;University of California REV)
Clinical and neuroimaging correlation of movement disorders in multiple sclerosis: case series and review of the literature.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, in which movement disorders (MD) have been reported very rarely. Anatomopathological studies of MS indicate two main processes: inflammation and neurodegeneration. The occurrence of the movement disorders symptoms in MS revises the question of aetiology of these two diseases. During the 10 years of observation in our out-patient clinic and MS units we examined about 2500 patients with clinically definite MS diagnosed according to the revised McDonald's criteria. Only in 10 cases we found coexistence of MS and MD signs. Below we present rare cases of patients with coexistence of MS and chorea, pseudoathetosis, dystonia and parkinsonism. Searching for the strategic focal lesion in our case series showed demyelinating plaques placed in the thalamus most often. Detailed analysis of the clinical, pharmacological and neuroimaging correlations may help to explain the character of movement disorders in MS. PMID:24729346
Potulska-Chromik, A; Rudzinska, M; Nojszewska, M; Podlecka-Pi?towska, A; Szczudlik, A; Zakrzewska-Pniewska, B; Go??biowski, M
Nonadiabatic dynamics of electron transfer in solution: Explicit and implicit solvent treatments that include multiple relaxation time scales
The development of efficient theoretical methods for describing electron transfer (ET) reactions in condensed phases is important for a variety of chemical and biological applications. Previously, dynamical dielectric continuum theory was used to derive Langevin equations for a single collective solvent coordinate describing ET in a polar solvent. In this theory, the parameters are directly related to the physical properties of the system and can be determined from experimental data or explicit molecular dynamics simulations. Herein, we combine these Langevin equations with surface hopping nonadiabatic dynamics methods to calculate the rate constants for thermal ET reactions in polar solvents for a wide range of electronic couplings and reaction free energies. Comparison of explicit and implicit solvent calculations illustrates that the mapping from explicit to implicit solvent models is valid even for solvents exhibiting complex relaxation behavior with multiple relaxation time scales and a short-time inertial response. The rate constants calculated for implicit solvent models with a single solvent relaxation time scale corresponding to water, acetonitrile, and methanol agree well with analytical theories in the Golden rule and solvent-controlled regimes, as well as in the intermediate regime. The implicit solvent models with two relaxation time scales are in qualitative agreement with the analytical theories but quantitatively overestimate the rate constants compared to these theories. Analysis of these simulations elucidates the importance of multiple relaxation time scales and the inertial component of the solvent response, as well as potential shortcomings of the analytical theories based on single time scale solvent relaxation models. This implicit solvent approach will enable the simulation of a wide range of ET reactions via the stochastic dynamics of a single collective solvent coordinate with parameters that are relevant to experimentally accessible systems.
Schwerdtfeger, Christine A.; Soudackov, Alexander V.; Hammes-Schiffer, Sharon
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Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence.
The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77; p = 0.026) and decreasing regional annual ambient UVR (r= -0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72; p = 0.046), although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia, and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are required.
Staples, Judith A; Ponsonby, Anne-Louise; Lim, Lynette L-Y; McMichael, Anthony J
Development and validation of the SDDS-PC screen for multiple mental disorders in primary care
and scale performance. Sensitivity, specificity, and posi- tive predictive value, respectively, were calculated for the following scales: alcohol abuse or dependence (62%, 98%, and 54%), generalized anxiety disorder (90%, 54%, and 5%), major depression (90%, 77%, and 40%), obsessive- compulsive disorder (65%, 73%, and 5%), panic disor- der (78%, 80%, and 21%), and suicidal ideation (43%, 91%, and 51%). Replication
W. Eugene Broadhead; Andrew C. Leon; Myrna M. Weissman; James E. Barrett; Robert S. Blacklow; Thomas T. Gilbert; Martin B. Keller; Mark Olfson; Edmund S. Higgins
Immediate-Release Methylphenidate for ADHD in Children With Comorbid Chronic Multiple Tic Disorder
ObjectiveTo examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit\\/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%).
A cassette with seven unique restriction sites, including octanucleotide sequences: extension of multiple-cloning-site plasmids.
A 27-bp synthetic DNA cassette was constructed which contains the restriction sites of the two rare-cutter enzymes NotI and SfiI and, in an overlapping arrangement, those of five enzymes with 6-bp recognition sequences: ApaI, BalI, NdeI, SacII, XmaIII. The protruding termini of the fragment allow its insertion into any EcoRI-cut DNA creating a new EcoRI site at one side of the cassette only. This fragment was integrated into the pUC18-like multiple-cloning-site (MCS) plasmids pTZ18R and pTZ19R, producing a set of vectors which carry seven additional unique restriction sites (giving a total of 17) within their MCS. They still provide the capabilities of simple recombinant selection by blue/white coloured colonies, creation of single-stranded DNA in the presence of a helper phage, and in vitro transcription of cloned DNA using T7 RNA-polymerase. Plasmids with two copies of the DNA cassette inserted into their MCS were also constructed. Beside the advantages they provide in some cloning procedures, these latter plasmids, which carry a tandem repeat, are valuable sources of related 27-bp fragments, with features similar to the original but with different cloning termini. PMID:2551781
Hoheisel, J D
Components of the Legionella pneumophila Flagellar Regulon Contribute to Multiple Virulence Traits, Including Lysosome Avoidance and Macrophage Death
Legionella pneumophila is a motile intracellular pathogen of macrophages and amoebae. When nutrients become scarce, the bacterium induces expression of transmission traits, some of which are dependent on the flagellar sigma factor FliA (?28). To test how particular components of the L. pneumophila flagellar regulon contribute to virulence, we compared a fliA mutant with strains whose flagellar construction is disrupted at various stages. We find that L. pneumophila requires FliA to avoid lysosomal degradation in murine bone marrow-derived macrophages (BMM), to regulate production of a melanin-like pigment, and to regulate binding to the dye crystal violet, whereas motility, flagellar secretion, and external flagella or flagellin are dispensable for these activities. Thus, in addition to flagellar genes, the FliA sigma factor regulates an effector(s) or regulator(s) that contributes to other transmissive traits, notably inhibition of phagosome maturation. Whether or not the microbes produced flagellin, all nonmotile L. pneumophila mutants bound BMM less efficiently than the wild type, resulting in poor infectivity and a loss of contact-dependent death of BMM. Therefore, bacterial motility increases contact with host cells during infection, but flagellin is not an adhesin. When BMM contact by each nonmotile strain was promoted by centrifugation, all the mutants bound BMM similarly, but only those microbes that synthesized flagellin induced BMM death. Thus, the flagellar regulon equips the aquatic pathogen L. pneumophila to coordinate motility with multiple traits vital to virulence.
Molofsky, A. B.; Shetron-Rama, L. M.; Swanson, Michele S.
Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data.
Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (n=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling-defined high risk, and the proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling-defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling-risk designation. (Clinicaltrials.gov identifier: NCT00081939). PMID:22733020
Waheed, Sarah; Mitchell, Alan; Usmani, Saad; Epstein, Joshua; Yaccoby, Shmuel; Nair, Bijay; van Hemert, Rudy; Angtuaco, Edgardo; Brown, Tracy; Bartel, Twyla; McDonald, James; Anaissie, Elias; van Rhee, Frits; Crowley, John; Barlogie, Bart
Latent introduction to the Netherlands of multiple antibiotic resistance including NDM-1 after hospitalisation in Egypt, August 2013.
We describe the introduction of various multi-drug resistant bacterial strains, including an NDM-1-producing Klebsiella pneumoniae, through a traveller returning from Egypt, where they had been admitted to a private hospital. All family members of the patient were colonised with one or more extended-spectrum beta-lactamase producing strains. These findings emphasise the importance of adherence to isolation precautions for returning patients and suggest the need for inclusion of Enterobacteriaceae in admission screening. PMID:24176580
Bathoorn, E; Friedrich, A W; Zhou, K; Arends, J P; Borst, D M; Grundmann, H; Rossen, J W
Mood Disorders
... depressive disorder Dysthymic disorder (a chronic, mild depression) Bipolar disorder (also called manic depression) Mood disorders can increase a person's risk for heart disease, diabetes, and other diseases. Treatments include medication, psychotherapy, or a combination of both. ...
Rapid Switching of Mood in Families With Multiple Cases of Bipolar Disorder
Background:Heterogeneitywithinthediagnosticcon- structofbipolardisorderismostlikelyanobstacletodis- covering its causes. Phenomena in the bipolar spec- trum,includingrapidcycling,cyclothymia,andaffective instability of borderline personality, may be important markers of etiologic heterogeneity. Rapid switching of mood may be central to these phenomena. Methods:Weperformedacase-controlstudy,usingdi- agnostic data from a multisite bipolar disorder linkage study, to explore clinical and demographic factors po- tentially related to rapid switching in bipolar disorder. Participantswere18yearsorolderandmembersofafam- ily in
Dean F. MacKinnon; Peter P. Zandi; Elliot Gershon; John I. Nurnberger; Theodore Reich; J. Raymond DePaulo
Treatment of depressive disorders in primary care - protocol of a multiple treatment systematic review of randomized controlled trials
Background Several systematic reviews have summarized the evidence for specific treatments of primary care patients suffering from depression. However, it is not possible to answer the question how the available treatment options compare with each other as review methods differ. We aim to systematically review and compare the available evidence for the effectiveness of pharmacological, psychological, and combined treatments for patients with depressive disorders in primary care. Methods/Design To be included, studies have to be randomized trials comparing antidepressant medication (tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), hypericum extracts, other agents) and/or psychological therapies (e.g. interpersonal psychotherapy, cognitive therapy, behavioural therapy, short dynamically-oriented psychotherapy) with another active therapy, placebo or sham intervention, routine care or no treatment in primary care patients in the acute phase of a depressive episode. Main outcome measure is response after completion of acute phase treatment. Eligible studies will be identified from available systematic reviews, from searches in electronic databases (Medline, Embase and Central), trial registers, and citation tracking. Two reviewers will independently extract study data and assess the risk of bias using the Cochrane Collaboration's corresponding tool. Meta-analyses (random effects model, inverse variance weighting) will be performed for direct comparisons of single interventions and for groups of similar interventions (e.g. SSRIs vs. tricyclics) and defined time-windows (up to 3 months and above). If possible, a global analysis of the relative effectiveness of treatments will be estimated from all available direct and indirect evidence that is present in a network of treatments and comparisons. Discussion Practitioners do not only want to know whether there is evidence that a specific treatment is more effective than placebo, but also how the treatment options compare to each other. Therefore, we believe that a multiple treatment systematic review of primary-care based randomized controlled trials on the most important therapies against depression is timely.
Insertional translocation leading to a 4q13 duplication including the EPHA5 gene in two siblings with attention-deficit hyperactivity disorder.
An insertional translocation (IT) can result in pure segmental aneusomy for the inserted genomic segment allowing to define a more accurate clinical phenotype. Here, we report on two siblings sharing an unbalanced IT inherited from the mother with a history of learning difficulty. An 8-year-old girl with developmental delay, speech disability, and attention-deficit hyperactivity disorder (ADHD), showed by GTG banding analysis a subtle interstitial alteration in 21q21. Oligonucleotide array comparative genomic hybridization (array-CGH) analysis showed a 4q13.1-q13.3 duplication spanning 8.6 Mb. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones confirmed the rearrangement, a der(21)ins(21;4)(q21;q13.1q13.3). The duplication described involves 50 RefSeq genes including the EPHA5 gene that encodes for the EphA5 receptor involved in embryonic development of the brain and also in synaptic remodeling and plasticity thought to underlie learning and memory. The same rearrangement was observed in a younger brother with behavioral problems and also exhibiting ADHD. ADHD is among the most heritable of neuropsychiatric disorders. There are few reports of patients with duplications involving the proximal region of 4q and a mild phenotype. To the best of our knowledge this is the first report of a duplication restricted to band 4q13. This abnormality could be easily missed in children who have nonspecific cognitive impairment. The presence of this behavioral disorder in the two siblings reinforces the hypothesis that the region involved could include genes involved in ADHD. PMID:23824631
Matoso, Eunice; Melo, Joana B; Ferreira, Susana I; Jardim, Ana; Castelo, Teresa M; Weise, Anja; Carreira, Isabel M
A Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization
Background Cardiac repolarization, the process by which cardiomyocytes return to their resting potential after each beat, is a highly regulated process that is critical for heart rhythm stability. Perturbations of cardiac repolarization increase the risk for life-threatening arrhythmias and sudden cardiac death. While genetic studies of familial long QT syndromes have uncovered several key genes in cardiac repolarization, the major heritable contribution to this trait remains unexplained. Identification of additional genes may lead to a better understanding of the underlying biology, aid in identification of patients at risk for sudden death, and potentially enable new treatments for susceptible individuals. Methods and Results We extended and refined a zebrafish model of cardiac repolarization by using fluorescent reporters of transmembrane potential. We then conducted a drug-sensitized genetic screen in zebrafish, identifying 15 genes, including GINS3, that affect cardiac repolarization. Testing these genes for human relevance in two concurrently completed genome wide association studies revealed that the human GINS3 ortholog is located in the 16q21 locus which is strongly associated with QT interval. Conclusions This sensitized zebrafish screen identified 15 novel myocardial repolarization genes. Among these genes is GINS3, the human ortholog of which is a major locus in two concurrent human genome wide association studies of QT interval. These results reveal a novel network of genes that regulate cardiac repolarization.
Milan, David J.; Kim, Albert M.; Winterfield, Jeffrey R.; Jones, Ian L.; Pfeufer, Arne; Sanna, Serena; Arking, Dan E.; Amsterdam, Adam H.; Sabeh, Khaled M.; Mably, John D.; Rosenbaum, David S.; Peterson, Randall T.; Chakravarti, Aravinda; Kaab, Stefan; Roden, Dan M.; MacRae, Calum A.
Optical observations of 23 distant Jupiter Family Comets, including 36P/Whipple at multiple phase angles
We present photometry on 23 Jupiter Family Comets (JFCs) observed at large heliocentric distance, primarily using the 2.5-m Isaac Newton Telescope (INT). Snapshot images were taken of 17 comets, of which five were not detected, three were active and nine were unresolved and apparently inactive. These include 103P/Hartley 2, the target of the NASA Deep Impact extended mission, EPOXI. For six comets we obtained time-series photometry and use this to constrain the shape and rotation period of these nuclei. The data are not of sufficient quantity or quality to measure precise rotation periods, but the time-series do allow us to measure accurate effective radii and surface colours. Of the comets observed over an extended period, 40P/Väisälä 1, 47P/Ashbrook-Jackson and P/2004 H2 (Larsen) showed faint activity which limited the study of the nucleus. Light curves for 94P/Russell 4 and 121P/Shoemaker-Holt 2 reveal rotation periods of around 33 and 10h, respectively, although in both cases these are not unique solutions. 94P was observed to have a large range in magnitudes implying that it is one of the most elongated nuclei known, with an axial ratio a/b >= 3. 36P/Whipple was observed at five different epochs, with the INT and ESO's 3.6-m NTT, primarily in an attempt to confirm the preliminary short rotation period apparent in the first data set. The combined data set shows that the rotation period is actually longer than 24h. A measurement of the phase function of 36P's nucleus gives a relatively steep ? = 0.060 +/- 0.019. Finally, we discuss the distribution of surface colours observed in JFC nuclei, and show that it is possible to trace the evolution of colours from the Kuiper Belt Object (KBO) population to the JFC population by applying a `dereddening' function to the KBO colour distribution. Based on observations collected at the European Southern Observatory, Chile (proposals: ESO Nos 74.C-0125, 278.C-5040), and at the Isaac Newton Group of telescopes on La Palma (proposals: I/2005A/11, I/2006A/7). E-mail: email@example.com ‡ Present address: NASA Jet Propulsion Laboratory, Science Division, 4800 Oak Grove Drive, Pasadena, CA 91101, USA.
Snodgrass, C.; Lowry, S. C.; Fitzsimmons, A.
[Post-traumatic stress disorder (PTSD): the syndrome with multiple faces].
We choose to discuss from the PTSD's point of view because this diagnostic reference is commonly used. We wish outline its restrictive sight which could prevent the professional from having a diagnosis of PTSD. We don't want to say there is a PTSD everywhere but it appears to us that a traumatic reading can be a precious advantage for the clinician to establish a real therapeutic relation with some patients. Post-traumatic syndrome differs from the majority of other diagnostic categories as it includes in its criteria the presumptive cause of the trauma (criterion A). In the case that this syndrome originates in war experiences, the presumed cause presents itself as an exceptional event overcoming the individual's resources. The notion of war traumatisation has been extended to other events such as catastrophes, physical attacks, rapes, child and wife battering, and sexual abuses. But the events which cause PTSD (Post-Traumatic Stress Disorder) are significantly more numerous. It can be seen that medical events such as giving birth, miscarriage, heart attack, cancer, or hospitalisation following resuscitation may give rise to PTSD. Further, people experiencing prolonged periods of distress may equally develop a post-traumatic syndrome without any particular event having occurred to surpass their defences. It's the case of the Prolonged Duress Stress Disorder (PDSD). The series of discontinuous stress "waste" the psychic balance and may give rise, at one moment, to posttraumatic symptoms described in DSM, without any specific stressful event. The existence of criterion A is therefore not a necessary prerequisite in establishing a diagnosis of PTSD. It is, in fact, very difficult to predict which events could cause a PTSD, and this, especially, as the subjective aspects count at least as much as the objective aspects. The clinician should have to carefully explore how the patient experienced the event or, how he apprehended the event itself and it's outcome, if he wants get the traumatic range of a life event. The feeling of deep distress, the feeling of being trapped, the loss of control, the collapse of basic beliefs, the feeling that one's life is in jeopardy, that the physical integrity is (really or in one's imagination) threatened, the feeling of helplessness, are quite as much clues for a possible PTSD which hides behind others clinical manifestations either psychological or somatic. Furthermore, the "pure" form described in the DSM and grouping together three further criteria (reliving events, avoiding stimuli associated with the trauma, hyper-reactivity) is extremely rare in the chronic form. An untreated post-traumatic syndrome evolves with time and may present, initially, with very different pathological symptoms giving rise to equally varied diagnoses. Different etiopathogenic models propose to account for the PTSD 's heterogeneous appearance and instability with time. The comorbidity concept sees the PTSD as an independent entity other independent pathologies coexist with. The typologic concept suggests that the PTSD is an independent entity which shows different clinical appearances based on symptomatic descriptions. The "cascade" concept suggests to see the PTSD as an independent entity which offers, with time, different symptomatic appearances, in evolution, because of events caused by after effects, in different areas of the PTSD itself. All of these concepts outline the transnosologic appearance of the PTSD which makes it hardly recognizable. The "chronic" syndrome is rarely diagnosed forming a real challenge to prevention. In effect, the present authors insist on the crucial nature of early detection of PTSD since the greater the time elapsed the more difficult it becomes due to the evolutionary aspect of the syndrome, which initially has more readily recognizable symptoms. The consequences of an unrecognised PTSD are serious and affect both the individual and his immediate family and friends, contributing further to the aggravation of the problems. When a PTSD is
Waddington, A; Ampelas, J-F; Mauriac, F; Bronchard, M; Zeltner, L; Mallat, V
Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders.
In a retrospective cohort of more than 4 million white and black male United States (US) veterans, we explored the role of specific prior autoimmune, infectious, inflammatory, and allergic disorders in the etiology of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Patients were selected from computerized inpatient discharge records at US Veterans Affairs hospitals. The analysis included 4641 patients (3040 white, 1601 black) and 2046 patients (1312 white; 734 black) with a discharge diagnosis of MM and MGUS, respectively. Using Poisson regression, we calculated age-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for the relationship between MM, MGUS, and specific prior medical conditions. Significantly elevated risks of MM were associated with broad categories of autoimmune (RR, 1.15; 95% CI, 1.02-1.28), infectious (RR, 1.29; 95% CI, 1.20-1.38), and inflammatory disorders (RR, 1.18; 95% CI, 1.10-1.27) and specific prior autoimmune (polymyositis/dermatomyositis, systemic sclerosis, autoimmune hemolytic anemia, pernicious anemia, and ankylosing spondylitis), infectious (pneumonia, hepatitis, meningitis, septicemia, herpes zoster, and poliomyelitis), and inflammatory (glomerulonephritis, nephrotic syndrome, and osteoarthritis) disorders. Risks for MGUS were generally of similar magnitude. Our results indicate that various types of immune-mediated conditions might act as triggers for MM/MGUS development. PMID:18239085
Brown, Linda Morris; Gridley, Gloria; Check, David; Landgren, Ola
Report from the European Myeloma Network on interphase FISH in multiple myeloma and related disorders
The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing procedure; 3) most importantly, PCs must be purified or specifically identified; 4) positive cut-off levels should be relatively conservative: 10% for fusion or break-apart probes, 20% for numerical abnormalities; 5) informative probes should be combined to best effect; 6) in specialist laboratories, a single experienced analyst is considered adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes should be available for clinically relevant abnormalities; 10) the clinical report should be expressed clearly and must state the percentage of PC involved and the method used for identification; 11) a retrospective European based FISH data bank linked to clinical data should be generated; and 12) prospective analysis should be centralized for upcoming trials based on the recommendations made. The European Myeloma Network aims to build on these recommendations to establish standards for a common European data base to define subgroups with prognostic significance.
Ross, Fiona M.; Avet-Loiseau, Herve; Ameye, Genevieve; Gutierrez, Norma C.; Liebisch, Peter; O'Connor, Sheila; Dalva, Klara; Fabris, Sonia; Testi, Adele M.; Jarosova, Marie; Hodkinson, Clare; Collin, Anna; Kerndrup, Gitte; Kuglik, Petr; Ladon, Dariusz; Bernasconi, Paolo; Maes, Brigitte; Zemanova, Zuzana; Michalova, Kyra; Michau, Lucienne; Neben, Kai; Hermansen, N. Emil U.; Rack, Katrina; Rocci, Alberto; Protheroe, Rebecca; Chiecchio, Laura; Poirel, Helene A; Sonneveld, Pieter; Nyegaard, Mette; Johnsen, Hans E.
Restraint and Cancellation: Multiple Inhibition Deficits in Attention Deficit Hyperactivity Disorder
We used variations of the stop signal task to study two components of motor response inhibition--the ability to withhold a strong response tendency (restraint) and the ability to cancel an ongoing action (cancellation)--in children with a diagnosis of attention deficit hyperactivity disorder (ADHD) and in non-ADHD controls of similar age (ages…
Schachar, Russell; Logan, Gordon D.; Robaey, Philippe; Chen, Shirley; Ickowicz, Abel; Barr, Cathy
Multiple Informant Agreement and the Anxiety Disorders Interview Schedule for Parents and Children
ObjectiveTo examine concordance of child, parent, and consensus agreement on the Anxiety Disorders Interview Schedule, Child and Parent versions (ADIS-C\\/P), for an outpatient sample of children and adolescents and to explore moderators of those relations. Child characteristics (age, gender, social desirability), a family environment variable (conflict), and type of diagnoses (internalizing, externalizing) were systematically examined.
Involvement of Youths with Autism Spectrum Disorders or Intellectual Disabilities in Multiple Public Service Systems
The objectives of this study were to estimate the prevalence of autism spectrum disorders (ASD) and intellectual disability (ID) among youths active in at least one of five public service systems: mental health (MH), educational services for youth with serious emotional disturbance (SED), child welfare (CW), juvenile justice (JJ), and alcohol and…
Brookman-Frazee, Lauren; Baker-Ericzen, Mary; Stahmer, Aubyn; Mandell, David; Haine, Rachel A.; Hough, Richard L.
Multiple Legionella pneumophila Type II Secretion Substrates, Including a Novel Protein, Contribute to Differential Infection of the Amoebae Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria lovaniensis
Type II protein secretion (T2S) by Legionella pneumophila is required for intracellular infection of host cells, including macrophages and the amoebae Acanthamoeba castellanii and Hartmannella vermiformis. Previous proteomic analysis revealed that T2S by L. pneumophila 130b mediates the export of >25 proteins, including several that appeared to be novel. Following confirmation that they are unlike known proteins, T2S substrates NttA, NttB, and LegP were targeted for mutation. nttA mutants were impaired for intracellular multiplication in A. castellanii but not H. vermiformis or macrophages, suggesting that novel exoproteins which are specific to Legionella are especially important for infection. Because the importance of NttA was host cell dependent, we examined a panel of T2S substrate mutants that had not been tested before in more than one amoeba. As a result, RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all proved to be required for optimal intracellular multiplication in H. vermiformis but not A. castellanii. Further examination of an lspF mutant lacking the T2S apparatus documented that T2S is also critical for infection of the amoeba Naegleria lovaniensis. Mutants lacking SrnA, PlaC, or ProA, but not those deficient for NttA, were defective in N. lovaniensis. Based upon analysis of a double mutant lacking PlaC and ProA, the role of ProA in H. vermiformis was connected to its ability to activate PlaC, whereas in N. lovaniensis, ProA appeared to have multiple functions. Together, these data document that the T2S system exports multiple effectors, including a novel one, which contribute in different ways to the broad host range of L. pneumophila.
Tyson, Jessica Y.; Pearce, Meghan M.; Vargas, Paloma; Bagchi, Sreya; Mulhern, Brendan J.
Taxonic structure of schizotypal personality disorder: a multiple-instrument, multi-sample study based on mixture models.
This study used a multi-sample, multiple-instrument strategy to evaluate the hypothesis that schizotypal personality disorder (SPD) is taxonic. In Study 1, 721 consecutively admitted inpatients and outpatients were evaluated with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) and the Personality Diagnostic Questionnaire-4+ (PDQ-4+). The data from both questionnaire types were submitted to multivariate normal mixture analysis, which was carried out on factor scores obtained from a three-factor model of SPD criteria; these results supported the hypothesis that SPD is taxonic. The same was true of Study 2, which administered the Semi-structured Interview for DSM-III-R Personality Disorders (SIDP-R) to an independent sample of 537 consecutively admitted outpatients. Similar findings were observed in Study 3, in which the SIDP-R was administered to 225 non-clinical subjects. The results show that the typology of DSM III-R and -IV SPD diagnosis is consistent with the latent structure of SPD features. PMID:16226811
Fossati, Andrea; Citterio, Alessandra; Grazioli, Federica; Borroni, Serena; Carretta, Ilaria; Maffei, Cesare; Battaglia, Marco
Extreme Appraisals of Internal States in Bipolar I Disorder: A Multiple Control Group Study
Thirty individuals with Bipolar I Disorder (16 individuals had relapsed within the last 2 years; 14 individuals had remained\\u000a well over this period) were hypothesized to score higher on extreme positive and negative appraisals of internal state (HAPPI;\\u000a Hypomanic Attitudes and Positive Predictions Inventory) than three control groups: remitted unipolar depression group (n = 22), and non-clinical controls with (n = 16) or without (n = 22)
Warren Mansell; Gemma Paszek; Karen Seal; Rebecca Pedley; Sarah Jones; Nia Thomas; Helena Mannion; Sari Saatsi; Alyson Dodd
Effects of methylphenidate on multiple components of attention in children with attention deficit hyperactivity disorder
Rationale Methylphenidate (MPH) has been shown to be effective in the treatment of attention deficits in children with attention deficit hyperactivity disorder (ADHD). Although a variety of studies have been performed, there is little available information as to which components of attentional functioning are disturbed in ADHD.Objectives The aim of the present study was to monitor the effect of MPH on various
Oliver Tucha; Sylvia Prell; Lara Mecklinger; Christiane Bormann-Kischkel; Sabine Kübber; Martin Linder; Susanne Walitza; Klaus W. Lange
The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGF?1, PTEN, p53 and fibronectin
Recent studies are reviewed indicating that the transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGF?1, PTEN, p53 and fibronectin. The downstream pathways of these factors display multiple nodes of interaction with each other suggesting the existence of a functional network of suppressor factors that serves to maintain normal growth regulation and resist the emergence of transformed variants. Paradoxically, Egr-1 is oncogenic in prostate cancer. In the majority of these cancers PTEN and/or p53 is inactive. It is suggested that these defects in the tumor suppressor network allow for the unopposed induction of TGF?1 and fibronectin, which favor transformation and survival of prostate tumor epithelial cells, explain the role of Egr1 in prostate cancer. Egr1 is a novel and logical target for intervention by gene therapy methods and targeting methods are discussed.
Baron, Veronique; Adamson, Eileen D.; Calogero, Antonella; Ragona, Giuseppe; Mercola, Dan
Neurobehavioral disorders.
Neurobehavioral disorders are composed of a large group of behavioral impairments seen in association with brain disease (e.g., stroke, multiple sclerosis, dementia, and neuro-oncological conditions), transient as well as permanent brain impairments (e.g., metabolic and toxic encephalopathies), and/or injury (e.g., trauma, hypoxia, and/or ischemia). The neurorehabilitative assessment and management of such disorders is often poorly addressed in the context of overall neurological, psychiatric, and rehabilitative care. Too often, more basic, yet critical, aspects of behavioral assessment and treatment are not addressed or only superficially addressed by evaluating clinicians. Physicians often overly rely on pharmacological interventions as initial and/or sole treatment approaches rather than taking a pragmatic biopsychosocial approach that focuses on holistic disease state management. This chapter provides readers with an overview of the common behavioral impairments associated with brain dysfunction due to disease, injury, or toxicity. Details regarding the nature of impairments such as localization-related syndromes, affective disorders and personality disorders, among others are expounded. Principles of neurobehavioral assessment and treatment are examined including general guidelines for eliciting a history and physical, behavioral analysis, and functional behavioral assessment. General treatment caveats are provided including discussion of impairment and disability adaptation, and creation of positive behavioral supports. The topic of pharmacological management of neurobehavioral disorders is covered in numerous other references including Chapter 33 of this text. PMID:23312657
Zasler, Nathan D; Martelli, Michael F; Jacobs, Harvey E
A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability
Abstract Objective The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods Literature databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success.
Gau, Susan Shur-Fen; Mendez, Luis; Montgomery, William; Monk, Julie A.; Altin, Murat; Wu, Shenghu; Lin, Chaucer C.H.; Duenas, Hector J.
The Roles of FMRP-Regulated Genes in Autism Spectrum Disorder: Single- and Multiple-Hit Genetic Etiologies
Autism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental condition characterized by impairments in social interaction and communication and restricted and repetitive behaviors. Although roles for both de novo and familial genetic variation have been documented, the underlying disease mechanisms remain poorly elucidated. In this study, we defined and explored distinct etiologies of genetic variants that affect genes regulated by Fragile-X mental retardation protein (FMRP), thought to play a key role in neuroplasticity and neuronal translation, in ASD-affected individuals. In particular, we developed the Trend test, a pathway-association test that is able to robustly detect multiple-hit etiologies and is more powerful than existing approaches. Exploiting detailed spatiotemporal maps of gene expression within the human brain, we identified four discrete FMRP-target subpopulations that exhibit distinct functional biases and contribute to ASD via different types of genetic variation. We also demonstrated that FMRP target genes are more likely than other genes with similar expression patterns to contribute to disease. We developed the hypothesis that FMRP targets contribute to ASD via two distinct etiologies: (1) ultra-rare and highly penetrant single disruptions of embryonically upregulated FMRP targets ("single-hit etiology") or (2) the combination of multiple less penetrant disruptions of nonembryonic, synaptic FMRP targets ("multiple-hit etiology"). The Trend test provides rigorous support for a multiple-hit genetic etiology in a subset of autism cases and is easily extendible to combining information from multiple types of genetic variation (i.e., copy-number and exome variants), increasing its value to next-generation sequencing approaches.
Steinberg, Julia; Webber, Caleb
Endurance of Multiplication Fact Fluency for Students with Attention Deficit Hyperactivity Disorder
This study examines the relationship between a critical learning outcome of behavioral fluency and endurance, by comparing the effects of two practice procedures on multiplication facts two through nine. The first procedure, called whole time practice trial, consisted of an uninterrupted 1 minute practice time. The second procedure, endurance…
Brady, Kelly K.; Kubina, Richard M., Jr.
Random multiplicative processes and transport in structures with correlated spatial disorder
We show that strong spatial correlations in a random resistor network can dramatically alter its transport properties. We calculate the average logarithmic resistance of a topologically one-dimensional model characterized by a random multiplicative process. We find a transport exponent that depends explicitly on the form of the spatial correlations; we also find that this problem is related to diffusion in
S. Havlin; R. Blumberg Selinger; M. Schwartz; H. E. Stanley; A. Bunde
A Multiple-Models Approach to Violence Risk Assessment Among People with Mental Disorder
Actuarial models for violencerisk assessment have proliferatedin recent years. In this article, we describe an approach that integrates the predictions of many actuarial risk-assessment models, each of which may capture a different but important facet of the interactive relationship between the measured risk factors and violence. Using this multiple-models approach, we ultimately combined the results of five prediction models generated
Steven M. Banks; Pamela Clark Robbins; Eric Silver; Roumen Vesselinov; Henry J. Steadman; John Monahan; Edward P. Mulvey; Paul S. Appelbaum; Thomas Grisso; Loren H. Roth
The objectives of this study were to estimate the prevalence of autism spectrum disorders (ASD) and intellectual disability (ID) among youths active in at least one of five public service systems - mental health [MH], educational services for youth with serious emotional disturbance [SED], child welfare [CW], juvenile justice [JJ], and alcohol and drug services [AD].This study also reports the characteristics and patterns of system involvement among these youths. Results indicate that approximately 12% of a random sample of youths involved in these public service systems had ID or ASD. These disabilities were particularly prevalent in youth in the SED (25%), MH (13%), and CW (13%) systems and were less prevalent in the JJ and AD systems (4% each). Youths with ID or ASD were more likely than other youths to be Caucasian, have a higher socioeconomic status, and be more likely to have externalizing psychiatric and other problems. Of those with ASD or ID, approximately one third were served in more than one service system, with the MH and SED systems most likely to be serving youths with externalizing psychiatric disorders. These findings have important implications for service provision, treatment planning, and workforce development.
Giant and multiple jejunal diverticula presenting as peritonitis a significant challenging disorder
Jejunal diverticula are an uncommon acquired disease that is usually silent and asymptomatic. When symptomatic, they present with chronic nonspecific symptoms like pain, nausea, malnutrition and sometimes with acute presentation like gastrointestinal hemorrhage, peritonitis and obstruction. The majority of complications seen as an acute abdomen similar to appendicitis, cholecystitis or colonic diverticulitis but they also may appear with atypical symptoms. We are presenting a 63-year-old male reported in emergency with painful abdomen and diagnosed as having peritonitis. On laparotomy, we incidentally found giant and multiple jejunal diverticula along with ileal perforation. Nothing was done to the jejunal diverticula, as these were multiple and non-obstructive. In the follow-up of 16 months, the patient was doing well. Jejuno-ileal diverticulosis is a rare condition that continues to present formidable challenges in diagnosis and treatment.
Singal, R; Gupta, S; Airon, A
Optical Detection of Multiple-Trapping Relaxation in Disordered Crystalline Semiconductors
Relaxation of optically excited carriers within localized continuum states in heavily doped crystalline GaAs is directly observed by picosecond luminescence experiments. The relaxation within localized states takes place via thermally activated multiple trapping. Saturation of the relaxation is observed at high temperatures and for small trap densities. The results demonstrate that heavily doped crystalline semiconductors can serve as a simple model for amorphous materials.
Göbel, E. O.; Graudszus, W.
Multiple Self-Healing Squamous Epithelioma in Different Ethnic Groups: More than a Founder Mutation Disorder?
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson–Smith Disease, is a rare cancer-associated genodermatosis with an autosomal dominant inheritance. Affected patients suffer from recurrent skin lesions, which clinically and histologically resemble keratoacanthomas or well-differentiated squamous cell carcinomas, but which, if left, undergo spontaneous regression, leaving pronounced scarring. The majority of MSSE cases previously described were of Scottish ancestry and
Mariella D'Alessandro; Stephanie E Coats; Susan M Morley; Lorna Mackintosh; Gianpaolo Tessari; Alberto Turco; Anne-Marie Gerdes; Gabriella Pichert; Sean Whittaker; Flemming Brandrup; Sigurd Broesby-Olsen; Macarena Gomez-Lira; Giampiero Girolomoni; John C Maize; Ron J Feldman; Naoko Kato; Yukiko Koga; Malcolm A Ferguson-Smith; David R Goudie
Phonological disorder
Articulation disorder; Developmental articulation disorder; Speech distortion; Sound distortion ... and bones that are used to make speech sounds. These changes may include cleft palate and problems ...
Obesity and Psychiatric Disorders: Frequently Encountered Clinical Questions
Obesity is a global epidemic and a health priority, and several psychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia, are associated with an elevated risk of comorbid obesity. Moreover, persons with psychiatric disorders often have multiple risk factors (e.g., poverty and use of psychotropic medications) for excess weight. Excess weight in turn is associated with serious health consequences,
Roger S. McIntyre; Jakub Z. Konarski
Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis.
This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients. PMID:24439517
McNamara, Robert K; Rider, Therese; Jandacek, Ronald; Tso, Patrick
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n?=?396 patients and n?=?659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P?=?0.004, OR?=?2.37, 95% CI?=?1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P?=?0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768
Leblond, Claire S; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemičre, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M; Poustka, Fritz; Freitag, Christine M; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M; Bourgeron, Thomas
Cerebellar Disorders
... Problems with the cerebellum include Cancer Genetic disorders Ataxias - failure of muscle control in the arms and legs that result in movement disorders Degeneration - disorders caused by brain cells decreasing in ...
Mental Disorders
... disorders Psychotic disorders, including schizophrenia There are many causes of mental disorders. Your genes and family history ... Biological factors can also be part of the cause. A traumatic brain injury can lead to a ...
Background Mutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias. Methodology/Principal Findings We evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n?=?11), ambiguous external genitalia without uterus (n?=?33) or hypospadias (n?=?33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein. Conclusions/Significance Mutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations.
Brauner, Raja; Lourenco, Diana; Boudjenah, Radia; Karageorgou, Vasiliki; Trivin, Christine; Lottmann, Henri; Lortat-Jacob, Stephen; Nihoul-Fekete, Claire; De Dreuzy, Olivier; McElreavey, Ken; Bashamboo, Anu
Diagnosis and Treatment of Alcohol-Dependent Patients With Comorbid Psychiatric Disorders
Psychiatric disorders occur more often among alcoholics than among the general population. The psychiatric disorders that alcoholics most frequently experience include mood disorders (e.g., depression), anxiety disorders, and antisocial personality disorder. The evaluation of psychiatric symptoms in alcoholic patients is complicated by the multiple relationships that exist among heavy drinking, psychiatric symptoms, and personality factors. For example, alcoholics with co-occurring
Vania Modesto-Lowe; Henry R. Kranzler
Kinome-wide RNAi studies in human multiple myeloma identify vulnerable kinase targets, including a lymphoid-restricted kinase, GRK6
A paucity of validated kinase targets in human multiple myeloma has delayed clinical deployment of kinase inhibitors in treatment strategies. We therefore conducted a kinome-wide small interfering RNA (siRNA) lethality study in myeloma tumor lines bearing common t(4;14), t(14;16), and t(11;14) translocations to identify critically vulnerable kinases in myeloma tumor cells without regard to preconceived mechanistic notions. Fifteen kinases were repeatedly vulnerable in myeloma cells, including AKT1, AK3L1, AURKA, AURKB, CDC2L1, CDK5R2, FES, FLT4, GAK, GRK6, HK1, PKN1, PLK1, SMG1, and TNK2. Whereas several kinases (PLK1, HK1) were equally vulnerable in epithelial cells, others and particularly G protein–coupled receptor kinase, GRK6, appeared selectively vulnerable in myeloma. GRK6 inhibition was lethal to 6 of 7 myeloma tumor lines but was tolerated in 7 of 7 human cell lines. GRK6 exhibits lymphoid-restricted expression, and from coimmunoprecipitation studies we demonstrate that expression in myeloma cells is regulated via direct association with the heat shock protein 90 (HSP90) chaperone. GRK6 silencing causes suppression of signal transducer and activator of transcription 3 (STAT3) phosphorylation associated with reduction in MCL1 levels and phosphorylation, illustrating a potent mechanism for the cytotoxicity of GRK6 inhibition in multiple myeloma (MM) tumor cells. As mice that lack GRK6 are healthy, inhibition of GRK6 represents a uniquely targeted novel therapeutic strategy in human multiple myeloma.
Zhu, Yuan Xiao; Schmidt, Jessica; Yin, Hongwei; Shi, Chang-Xin; Que, Qiang; Basu, Gargi; Azorsa, David; Perkins, Louise M.; Braggio, Esteban; Fonseca, Rafael; Bergsagel, P. Leif; Mousses, Spyro; Stewart, A. Keith
Mutations in CCNO result in congenital mucociliary clearance disorder with reduced generation of multiple motile cilia.
Using a whole-exome sequencing strategy, we identified recessive CCNO (encoding cyclin O) mutations in 16 individuals suffering from chronic destructive lung disease due to insufficient airway clearance. Respiratory epithelial cells showed a marked reduction in the number of multiple motile cilia (MMC) covering the cell surface. The few residual cilia that correctly expressed axonemal motor proteins were motile and did not exhibit obvious beating defects. Careful subcellular analyses as well as in vitro ciliogenesis experiments in CCNO-mutant cells showed defective mother centriole generation and placement. Morpholino-based knockdown of the Xenopus ortholog of CCNO also resulted in reduced MMC and centriole numbers in embryonic epidermal cells. CCNO is expressed in the apical cytoplasm of multiciliated cells and acts downstream of multicilin, which governs the generation of multiciliated cells. To our knowledge, CCNO is the first reported gene linking an inherited human disease to reduced MMC generation due to a defect in centriole amplification and migration. PMID:24747639
Wallmeier, Julia; Al-Mutairi, Dalal A; Chen, Chun-Ting; Loges, Niki Tomas; Pennekamp, Petra; Menchen, Tabea; Ma, Lina; Shamseldin, Hanan E; Olbrich, Heike; Dougherty, Gerard W; Werner, Claudius; Alsabah, Basel H; Köhler, Gabriele; Jaspers, Martine; Boon, Mieke; Griese, Matthias; Schmitt-Grohé, Sabina; Zimmermann, Theodor; Koerner-Rettberg, Cordula; Horak, Elisabeth; Kintner, Chris; Alkuraya, Fowzan S; Omran, Heymut
The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder
Background Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Methods Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. Results In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Conclusions Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of 'reactive' depression caused by early stressors differs considerably from that of 'reactive' depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD.
Parental Perspectives on the Importance and Likelihood of Adult Outcomes for Children with Autism Spectrum Disorders, Intellectual Disabilities or Multiple Disabilities
Aims: This study examined parental perspectives on the importance and likelihood of future adult outcomes for children with Autism Spectrum Disorders (ASD), Intellectual Disabilities (ID), or Multiple Disabilities (MD) and some of the factors that may affect parental aspirations. Methods: Parents of 105 children with ASD, ID, or MD were presented…
Poon, Kenneth K.; Koh, Lynette; Magiati, Iliana
The effect of intellectual ability on functional activation in a neurodevelopmental disorder: preliminary evidence from multiple fMRI studies in Williams syndrome
Background Williams syndrome (WS) is a rare genetic disorder caused by the deletion of approximately 25 genes at 7q11.23 that involves mild to moderate intellectual disability (ID). When using functional magnetic resonance imaging (fMRI) to compare individuals with ID to typically developing individuals, there is a possibility that differences in IQ contribute to between-group differences in BOLD signal. If IQ is correlated with BOLD signal, then group-level analyses should adjust for IQ, or else IQ should be matched between groups. If, however, IQ is not correlated with BOLD signal, no such adjustment or criteria for matching (and exclusion) based on IQ is necessary. Methods In this study, we aimed to test this hypothesis systematically using four extant fMRI datasets in WS. Participants included 29 adult subjects with WS (17 men) demonstrating a wide range of standardized IQ scores (composite IQ mean = 67, SD = 17.2). We extracted average BOLD activation for both cognitive and task-specific anatomically defined regions of interest (ROIs) in each individual and correlated BOLD with composite IQ scores, verbal IQ scores and non-verbal IQ scores in Spearman rank correlation tests. Results Of the 312 correlations performed, only six correlations (2%) in four ROIs reached statistical significance at a P value < 0.01, but none survived correction for multiple testing. All six correlations were positive. Therefore, none supports the hypothesis that IQ is negatively correlated with BOLD response. Conclusions These data suggest that the inclusion of subjects with below normal IQ does not introduce a confounding factor, at least for some types of fMRI studies with low cognitive load. By including subjects who are representative of IQ range for the targeted disorder, findings are more likely to generalize to that population.
Institute for Mathematics and Applications: Mathematics of Materials and Macromolecules: Multiple Scales, Disorder, and Singularities
The Institute for Mathematics and Applications (IMA) developed this website to promote its conferences and workshops dealing with the applications of mathematics in the study of materials and molecules. Visitors can find information on a particular event's schedule, participants, and accommodations as well as abstracts. The events dealing with the physical sciences include workshops dealing with atomic motion, macroscopic models, and biophysics as well as a program about environmental and geophysical modeling.
MiR-7 Triggers Cell Cycle Arrest at the G1/S Transition by Targeting Multiple Genes Including Skp2 and Psme3
MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress.
Sanchez, Noelia; Gallagher, Mark; Lao, Nga; Gallagher, Clair; Clarke, Colin; Doolan, Padraig; Aherne, Sinead; Blanco, Alfonso; Meleady, Paula
Mean Field Theory of Disordered Neural Networks with Multiple Neuron Interactions.
In this thesis we investigate the effect of including neuron interactions of orders greater than the traditional two (pairwise interactions). To this end we first survey neural network models of the Hopfield type which use mean field theory in their analysis. We then analyze a Hopfield type network model generalized to include higher order interactions and investigate the model numerically and analytically. The numerical analysis consists of the utilization of optimization curves; a technique developed in this thesis. The analytic investigation is by means of a mean field theory. Higher order interactions must be included in neural networks to achieve more accurate physiological realism. Structurally, real neural networks are highly interconnected and neurons are extensively arborized. We find that the storage capacity increases greatly when the order of the interactions is increased. Furthermore, the mean field theory results indicate there is a discontinuous jump in the order parameter from the trivial solution to a solution which has an overlap with only one memory state for orders of interaction greater than three. This makes the memory states of the model very stable against the simultaneous flipping of a large number of neurons. Our results accord with observations on the architecture of actual neural systems in achieving functional efficiency, viz. the 'cost' to make a neuron is very high, whereas the cost to make a connection is very much lower. Real networks can thus efficiently increase their storage capacity and their memory stability by increasing the order of their interactions, without a costly increase in the number of neurons.
Busch, Allan Einar
The revised international autoimmune hepatitis score in chronic liver diseases including autoimmune hepatitis\\/overlap syndromes and autoimmune hepatitis with concurrent other liver disorders
BACKGROUND: We conducted a study in order to determine the usefulness and diagnostic value of International Autoimmune Hepatitis Group (IAHG) score in non-autoimmune hepatitis (AIH) hepatic disorders as well as in AIH\\/overlap syndromes and in cases with coexistence of AIH and other liver diseases. METHODS: We applied the IAHG score in 423 patients with liver diseases excluding patients with AIH,
Panagiotis A Papamichalis; Kalliopi Zachou; George K Koukoulis; Aikaterini Veloni; Efthimia G Karacosta; Lampros Kypri; Ioannis Mamaloudis; Stella Gabeta; Eirini I Rigopoulou; Ansgar W Lohse; George N Dalekos
A progressive neurologic disorder with multiple CNS lesions: a neuroimaging clinicopathologic correlation. Progressive multifocal leukoencephalopathy (PML).
A 51-year-old man with a diagnosis of myelodysplasia and non-Hodgkin's lymphoma underwent an unmatched allogenic bone marrow transplantation and was treated posttransplant with chronic immunosuppressive medication. Eight months following transplantation, he presented with progressive dysarthria, cognitive and visual decline. Evaluation included brain magnetic resonance (MR) imaging demonstrating multifocal areas of increased T2 and FLAIR (fluid attenuated inversion recovery) signals involving the left frontal, parietal, and occipital lobes. The MR lesions demonstrated diffuse increased signal on DWI (diffusion-weighted images) and normal to low signal on ADC (apparent diffusion coefficients). Contrast-enhanced T1 images were unremarkable. Lumbar puncture revealed a mild elevation in cerebrospinal fluid (CSF) protein. CSF PCR assay for viral DNA fragments were negative on two occasions. Serum serology for HIV was negative as well. A brain biopsy was subsequently performed. The clinical and neuroimaging differential diagnoses as well as neuropathologic correlation are presented. PMID:18819185
Chowdhary, Sajeel; Chamberlain, Marc
Activator Gcn4 Employs Multiple Segments of Med15/Gal11, Including the KIX Domain, to Recruit Mediator to Target Genes in Vivo*?
Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4? cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.
Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J.; Palmer, Ira; Kaufman, Joshua D.; Nadaud, Philippe S.; Mukherjee, Sujoy; Wingfield, Paul T.; Jaroniec, Christopher P.; Hinnebusch, Alan G.
Eating Disorders
Eating disorders are serious behavior problems. They can include severe overeating or not consuming enough food to stay ... concern about your shape or weight. Types of eating disorders include Anorexia nervosa, in which you become too ...
Kinetics of 3 H-Serotonin uptake by platelets in infantile autism and developmental language disorder (including five pairs of twins)
The kinetics of 5-HT uptake by platelets was studied in cases of infantile autism and developmental language disorder (DLD) and normal subjects. Two patients of the autism group were twins, and the seven patients of the DLD group were members of four pairs of twins. The Vmax values (means ±SD) for autism and DLD were 6.46±.90 pmol 5-HT\\/107 cells\\/min and
Takemi Katsui; Masahide Okuda; Sagako Usuda; Takeshi Koizumi
Characterization of a Fission Yeast SUMO-1 Homologue, Pmt3p, Required for Multiple Nuclear Events, Including the Control of Telomere Length and Chromosome Segregation
Unlike ubiquitin, the ubiquitin-like protein modifier SUMO-1 and its budding yeast homologue Smt3p have been shown to be more important for posttranslational protein modification than for protein degradation. Here we describe the identification of the SUMO-1 homologue of fission yeast, which we show to be required for a number of nuclear events including the control of telomere length and chromosome segregation. A disruption of the pmt3+ gene, the Schizosaccharomyces pombe homologue of SMT3, was not lethal, but mutant cells carrying the disrupted gene grew more slowly. The pmt3? cells showed various phenotypes such as aberrant mitosis, sensitivity to various reagents, and high-frequency loss of minichromosomes. Interestingly, we found that pmt3+ is required for telomere length maintenance. Loss of Pmt3p function caused a striking increase in telomere length. When Pmt3p synthesis was restored, the telomeres became gradually shorter. This is the first demonstration of involvement of one of the Smt3p/SUMO-1 family proteins in telomere length maintenance. Fusion of Pmt3p to green fluorescent protein (GFP) showed that Pmt3p was predominantly localized as intense spots in the nucleus. One of the spots was shown to correspond to the spindle pole body (SPB). During prometaphase- and metaphase, the bright GFP signals at the SPB disappeared. These observations suggest that Pmt3p is required for kinetochore and/or SPB functions involved in chromosome segregation. The multiple functions of Pmt3p described here suggest that several nuclear proteins are regulated by Pmt3p conjugation.
Tanaka, Katsunori; Nishide, Junko; Okazaki, Koei; Kato, Hiroaki; Niwa, Osami; Nakagawa, Tsuyoshi; Matsuda, Hideyuki; Kawamukai, Makoto; Murakami, Yota
Kinetics of 3H-serotonin uptake by platelets in infantile autism and developmental language disorder (including five pairs of twins)
The kinetics of 5-HT uptake by platelets was studied in cases of infantile autism and developmental language disorder (DLD) and normal subjects. Two patients of the autism group were twins, and the seven patients of the DLD group were members of four pairs of twins. The Vmax values (means +/- SD) for autism and DLD were 6.46 +/- .90 pmol 5-HT/10(7) cells/min and 4.85 +/- 1.50 pmol 5-HT/10(7) cells/min, respectively. These values were both significantly higher than that of 2.25 +/- .97 pmole 5-HT/10(7) cells/min for normal children. The Km values of the three groups were not significantly different. Data on the five pairs of twins examined suggested that the elevated Vmax of 5-HT uptake by platelets was determined genetically.
Katsui, T.; Okuda, M.; Usuda, S.; Koizumi, T.
Deletions in chromosome 6p22.3-p24.3, including ATXN1, are associated with developmental delay and autism spectrum disorders
Interstitial deletions of the short arm of chromosome 6 are rare and have been associated with developmental delay, hypotonia, congenital anomalies, and dysmorphic features. We used array comparative genomic hybridization in a South Carolina Autism Project (SCAP) cohort of 97 subjects with autism spectrum disorders (ASDs) and identified an ~ 5.4 Mb deletion on chromosome 6p22.3-p23 in a 15-year-old patient with intellectual disability and ASDs. Subsequent database queries revealed five additional individuals with overlapping submicroscopic deletions and presenting with developmental and speech delay, seizures, behavioral abnormalities, heart defects, and dysmorphic features. The deletion found in the SCAP patient harbors ATXN1, DTNBP1, JARID2, and NHLRC1 that we propose may be responsible for ASDs and developmental delay.
Reliability and Diagnostic Efficiency of the Diagnostic Inventory for Disharmony (DID) in Youths with Pervasive Developmental Disorder and Multiple Complex Developmental Disorder
The Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) category is a psychopathological entity few have described and is poorly, and mainly negatively, defined by autism exclusion. In order to limit PDD-NOS heterogeneity, alternative clinical constructs have been developed. This study explored the reliability and the diagnostic…
Xavier, Jean; Vannetzel, Leonard; Viaux, Sylvie; Leroy, Arthur; Plaza, Monique; Tordjman, Sylvie; Mille, Christian; Bursztejn, Claude; Cohen, David; Guile, Jean-Marc
Zinc-finger domains of the transcriptional repressor KLF15 bind multiple sites in rhodopsin and IRBP promoters including the CRS1 and G-rich repressor elements
BACKGROUND: In the retina, many of the genes that encode components of the visual transduction cascade and retinoid recycling are exclusively expressed in photoreceptor cells and show highly stereotyped temporal and spatial expression patterns. Multiple transcriptional activators of photoreceptor-specific genes have been identified, but little is known about negative regulation of gene expression in the retina. We recently identified KLF15,
Deborah C Otteson; Hong Lai; Yuhui Liu; Donald J Zack
Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome
Claire S. Leblond; Jutta Heinrich; Richard Delorme; Christian Proepper; Catalina Betancur; Guillaume Huguet; Marina Konyukh; Pauline Chaste; Elodie Ey; Maria Rastam; Henrik Anckarsäter; Gudrun Nygren; I. Carina Gillberg; Jonas Melke; Roberto Toro; Beatrice Regnault; Fabien Fauchereau; Oriane Mercati; Nathalie Lemičre; David Skuse; Martin Poot; Richard Holt; Anthony P. Monaco; Irma Järvelä; Katri Kantojärvi; Raija Vanhala; Sarah Curran; David A. Collier; Patrick Bolton; Andreas Chiocchetti; Sabine M. Klauck; Fritz Poustka; Christine M. Freitag; Regina Waltes; Marnie Kopp; Eftichia Duketis; Elena Bacchelli; Fiorella Minopoli; Liliana Ruta; Agatino Battaglia; Luigi Mazzone; Elena Maestrini; Ana F. Sequeira; Barbara Oliveira; Astrid Vicente; Guiomar Oliveira; Dalila Pinto; Stephen W. Scherer; Diana Zelenika; Marc Delepine; Mark Lathrop; Dominique Bonneau; Vincent Guinchat; Françoise Devillard; Brigitte Assouline; Marie-Christine Mouren; Marion Leboyer; Christopher Gillberg; Tobias M. Boeckers; Thomas Bourgeron
Dexamethasone suppression and multiple hormonal responses (TSH, prolactin and growth hormone) to TRH in some psychiatric disorders
Summary Baseline and TRH-induced changes of thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) were measured in 15 healthy control subjects and 63 psychiatric inpatients with DSM-III diagnoses of major depression (n = 19), schizophrenic disorder (n = 20), alcohol dependence (n = 10), and adjustment disorder (n = 14); baseline and postdexamethasone cortisol (CS) were also determined
Csaba M. Banki; Maria Vojnik; Mihaly Arato; Zsuzsa Papp; Zsuzsa Kovacs
Subthreshold Conditions as Precursors for Full Syndrome Disorders: A 15-Year Longitudinal Study of Multiple Diagnostic Classes
Background: There has been increasing interest in the distinction between subthreshold and full syndrome disorders and specifically whether subthreshold conditions escalate or predict the onset of full syndrome disorders over time. Most of these studies, however, examined whether a single subthreshold condition escalates into the full syndrome…
Shankman, Stewart A.; Lewinsohn, Peter M.; Klein, Daniel N.; Small, Jason W.; Seeley, John R.; Altman, Sarah E.
The crystal structure of disordered (Zr,Ti)O2 solid solution including srilankite: evolution towards tetragonal ZrO2 with increasing Zr
Crystal structure data are presented for seven synthetic samples of disordered zirconium-titanate solid solution (Zr,Ti)O2, ranging in composition from x Ti=0.43 to 0.67, thus covering compounds such as ZrTiO4, Zr5Ti7O24, and ZrTi2O6 (srilankite). The compounds, synthesized at high temperatures and various pressures in their respective stability fields, are well crystallized and of homogeneous composition. The resulting structure data are less scattered compared to previous studies that were based on compounds synthesized metastably at low temperatures and room pressure. The compounds have the structure of scrutinyite (?-PbO2) with space group Pbcn, Z=4, unit cell parameters a=4.8495(3) Ĺ, b=5.4635(3) Ĺ, c=5.0462(3) Ĺ at x Ti=0.425 to a=4.7112(2) Ĺ, b=5.4944(1) Ĺ, c=4.9962(1) Ĺ at x Ti=0.666. The first structure refinement of pure, synthetic srilankite is presented, which is in good agreement with that of the natural counterpart. Structural trends observed in disordered zirconium-titanate solid solution along the binary join ZrO2-TiO2 are relatively smooth and continuous, except for rapid lengthening of an unshared octahedral edge which is anomalously short in scrutinyite-structure TiO2. The shortness of this edge may explain the observed instability of this structure with the relatively small Ti as the dominant cation. With increasing Zr content, the average cation position moves off-centre inside the octahedron, away from two shared edges, which permits the 12 closest cation-cation distances in the structure to become more equal. The shortening of the b dimension with increasing amount of the larger cation Zr decreases the distance between octahedral Zr and two additional oxygens in an adjacent chain of edge-sharing octahedra, implying that the Zr environment is evolving towards eightfold coordination. If the two additional oxygens are considered as part of the Zr coordination polyhedron, the bonding topology of tetragonal zirconia is obtained. The compositional evolution of the cell parameters, Zr atomic coordinates and Zr coordination environment is consistent with the idea that the structure is evolving towards that of tetragonal ZrO2. Group-theoretical relationships between scrutinyite, tetragonal zirconia, baddeleyite and fluorite structures show that the sequence of structures fluorite > tetragonal zirconia > scrutinyite > baddeleyite are all related by potentially diffusionless phase transitions driven by wavelike displacements of the oxygen substructure. The scrutinyite and tetragonal structures can act outside their stability fields as "transition states" between the structures on either side.
Troitzsch, U.; Christy, A. G.; Ellis, D. J.
Probing the role of AMPAR endocytosis and long-term depression in behavioural sensitization: relevance to treatment of brain disorders, including drug addiction
Modifying the function of postsynaptic ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate receptors (AMPARs) is one of the most important mechanisms by which the efficacy of synaptic transmission at excitatory glutamatergic synapses in the mammalian brain is regulated. Traditionally these types of modifications have been thought to be achieved mainly by altering the channel gating properties or conductance of the receptors. A large body of evidence accumulated from recent studies strongly suggests that AMPARs, like most integral plasma membrane proteins, are continuously recycled between the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating certain forms of synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD). These studies have significantly advanced our understanding of the molecular mechanisms underlying LTP and LTD, and their potential contributions to learning and memory-related behaviours. Here I provide a brief summary of the current state of knowledge concerning clathrin-mediated AMPAR endocytosis and its relationship to the expression of certain forms of LTD in several brain areas. The potential impact of recent advancements on our efforts to probe the roles of synaptic plasticity in learning and memory-related behaviours, and their relevance to some brain disorders, particularly drug addiction, are also discussed.
Wang, Y T
Monoclonal gammopathies and associated skin disorders
The monoclonal gammopathies are characterized by clonal proliferation of plasma cells and other clonally related cells in the B-cell lineage. These disorders include monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström macroglobulinemia, heavy chain diseases, plasmacytoma, and primary amyloidosis. Many skin disorders have been described in association with monoclonal gammopathies. This article provides an introduction to the definition, detection, natural
Mazen S. Daoud; John A. Lust; Robert A. Kyle; Mark R. Pittelkow
Alcohol Consumption Has a Protective Effect against Hematological Malignancies: a Population-Based Study in Sweden Including 420,489 Individuals with Alcohol Use Disorders12345
BACKGROUND: It has been suggested that alcohol consumption is associated with increased risk of a few solid cancers, although studies that examined the association with hematological malignancies have shown inconsistent results. In this study, we examined the risk of hematological malignancies among individuals who had alcohol use disorders (AUDs) in Sweden. METHODS: Individuals with AUDs were identified from the nationwide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios (SIRs) of hematological malignancies, using those Swedes without AUDs as a reference. In addition, we used a quasi-experimental sibling design to investigate the odds ratios among sibling pairs who were discordant with AUDs. RESULTS: A total of 420,489 individuals were identified with AUDs. After more than 15 million person-years of follow-up, a total of 1755 individuals developed hematological malignancies demonstrating a low risk, i.e., SIR = 0.60 (95% confidence interval = 0.57-0.63). People with AUDs had low risks for developing specific types of malignancies. The lowest risk (0.51) was for leukemia, followed by myeloma (0.52), non-Hodgkin lymphoma (0.65), and Hodgkin disease (0.71). The risk was lower among AUDs identified at an older age. The low risks of hematological malignancies were also noted using sibling analysis. CONCLUSIONS: Our data suggest that alcohol consumption has a protective effect against hematological malignancies. However, further studies are needed to identity the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies.
Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina
Multiple Approaches to Investigate the Transport and Activity-Dependent Release of BDNF and Their Application in Neurogenetic Disorders
Studies utilizing genetic and pharmacological manipulations in rodent models and neuronal cultures have revealed myriad roles of brain-derived neurotrophic factor (BDNF). Currently, this knowledge of BDNF function is being translated into improvement strategies for several debilitating neurological disorders in which BDNF abnormalities play a prominent role. Common among the BDNF-related disorders are irregular trafficking and release of mature BDNF (mBDNF) and/or its prodomain predecessor, proBDNF. Thus, investigating the conditions required for proper trafficking and release of BDNF is an essential step toward understanding and potentially improving these neurological disorders. This paper will provide examples of disorders related to BDNF release and serve as a review of the techniques being used to study the trafficking and release of BDNF.
Hartmann, David; Drummond, Jana; Handberg, Erik; Ewell, Sharday; Pozzo-Miller, Lucas
The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function
Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.
Raman, Jayanthi; Smith, Evelyn; Hay, Phillipa
Predicting quality of life in multiple sclerosis: accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change
Health-related quality of life (HQOL) is poor in multiple sclerosis (MS) but the clinical precipitants of the problem are not well understood. Previous correlative studies demonstrated relationships between various clinical parameters and diminished HQOL in MS. Unfortunately, these studies failed to account for multiple predictors in the same analysis. We endeavored to determine what clinical parameters account for most variance
Ralph H. B. Benedict; Elizabeth Wahlig; Rohit Bakshi; Inna Fishman; Frederick Munschauer; Robert Zivadinov; Bianca Weinstock-Guttman
Background Si-doping effects on Zn diffusion-induced disordering in GaAs\\/AlGaAs multiple-quantum-well structures
Identical GaAs\\/Al0.2Ga0.8As multiple-quantum-well (MQW) structures uniformly doped with Si at various concentrations ranging from 1×1017 to 1×1019 cm?3 are grown by molecular-beam epitaxy to study the effects of the background Si-doping level on the Zn diffusion-induced disordering process. After Zn diffusions at 575 °C for 4 and 16 h, the structures are investigated by secondary-ion-mass spectrometry, and by transmission electron
Nguyen Hong Ky; F. K. Reinhart; B. Blanchard
Multiple Sclerosis
Multiple sclerosis (MS) was first recognized as a disorder in the late nineteenth century, but only by the nineteen sixties did ... The first standard guidelines for the diagnosis of MS and a disability rating scale were also established ...
Multiple myeloma
Plasma cell dyscrasia; Plasma cell myeloma; Malignant plasmacytoma; Plasmacytoma of bone; Myeloma - multiple ... Elsevier Churchill-Livingstone; 2008:chap 110. Rajkumar SV. Plasma cell disorders. In: Goldman L, Schafer AI, eds. ...
Neurology of rheumatologic disorders.
Rheumatologic diseases encompass autoimmune and inflammatory disorders of the joints and soft tissues that often involve multiple organ systems, including the central and peripheral nervous systems. Common features include constitutional symptoms, arthralgia and arthritis, myalgia, and sicca symptoms. Neurological manifestations may present in patients with preexisting rheumatologic diagnoses, occur concurrently with systemic signs and symptoms, or precede systemic manifestations by months to years. Rheumatic disorders presenting as neurological syndromes may pose diagnostic challenges. Advances in immunosuppressive treatment of rheumatologic disease have expanded the treatment armamentarium. However, serious neurotoxic effects have been reported with both old and newer agents. Familiarity with neurological manifestations of rheumatologic diseases, diagnosis, and potential nervous system consequences of treatment is important for rapid diagnosis and appropriate intervention. This article briefly reviews the diverse neurological manifestations and key clinical features of rheumatic disorders and the potential neurological complications of agents commonly used for treatment. PMID:24871965
Nouh, Amre; Carbunar, Olimpia; Ruland, Sean
Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)
These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) have been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.
Sloan, J.W.
GSK3 inhibitors regulate MYCN mRNA levels and reduce neuroblastoma cell viability through multiple mechanisms, including p53 and Wnt signaling.
Neuroblastoma is an embryonal tumor accounting for approximately 15% of childhood cancer deaths. There exists a clinical need to identify novel therapeutic targets, particularly for treatment-resistant forms of neuroblastoma. Therefore, we investigated the role of the neuronal master regulator GSK3 in controlling neuroblastoma cell fate. We identified novel GSK3-mediated regulation of MYC (c-MYC and MYCN) mRNA levels, which may have implications for numerous MYC-driven cancers. In addition, we showed that certain GSK3 inhibitors induced large-scale cell death in neuroblastoma cells, primarily through activating apoptosis. mRNA-seq of GSK3 inhibitor-treated cells was performed and subsequent pathway analysis revealed that multiple signaling pathways contributed to the loss of neuroblastoma cell viability. The contribution of two of the signaling pathways highlighted by the mRNA-seq analysis was functionally validated. Inhibition of the p53 tumor suppressor partly rescued the cell death phenotype, whereas activation of canonical Wnt signaling contributed to the loss of viability, in a p53-independent manner. Two GSK3 inhibitors (BIO-acetoxime and LiCl) and one small-molecule Wnt agonist (Wnt Agonist 1) demonstrated therapeutic potential for neuroblastoma treatment. These inhibitors reduced the viability of numerous neuroblastoma cell lines, even those derived from high-risk MYCN-amplified metastatic tumors, for which effective therapeutics are currently lacking. Furthermore, although LiCl was lethal to neuroblastoma cells, it did not reduce the viability of differentiated neurons. Taken together our data suggest that these small molecules may hold potential as effective therapeutic agents for the treatment of neuroblastoma and other MYC-driven cancers. PMID:24282277
Duffy, David J; Krstic, Aleksandar; Schwarzl, Thomas; Higgins, Desmond G; Kolch, Walter
Somatosensory processing in neurodevelopmental disorders.
The purpose of this article is to review the role of somatosensory perception in typical development, its aberration in a range of neurodevelopmental disorders, and the potential relations between tactile processing abnormalities and central features of each disorder such as motor, communication, and social development. Neurodevelopmental disorders that represent a range of symptoms and etiologies, and for which multiple peer-reviewed articles on somatosensory differences have been published, were chosen to include in the review. Relevant studies in animal models, as well as conditions of early sensory deprivation, are also included. Somatosensory processing plays an important, yet often overlooked, role in typical development and is aberrant in various neurodevelopmental disorders. This is demonstrated in studies of behavior, sensory thresholds, neuroanatomy, and neurophysiology in samples of children with Fragile X syndrome, autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and cerebral palsy (CP). Impaired somatosensory processing is found in a range of neurodevelopmental disorders and is associated with deficits in communication, motor ability, and social skills in these disorders. Given the central role of touch in early development, both experimental and clinical approaches should take into consideration the role of somatosensory processing in the etiology and treatment of neurodevelopmental disorders. PMID:22127855
Cascio, Carissa J
Project HAPI (Handicapped Achievement Program Improvement): Assessment plus Intervention equal I.E.P. A Handbook on How To Write an Individualized Education Program for Severe Disorders of Language, Including Aphasia and Other Speech-Language Handicapped (Communication Disorders). Book One.
The first of five handbooks developed by Project HAPI (Handicapped Achievement Program Improvement), a multimedia staff development program to help teachers and specialists write effective individualized education programs (IEPs), is in looseleaf workbook format and focuses on children with severe disorders of language, including aphasia and other…
Chapman, Jean
Collaborative Care for patients with severe borderline and NOS personality disorders: A comparative multiple case study on processes and outcomes
Background Structured psychotherapy is recommended as the preferred treatment of personality disorders. A substantial group of patients,\\u000a however, has no access to these therapies or does not benefit. For those patients who have no (longer) access to psychotherapy\\u000a a Collaborative Care Program (CCP) is developed. Collaborative Care originated in somatic health care to increase shared decision\\u000a making and to enhance self
Barbara Stringer; Berno van Meijel; Bauke Koekkoek; A. J. F. M. Kerkhof; Aartjan Beekman
First-principles study of multiple order-disorder transitions in Cd{sub 2}AgAu Heusler alloys
The bcc-based Heusler alloys exhibit a series of order-disorder phase transitions as a function of temperature. The high-temperature phase is a disordered bcc solid solution, and the low-temperature phase is the Heusler structure. An intermediate ordered phase is also typically observed in real systems. A prototype cluster variation method (CVM) analysis is presented that shows that the relative stabilities of the Heusler and intermediate phases can vary continuously, depending on a fine balance between ordering tendencies in the constituent binary systems. Given these basic conclusions, a first-principles analysis of order-disorder transitions in Cd{sub 2}AgAu was performed. A cluster expansion Hamiltonian was constructed based on a series of linearized muffin-tin orbital calculations in the atomic sphere approximation. CVM calculations were then performed in the ternary bcc tetrahedron approximation. In addition to the transition temperatures, long-range order parameters, and sublattice occupations for Cd{sub 2}AgAu, an isoplethal section of the ternary phase diagram was also calculated. In general, agreement with experiment is excellent, given the first-principles nature of the calculation. This study clearly demonstrates the ability of first-principles statistical-mechanical calculations to treat complex ordering phenomena in {ital ternary} systems. {copyright} {ital 1996 The American Physical Society.}
McCormack, R.; de Fontaine, D. [Department of Materials Science, University of California, Berkeley, California 94720 (United States)] [Department of Materials Science, University of California, Berkeley, California 94720 (United States); [Lawrence Berkeley Laboratory, Materials Science Division, Berkeley, California 94720 (United States)
Multiple Domains in MtENOD8 Protein Including the Signal Peptide Target It to The Symbiosome1[W][OA
Symbiotic nitrogen fixation occurs in nodules, specialized organs on the roots of legumes. Within nodules, host plant cells are infected with rhizobia that are encapsulated by a plant-derived membrane forming a novel organelle, the symbiosome. In Medicago truncatula, the symbiosome consists of the symbiosome membrane, a single rhizobium, and the soluble space between them, called the symbiosome space. The symbiosome space is enriched with plant-derived proteins, including the M. truncatula EARLY NODULIN8 (MtENOD8) protein. Here, we present evidence from green fluorescent protein (GFP) fusion experiments that the MtENOD8 protein contains at least three symbiosome targeting domains, including its N-terminal signal peptide (SP). When ectopically expressed in nonnodulated root tissue, the MtENOD8 SP delivers GFP to the vacuole. During the course of nodulation, there is a nodule-specific redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates and subsequently to symbiosomes, with redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates preceding intracellular rhizobial infection. Experiments with M. truncatula mutants having defects in rhizobial infection and symbiosome development demonstrated that the MtNIP/LATD gene is required for redirection of the MtENOD8-SP-GFP from the vacuoles to punctate intermediates in nodules. Our evidence shows that MtENOD8 has evolved redundant targeting sequences for symbiosome targeting and that intracellular localization of ectopically expressed MtENOD8-SP-GFP is useful as a marker for monitoring the extent of development in mutant nodules.
Meckfessel, Matthew H.; Blancaflor, Elison B.; Plunkett, Michael; Dong, Qunfeng; Dickstein, Rebecca
Proteus Syndrome with Multiple Genitourinary Abnormalities
Proteus syndrome is a rare hamartomatous disorder comprising a broad spectrum of congenital malformations and overgrowth of multiple tissues. Some rare urogenital malformations have been reported before. This case is unique for the presence of multiple genitourinary anomalies including retroperitoneal cystic mass, intra-abdominal testicle with hematoma and ureterovesical stricture apart from common clinic findings of proteus syndrome.
Ayhan Karabulut; Melih Sunay; Levent Emir; Demokan Erol
Relationship of the Brief UCSD Performance-based Skills Assessment (UPSA-B) to multiple indicators of functioning in people with schizophrenia and bipolar disorder
Objective This study assessed the relationship between multiple indicators of 'real-world' functioning and scores on a brief performance-based measure of functional capacity known as the Brief University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA-B) in a sample of 205 patients with either serious bipolar disorder (n = 89) or schizophrenia (n = 116). Methods Participants were administered the UPSA-B and assessed on the following functional domains: (i) independent living status (e.g., residing independently as head of household, living in residential care facility); (ii) informant reports of functioning (e.g., work skills, daily living skills); (iii) educational attainment and estimated premorbid IQ as measured by years of education and Wide Range Achievement Test reading scores, respectively; and (iv) employment. Results Better scores on the UPSA-B were associated with greater residential independence after controlling for age, diagnosis, and symptoms of psychopathology. Among both bipolar disorder and schizophrenia patients, higher UPSA-B scores were significantly related to better informant reports of functioning in daily living skills and work skills domains. Greater estimated premorbid IQ was associated with higher scores on the UPSA-B for both schizophrenia and bipolar disorder participants. Participants who were employed scored higher on the UPSA-B when controlling for age and diagnosis, but not when controlling for symptoms of psychopathology. Conclusions These data suggest the UPSA-B may be useful for assessing capacity for functioning in a number of domains in both people diagnosed with schizophrenia and bipolar disorder.
Mausbach, Brent T; Harvey, Philip D; Pulver, Ann E; Depp, Colin A; Wolyniec, Paula S; Thornquist, Mary H; Luke, James R; McGrath, John A; Bowie, Christopher; Patterson, Thomas L
Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.
Abnormalities in brain-derived neurotrophic factor (BDNF)/trkB signaling have been implicated in the etiology of schizophrenia and mood disorders. Patients with schizophrenia, bipolar disorder (BPD) and major depression (MDD) have reduced levels of neurotrophins in their brains when compared with normal unaffected individuals; however, only a few brain areas have been examined to date. Owing to the broad range of symptoms manifested in these disorders, we hypothesized that multiple associative areas of the neocortex may be implicated and that the degree of change in BDNF and trkB-TK+ mRNA expression and the cortical region or layers involved may vary according to Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis. We compared BDNF and trkB-TK+ mRNA levels across all layers of the prefrontal cortex (dorsolateral prefrontal cortex, DLPFC), orbital frontal cortex (OFC), anterior cingulate cortex (ACC), inferior temporal gyrus (ITG) and superior temporal gyrus (STG) in four groups: schizophrenia, BPD, MDD and unaffected controls (n=60). BDNF mRNA levels were significantly decreased in layers IV and V of DLPFC in schizophrenia patients, in layer VI of ACC in schizophrenia and MDD and in layer VI of ITG in schizophrenia, BPD and MDD. BDNF mRNA levels were also significantly decreased in layer V and/or VI of STG in schizophrenia, BPD and MDD. TrkB-TK+ mRNA levels were only significantly decreased in the cortical layer VI of OFC in BPD. The shared and distinct patterns of neurotrophin transcript reductions, with some specific to each group, may compromise the function and plasticity of distinct cortical areas to various degrees in the different groups and contribute to the range and overlap of symptoms manifested across the diagnoses. PMID:24802307
Ray, M T; Shannon Weickert, C; Webster, M J
Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders
Abnormalities in brain-derived neurotrophic factor (BDNF)/trkB signaling have been implicated in the etiology of schizophrenia and mood disorders. Patients with schizophrenia, bipolar disorder (BPD) and major depression (MDD) have reduced levels of neurotrophins in their brains when compared with normal unaffected individuals; however, only a few brain areas have been examined to date. Owing to the broad range of symptoms manifested in these disorders, we hypothesized that multiple associative areas of the neocortex may be implicated and that the degree of change in BDNF and trkB?TK+ mRNA expression and the cortical region or layers involved may vary according to Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis. We compared BDNF and trkB?TK+ mRNA levels across all layers of the prefrontal cortex (dorsolateral prefrontal cortex, DLPFC), orbital frontal cortex (OFC), anterior cingulate cortex (ACC), inferior temporal gyrus (ITG) and superior temporal gyrus (STG) in four groups: schizophrenia, BPD, MDD and unaffected controls (n=60). BDNF mRNA levels were significantly decreased in layers IV and V of DLPFC in schizophrenia patients, in layer VI of ACC in schizophrenia and MDD and in layer VI of ITG in schizophrenia, BPD and MDD. BDNF mRNA levels were also significantly decreased in layer V and/or VI of STG in schizophrenia, BPD and MDD. TrkB?TK+ mRNA levels were only significantly decreased in the cortical layer VI of OFC in BPD. The shared and distinct patterns of neurotrophin transcript reductions, with some specific to each group, may compromise the function and plasticity of distinct cortical areas to various degrees in the different groups and contribute to the range and overlap of symptoms manifested across the diagnoses.
Netrin-1 Promotes Glioblastoma Cell Invasiveness and Angiogenesis by Multiple Pathways Including Activation of RhoA, Cathepsin B, and cAMP-response Element-binding Protein*
Glioblastomas are very difficult tumors to treat because they are highly invasive and disseminate within the normal brain, resulting in newly growing tumors. We have identified netrin-1 as a molecule that promotes glioblastoma invasiveness. As evidence, netrin-1 stimulates glioblastoma cell invasion directly through Matrigel-coated transwells, promotes tumor cell sprouting and enhances metastasis to lymph nodes in vivo. Furthermore, netrin-1 regulates angiogenesis as shown in specific angiogenesis assays such as enhanced capillary endothelial cells (EC) sprouting and by increased EC infiltration into Matrigel plugs in vivo, as does VEGF-A. This netrin-1 signaling pathway in glioblastoma cells includes activation of RhoA and cyclic AMP response element-binding protein (CREB). A novel finding is that netrin-1-induced glioblastoma invasiveness and angiogenesis are mediated by activated cathepsin B (CatB), a cysteine protease that translocates to the cell surface as an active enzyme and co-localizes with cell surface annexin A2 (ANXA2). The specific CatB inhibitor CA-074Me inhibits netrin-1-induced cell invasion, sprouting, and Matrigel plug angiogenesis. Silencing of CREB suppresses netrin-1-induced glioblastoma cell invasion, sprouting, and CatB expression. It is concluded that netrin-1 plays an important dual role in glioblastoma progression by promoting both glioblastoma cell invasiveness and angiogenesis in a RhoA-, CREB-, and CatB-dependent manner. Targeting netrin-1 pathways may be a promising strategy for brain cancer therapy.
Shimizu, Akio; Nakayama, Hironao; Wang, Priscilla; Konig, Courtney; Akino, Tomoshige; Sandlund, Johanna; Coma, Silvia; Italiano, Joseph E.; Mammoto, Akiko; Bielenberg, Diane R.; Klagsbrun, Michael
Netrin-1 promotes glioblastoma cell invasiveness and angiogenesis by multiple pathways including activation of RhoA, cathepsin B, and cAMP-response element-binding protein.
Glioblastomas are very difficult tumors to treat because they are highly invasive and disseminate within the normal brain, resulting in newly growing tumors. We have identified netrin-1 as a molecule that promotes glioblastoma invasiveness. As evidence, netrin-1 stimulates glioblastoma cell invasion directly through Matrigel-coated transwells, promotes tumor cell sprouting and enhances metastasis to lymph nodes in vivo. Furthermore, netrin-1 regulates angiogenesis as shown in specific angiogenesis assays such as enhanced capillary endothelial cells (EC) sprouting and by increased EC infiltration into Matrigel plugs in vivo, as does VEGF-A. This netrin-1 signaling pathway in glioblastoma cells includes activation of RhoA and cyclic AMP response element-binding protein (CREB). A novel finding is that netrin-1-induced glioblastoma invasiveness and angiogenesis are mediated by activated cathepsin B (CatB), a cysteine protease that translocates to the cell surface as an active enzyme and co-localizes with cell surface annexin A2 (ANXA2). The specific CatB inhibitor CA-074Me inhibits netrin-1-induced cell invasion, sprouting, and Matrigel plug angiogenesis. Silencing of CREB suppresses netrin-1-induced glioblastoma cell invasion, sprouting, and CatB expression. It is concluded that netrin-1 plays an important dual role in glioblastoma progression by promoting both glioblastoma cell invasiveness and angiogenesis in a RhoA-, CREB-, and CatB-dependent manner. Targeting netrin-1 pathways may be a promising strategy for brain cancer therapy. PMID:23195957
Shimizu, Akio; Nakayama, Hironao; Wang, Priscilla; König, Courtney; Akino, Tomoshige; Sandlund, Johanna; Coma, Silvia; Italiano, Joseph E; Mammoto, Akiko; Bielenberg, Diane R; Klagsbrun, Michael
TMEFF2 Is a PDGF-AA Binding Protein with Methylation-Associated Gene Silencing in Multiple Cancer Types Including Glioma
Background TMEFF2 is a protein containing a single EGF-like domain and two follistatin-like modules. The biological function of TMEFF2 remains unclear with conflicting reports suggesting both a positive and a negative association between TMEFF2 expression and human cancers. Methodology/Principal Findings Here we report that the extracellular domain of TMEFF2 interacts with PDGF-AA. This interaction requires the amino terminal region of the extracellular domain containing the follistatin modules and cannot be mediated by the EGF-like domain alone. Furthermore, the extracellular domain of TMEFF2 interferes with PDGF-AA–stimulated fibroblast proliferation in a dose–dependent manner. TMEFF2 expression is downregulated in human brain cancers and is negatively correlated with PDGF-AA expression. Suppressed expression of TMEFF2 is associated with its hypermethylation in several human tumor types, including glioblastoma and cancers of ovarian, rectal, colon and lung origins. Analysis of glioma subtypes indicates that TMEFF2 hypermethylation and decreased expression are associated with a subset of non-Proneural gliomas that do not display CpG island methylator phentoype. Conclusions/Significance These data provide the first evidence that TMEFF2 can function to regulate PDGF signaling and that it is hypermethylated and downregulated in glioma and several other cancers, thereby suggesting an important role for this protein in the etiology of human cancers.
Lin, Kui; Taylor, James R.; Wu, Thomas D.; Gutierrez, Johnny; Elliott, J. Michael; Vernes, Jean-Michel; Koeppen, Hartmut; Phillips, Heidi S.; de Sauvage, Frederic J.; Meng, Y. Gloria
Tooth Disorders
... made of a hard, bonelike material. Inside the tooth are nerves and blood vessels. You need your ... These include eating, speaking and even smiling. But tooth disorders are nothing to smile about. They include ...
Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance.
Mutations in nuclear genes involved in mitochondrial DNA (mtDNA) maintenance cause a wide range of clinical phenotypes associated with the secondary accumulation of multiple mtDNA deletions in affected tissues. The majority of families with autosomal dominant progressive external ophthalmoplegia (PEO) harbour mutations in genes encoding one of three well-characterized proteins--pol gamma, Twinkle or Ant 1. Here we show that a heterozygous mis-sense mutation in OPA1 leads to multiple mtDNA deletions in skeletal muscle and a mosaic defect of cytochrome c oxidase (COX). The disorder presented with visual failure and optic atrophy in childhood, followed by PEO, ataxia, deafness and a sensory-motor neuropathy in adult life. COX-deficient skeletal muscle fibres contained supra-threshold levels of multiple mtDNA deletions, and genetic linkage, sequencing and expression analysis excluded POLG1, PEO1 and SLC25A4, the gene encoding Ant 1, as the cause. This demonstrates the importance of OPA1 in mtDNA maintenance, and implicates OPA1 in diseases associated with secondary defects of mtDNA. PMID:18065439
Hudson, Gavin; Amati-Bonneau, Patrizia; Blakely, Emma L; Stewart, Joanna D; He, Langping; Schaefer, Andrew M; Griffiths, Philip G; Ahlqvist, Kati; Suomalainen, Anu; Reynier, Pascal; McFarland, Robert; Turnbull, Douglass M; Chinnery, Patrick F; Taylor, Robert W
Intricate Crystal Structure of Dihydrolipoamide Dehydrogenase (E3) with its Binding Protein: Multiple Copies, Dynamic and Static Disorders
Human E3 and binding protein E3BP are two components of the pyruvate dehydrogenase complex. Crystallization of E3 with 221-amino acid fragment of E3BP (E3BPdd) led to crystals that diffracted to a resolution of 2.6 Angstroms. Structure determination involved molecular replacement using a dimer of E3 homolog as a search model and de novo building of the E3BPdd peptide. Solution was achieved by inclusion of one E3 dimer at a time, followed by refinement until five E3 dimers were located. This complete content of E3 provided electron density maps suitable for tracing nine peptide chains of E3BPdd, eight of them being identified with partial occupancies. Final content of the asymmetric unit consists of five E3 dimers, each binding one E3BPdd molecule. In four of these molecular complexes, E3BPdd is in static disorder resulting in E3BPdd binding to either one or the other monomer of the E3 dimer. However, E3BPdd of the fifth E3 dimer forms specific contacts that lock it at one monomer. In addition to this static disorder, E3BPdd reveals high mobility in the limited space of the crystal lattice. Support from NIH and NASA.
Makal, A.; Hong, Y. S.; Potter, R.; Vettaikkorumakankauv, A. K.; Korotchkina, L. G.; Patel, M. S.; Ciszak, E.
The close relationship between life-threatening breathing disorders and urine storage dysfunction in multiple system atrophy
Survival of multiple system atrophy (MSA) depends on whether a variety of sleep-related breathing problems as well as autonomic\\u000a failure (AF) occur. Since the brainstem lesions that cause respiratory and autonomic dysfunction overlap with each other,\\u000a these critical manifestations might get worse in parallel. If so, the detection of AF, which is comparatively easy, might\\u000a be predictive of a latent
Kazushi DeguchiKazuyo; Kazuyo Ikeda; Rieko Goto; Masago Tsukaguchi; Yoshiteru Urai; Kazutaka Kurokohchi; Tetsuo Touge; Nozomu Mori; Tsutomu Masaki
Compulsive disorders.
Compulsive disorders include a diverse group of conditions characterized by excessive thoughts or preoccupations combined with poorly controlled behaviors. They include trichotillomania, kleptomania, pathologic gambling, compulsive buying disorder, compulsive sexual behavior, and compulsive computer use. Some investigators have suggested that these conditions constitute a spectrum of disorders linked to obsessive-compulsive disorder. Others have questioned the validity of this conceptualization, and have debated the relationship between these disorders. Nevertheless, much has been learned about compulsive disorders, and there have been some successes with psychotherapeutic and psychopharmacologic treatments. Recent therapy-based interventions have moved from psychodynamic treatments toward cognitive-behavioral modalities. Serotonin reuptake inhibitors remain the best-studied pharmacologic treatment, but researchers have also explored other antidepressants, opioid agonists, mood stabilizers, and atypical antipsychotics. PMID:14738707
Kuzma, John M; Black, Donald W
Spectrum of mast cell activation disorders.
Mast cell (MC) activation disorders present with multiple symptoms including flushing, pruritus, hypotension, gastrointestinal complaints, irritability, headaches, concentration/memory loss and neuropsychiatric issues. These disorders are classified as: cutaneous and systemic mastocytosis with a c-kit mutation and clonal MC activation disorder, allergies, urticarias and inflammatory disorders and mast cell activation syndrome (MCAS), idiopathic urticaria and angioedema. MCs are activated by IgE, but also by cytokines, environmental, food, infectious, drug and stress triggers, leading to secretion of multiple mediators. The symptom profile and comorbidities associated with these disorders, such as chronic fatigue syndrome and fibromyalgia, are confusing. We propose the use of the term 'spectrum' and highlight the main symptoms, useful diagnostic tests and treatment approaches. PMID:24784142
Petra, Anastasia I; Panagiotidou, Smaro; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C
The effect of multiple doses of cimetidine on the steady-state pharmacokinetics of quetiapine in men with selected psychotic disorders.
Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders. PMID:11910267
Strakowski, Stephen M; Keck, Paul E; Wong, Y W James; Thyrum, Per T; Yeh, Chiao
Diversity in Pathways to Common Childhood Disruptive Behavior Disorders
Oppositional-Defiant Disorder (ODD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are highly comorbid, a phenomenon thought to be due to shared etiological factors and mechanisms. Little work has attempted to chart multiple-level-of-analysis pathways (i.e., simultaneously including biological, environmental, and trait influences) to ODD and…
Martel, Michelle M.; Nikolas, Molly; Jernigan, Katherine; Friderici, Karen; Nigg, Joel T.
The genetics of autism spectrum disorders
Epidemiological twin studies demonstrate that autism spectrum disorders (ASDs) represent genetic disorders. Subsequent analyses\\u000a indicate that the causes of ASDs include less common single-gene mutations and chromosomal abnormalities, as well as ASDs\\u000a caused by multiple interacting genes of weak effect. Genome-wide linkage analysis has identified several susceptibility loci\\u000a for the ASDs, and positional and functional candidate genes have been identified
Dorothy E. Grice; Joseph D. Buxbaum
Disorderly Light.
The relationship between theories about electrical conductivity in microscopic wires and laser speckle patterns is described. Practical applications of laser speckle patterns are included. Wave ideas are being used to describe and predict novel phenomena in disordered solids. (KR)
Peterson, Ivars
Multiple White Matter Volume Reductions in Patients with Panic Disorder: Relationships between Orbitofrontal Gyrus Volume and Symptom Severity and Social Dysfunction
Numerous brain regions are believed to be involved in the neuropathology of panic disorder (PD) including fronto-limbic regions, thalamus, brain stem, and cerebellum. However, while several previous studies have demonstrated volumetric gray matter reductions in these brain regions, there have been no studies evaluating volumetric white matter changes in the fiber bundles connecting these regions. In addition, although patients with PD typically exhibit social, interpersonal and occupational dysfunction, the neuropathologies underlying these dysfunctions remain unclear. A voxel-based morphometry study was conducted to evaluate differences in regional white matter volume between 40 patients with PD and 40 healthy control subjects (HC). Correlation analyses were performed between the regional white matter volumes and patients' scores on the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF). Patients with PD demonstrated significant volumetric reductions in widespread white matter regions including fronto-limbic, thalamo-cortical and cerebellar pathways (p<0.05, FDR corrected). Furthermore, there was a significant negative relationship between right orbitofrontal gyrus (OFG) white matter volume and the severity of patients' clinical symptoms, as assessed with the PDSS. A significant positive relationship was also observed between patients' right OFG volumes and their scores on the GAF. Our results suggest that volumetric reductions in widespread white matter regions may play an important role in the pathology of PD. In particular, our results suggest that structural white matter abnormalities in the right OFG may contribute to the social, personal and occupational dysfunction typically experienced by patients with PD.
Konishi, Jun; Asami, Takeshi; Hayano, Fumi; Yoshimi, Asuka; Hayasaka, Shunsuke; Fukushima, Hiroshi; Whitford, Thomas J.; Inoue, Tomio; Hirayasu, Yoshio
Heterogeneous Ordered-Disordered Structure of the Mesodomain in Frozen Sucrose-Water Solutions Revealed by Multiple Electron Paramagnetic Resonance Spectroscopies
The microscopic structure of frozen aqueous sucrose solutions, over concentrations of 0–75% (w/v), is characterized by using multiple continuous-wave and pulsed electron paramagnetic resonance (EPR) spectroscopic and relaxation techniques and the paramagnetic spin probe, TEMPOL. The temperature dependence of the TEMPOL EPR lineshape anisotropy reveals a mobility transition, specified at 205 K in pure water and 255 ±5 K for >1% (w/v) added sucrose. The transition temperature is >>Tg, where Tg is the homogeneous water glass transition temperature, which shows that TEMPOL resides in the mesoscopic domain (mesodomain) at water-ice crystallite boundaries, and that the mesodomain sucrose concentrations are comparable at >1% (w/v) added sucrose. Electron spin echo envelope modulation (ESEEM) spectroscopy of TEMPOL-2H2-sucrose hyperfine interactions also indicates comparable sucrose concentrations in mesodomains at >1% (w/v) added sucrose. Electron spin echo (ESE) – detected longitudinal and phase memory relaxation times (T1 and TM, respectively) at 6 K indicate a general trend of increased mesodomain volume with added sucrose, in three stages: 1-15, 20-50, and >50% (w/v). The calibrated TEMPOL concentrations indicate that the mesodomain volume is less than the predicted maximally freeze-concentrated value [80 (w/w); 120% (w/v)], with transitions at 15-20% and 50% (w/v) starting sucrose. An ordered sucrose hydrate phase, which excludes TEMPOL, and a disordered, amorphous sucrose-water glass phase, in which TEMPOL resides, are proposed to compose a heterogeneous mesodomain. The results show that the ratio of ordered and disordered volume fractions in the mesodomain is exquisitely sensitive to the starting sucrose concentration.
Chen, Hanlin; Sun, Li; Warncke, Kurt
Pharmacodynamics and safety of ferric carboxymaltose: a multiple-dose study in patients with iron-deficiency anaemia secondary to a gastrointestinal disorder.
This multiple-dose Phase I/II study provided pharmacodynamics and pharmacokinetics data on the therapeutic benefit of ferric carboxymaltose (FCM, Ferinject) and evaluated the safety and tolerability of this intravenous (i.v.) iron preparation. Two doses of iron as FCM were given as i.v. infusion over 15 min, 500 mg iron given once weekly for up to 4 weeks (Cohort 1) or 1000 mg iron weekly for 2 weeks (Cohort 2), in patients with a total requirement > or = 1000 mg iron (total cumulative maximum dose < or = 2000 mg iron). Adults with moderate to severe, stable iron-deficiency anaemia (IDA) (haemoglobin [Hb] < or = 11.0 g/dl, serum ferritin < 100 microg/l, transferrin saturation [TSAT] < 16%) due to a gastrointestinal (GI) disorder were included. Pharmacodynamics variables: proportion of patients achieving values within the reference range for Hb (men: 14.0-18.0 g/dl, women: 12.0-16.0 g/dl), serum ferritin (20-500 microg/l), TSAT (16-45%) and proportion of patients with an increase in Hb of at least 2.0 g/dl. Pharmacokinetics variables: total serum iron levels at time of maximum serum iron concentration during the fast elimination phase and at trough time-points. Safety assessments: the incidence of adverse events (AEs) and changes in vital signs, physical examinations, and clinical laboratory parameters. In Cohorts 1 and 2, 14/20 (70%) versus 19/26 (73%) of patients completed the study. Individual calculated iron deficits were 1000-2100 mg. The mean cumulative dose of FCM in Cohorts 1 and 2 was 1800 mg and 1563 mg iron, respectively. At baseline, patients in both cohorts had similar Hb levels (mean 8.7 g/dl in both cohorts). More than 97% of patients demonstrated a clinically meaningful increase in Hb levels (> or = 1.0 g/dl) during the study. By the week 4 follow-up visit, an increase of at least 2.0 g/dl was achieved by 15/20 (75%) and by 19/26 (73.1%) patients in Cohorts 1 and 2, respectively, and the mean increase in Hb was 3.2 g/dl in Cohort 1 and 3.3 g/dl in Cohort 2. By day 28, 3/6 (50%) patients in Cohort 1 had achieved normal Hb levels, and by the 4-week post-treatment followup visit 7/19 patients (37%) in Cohort 1 and 12/25 (48%) in Cohort 2 had reached Hb levels within the reference range. Serum ferritin levels increased rapidly at the start of treatment and remained in the reference range throughout the study; increases were greater in Cohort 2. Mean baseline TSAT values were similar in both cohorts (24.2% in Cohort 1, 20.7% in Cohort 2), and were within the reference range at the week 4 follow-up visit for 41.0 and 39.1% of the patients in Cohorts 1 and 2, respectively. The incidence of AEs occurring after the first administration of FCM (treatment-emergent AEs, TEAE) was generally low and similar in Cohorts 1 (11/20 [55.0%]) and 2 (13/26 [50.0%]). Most TEAEs were mild; only 2/ 20 patients (10.0%) in Cohort 1 and 3/26 (11.5%) in Cohort 2 had TEAEs of moderate intensity. There were no AEs of severe intensity, serious AEs, or deaths. Most AEs were considered by the investigator to be unrelated or unlikely to be related to the study medication. Since accumulation of serum iron was not observed, a dosing interval of 3-4 days (500 mg iron) or 1 week (1000 mg iron) was demonstrated to be adequate. The increase in serum ferritin and TSAT at the 4-week follow-up visit is indicative of a repletion of the iron stores. The results suggest that doses up to 1000 mg i.v. iron administered as FCM over 15 min arewell tolerated and effective in the treatment of patients with IDA due to a GI disorder. PMID:20648929
Geisser, Peter; Rumyantsev, Vitaly
Overview of sleep & sleep disorders.
Sleep is defined on the basis of behavioural and physiological criteria dividing it into two states: non rapid eye movement (NREM) sleep which is subdivided into three stages (N1, N2, N3); and rapid eye movement (REM) sleep characterized by rapid eye movements, muscle atonia and desynchronized EEG. Circadian rhythm of sleep-wakefulness is controlled by the master clock located in the suprachiasmatic nuclei of the hypothalamus. The neuroanatomical substrates of the NREM sleep are located principally in the ventrolateral preoptic nucleus of the hypothalamus and those of REM sleep are located in pons. A variety of significant physiological changes occur in all body systems and organs during sleep as a result of functional alterations in the autonomic and somatic nervous systems. The international classification of sleep disorders (ICSD, ed 2) lists eight categories of sleep disorders along with appendix A and appendix B. The four major sleep complaints include excessive daytime sleepiness, insomnia, abnormal movements or behaviour during sleep and inability to sleep at the desired time. The most important step in assessing a patient with a sleep complaint is obtaining a detailed history including family and previous histories, medical, psychiatric, neurological, drug, alcohol and substance abuse disorders. Some important laboratory tests for investigating sleep disorders consist of an overnight polysomnography, multiple sleep latency and maintenance of wakefulness tests as well as actigraphy. General physicians should have a basic knowledge of the salient clinical features of common sleep disorders, such as insomnia, obstructive sleep apnoea syndrome, narcolepsy-cataplexy syndrome, circadian rhythm sleep disorders (e.g., jet leg, shift work disorder, etc.) and parasomnias (e.g., partial arousal disorders, REM behaviour disorder, etc.) and these are briefly described in this chapter. The principle of treatment of sleep disorders is first to find cause of the sleep disturbance and vigorously treat the co-morbid conditions causing the sleep disturbance. If a satisfactory treatment is not available for the primary condition or does not resolve the problem, the treatment should be directed at the specific sleep disturbance. Most sleep disorders, once diagnosed, can be managed with limited consultations. The treatment of primary sleep disorders, however, is best handled by a sleep specialist. An overview of sleep and sleep disorders viz., Basic science; international classification and approach; and phenomenology of common sleep disorders are presented. PMID:20308738
Chokroverty, S
The Off-Label Use of Prazosin for Sleep Disturbances in Noncombat Posttraumatic Stress Disorder
Background: Posttraumatic stress disorder (PTSD) is a form of anxiety disorder that arises after exposure to a traumatic event or stressor. It is characterized by persistent invasive thoughts, emotional detachment, hypervigilance and sleep disturbances. These sleep disturbances include nightmares, insomnia and distressed awakenings and are often refractory to multiple medications, including SSRIs, which are the only FDA approved medication for
DuRoss John D. III
Disordered photonics
What do lotus flowers have in common with human bones, liquid crystals with colloidal suspensions, and white beetles with the beautiful stones of the Taj Mahal? The answer is they all feature disordered structures that strongly scatter light, in which light waves entering the material are scattered several times before exiting in random directions. These randomly distributed rays interfere with each other, leading to interesting, and sometimes unexpected, physical phenomena. This Review describes the physics behind the optical properties of disordered structures and how knowledge of multiple light scattering can be used to develop new applications. The field of disordered photonics has grown immensely over the past decade, ranging from investigations into fundamental topics such as Anderson localization and other transport phenomena, to applications in imaging, random lasing and solar energy.
Wiersma, Diederik S.
Self-interstitial mechanism for Zn diffusion-induced disordering of GaAs\\/AlxGa1 - xAs (x=0.1 - 1) multiple-quantum-well structures
GaAs\\/AlxGa1?xAs multiple-quantum-well (MQW) structures with identical well thicknesses but with different Al contents x in the barrier (x≊0.1, 0.2, 0.45, and 1) were grown by molecular-beam epitaxy to study the impurity-induced disordering mechanism. The disordering of the structures is observed directly by transmission electron microscopy on cleaved wedges of the sample, by the secondary electron imaging mode of scanning electron
Nguyen Hong Ky; J. D. Ganičre; M. Gailhanou; B. Blanchard; L. Pavesi; G. Burri; D. Araújo; F. K. Reinhart
Cytogenetic findings in 200 patients with multiple myeloma
Cytogenetic studies were performed on 200 consecutive patients with multiple myeloma and related disorders. Structurally or numerically abnormal clones were found in 63 patients (32%), including 8 of 45 untreated patients (18%), and 55 of 155 treated patients (35%). The abnormal karyotypes generally showed numerous numerical and structural aberrations and in some patients multiple abnormal clones. The most striking feature
Jeffrey R. Sawyer; James A. Waldron; Sundar Jagannath; Bart Barlogie
Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders
A dysfunction of cortical and limbic GABAergic circuits has been postulated to contribute to multiple neurodevelopmental disorders in humans, including schizophrenia, autism, and epilepsy. In the current paper, I summarize the characteristics that underlie the great diversity of cortical GABAergic interneurons and explore how the multiple roles of these cells in developing and mature circuits might contribute to the aforementioned disorders. Furthermore, I review the tightly controlled genetic cascades that determine the fate of cortical interneurons and summarize how the dysfunction of genes important for the generation, specification, maturation, and function of cortical interneurons might contribute to these disorders.
Rossignol, E.
Bipolar disorder: diagnostic issues
Bipolar disorders are cyclical mood disorders with clinical features including distinct sustained periods of mood elevation. • Briefer (4 days or more), mild episodes of mood elevation define bipolar II disorder; lengthier (7 days or more), more severe episodes (or those requiring hospitalisation), with or without psychotic features, define bipolar I disorder. • Depressive periods are more common and lengthier
John W G Tiller; Isaac Schweitzer
Doctoral Disorder of Adulthood.
Humorously proposes doctoral disorder of adulthood as a developmental disorder needing further study. Included are discussions of age at onset, the course of the disorder, prevalence, impairment, complications, predisposing factors, sex ratio, familial pattern, and differential diagnosis. Diagnostic criteria for doctoral disorder of adulthood are…
Dooley-Dickey, Katherine; Satcher, Jamie
Psychiatric disorders in neurology.
Psychiatric disorders (PDs) in neurology are more frequent then it verified in routine exam, not only in the less developed but also in large and very developed neurological departments. Furthermore, psychiatric symptoms (PSs) in neurological disorders (NDs) among primary health care physicians and other specialties are often neglected. Anxiety and depression are most common, but hallucinations, delusions, obsessive-compulsive disorder and delirium or confusional state are also frequent comorbidity in many neurological conditions such as stroke, epilepsy, multiple sclerosis (MS), Parkinson disease (PD). Depression and NDs also have a bidirectional relationship, as not only are patients, for example with stroke at greater risk of developing depression, but patients with depression have a two-fold greater risk of developing a stroke, even after controlling for other risk factors. Dementia or cognitive impairment are part of clinical picture of PD, stroke patients, patients with MS, Huntington disease etc. The prototype of dementia in PD and other NDs is a dysexecutive syndrome with impaired attention, executive functions and secondarily impaired memory. So-called "functional" (or psychogenic or hysterical/conversion) symptoms are relatively infrequent in "neurological" conditions, but very often unrecognized and not properly treated. Treatment of PSs in neurology, basically are not different then treatment of these symptoms in psychiatry and should be include pharmacotherapy and psychiatry. This presentation gives an overview of frequency and type of PSs underlying necessity to recognize these disorders in every day routine exam and properly treatment. PMID:23114812
Sinanovi?, Osman
Spleen Disorders
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Neurologic aspects of plasma cell disorders.
Plasma cell disorders make up a broad spectrum of diseases that are characterized by the appearance of an abnormal clone of plasma cells, which typically manifests as a production of monoclonal immunoglobulin protein (monoclonal gammopathy). The overproduction of plasma cells and subsequent monoclonal gammopathy may be malignant or a premalignant process. Monoclonal gammopathy of undetermined significance (MGUS) is an example of a benign process with a malignant potential. Multiple myeloma, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, and AL amyloidosis (immunoglobulin light chain amyloidosis) are examples of malignant plasma cell disorders which require treatment. Neurologic manifestations of an underlying plasma cell disorder can be variable and typically challenging to treat. They can range from mild symptoms resulting from therapy to treat the disorder to clinically significant and life-threatening complications related to the disease itself. The peripheral nervous system is more commonly affected than the central nervous system. Peripheral neuropathy is a frequent manifestation and is associated with all of the plasma cell disorders (MGUS, multiple myeloma, POEMS syndrome, Waldenström macroglobulinemia and AL amyloidosis) with notable differences in the signs and symptoms among the different groups. Examples of central nervous system manifestations include spinal cord pathology, such as spinal cord compression from vertebral collapse or plasmacytoma. Intracranial involvement is rare but can occur from brain parenchyma infiltration, leptomeningeal involvement, and tumor-like lesions, such as amyloidoma in AL amyloidosis and plasmacytoma in multiple myeloma. Encephalopathy can occur due to metabolic disturbances related to the underlying plasma cell disorder, including hypercalcemia and uremia in multiple myeloma and hyperviscosity in Waldenström macroglobulinemia. Included in this chapter is a detailed discussion of the various plasma cell disorders and their spectrum of neurologic manifestations. PMID:24365373
Sobol, Urszula; Stiff, Patrick
Aggregation of Lifetime Axis I Psychiatric Disorders through Age 30: Incidence, Predictors, and Associated Psychosocial Outcomes
Longitudinal data from representative birth cohorts on the aggregation of psychiatric disorders, or the cumulative number of unique diagnosed disorders experienced by persons within a circumscribed period, are limited. Consequently, risk factors for and psychosocial implications of lifetime disorder aggregation in the general population remain largely unknown. This research evaluates the incidence, predictors, and psychosocial sequela of lifetime disorder aggregation from childhood through age 30. Over a 14-year period, participants in the Oregon Adolescent Depression Project (probands; N = 816) were repeatedly evaluated for psychiatric disorders and assessed with multiple measures of psychosocial functioning. First-degree relatives of probands (N = 2,414) were also interviewed to establish their lifetime psychiatric history. The cumulative prevalence of common lifetime psychiatric disorders for the proband sample was 71%. Three-quarters of all proband psychiatric disorders occurred among 37% of the sample, and 82% of all disorder diagnoses were made among persons who met criteria for at least one other lifetime disorder. Lifetime disorder aggregation in probands was predicted by lifetime psychiatric disorder densities among first-degree relatives and was related to heterotypic comorbidity patterns that included disorders from both internalizing and externalizing domains, most notably major depressive and alcohol use disorders. By age 30, disorder aggregation was significantly associated with mental health care service utilization and predictive of personality disorder pathology and numerous indicators of poor psychosocial functioning. Possible implications of disorder aggregation on the conceptualization of lifetime psychiatric disorder comorbidity are discussed.
Farmer, Richard F.; Kosty, Derek B.; Seeley, John R.; Olino, Thomas M.; Lewinsohn, Peter M.
Recent developments in multiple sclerosis therapeutics
Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-?, glatiramer acetate or natalizumab for
Rebecca I Spain; Michelle H Cameron; Dennis Bourdette
Epilepsy associated with systemic autoimmune disorders.
Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders-and specifically factors predisposing these patients-are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness. PMID:23646005
Devinsky, Orrin; Schein, Adam; Najjar, Souhel
Epilepsy Associated with Systemic Autoimmune Disorders
Systemic autoimmune disorders affect multiple organ systems. Brain involvement commonly causes seizures, which may be the presenting symptom. Systemic lupus erythematosus, Sjorgren's syndrome, Wegener's granulomatosis, sarcoidsosis, celiac disease, Crohn's disease, Behcet's, and Hashimoto's encephalopathy are reviewed. Mechanisms underlying CNS pathology in systemic autoimmune disorders—and specifically factors predisposing these patients—are discussed, including vascular disease (e.g., prothrombotic state, anticardiolipin antibody, emboli, vasculitis), antineuronal antibodies, immune complexes, cytokines, metabolic disorders, infection, and therapy. Diagnostic and therapeutic strategies must be individualized for both the disorder and the patient. Systemic autoimmune disorders affect multiple organ systems and frequently involve the central and peripheral nervous systems. Seizures are among the most common neurological manifestation and occasionally can be the presenting symptom. There are many causes of seizures in systemic autoimmune disorders (Table 1), and the first clinical challenge is to determine not only the cause but also the significance of seizures. In some cases, they are clues to metabolic or infectious disorders or medication toxicity; in other cases, seizures herald a life-threatening progression of the underlying illness.
A high-density single-nucleotide polymorphism screen of 23 candidate genes in attention deficit hyperactivity disorder: suggesting multiple susceptibility genes among Chinese Han population
Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset behavioral disorder with a definite genetic component. The search for genes predisposing to ADHD has focused on genes involved in the regulation of monoamine systems. In this study, we emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245
L Guan; B Wang; Y Chen; L Yang; J Li; Q Qian; Z Wang; S V Faraone; Y Wang
Development of a universal psycho-educational intervention to prevent common postpartum mental disorders in primiparous women: a multiple method approach
BACKGROUND: Prevention of postnatal mental disorders in women is an important component of comprehensive health service delivery because of the substantial potential benefits for population health. However, diverse approaches to prevention of postnatal depression have had limited success, possibly because anxiety and adjustment disorders are also problematic, mental health problems are multifactorially determined, and because relationships amongst psychosocial risk factors
Heather J Rowe; Jane RW Fisher
Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis.
Abstract Background: New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Objective: Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Methods: Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. Results: A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Conclusions: Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD. PMID:24188102
Ma, Dongfeng; Zhang, Zhijun; Zhang, Xiangrong; Li, Lingjiang
[Headache disorders].
Primary headache disorders such as migraine, tension-type headache, and cluster headache are prevalent and disabling neurological disorders. Although most headache disorders are largely treatable, they are under-recognized, under-diagnosed, and under-treated. Many headache sufferers in Japan do not receive appropriate and effective health care; hence, the illness, which should be relieved, persists and acts as an individual and societal burden. One of the barriers most responsible for this is poor awareness of the disorders. For lifting the burden, health care must be improved. Education is an essential way to resolve these issues at multiple levels. We have a Japanese version of the international headache classification and diagnostic criteria II (ICHD-II) and guidelines for the management of chronic headaches. Utilization of these resources is key for the improvement of headache management in our country. Not only neurologists, but also neurosurgeons and other medical specialists are participating in headache care in Japan. The Japanese Headache Society and the Japanese Society for Neurology should play major roles in health care service, education programs, as well as clinical and basic research for headache disorders. The road map for realizing our aim on headache treatment is as follows: (1) increase the number of units concerning headache in lectures for medical students, implement training programs for residents and neurologists, and offer continuous medical educations for physicians and neurologists; (2) secure more funding for headache research; (3) propagate medical care for headache in primary care settings and regional fundamental hospitals; (4) reform the health care system for headache and incentivize appropriate compensation for headache care in public health insurance; and (5) spread appropriate information on medical and socio-ethical issues related to headache for the sufferers and citizens. The authors expect that many neurologists have an interest in headache and understanding headaches, and better health care for headache disorders will bring great benefits for the sufferers. PMID:24018741
Takeshima, Takao; Kikui, Shoji
[Anxiety disorder].
Anxiety disorder (AD) often is under diagnosed and under treated in older adults, especially when the clinical presentation of anxiety. Symptoms often overlap with medical conditions. Of all the anxiety disorders in later life, generalized anxiety disorder (GAD) is one of the most frequently diagnosed. AD is often comorbid with depression. AD is associated with excess disability. Anxiety in older adults has traditionally been treated pharmacology, often with benzodiazepine. However, the clinical recommendations for pharmacologic treatment actually have been much broader, including suggestions to consider serotonergic antidepressants. Selective serotonin reuptake inhibitors (SSRIs) and serotonin nor epinephrine reuptake inhibitors (SNRIs) generally are safe and procedure fewer side effects compared with tricyclic antidepressants (TCAs), in older patients. Effective treatment includes pharmacotherapy and psychotherapy, and complementary and alternative therapies. Late life AD is associated with substantial impairments in quality of life. Effective treatment for AD may be one of the most predictors of improvement of QOL. PMID:24261208
Hayashida, Maiko; Horiguchi, Jun
Speech and Communication Disorders
Many disorders can affect our ability to speak and communicate. They range from saying sounds incorrectly to ... speak or understand speech. Causes include Hearing disorders and deafness Voice problems, such as dysphonia or those ...
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Prevention of eating disorders in female athletes.
Eating disorders are serious mental diseases that frequently appear in female athletes. They are abnormal eating behaviors that can be diagnosed only by strict criteria. Disordered eating, although also characterized as abnormal eating behavior, does not include all the criteria for diagnosing eating disorders and is therefore a way to recognize the problem in its early stages. It is important to identify factors to avoid clinical progression in this high-risk population. Therefore, the purpose of this review is to discuss critical information for the prevention of eating disorders in female athletes. This review discusses the major correlates for the development of an eating disorder. We also discuss which athletes are possibly at highest risk for eating disorders, including those from lean sports and female adolescent athletes. There is an urgent need for the demystification of myths surrounding body weight and performance in sports. This review includes studies that tested different prevention programs' effectiveness, and the majority showed positive results. Educational programs are the best method for primary prevention of eating disorders. For secondary prevention, early identification is essential and should be performed by preparticipation exams, the recognition of dietary markers, and the use of validated self-report questionnaires or clinical interviews. In addition, more randomized clinical trials are needed with athletes from multiple sports in order for the most reliable recommendations to be made and for some sporting regulations to be changed. PMID:24891817
Coelho, Gabriela Morgado de Oliveira; Gomes, Ainá Innocencio da Silva; Ribeiro, Beatriz Gonçalves; Soares, Eliane de Abreu
Prevention of eating disorders in female athletes
Eating disorders are serious mental diseases that frequently appear in female athletes. They are abnormal eating behaviors that can be diagnosed only by strict criteria. Disordered eating, although also characterized as abnormal eating behavior, does not include all the criteria for diagnosing eating disorders and is therefore a way to recognize the problem in its early stages. It is important to identify factors to avoid clinical progression in this high-risk population. Therefore, the purpose of this review is to discuss critical information for the prevention of eating disorders in female athletes. This review discusses the major correlates for the development of an eating disorder. We also discuss which athletes are possibly at highest risk for eating disorders, including those from lean sports and female adolescent athletes. There is an urgent need for the demystification of myths surrounding body weight and performance in sports. This review includes studies that tested different prevention programs' effectiveness, and the majority showed positive results. Educational programs are the best method for primary prevention of eating disorders. For secondary prevention, early identification is essential and should be performed by preparticipation exams, the recognition of dietary markers, and the use of validated self-report questionnaires or clinical interviews. In addition, more randomized clinical trials are needed with athletes from multiple sports in order for the most reliable recommendations to be made and for some sporting regulations to be changed.
Coelho, Gabriela Morgado de Oliveira; Gomes, Aina Innocencio da Silva; Ribeiro, Beatriz Goncalves; Soares, Eliane de Abreu
Putative neuroprotective agents in neuropsychiatric disorders.
In many individuals with major neuropsychiatric disorders including depression, bipolar disorder and schizophrenia, their disease characteristics are consistent with a neuroprogressive illness. This includes progressive structural brain changes, cognitive and functional decline, poorer treatment response and an increasing vulnerability to relapse with chronicity. The underlying molecular mechanisms of neuroprogression are thought to include neurotrophins and regulation of neurogenesis and apoptosis, neurotransmitters, inflammatory, oxidative and nitrosative stress, mitochondrial dysfunction, cortisol and the hypothalamic-pituitary-adrenal axis, and epigenetic influences. Knowledge of the involvement of each of these pathways implies that specific agents that act on some or multiple of these pathways may thus block this cascade and have neuroprotective properties. This paper reviews the potential of the most promising of these agents, including lithium and other known psychotropics, aspirin, minocycline, statins, N-acetylcysteine, leptin and melatonin. These agents are putative neuroprotective agents for schizophrenia and mood disorders. PMID:23178231
Dodd, Seetal; Maes, Michael; Anderson, George; Dean, Olivia M; Moylan, Steven; Berk, Michael
Oppositional Defiant and Conduct Disorder Behaviors in Boys With Autism Spectrum Disorder With and Without Attention-Deficit Hyperactivity Disorder Versus Several Comparison Samples
We compared disruptive behaviors in boys with either autism spectrum disorder (ASD) plus ADHD (n = 74), chronic multiple tic disorder plus ADHD (n = 47), ADHD Only (n = 59), or ASD Only (n = 107). Children were evaluated with parent and teacher versions of the Child Symptom Inventory-4 including parent- (n = 168) and teacher-rated (n = 173) community controls. Parents rated children in the three ADHD groups comparably for
Sarit Guttmann-Steinmetz; Kenneth D. Gadow; Carla J. DeVincent
Common Anorectal Disorders
Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management.
Foxx-Orenstein, Amy E.; Umar, Sarah B.; Crowell, Michael D.
Special considerations in the treatment of patients with bipolar disorder and medical co-morbidities
BACKGROUND: The pharmacological treatment of bipolar disorder has dramatically improved with multiple classes of agents being used as mood-stabilizers, including lithium, anticonvulsants, and atypical antipsychotics. However, the use of these medications is not without risk, particularly when a patient with bipolar disorder also has comorbid medical illness. As the physician who likely has the most contact with patients with bipolar
Kimberly D McLaren; Lauren B Marangell
Reactions of column-III vacancies and interstitials during Zn diffusion-induced disordering of GaAs\\/AlGaAs multiple-quantum-well structures
Different effects related to the reactions of column-III vacancies and interstitials during Zn diffusion into undoped, Si-doped and Be-doped GaAs\\/AlxGal?xAs multilayered structures are investigated by secondary-ion mass spectrometry and photoluminescence. The disordering is observed behind the Zn diffusion front in all multilayered structures. The disordering rate increases with increasing x. The Be out-diffusion is enhanced in the Zn-diffused region. The
Nguyen Hong Ky
Different effects related to the reactions of column-III vacancies and interstitials during Zn diffusion into undoped, Si-doped and Be-doped GaAs\\/AlxGal-xAs multilayered structures are investigated by secondary-ion mass spectrometry and photoluminescence. The disordering is observed behind the Zn diffusion front in all multilayered structures. The disordering rate increases with increasing \\/x. The Be out-diffusion is enhanced in the Zn-diffused region. The
N. H. Ky
[The prognostic significance of brain-derived neurotrophic factor (BDNF) for phobic anxiety disorders, vegetative and cognitive impairments during conservative treatment including adaptol of some functional and organic diseases of nervous system].
We have studied the efficacy of adaptol in the treatment of 45 patients with somatoform dysfunction of the autonomic nervous system and 30 patients with closed head injury. The condition of patients during the treatment was evaluated with clinical and neuropsychological scales. The serum level of BDNF before and after the treatment has been studied as well. Adaptol has been shown to enhance the production of BDNF, reduce significantly the intensity of anxiety, autonomic disorders and improve intellectual processes. The dose-dependent effect of the drug has been demonstrated. In conclusion, adaptol can be recommended for treatment of diseases that demand stimulation of neuroplasticity in the CNS. PMID:22810739
Zhivolupov, S A; Samartsev, I N; Marchenko, A A; Puliatkina, O V
Traumatic Brain Injury and Sleep Disorders
SYNOPSIS Sleep disturbance is common following traumatic brain injury (TBI), affecting 30–70% of individuals, many occurring after mild injuries. Insomnia, fatigue and sleepiness are the most frequent post-TBI sleep complaints with narcolepsy (with or without cataplexy), sleep apnea (obstructive and/or central), periodic limb movement disorder, and parasomnias occurring less commonly. In addition, depression, anxiety and pain are common TBI co-morbidities with substantial influence on sleep quality. Two types of TBI negatively impact sleep: contact injuries causing focal brain damage and acceleration/deceleration injuries causing more generalized brain damage. Diagnosis of sleep disorders after TBI may involve polysomnography, multiple sleep latency testing and/or actigraphy. Treatment is disorder specific and may include the use of medications, continuous positive airway pressure (or similar device) and/or behavioral modifications. Unfortunately, treatment of sleep disorders associated with TBI often does not improve sleepiness or neuropsychological function.
Viola-Saltzman, Mari; Watson, Nathaniel F.
The relationship between creativity and mood disorders
Research designed to examine the relationship between creativity and mental illnesses must confront multiple challenges. What is the optimal sample to study? How should creativity be defined? What is the most appropriate comparison group? Only a limited number of studies have examined highly creative individuals using personal interviews and a noncreative comparison group. The majority of these have examined writers. The preponderance of the evidence suggests that in these creative individuals the rate of mood disorder is high, and that both bipolar disorder and unipolar depression are quite common. Clinicians who treat creative individuals with mood disorders must also confronta variety of challenges, including the fear that treatment may diminish creativity, in the case of bipolar disorder, hovt/ever, it is likely that reducing severe manic episodes may actually enhance creativity in many individuals.
Andreasen, Nancy C.
Neurodegenerative disorders and nanoformulated drug development
Degenerative and inflammatory diseases of the CNS include, but are not limited to, Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, stroke, multiple sclerosis and HIV-1-associated neurocognitive disorders. These are common, debilitating and, unfortunately, hold few therapeutic options. In recent years, the application of nanotechnologies as commonly used or developing medicines has served to improve pharmacokinetics and drug delivery specifically to CNS-diseased areas. In addition, nanomedical advances are leading to therapies that target CNS pathobiology and as such, can interrupt disordered protein aggregation, deliver functional neuroprotective proteins and alter the oxidant state of affected neural tissues. This article focuses on the pathobiology of common neurodegenerative disorders with a view towards how nanomedicine may be used to improve the clinical course of neurodegenerative disorders.
Nowacek, Ari; Kosloski, Lisa M; Gendelman, Howard E
Cyclothymic disorder
The causes of cyclothymic disorder are unknown. Major depression, bipolar disorder , and cyclothymia often occur together in families. This suggests that these mood disorders share similar causes. ...
Conversion and somatization disorders
ObjectiveThere is a difference in classification of conversion disorder in ICD-10 and DSM-IV. Conversion disorder is included in dissociative disorders in ICD-10. In view of this, we aimed to clarify this discrepancy in the classification of this diagnosis.
Hatice Guz; Zahide Doganay; Aysen Ozkan; Esra Colak; Ays?n Tomac; Gokhan Sarisoy
Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the ... and your body, leading to the symptoms of MS. They can include Visual disturbances Muscle weakness Trouble ...
... of eating disorders, anorexia nervosa , bulimia nervosa , and binge eating disorder . People with anorexia nervosa and bulimia nervosa tend ... kidney problems • Severe dehydration from purging of fluids Binge Eating Disorder Presently, the criteria for binge eating disorder are ...
Eosinophilic Disorders
... Blood Cell Disorders Plasma Cell Disorders Leukemias Lymphomas Myeloproliferative Disorders Spleen Disorders Topics in White Blood Cell ... Trade Names GLEEVEC , a drug used to treat cancer. If these drugs fail, various other drugs may ...
Brain transcriptome perturbations in the transferrin receptor 2 mutant mouse support the case for brain changes in iron loading disorders, including effects relating to long-term depression and long-term potentiation.
Iron abnormalities within the brain are associated with several rare but severe neurodegenerative conditions. There is growing evidence that more common systemic iron loading disorders such as hemochromatosis can also have important effects on the brain. To identify features that are common across different forms of hemochromatosis, we used microarray and real-time reverse transcription polymerase chain reaction (RT-PCR) to assess brain transcriptome profiles of transferrin receptor 2 mutant mice (Tfr2(mut)), a model of a rare type of hereditary hemochromatosis, relative to wildtype control mice. The results were compared with our previous findings in dietary iron-supplemented wildtype mice and Hfe(-/-) mice, a model of a common type of hereditary hemochromatosis. For transcripts showing significant changes relative to controls across all three models, there was perfect (100%) directional concordance (i.e. transcripts were increased in all models or decreased in all models). Comparison of the two models of hereditary hemochromatosis, which showed more pronounced changes than the dietary iron-supplemented mice, revealed numerous common molecular effects. Pathway analyses highlighted changes for genes relating to long-term depression (6.8-fold enrichment, p=5.4×10(-7)) and, to a lesser extent, long-term potentiation (3.7-fold enrichment, p=0.01), with generalized reductions in transcription of key genes from these pathways, which are involved in modulating synaptic strength and efficacy and are essential for memory and learning. The agreement across the models suggests the findings are robust and strengthens previous evidence that iron loading disorders affect the brain. Perturbations of brain phenomena such as long-term depression and long-term potentiation might partly explain neurologic symptoms reported for some hemochromatosis patients. PMID:23333676
Acikyol, B; Graham, R M; Trinder, D; House, M J; Olynyk, J K; Scott, R J; Milward, E A; Johnstone, D M
Multiple osteochondromas
Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. The prevalence is estimated at 1:50,000, and it seems to be higher in males (male-to-female ratio 1.5:1). Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. They are pedunculated or sessile (broad base) and can vary widely in size. The number of osteochondromas may vary significantly within and between families, the mean number of locations is 15–18. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The facial bones are not affected. Osteochondromas may cause pain, functional problems and deformities, especially of the forearm, that may be reason for surgical removal. The most important complication is malignant transformation of osteochondroma towards secondary peripheral chondrosarcoma, which is estimated to occur in 0.5–5%. MO is an autosomal dominant disorder and is genetically heterogeneous. In almost 90% of MO patients germline mutations in the tumour suppressor genes EXT1 or EXT2 are found. The EXT genes encode glycosyltransferases, catalyzing heparan sulphate polymerization. The diagnosis is based on radiological and clinical documentation, supplemented with, if available, histological evaluation of osteochondromas. If the exact mutation is known antenatal diagnosis is technically possible. MO should be distinguished from metachondromatosis, dysplasia epiphysealis hemimelica and Ollier disease. Osteochondromas are benign lesions and do not affect life expectancy. Management includes removal of osteochondromas when they give complaints. Removed osteochondromas should be examined for malignant transformation towards secondary peripheral chondrosarcoma. Patients should be well instructed and regular follow-up for early detection of malignancy seems justified. For secondary peripheral chondrosarcoma, en-bloc resection of the lesion and its pseudocapsule with tumour-free margins, preferably in a bone tumour referral centre, should be performed.
Bovee, Judith VMG
Therapeutic horseback riding outcomes of parent-identified goals for children with autism spectrum disorder: an ABA' multiple case design examining dosing and generalization to the home and community.
We examined whether different doses of therapeutic riding influenced parent-nominated target behaviors of children with autism spectrum disorder (ASD) (a) during the session (b) at home, and (c) in the community. We used a single subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5 times/week. Three boys with ASD, 6-8 years of age participated, and counts of target behaviors were collected in each setting and phase of the study. Compared to Baseline, 70% of the target behaviors were better during Intervention and improvement was retained in 63% of the behaviors during Withdrawal. Increased doses of therapeutic riding were significant for magnitude of change, and the effect of the therapeutic riding sessions generalized to home and community. PMID:24091469
Holm, Margo B; Baird, Joanne M; Kim, Young Joo; Rajora, Kuwar B; D'Silva, Delma; Podolinsky, Lin; Mazefsky, Carla; Minshew, Nancy
Pervasive Developmental Disorders in Girls
Pervasive developmental disorders are a group of conditions sharing as their common features impairment in social reciprocity,\\u000a developmental disturbances affecting communication, and manifestation of restricted and repetitive behaviors. Autism is the\\u000a prototypical pervasive developmental disorder, and others include Asperger's Disorder, Rett's Disorder, Childhood Disintegrative\\u000a Disorder, and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). Critical to understanding these conditions\\u000a is appreciation of
Kathleen Koenig; Katherine D. Tsatsanis
Autoantibody-associated movement disorders.
Autoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR. The movement disorder phenotype is diverse and often generalized in young children. Although orofacial dyskinesia was the initial movement phenotype, chorea, dystonia, catatonia, and stereotypical movements are now described. The stereotypical movements can be bizarre and include cycling movements and compulsive self-injurious behavior. Autoimmune basal ganglia encephalitis is an inflammatory encephalitis localizing to the basal ganglia that is sometimes associated with serum antibodies against dopamine-2 receptor. Although psychiatric features are common, the dominant problem is a movement disorder, with dystonia-parkinsonism being characteristic. Sydenham chorea is the prototypic poststreptococcal autoimmune neuropsychiatric disorder and several autoantibodies may be involved in disease generation. The syndrome is characterized by a pure chorea, although hypotonia, dysarthria, and emotional lability are common. Progressive encephalomyelitis with rigidity and myoclonus is a rare autoimmune disorder causing rigidity, stimulus sensitive spasms, and myoclonus of nonepileptic origin and is associated with autoantibodies of multiple types including those against the glycine receptor. These disorders are important to recognize and diagnose, as immune therapy can shorten disease duration and improve outcome. PMID:24203856
Mohammad, Shekeeb S; Ramanathan, Sudarshini; Brilot, Fabienne; Dale, Russell C
The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting
Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…
Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.
Multiple List Learning in Adults with Autism Spectrum Disorder: Parallels with Frontal Lobe Damage or Further Evidence of Diminished Relational Processing?
To test the effects of providing relational cues at encoding and/or retrieval on multi-trial, multi-list free recall in adults with high-functioning autism spectrum disorder (ASD), 16 adults with ASD and 16 matched typical adults learned a first followed by a second categorised list of 24 words. Category labels were provided at encoding,…
Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.
Integrating Case Topics in Medical School Curriculum to Enhance Multiple Skill Learning: Using Fetal Alcohol Spectrum Disorders as an Exemplary Case
Objectives: This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. Methods: In collaboration with the Centers for Disease…
Paley, Blair; O'Connor, Mary J.; Baillie, Susan J.; Guiton, Gretchen; Stuber, Margaret L.
Community Report from the Autism and Developmental Disabilities Monitoring (ADDM) Network: Prevalence of Autism Spectrum Disorders (ASDs) among Multiple Areas of the United States in 2008
The Centers for Disease Control and Prevention (CDC) estimates that about 1 in 88 children has been identified with an autism spectrum disorder (ASD). CDC's estimate comes from the Autism and Developmental Disabilities Monitoring (ADDM) Network, which monitors the number of 8-year-old children with ASDs living in diverse communities throughout the…
Centers for Disease Control and Prevention, 2012
Endocrine and Metabolic Disorders
... congenital adrenal hyperplasia, diseases of the parathyroid gland, diabetes mellitus, diseases of the adrenal glands (including Cushing's syndrome and Addison's disease), and ovarian dysfunction (including polycystic ovary syndrome), among others. Some examples of metabolic disorders include ...
Insulin-like growth factor I induces proliferation and migration of porcine trophectoderm cells through multiple cell signaling pathways, including protooncogenic protein kinase 1 and mitogen-activated protein kinase.
During early pregnancy, the developing conceptus is dependent upon a wide range of growth factors and nutrients that are secreted by or transported by uterine epithelia into the uterus at the maternal-conceptus interface for successful implantation and placentation. Among these factors, insulin-like growth factor-I (IGF-I) is known to play an important role in development of the early embryo and uterine endometrium. However, few studies have been conducted with pigs to determine IGF-I-induced functional effects on peri-implantation embryos such as activation of cell signaling cascades responsible for growth, proliferation and differentiation of cells of the conceptus. Therefore, the aim of this study was to analyze mRNA expression of endometrial IGF-I and its receptor, to examine the functional role of IGF-I on primary porcine trophectoderm (pTr) cells and to assess potential signaling pathways responsible for biological activities of IGF-1. In the present study, expression of endometrial type I IGF receptor (IGF-IR) mRNA increased significantly from Day 10 to Day 12 of pregnancy and the increase was greater for pregnant than cyclic gilts. Both IGF-I and IGF-IR mRNAs were abundant in endometrial luminal-, glandular epithelia, and stratum compactum stroma on Day 12 of pregnancy. In addition, IGF-I significantly induced phosphorylation of AKT1, ERK1/2 and RPS6 in a time- and concentration-dependent manner in pTr cells. Immunofluorescence microscopy revealed that IGF-I treated pTr cells exhibited increased abundance of phosphorylated (p)-AKT1 and p-ERK1/2 MAPK proteins in the nucleus and cytoplasm, and p-RPS6 proteins in the cytosol as compared to non-treated pTr cells. In the presence of the ERK1/2 MAPK inhibitor (U0126), IGF-I-induced AKT1 phosphorylation was not affected, whereas the PI3K inhibitor (LY294002) decreased IGF-I-induced phosphorylation of ERK1/2 and AKT1 proteins, and both the PI3K-AKT1 and ERK1/2 MAPK pathways were blocked by LY294002. Furthermore, IGF-I significantly stimulated both proliferation and migration of pTr cells, but these effects were blocked by P38 inhibitor (SB203580), U0126, MTOR inhibitor (rapamycin) and LY294002. Taken together, these results indicate that IGF-I coordinately regulates multiple cell signaling pathways including PI3K-AKT1-RPS6 and ERK1/2 MAPK signaling pathways that are critical to proliferation, migration and survival of trophectoderm cells during early pregnancy in pigs. PMID:24508636
Jeong, Wooyoung; Song, Gwonhwa; Bazer, Fuller W; Kim, Jinyoung
Depression and neurological disorders.
Depression is the most common psychiatric disorder in neurological disorders such as epilepsy, multiple sclerosis, stroke, and Parkinsons disease. It is associated with reduction of quality of life, functional impairment, and higher mortality. The diagnosis of depression in neurological disorders is difficult because of the overlapping symptoms. Neurological disorders are usually associated with sleep and appetite disturbances, fatigue, apathy, and lack of concentration, which is similar to those of depression. The etiology of depression with neurological disorders is unknown, but the interaction between biological, psychosocial, and neuropathological factors could be responsible for it. Few controlled trials have been carried out to investigate the efficacy of psychotherapeutic and pharmacological interventions in this population, and it seems that they are effective in improving depression, quality of life, and survival. Studies pertaining to prevention of depression in neurological disorders are promising. PMID:21048620
Bassiony, Medhat M
Movement disorders in paraneoplastic and autoimmune disease
Purpose of review The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment. Recent findings Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens). Summary Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy.
Panzer, Jessica; Dalmau, Josep
Geriatric Disorders
At one time, the psychiatry of old age was believed to be "the darkest area of psychiatry." The often confounding nature of\\u000a psychiatric disorder in the elderly is illustrated by the large number of terms used over the years to address the diversity\\u000a among geriatric psychiatric patients, including "late paraphrenia," "vascular depression," "pseudodementia," and "masked depression."\\u000a Many of these labels
Colin A. Depp; Jody Corey-Bloom
Vitamin D and autoimmune rheumatologic disorders.
Vitamin D levels depend on many variables, including sun exposure, age, ethnicity, body mass index, use of medications and supplements. A much higher oral vitamin D intake than the current guidelines is necessary to maintain adequate circulating 25(OH)D levels in the absence of UVB radiation of the skin. In addition to the traditional known metabolic activities, vitamin D has been shown to modulate the immune system, and its deficiency has been linked to the development of several autoimmune disorders including type 1 diabetes and multiple sclerosis. Experimental use of vitamin D has revealed a novel role in the immunopathogenesis of autoimmune diseases. Disorders such as systemic lupus erythematosus, rheumatoid arthritis, Behçet's, polymyositis/dermatomyositis and systemic scleroderma have all been associated to some extent to vitamin D deficiency. If vitamin D deficiency occurs at a higher rate in patients with autoimmune disorders, then appropriate supplementation may be indicated. PMID:20146942
Pelajo, Christina F; Lopez-Benitez, Jorge M; Miller, Laurie C
High efficient production of Pr55 gag virus-like particles expressing multiple HIV1 epitopes, including a gp120 protein derived from an Ugandan HIV1 isolate of subtype A
The main goal of this study was to investigate a novel approach for an efficient and reproducible production of Virus-Like Particles (VLPs) expressing multiple HIV-1 epitopes. The HIV-1 Pr55gag-based VLPs have been produced in a Baculovirus expression system, using a transfer vector able to support the independent expression of different open reading frames (ORFs). In this regard, the gp120 derived
L. Buonaguro; F. M. Buonaguro; M. L. Tornesello; D. Mantas; E. Beth-Giraldo; R. Wagner; S. Michelson; M.-C. Prevost; H. Wolf; G. Giraldo
[Dysmorphophobia (body dysmorphic disorder)].
This article reviews the historical and terminological origins of dysmorphophobia from Herodotus to today. It explains the differences pointed out by many authors, including the DSM-III-R, between body dismorphic disorder and delusional disorder somatic type, which are referred to as monosymptomatic hypochondriacal psychoses in Europe. Epidemiological data, clinical characteristics and outcome are discussed. Explicative theories and neurobiological, developmental and analytical aspects of body image are presented. The association between body dismorphic disorder and other disorders is analyzed, and treatment possibilities are discussed. The authors suggest that body dismorphic disorder be classified with obsessive compulsive disorder, whatever the intensity of symptomatology, rather than with somatoform or delusional disorder, and treated with serotonin uptake inhibitors or neureptics that have been proven to be effective for the treatment of this disorder, such as pimozide. PMID:1423148
Filteau, M J; Pourcher, E; Baruch, P; Bouchard, R H; Vincent, P
Diagnostic Evaluation of Autism Spectrum Disorders
Synopsis Research on the identification and evaluation of autism spectrum disorders (ASD) is reviewed and best practices for clinical work are discussed. The latest research on diagnostic tools, and their recommended use, is also reviewed. Recommendations include the use of instruments designed to assess multiple domains of functioning and behavior, the inclusion of parents and caregivers as active partners, and the consideration of developmental factors throughout the diagnostic process.
Huerta, Marisela; Lord, Catherine
Absence of evidence for bornavirus infection in schizophrenia, bipolar disorder and major depressive disorder
In 1983, reports of antibodies in subjects with major depressive disorder to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to the molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV).1,2 This advance enabled the development of new diagnostic assays including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990 more than 80 studies have reported an association between BDV and a wide range of human illnesses that include major depressive disorder, bipolar disorder, schizophrenia, anxiety disorder, chronic fatigue syndrome, multiple sclerosis, amyotrophic lateral sclerosis, dementia and glioblastoma multiforme.3,4 However, to date there has been no blinded case-control study of the epidemiology of BDV infection. Here, in a United States-based, multi-center, yoked case-control study with standardized methods for clinical assessment and blinded serologic and molecular analysis, we report the absence of association of psychiatric illness with antibodies to BDV or with BDV nucleic acids in serially-collected serum and white blood cell samples from 396 subjects, a study population comprised of 198 matched pairs of patients and healthy controls (52 schizophrenia/control pairs, 66 bipolar disorder/control pairs, and 80 major depressive disorder/control pairs). Our results argue strongly against a role for BDV in the pathogenesis of these psychiatric disorders.
Hornig, Mady; Briese, Thomas; Licinio, Julio; Khabbaz, Rima F.; Altshuler, Lori L.; Potkin, Steven G.; Schwemmle, Martin; Siemetzki, Ulrike; Mintz, Jim; Honkavuori, Kirsi; Kraemer, Helena C.; Egan, Michael F.; Whybrow, Peter C.; Bunney, William E.; Lipkin, W. Ian
White matter in learning, cognition and psychiatric disorders
White matter is the brain region underlying the gray matter cortex, composed of neuronal fibers coated with electrical insulation called myelin. Previously of interest in demyelinating diseases such as multiple sclerosis, myelin is attracting new interest as an unexpected contributor to a wide range of psychiatric disorders, including depression and schizophrenia. This is stimu- lating research into myelin involvement in
R. Douglas Fields
Gene Transfer Strategies for Correction of Lysosomal Storage Disorders
Lysosomal storage diseases (LSDs) represent a large group of monogenic disorders of metabolism, which affect approximately 1 in 5,000 live births. LSDs result from a single or multiple deficiency of specific lysosomal hydrolases, the enzymes responsible for the luminal catabolization of macromolecular substrates. The consequent accumulation of undigested metabolites in lysosomes leads to polysystemic dysfunction, including progressive neurologic deterioration, mental
Alessandra d'Azzo
Multiple genes and factors associated with bipolar disorder converge on growth factor and stress activated kinase pathways controlling translation initiation: Implications for oligodendrocyte viability
Famine and viral infection, as well as interferon therapy have been reported to increase the risk of developing bipolar disorder. In addition, almost 100 polymorphic genes have been associated with this disease. Several form most of the components of a phosphatidyl-inositol signalling\\/AKT1 survival pathway (PIK3C3, PIP5K2A, PLCG1, SYNJ1, IMPA2, AKT1, GSK3B, TCF4) which is activated by growth factors (BDNF, NRG1)
C. J. Carter
Assessing Multiple Outcomes for Women with Co-Occurring Disorders and Trauma in a Multi-Site Trial: A Propensity Score Approach
The current study assesses the ability of two promising propensity scoring methods to reduce selection bias in a set of secondary\\u000a data from the women with co-occurring disorders and violence study (WCDVS), whose purpose was to evaluate the effect of integrated\\u000a treatment for women with mental health, substance use, and trauma issues (N = 2,729). Weighting, the more successful method, is demonstrated
Alan R. Ellis; Joseph P. Morrissey
[Disorders of sex chromosome].
Disorders of sex chromosome, X and Y, consist of abnormality of the number or structure of the sex chromosome. Because sex chromosomes have a variety of genes related to sexual differentiation, disorders of sex chromosome induce a variety of disorders of sexual differentiation. At first, in this title, the process of normal sexual differentiation is shown. Classical disorders of sex chromosome are Klinefelter syndrome, XX male, XYY male, Turner syndrome, XXX female, and XY female. True hermphroiditism, mixed gonadal dysgenesis, and pure gonadal dysgenesis are also included, because most of these disorders have abnormal sex chromosome. Molecular analysis of sex chromosome is clarifying disorders with a minute abnormality of sex chromosome. They include male infertility, premature ovarian failure, and fragile X syndrome. Explanations of the above disorders are given briefly. PMID:9396296
Namiki, M; Koh, E
Autoimmune basal ganglia disorders.
The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771
Dale, Russell C; Brilot, Fabienne
Interstitial deletion of 11(p11.2p12): A newly described contiguous gene deletion syndrome involving the gene for hereditary multiple exostoses
Individuals with deletions of the proximal portion of the short arm of chromosome 11 share many manifestations including mental retardation, biparietal foramina, minor facial anomalies, and multiple cartilaginous exostoses. The finding of multiple exostoses in these patients is remarkable as the disorder hereditary multiple exostoses, which is inherited in an autosomal dominant manner, has recently been mapped by linkage to
L. Potocki; L. G. Shaffer
Diagnostic issues in bipolar disorder
Bipolar disorder is a highly recurrent and chronic psychiatric condition that shortens life expectancy, causes functional impairment and disruption to social, work and family life. Several forms of bipolar disorder are recognised, including both bipolar I and bipolar II disorder. Bipolar I is characterised by recurrent episodes of depression and mania whereas bipolar II disorder is characterised by recurrent depression
Jules Angst; Alex Gamma; Franco Benazzi; Vladeta Ajdacic; Dominique Eich; Wulf Rössler
Immunotherapies in neurologic disorders.
Therapy for autoimmune demyelinating disorders has evolved rapidly over the past 10 years to include traditional immunosuppressants as well as novel biologicals. Antibody-mediated neuromuscular disorders are treated with therapies that acutely modulate pathogenic antibodies or chronically inhibit the humoral immune response. In other inflammatory autoimmune disorders of the peripheral and central nervous system, corticosteroids, often combined with conventional immunosuppression, and immunomodulatory treatments are used. Because autoimmune neurologic disorders are so diverse, evidence from randomized controlled trials is limited for most of the immunotherapies used in neurology. This review provides an overview of the immunotherapies currently used for neurologic disorders. PMID:22703853
Graves, Donna; Vernino, Steven
Geriatric bipolar disorder.
Because the elderly are the fastest growing segment of the population, the number of older adults with bipolar disorder is increasing. Geriatric bipolar disorder is relatively rare, with an estimated lifetime prevalence of 0.5% to 1%, although approximately 4% to 17% of older patients in clinical psychiatric settings have bipolar disorder. Bipolar elders are disproportionately affected by medical burden. Given the complex nature of this disorder, comorbidity, and behavioral disturbances, various interventions may be indicated, including pharmacotherapies, electroconvulsive therapy, psychotherapies, and integrated care models. Additional research is needed to better understand the epidemiology, phenomenology, and treatment of geriatric bipolar disorder. PMID:21536161
Sajatovic, Martha; Chen, Peijun
QEEG profiles of psychiatric disorders.
While reports of EEG correlates of psychiatric disorders date back five decades, clinical sensitivity of the EEG to psychiatric disorders has been greatly enhanced with the advent of quantitative methods of analysis (QEEG). Using a QEEG methodology known as neurometrics we have identified distinctive electrophysiological profiles associated with different psychiatric disorders. With this method quantitative features are extracted from 2 minutes of artifact- free eyes closed resting EEG data, log transformed to obtain Gaussianity, age-regressed, and Z-transformed relative to population norms. Using small subsets of neurometric features, multiple stepwise discriminant analyses were used to construct mathematical classifier functions, the values of which are different for members of different a priori defined diagnostic groups. Using this approach, we have demonstrated high discriminant accuracy in independent replications separating many populations of psychiatric patients from normal as well as from each other, including major affective disorder, schizophrenia, dementia, alcoholism, and learning disabilities, as well as high accuracy of discrimination between known subtypes of depression (unipolar vs bipolar). The use of classification accuracy curves (CACs) which allow one to assess the sensitivity and specificity achieved by the discriminant functions is discussed. In addition, using cluster analysis, neurometric subtypes can be identified in several clinically homogenous populations. Preliminary results suggest that baseline membership in some neurometric subtypes may be highly correlated with response to treatment. PMID:1510868
Prichep, L S; John, E R
Once-Daily Atomoxetine Treatment for Children With Attention-Deficit\\/ Hyperactivity Disorder, Including an Assessment of Evening and Morning Behavior: A Double-Blind, Placebo-Controlled Trial
Objectives. Atomoxetine seems to be as effective for treating attention-deficit\\/hyperactivity dis- order (ADHD) when the daily dose is administered once in the morning as when the dose is divided and admin- istered in the morning and evening. In the present study, the efficacy of atomoxetine administered once daily among children with ADHD was assessed throughout the day, including the evening
Douglas K. Kelsey; Calvin R. Sumner; Charles D. Casat; Daniel L. Coury; Humberto Quintana; Keith E. Saylor; Virginia K. Sutton; Jill Gonzales; Sandra K. Malcolm; Kory J. Schuh; Albert J. Allen
Central nervous system stimulants for secondary attention deficit-hyperactivity disorder after paediatric traumatic brain injury: a rationale and protocol for single patient (n-of-1) multiple cross-over trials
Background It is estimated that 22,800 children were living with an Acquired Brain Injury (ABI) (0.6% of children aged under 15 years) in Australia during 2003. Many children after a traumatic brain injury will experience difficulties with attention and concentration; a condition termed secondary Attention Deficit-Hyperactivity Disorder. There is conflicting evidence on whether treatment with stimulant therapy with medications such as methylphenidate or dexamphetamine will improve the attention and behavior of children with this condition. Methods/Design Single patient trials (n-of-1s or SPTs) evaluate the effect of titrated doses of psychostimulants methylphenidate or dexamphetamine compared to placebo on attention and behavior, in children with TBI and secondary ADHD. The aggregation of multiple SPTs will produce a population estimate of the benefit. Forty-two children will be registered into the trial through rehabilitation services at three large children's hospitals in Australia. Patients will complete up to 3 cycles of treatment. Each cycle is 2 weeks long comprising seven days each of treatment and placebo, with the first two days of each cycle considered a washout period and the data not analysed. The order of treatment and placebo is randomly allocated for each cycle. The Conners' Parent Rating Scales long forms will be employed to measure change in attention-deficit/hyperactivity and related problems of the child, and the primary outcome measure is the Conners' Global Index Parent Version. Secondary outcomes include the teacher and child (if aged > 12 years) Conners' Rating Scales, the Behaviour Rating Inventory of Executive Function among other measures. This study will provide high-level evidence using a novel methodological approach to inform clinicians about the most appropriate treatment for individual children. Through aggregation of individual trials, a population estimate of treatment effect will be provided to guide clinical practice in the treatment of children with secondary ADHD after a traumatic brain injury. Discussion This study employs an innovative methodological approach on the effectiveness of CNS stimulants for secondary ADHD from a brain injury. The findings will both guide clinicians on treatment recommendations, and inform the concept and acceptance of SPTs in paediatric research. Trial registration Australian New Zealand Clinical Trials Registry. ACTRN12609000873224
Immune Disorders and Its Correlation with Gut Microbiome
Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders.
Hwang, Ji-Sun; Im, Chang-Rok
Epistatic Interactions between CREB and CREM Variants in Affective Disorder
The aim of the present work is to investigate the existence of epistatic interactions possibly influencing psychotropic agents' response between rs6740584 within Cyclic adenosine monophosphate Response Element Binding (CREB) and rs12775799 within cAMP response element-modulator (CREM) variants in bipolar disorder (BD) and major depressive disorder (MDD). All BD and MDD patients were administered with the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAMD) at baseline and at endpoint, respectively. A multiple regression model was employed to investigate the existence of possible epistatic interactions between the two variants and diverse clinical factors including drug response in affective disorders. No significant epistatic interaction was observed between rs6740584 within CREB and rs12775799 within CREM on both symptom improvement and other clinical factors in affective disorders. Our preliminary results suggest that no epistatic interaction between rs6740584 within CREB and rs12775799 within CREM should exist on clinical improvement and clinical factors in affective disorders.
Chiesa, Alberto; Marsano, Agnese; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Serretti, Alessandro
Diabetes and psychiatric disorders
Interface of diabetes and psychiatry has fascinated both endocrinologists and mental health professionals for years. Diabetes and psychiatric disorders share a bidirectional association -- both influencing each other in multiple ways. The current article addresses different aspects of this interface. The interaction of diabetes and psychiatric disorders has been discussed with regard to aetio-pathogenesis, clinical presentation, and management. In spite of a multifaceted interaction between the two the issue remains largely unstudied in India.
Balhara, Yatan Pal Singh
A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.
Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. PMID:1328867
Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C
Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images
Mink, S; Hartig, E; Jennewein, P; Doppler, W; Cato, A C
Genetic Disorders
... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...
... normal weight or can be overweight. Continue Binge Eating Disorder This eating disorder is similar to anorexia and ... and celebrations involving food Back Continue What Causes Eating Disorders? No one is really sure what causes eating ...
Order a free hardcopy En Espańol What are eating disorders? An eating disorder is an illness that causes ... population. 5 What are the different types of eating disorders? Anorexia nervosa Anorexia nervosa is characterized by: Extreme ...
Mathematics disorder
Mathematics disorder is a condition in which a child's math ability is far below normal for their ... Children who have mathematics disorder may have trouble performing ... adding. Mathematical disorder may appear with: Developmental ...
Multiple sclerosis.
Multiple sclerosis is the prototype inflammatory autoimmune disorder of the central nervous system and, with a lifetime risk of one in 400, potentially the most common cause of neurological disability in young adults. As with all complex traits, the disorder results from an interplay between as yet unidentified environmental factors and susceptibility genes. Together, these factors trigger a cascade of events, involving engagement of the immune system, acute inflammatory injury of axons and glia, recovery of function and structural repair, post-inflammatory gliosis, and neurodegeneration. The sequential involvement of these processes underlies the clinical course characterised by episodes with recovery, episodes leaving persistent deficits, and secondary progression. The aim of treatment is to reduce the frequency, and limit the lasting effects, of relapses, relieve symptoms, prevent disability arising from disease progression, and promote tissue repair. Despite limited success in each of these categories, everyone touched by multiple sclerosis looks for a better dividend from applying an improved understanding of the pathogenesis to clinical management. PMID:11955556
Compston, Alastair; Coles, Alasdair
Trousseau's syndrome: multiple definitions and multiple mechanisms
In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet- and endotheliumum-based selectin-dependent microangiopathy associated with mucin-producing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.
Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways
Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood-stabilizing drugs, such as tricyclic antidepressants, lithium, and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder.
Kerner, Berit; Rao, Aliz R.; Christensen, Bryce; Dandekar, Sugandha; Yourshaw, Michael; Nelson, Stanley F.
Rare Genomic Variants Link Bipolar Disorder with Anxiety Disorders to CREB-Regulated Intracellular Signaling Pathways.
Bipolar disorder is a common, complex, and severe psychiatric disorder with cyclical disturbances of mood and a high suicide rate. Here, we describe a family with four siblings, three affected females and one unaffected male. The disease course was characterized by early-onset bipolar disorder and co-morbid anxiety spectrum disorders that followed the onset of bipolar disorder. Genetic risk factors were suggested by the early onset of the disease, the severe disease course, including multiple suicide attempts, and lack of adverse prenatal or early life events. In particular, drug and alcohol abuse did not contribute to the disease onset. Exome sequencing identified very rare, heterozygous, and likely protein-damaging variants in eight brain-expressed genes: IQUB, JMJD1C, GADD45A, GOLGB1, PLSCR5, VRK2, MESDC2, and FGGY. The variants were shared among all three affected family members but absent in the unaffected sibling and in more than 200 controls. The genes encode proteins with significant regulatory roles in the ERK/MAPK and CREB-regulated intracellular signaling pathways. These pathways are central to neuronal and synaptic plasticity, cognition, affect regulation and response to chronic stress. In addition, proteins in these pathways are the target of commonly used mood-stabilizing drugs, such as tricyclic antidepressants, lithium, and valproic acid. The combination of multiple rare, damaging mutations in these central pathways could lead to reduced resilience and increased vulnerability to stressful life events. Our results support a new model for psychiatric disorders, in which multiple rare, damaging mutations in genes functionally related to a common signaling pathway contribute to the manifestation of bipolar disorder. PMID:24348429
Kerner, Berit; Rao, Aliz R; Christensen, Bryce; Dandekar, Sugandha; Yourshaw, Michael; Nelson, Stanley F
Fulminant multiple sclerosis (MS).
Fulminant multiple sclerosis (MS) is the most malignant form of MS which usually leads to death in few weeks. Although it can be accompanied by optic neuritis (ON), but long interval between ON and the grave onset has not been reported. Fulminant MS usually occurs as the first onset and previous ON is not common. We report a rare case of 30-year-old woman with a history of ON 1 year ago. The rapid deterioration to vegetative state followed by a seizure and previous ON differentiated this case from previous reported cases. The differential diagnosis of a rapidly progressive leucoencephalopathy in this patient includes inflammatory, vascular, infectious and toxic disorders. Regarding the previous history of optic neuritis with positive brain MRI (multiple T2 hyperintense lesions in white matter) in our patient, multiple sclerosis is the most probable diagnosis. More effective treatments, such as plasmapheresis and cyclophosphamide, that influenced on the prognosis of some previous patients could be useful, but should be performed before progressive brain atrophy emerges. PMID:21863271
Rohani, Mohammad; Ghourchian, Shadi
Atypical progression of multiple myeloma with extensive extramedullary disease
Multiple myeloma is a neoplastic disorder caused by the proliferation of a transformed B lymphoid progenitor cell that gives rise to a clone of immunoglobulin-secreting cells. Other plasma cell tumours include solitary plasmacytoma of bone (SPB) and extramedullary plasmacytomas (EMP). Despite an apparent common origin there exist pathological and clinical differences between these neoplasms and the association between them is
S N Jowitt; A Jacobs; P A Batman; D A Sapherson
The glial perspective of autism spectrum disorders.
The aetiology of autism spectrum disorders remains unclear although a growing number of associated genetic abnormalities and environmental factors have been discovered in recent decades. These advancements coincided with a remarkable increase in the comprehension of physiological functions and pathological potential of neuroglia in the central nervous system that led to a notion of fundamental contribution of glial cells into multiple neuropathologies, including neuropsychiatric and developmental disorders. Growing evidence indicates a role for deregulation of astroglial control over homeostasis and plastic potential of neural networks as well as microglial malfunction and neuroinflammatory response in the brains of autistic patients. In this review, we shall summarize the status and pathological potential of neuroglia and argue for neuroglial roots of autistic disorders. PMID:24300694
Zeidán-Chuliá, Fares; Salmina, Alla B; Malinovskaya, Natalia A; Noda, Mami; Verkhratsky, Alexei; Moreira, José Cláudio Fonseca
Ventilatory disorders.
Breathing is a primal homeostatic neural process, regulating levels of oxygen and carbon dioxide in blood and tissues, which are crucial for life. Rhythmic respiratory movements must occur continuously throughout life and originate from neural activity generated by specially organized macro- and microcircuits in the brainstem. In the respiratory network there is a spatial and dynamic hierarchy of interacting circuits, each of which controls different aspects of respiratory rhythm generation and pattern formation, which can be revealed as the network is progressively reduced. The motor pattern during normal breathing is considered to consist of three phases: inspiration, post-inspiration and expiration. The expression of each rhythmogenic mechanism is state-dependent and produces specific motor patterns likely to underpin distinct motor behaviors. Vascular neurological disorders affecting these areas or the respiratory motor unit may lead to impaired respiratory activity. Manifestations associated with disorders of this network include sleep apnea and dysrhythmic breathing frequently associated with disturbances of cardiovagal and sympathetic vasomotor control. Respiratory dysfunction constitutes an early and relatively major manifestation of vascular neurologic disorders; ventilation control and breathing behavior correction are necessary to improve stroke management. PMID:22377872
Silvestrelli, Giorgio; Lanari, Alessia; Droghetti, Andrea
Parental psychiatric disorders and autism spectrum disorders
The present population-based, case-control study examines associations between specific parental psychiatric disorders and autism spectrum disorders (ASD) including childhood autism, Asperger's syndrome and pervasive developmental disorder (PDD-NOS). The cohort includes 4713 children born between 1987 and 2005 with diagnoses of childhood autism, Asperger's syndrome or PDD-NOS. Cases were ascertained from the Finnish Hospital Discharge Register, and each was matched to four controls by gender, date of birth, place of birth, and residence in Finland. Controls were selected from the Finnish Medical Birth Register. Parents were identified through the Finnish Medical Birth Register and Finnish Central Population Register. Parental psychiatric diagnoses from inpatient care were collected from the Finnish Hospital Discharge Register. Conditional logistic regression models were used to assess whether parents' psychiatric disorders predicted ASD after controlling for parents' age, smoking during pregnancy and weight for gestational age. In summary, parental schizophrenia spectrum disorders and affective disorders were associated with the risk of ASD regardless of the subgroup. PDD-NOS was associated with all parental psychiatric disorders investigated. Further studies are needed to replicate these findings. These results may facilitate the investigation of shared genetic and familial factors between ASD and other psychiatric disorders.
Jokiranta, Elina; Brown, Alan S.; Heinimaa, Markus; Cheslack-Postava, Keely; Partanen, Auli; Sourander, Andre
Common comorbidities seen in adolescents with attention-deficit/hyperactivity disorder.
This article provides an overview of key research on significant comorbidities that occur among adolescents with attention-deficit/hyperactivity disorder, including disruptive behaviors. Such comorbidities include oppositional defiant disorder and conduct disorder, as well as depressive disorders, anxiety disorders, personality disorders, suicidality, eating disorders, sleep disorders, learning disabilities, Internet "addiction," tic disorders, new-onset pediatric epilepsy, and celiac disease. PMID:18822828
Young, Joel
Vitamin D and multiple sclerosis
Multiple sclerosis (MS) is a chronic demyelinating disease and also is one of the most common disabling neurological disorders in young and middle-aged adults. The main pathogenesis of MS has long been thought to be an immune mediated disorder of the central nervous system. The function of the immune system is under the influence of vitamin D which as a modulator of immune response could play a role in autoimmune diseases including MS. Deficiency of vitamin D or variations in DNA sequence (polymorphism) of vitamin D receptor gene diminishes its optimal function on immune system that consequently could lead to increasing risk of MS. However, its role in development and modulating the course of MS is still under investigation. In this review we aimed to discuss the role of vitamin D in body, immune system and consequently altering the risk of MS.
Harandi, Ali Amini; Pakdaman, Hossein; Sahraian, Mohammad Ali
The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic stress disorder and psychiatric co-morbidity following epileptic seizures: a moderated mediation analysis.
This study investigated the incidence of posttraumatic stress disorder (PTSD) and psychiatric co-morbidity following epileptic seizure, whether alexithymia mediated the relationship between self-efficacy and psychiatric outcomes, and whether the mediational effect was moderated by the severity of PTSD from other traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited from support groups in the United Kingdom completed the Posttraumatic Stress Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and 22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD following one other traumatic life event respectively. For the control group, 24% met the diagnostic criteria for PTSD following other traumatic life events. The epilepsy group reported significantly more anxiety and depression than the control. Partial least squares (PLS) analysis showed that self-efficacy was significantly correlated with alexithymia, post-epileptic seizure PTSD and psychiatric co-morbidity. Alexithymia was also significantly correlated with post-epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed that alexithymia mediated the path between self-efficacy and post-epileptic seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed that self-efficacy and PTSD from one other trauma moderated the effect of alexithymia on outcomes. To conclude, people can develop posttraumatic stress disorder symptoms and psychiatric co-morbidity following epileptic seizure. These psychiatric outcomes are closely linked with their belief in personal competence to deal with stressful situations and regulate their own functioning, to process rather than defend against distressing emotions, and with the degree of PTSD from other traumas. PMID:23978734
Chung, Man Cheung; Allen, Rachel D; Dennis, Ian
Conditional disorder in chaperone action
Protein disorder remains an intrinsically fuzzy concept. Its role in protein function is difficult to conceptualize and its experimental study is challenging. Although a wide variety of roles for protein disorder have been proposed, establishing that disorder is functionally important, particularly in vivo, is not a trivial task. Several molecular chaperones have now been identified as conditionally disordered proteins; fully folded and chaperone-inactive under non-stress conditions, they adopt a partially disordered conformation upon exposure to distinct stress-conditions. This disorder appears to be vital for their ability to bind multiple aggregation-sensitive client proteins and to protect cells against the stressors. The study of these conditionally disordered chaperones should prove useful in understanding the functional role for protein disorder in molecular recognition.
Bardwell, James C. A.; Jakob, Ursula
Health Care Costs and Resource Utilization, Including Patient Burden, Associated With Novel-Agent-Based Treatment Versus Other Therapies for Multiple Myeloma: Findings Using Real-World Claims Data
Background. Treatment of multiple myeloma has dramatically improved with the introduction of bortezomib (BOR), thalidomide (THAL), and lenalidomide (LEN). Studies assessing health care costs, particularly economic burden on patients, are limited. We conducted a claims-based, retrospective analysis of total health care costs as well as patient burden (patient out-of-pocket costs and number of ambulatory/hospital visits) associated with BOR/THAL/LEN treatment versus other therapies (OTHER). Methods. Treatment episodes starting between January 1, 2005 and September 30, 2010 were identified from the claims database of a large U.S. health plan. Health care costs and utilization were measured during 1 year after initiation and analyzed per treatment episode. Multivariate analyses were used to adjust for patient characteristics, comorbidities, and line of treatment. Results. A total of 4,836 treatment episodes were identified. Mean adjusted total costs were similar between BOR ($112,889) and OTHER ($111,820), but higher with THAL ($129,412) and LEN ($158,428). Mean adjusted patient out-of-pocket costs were also similar for BOR ($3,846) and OTHER ($3,900) but remained higher with THAL ($4,666) and LEN ($4,483). Mean adjusted rates of ambulatory visits were similar across therapies (BOR: 69.67; THAL: 66.31; LEN: 65.60; OTHER: 69.42). Conclusions. Adjusted analyses of real-world claims data show that total health care costs, as well as patient out-of-pocket costs, are higher with THAL/LEN treatment episodes than with BOR/OTHER therapies. Additionally, similar rates of ambulatory visits suggest that any perceived advantage in patient convenience of the orally administered drugs THAL/LEN is not supported by these data.
Teitelbaum, April; Ba-Mancini, Abbie; Huang, Hui
Pharmacological evidence that multiple phospholipid signaling pathways link Rhizobium nodulation factor perception in Medicago truncatula root hairs to intracellular responses, including Ca2+ spiking and specific ENOD gene expression.
Rhizobium nodulation (Nod) factors are specific lipochito-oligosaccharide signals essential for initiating in root hairs of the host legume developmental responses that are required for controlled entry of the microsymbiont. In this article, we focus on the Nod factor signal transduction pathway leading to specific and cell autonomous gene activation in Medicago truncatula cv Jemalong in a study making use of the Nod factor-inducible MtENOD11 gene. First, we show that pharmacological antagonists that interfere with intracellular ion channel and Ca2+ pump activities are efficient blockers of Nod factor-elicited pMtENOD11-beta-glucuronidase (GUS) expression in root hairs of transgenic M. truncatula. These results indicate that intracellular Ca2+ release and recycling activities, essential for Ca2+ spiking, are also required for specific gene activation. Second, pharmacological effectors that inhibit phospholipase D and phosphoinositide-dependent phospholipase C activities are also able to block pMtENOD11-GUS activation, thus underlining a central role for multiple phospholipid signaling pathways in Nod factor signal transduction. Finally, pMtENOD11-GUS was introduced into all three Nod-/Myc- dmi M. truncatula mutant backgrounds, and gene expression was evaluated in response to the mastoparan peptide agonist Mas7. We found that Mas7 elicits root hair MtENOD11 expression in dmi1 and dmi2 mutants, but not in the dmi3 mutant, suggesting that the agonist acts downstream of DMI1/DMI2 and upstream of DMI3. In light of these results and the recently discovered identities of the DMI gene products, we propose an integrated cellular model for Nod factor signaling in legume root hairs in which phospholipids play a key role in linking the Nod factor perception apparatus to downstream components such as Ca2+ spiking and ENOD gene expression. PMID:15489277
Charron, Dorothée; Pingret, Jean-Luc; Chabaud, Mireille; Journet, Etienne-Pascal; Barker, David G
Testing multiple levels of influence in the intergenerational transmission of alcohol disorders from a developmental perspective: the example of alcohol use promoting peers and ?-opioid receptor M1 variation.
This study examined the interplay between the influence of peers who promote alcohol use and ?-opioid receptor M1 (OPRM1) genetic variation in the intergenerational transmission of alcohol use disorder (AUD) symptoms while separating the "traitlike" components of AUD symptoms from their age-specific manifestations at three ages from emerging adulthood (17-23 years) to adulthood (29-40 years). The results for males were consistent with genetically influenced peer selection mechanisms as mediators of parent alcoholism effects. Male children of alcoholics were less likely to be carriers of the G allele in single nucleotide polymorphism A118G (rs1799971), and those who were homozygous for the A allele were more likely to affiliate with alcohol use promoting peers who increased the risk for AUD symptoms at all ages. There was evidence for women of an interaction between OPRM1 variation and peer affiliations but only at the earliest age band. Peer influences had stronger effects among women who were G-carriers. These results illustrate the complex ways in which the interplay between influences at multiple levels of analysis can underlie the intergenerational transmission of alcohol disorders as well as the importance of considering age and gender differences in these pathways. PMID:22781865
Chassin, Laurie; Lee, Matthew R; Cho, Young Il; Wang, Frances L; Agrawal, Arpana; Sher, Kenneth J; Lynskey, Michael T
Busulfan 12 mg/kg plus melphalan 140 mg/m2 versus melphalan 200 mg/m2 as conditioning regimens for autologous transplantation in newly diagnosed multiple myeloma patients included in the PETHEMA/GEM2000 study
Background The aim of this study was to compare the long-term safety and efficacy of oral busulfan 12 mg/kg plus melphalan 140 mg/m2 and melphalan 200 mg/m2 as conditioning regimens for autologous stem cell transplantation in newly diagnosed patients with multiple myeloma in the GEM2000 study. Design and Methods The first 225 patients received oral busulfan 12 mg/kg plus melphalan 140 mg/m2; because of a high frequency of veno-occlusive disease, the protocol was amended and a further 542 patients received melphalan 200 mg/m2. Results Engraftment and hospitalization times were similar in both groups. Oral busulfan 12 mg/kg plus melphalan 140 mg/m2 resulted in higher transplant-related mortality (8.4% versus 3.5%; P=0.002) due to the increased frequency of veno-occlusive disease in this group. Response rates were similar in both arms. With respective median follow-ups of 72 and 47 months, the median progression-free survival was significantly longer with busulfan plus melphalan (41 versus 31 months; P=0.009), although survival was similar to that in the melphalan 200 mg/m2 group. However, access to novel agents as salvage therapy after relapse/progression was significantly lower for patients receiving busulfan plus melphalan (43%) than for those receiving melphalan 200 mg/m2 (58%; P=0.01). Conclusions Conditioning with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 was associated with longer progression-free survival but equivalent survival to that achieved with melphalan 200 mg/m2 but this should be counterbalanced against the higher frequency of veno-occlusive disease-related deaths. This latter fact together with the limited access to novel salvage therapies in patients conditioned with oral busulfan 12 mg/kg plus melphalan 140 mg/m2 may explain the absence of a survival difference. Oral busulfan was used in the present study; use of the intravenous formulation may reduce toxicity and result in greater efficacy, and warrants further investigation in myeloma patients. (Clinicaltrials.gov identifier: NCT00560053).
Lahuerta, Juan Jose; Mateos, Maria Victoria; Martinez-Lopez, Joaquin; Grande, Carlos; de la Rubia, Javier; Rosinol, Laura; Sureda, Anna; Garcia-Larana, Jose; Diaz-Mediavilla, Joaquin; Hernandez-Garcia, Miguel T.; Carrera, Dolores; Besalduch, Joan; de Arriba, Felipe; Oriol, Albert; Escoda, Lourdes; Garcia-Frade, Javier; Rivas-Gonzalez, Concepcion; Alegre, Adrian; Blade, Joan; San Miguel, Jesus F.
Newly discovered quick, non-invasive screening method of bone marrow malignancies including various leukemias, Hodgkin's lymphoma, non-Hodgkin's lymphoma, & multiple myeloma by abnormality of small rectangular area within bone marrow organ representation areas of the face.
Diagnoses of bone marrow associated malignancies such as Acute & Chronic Lymphocytic Leukemia, Acute & Chronic Myelogenous (Myeloid) Leukemia, Hodgkin's Lymphoma & Non-Hodgkin's Lymphoma, and Multiple Myeloma are often missed without a blood test. However, in 2008, Omura Y reported several newly discovered organ representation areas that exist between the lower end of the eyebrows and upper end of the upper eyelid. This space was divided into 5 organ representation areas. The first space (more than 1/4 of entire space) near the side of the face (temple) is the bone marrow representation area (BMRA). Therefore, we examined the bone marrow representation areas non-invasively using the Bi-Digital O-Ring Test (BDORT). When the small rectangular shaped part of the BMRA is strong negative (-) with more than -2, often there is a malignancy associated with bone marrow. In this area, we found 1) Integrin alpha5beta1 & Oncogen C-fos Ab2 increased very significantly between 125-300 ng BDORT units; 2) very high Chrysotile Asbestos (0.11-0.14 mg); 3) markedly reduced Acetylcholine of less than 1 ng; 4) significantly reduced telomere of less than 1 yg (= 10(-24) g); and 5) Increased 8-OH-dG (often more than 5 ng). Once the abnormal small rectangular area is localized by BDORT, by detecting the specific microscope slide which produces EMF (electromagnetic field) resonance, one can diagnose these malignancies non-invasively in about 10 minutes. When a subject has any one of the above 7 types of bone marrow associated malignancies, the 5 aforementioned abnormal parameters can be detected. When Acetylcholine is markedly reduced to 0.25 ng or less, 8-OH-dG is 10 ng or higher, and Sirtuin 1 (one of the 7 mammalian longevity genes products) in both the Hippocampus and the body is 0.025 pg or less, most of the patients have a very poor prognosis. However, we found that increasing normal cell telomere & longevity gene product Sirtuin 1 can often improve both pathology & prognosis. All measurements are in BDORT units (the weight required to produce maximum EMF resonance). PMID:22852211
Omura, Yoshiaki; O'Young, Brian; Jones, Marilyn; Nihrane, Abdalla; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu
Many Bipolar Patients Take Multiple Psychiatric Meds
... Preidt Friday, February 7, 2014 Related MedlinePlus Pages Bipolar Disorder Medicines FRIDAY, Feb. 7, 2014 (HealthDay News) -- Many people with bipolar disorder take multiple medications to manage the symptoms, which ...
Development and characterization of a mouse with profound biotinidase deficiency: A biotin-responsive neurocutaneous disorder
Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some
Kirit Pindolia; Megan Jordan; Caiying Guo; Nell Matthews; Donald M. Mock; Erin Strovel; Miriam Blitzer; Barry Wolf
Somatosensory processing in neurodevelopmental disorders
The purpose of this article is to review the role of somatosensory perception in typical development, its aberration in a\\u000a range of neurodevelopmental disorders, and the potential relations between tactile processing abnormalities and central features\\u000a of each disorder such as motor, communication, and social development. Neurodevelopmental disorders that represent a range\\u000a of symptoms and etiologies, and for which multiple peer-reviewed
Carissa J. Cascio
A Review of Co-Morbid Disorders of Asperger's Disorder and the Transition to Adulthood
This review includes empirical peer-reviewed articles which support the examination of Asperger's Disorder and co-morbid disorders, as well as an analysis of how adolescents with Asperger's Disorder transition to adulthood. Although the focus was on Asperger's Disorder, some studies include Autism Spectrum Disorder samples. It was found that…
Robinson, Stephanie; Curwen, Tracey; Ryan, Thomas G.
Movement Disorders in 2012
Standfirst Research in movement disorders in 2012 had led to advances in understanding the pathogenic mechanisms of disease and to development of potential novel therapeutic approaches. Key advances include elucidating mechanisms of spreading neurodegenerative pathology, immunotherapy, stem cells, genetics and deep brain stimulation in Parkinsonisms and related disorders.
McFarland, Nikolaus R.; Okun, Michael S.
Preventing eating disorder pathology: common and unique features of successful eating disorders prevention programs.
Over the past two decades, the field of eating disorders has made remarkable strides in identifying, evaluating, and disseminating successful prevention programs. The current review identifies and discusses nine distinct eating disorders prevention programs that reduce existing eating disorder pathology or prevent the onset of future pathology. Each program was evaluated in one or more controlled trial with a follow-up period of at least six months. We review the evidence base for these nine successful programs and discuss their common and unique features. Based on authors' descriptions of their programs in published trials, we found that all programs were theory-driven, targeted one or more eating disorder risk factor (e.g., body dissatisfaction), were delivered across multiple group sessions, and included at least some interactive content. Most programs included content related to healthy eating/nutrition, media literacy/sociocultural pressures, and body acceptance/body satisfaction. Notably, there was wide variation in some participant features (e.g., participant age, sex, risk status) and intervention features (e.g., setting and format, length and dose, providers), suggesting that a variety of programs are beneficial in impacting eating disorder pathology. Implications and directions for future research are discussed, including an increased focus on universal and indicated prevention programs, expanding programs to a wider age range and a broader spectrum of weight-related problems, and rigorous evaluation of programs through efficacy, effectiveness, and implementation research. PMID:24821099
Ciao, Anna C; Loth, Katie; Neumark-Sztainer, Dianne
Psychopharmacology of pediatric bipolar disorder: a review
Rationale Pediatric bipolar disorder (PBD) is a chronic and debilitating psychiatric illness. It is associated with many short-term\\u000a and long-term complications including poor academic and social performance, legal problems and increased risk of suicide.\\u000a Moreover, it is often complicated by other serious psychiatric disorders including attention deficit hyperactivity disorder,\\u000a oppositional defiant disorder, conduct disorder and substance use disorders. For these reasons,
Sylvester Smarty; Robert L. Findling
Response Inhibition in Motor Conversion Disorder
Conversion disorders (CDs) are unexplained neurological symptoms presumed to be related to a psychological issue. Studies focusing on conversion paralysis have suggested potential impairments in motor initiation or execution. Here we studied CD patients with aberrant or excessive motor movements and focused on motor response inhibition. We also assessed cognitive measures in multiple domains. We compared 30 CD patients and 30 age-, sex-, and education-matched healthy volunteers on a motor response inhibition task (go/no go), along with verbal motor response inhibition (color-word interference) and measures of attention, sustained attention, processing speed, language, memory, visuospatial processing, and executive function including planning and verbal fluency. CD patients had greater impairments in commission errors on the go/no go task (P <.001) compared with healthy volunteers, which remained significant after Bonferroni correction for multiple comparisons and after controlling for attention, sustained attention, depression, and anxiety. There were no significant differences in other cognitive measures. We highlight a specific deficit in motor response inhibition that may play a role in impaired inhibition of unwanted movement such as the excessive and aberrant movements seen in motor conversion. Patients with nonepileptic seizures, a different form of conversion disorder, are commonly reported to have lower IQ and multiple cognitive deficits. Our results point toward potential differences between conversion disorder subgroups.
Voon, Valerie; Ekanayake, Vindhya; Wiggs, Edythe; Kranick, Sarah; Ameli, Rezvan; Harrison, Neil A.; Hallett, Mark
Copy number variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders
Recently discovered genome-wide rare copy number variants (CNVs) have unprecedented levels of statistical association with many developmental neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, intellectual disability and attention deficit hyperactivity disorder. However, as CNVs often include multiple genes, causal genes responsible for CNV-associated diagnoses and traits are still poorly understood. Mouse models of CNVs are in use to delve into the precise mechanisms through which CNVs contribute to disorders and associated traits. Based on human and mouse model studies on rare CNVs within human chromosome 22q11.2, we propose that alterations of a distinct set of multiple, noncontiguous genes encoded in this chromosomal region, in concert with modulatory impacts of genetic background and environmental factors, variably shift the probabilities of phenotypes along a predetermined developmental trajectory. This model can be further extended to the study of other CNVs and may serve as a guide to help characterize the impact of genes in developmental neuropsychiatric disorders.
Hiroi, N; Takahashi, T; Hishimoto, A; Izumi, T; Boku, S; Hiramoto, T
Integrated Genomic Analysis of Nodular Tissue in Macronodular Adrenocortical Hyperplasia: Progression of Tumorigenesis in a Disorder Associated with Multiple Benign Lesions
Context: Massive macronodular adrenocortical disease or ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a clinically and genetically heterogeneous disorder. Objective and Design: Whole-genome expression profiling and oligonucleotide array comparative genomic hybridization changes were analyzed in samples of different nodules from the same patients with AIMAH. Quantitative RT-PCR and staining were employed to validate the mRNA array data. Results: Chromosomal gains were more frequent in larger nodules when compared with smaller nodules from the same patients. Among the 50 most overexpressed genes, 50% had a chromosomal locus that was amplified in the comparative genomic hybridization data. Although the list of most over- and underexpressed genes was similar between the nodules of different size, the gene set enrichment analysis identified different pathways associated with AIMAH that corresponded to the size; the smaller nodules were mainly enriched for metabolic pathways, whereas p53 signaling and cancer genes were enriched in larger nodules. Confirmatory studies demonstrated that BCL2, E2F1, EGF, c-KIT, MYB, PRKCA, and CTNNB1 were overexpressed in the larger nodules at messenger and/or protein levels. Chromosomal enrichment analysis showed that chromosomes 20q13 and 14q23 might be involved in progression of AIMAH from smaller to larger tumors. Conclusion: Integrated transcriptomic and genomic data for AIMAH provides supporting evidence to the hypothesis that larger adrenal lesions, in the context of this chronic, polyclonal hyperplasia, accumulate an increased number of genomic and, subsequently, transcript abnormalities. The latter shows that the disease appears to start with mainly tissue metabolic derangements, as suggested by the study of the smaller nodules, but larger lesions showed aberrant expression of oncogenic pathways.
Almeida, Madson Q.; Harran, Michelle; Bimpaki, Eirini I.; Hsiao, Hui-Pin; Horvath, Anelia; Cheadle, Chris; Watkins, Tonya; Nesterova, Maria
Attention Deficit Hyperactivity Disorder
Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder's pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder.
Matthews, Marguerite; Nigg, Joel T.
Phosphorylation of Simian Cytomegalovirus Assembly Protein Precursor (pAPNG.5) and Proteinase Precursor (pAPNG1): Multiple Attachment Sites Identified, Including Two Adjacent Serines in a Casein Kinase II Consensus Sequence
The assembly protein precursor (pAP) of cytomegalovirus (CMV), and its homologs in other herpesviruses, functions at several key steps during the process of capsid formation. This protein, and the genetically related maturational proteinase, is distinguished from the other capsid proteins by posttranslational modifications, including phosphorylation. The objective of this study was to identify sites at which pAP is phosphorylated so that the functional significance of this modification and the enzyme(s) responsible for it can be determined. In the work reported here, we used peptide mapping, mass spectrometry, and site-directed mutagenesis to identify two sets of pAP phosphorylation sites. One is a casein kinase II (CKII) consensus sequence that contains two adjacent serines, both of which are phosphorylated. The other site(s) is in a different domain of the protein, is phosphorylated less frequently than the CKII site, does not require preceding CKII-site phosphorylation, and causes an electrophoretic mobility shift when phosphorylated. Transfection/expression assays for proteolytic activity showed no gross effect of CKII-site phosphorylation on the enzymatic activity of the proteinase or on the substrate behavior of pAP. Evidence is presented that both the CKII sites and the secondary sites are phosphorylated in virus-infected cells and plasmid-transfected cells, indicating that these modifications can be made by a cellular enzyme(s). Apparent compartmental differences in phosphorylation of the CKII-site (cytoplasmic) and secondary-site (nuclear) serines suggest the involvement of more that one enzyme in these modifications.
Plafker, Scott M.; Woods, Amina S.; Gibson, Wade
Growth inhibition of pancreatic cancer cells by Histone Deacetylase inhibitor belinostat through suppression of multiple pathways including HIF, NFkB, and mTOR signaling in vitro and in vivo.
Pancreatic ductal adenocarcinoma is a devastating disease with few therapeutic options. Histone deacetylase inhibitors are a novel therapeutic approach to cancer treatment; and two new pan-histone deacetylase inhibitors (HDACi), belinostat and panobinostat, are undergoing clinical trials for advanced hematologic malignancies, non-small cell lung cancers and advanced ovarian epithelial cancers. We found that belinostat and panobinostat potently inhibited, in a dose-dependent manner, the growth of six (AsPc1, BxPc3, Panc0327, Panc0403, Panc1005, MiaPaCa2) of 14 human pancreatic cancer cell lines. Belinostat increased the percentage of apoptotic pancreatic cancer cells and caused prominent G2 /M growth arrest of most pancreatic cancer cells. Belinostat prominently inhibited PI3K-mTOR-4EBP1 signaling with a 50% suppression of phorphorylated 4EBP1 (AsPc1, BxPc3, Panc0327, Panc1005 cells). Surprisingly, belinostat profoundly blocked hypoxia signaling including the suppression of hypoxia response element reporter activity; as well as an approximately 10-fold decreased transcriptional expression of VEGF, adrenomedullin, and HIF1? at 1% compared to 20% O2 . Treatment with this HDACi decreased levels of thioredoxin mRNA associated with increased levels of its endogenous inhibitor thioredoxin binding protein-2. Also, belinostat alone and synergistically with gemcitabine significantly (P?=?0.0044) decreased the size of human pancreatic tumors grown in immunodeficiency mice. Taken together, HDACi decreases growth, increases apoptosis, and is associated with blocking the AKT/mTOR pathway. Surprisingly, it blocked hypoxic growth related signals. Our studies of belinostat suggest it may be an effective drug for the treatment of pancreatic cancers when used in combination with other drugs such as gemcitabine. © 2013 Wiley Periodicals, Inc. PMID:23475695
Chien, Wenwen; Lee, Dhong Hyun; Zheng, Yun; Wuensche, Peer; Alvarez, Rosie; Wen, Ding Ling; Aribi, Ahmed M; Thean, Su Ming; Doan, Ngan B; Said, Jonathan W; Koeffler, H Phillip
Developmental Vulnerability of Synapses and Circuits Associated with Neuropsychiatric Disorders
Psychiatric and neurodegenerative disorders, including intellectual disability (ID), autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease (AD), pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance – modulated largely by dopamine – critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan.
Penzes, Peter; Buonanno, Andres; Passafarro, Maria; Sala, Carlo; Sweet, Robert A.
Priorities for autism spectrum disorder risk communication and ethics.
Autism spectrum disorders are an issue of increasing public health significance. The incidence of autism spectrum disorders has been increasing in recent years, and they are associated with significant personal and financial impacts for affected persons and their families. In recent years, a large number of scientific studies have been undertaken, which investigate genetic and environmental risk factors for autism, with more studies underway. At present, much remains unknown regarding autism spectrum disorder risk factors, but the emerging picture of causation is in many cases complex, with multiple genes and gene-environment interactions being at play. The complexity and uncertainty surrounding autism spectrum disorder risk factors raise a number of questions regarding the ethical considerations that should be taken into account when undertaking autism spectrum disorder risk communication. At present, however, little has been written regarding autism spectrum disorder risk communication and ethics. This article summarizes the findings of a recent conference investigating ethical considerations and policy recommendations in autism spectrum disorder risk communication, which to the authors' knowledge is the first of its kind. Here, the authors discuss a number of issues, including uncertainty; comprehension; inadvertent harm; justice; and the appropriate roles of clinicians, scientists, and the media in autism spectrum disorder risk communication. PMID:22917844
Yudell, Michael; Tabor, Holly K; Dawson, Geraldine; Rossi, John; Newschaffer, Craig
Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6
Background Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. Results We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. Conclusions These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a positive feedback mechanism involving GATA factors that maintains lin-39 expression in the vulval lineage. This work indicates that, as in other organisms, the regulation of Hox gene expression in C. elegans is complicated, redundant and robust.
Report of Fertility in a Woman with a Predominantly 46,XY Karyotype in a Family with Multiple Disorders of Sexual Development
Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X). Patients: A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis. Results: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage. Conclusions: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.
Dumic, Miroslav; Lin-Su, Karen; Leibel, Natasha I.; Ciglar, Srecko; Vinci, Giovanna; Lasan, Ruzica; Nimkarn, Saroj; Wilson, Jean D.; McElreavey, Ken; New, Maria I.
Latest advances in connective tissue disorders
The connective tissue disorders comprise a number of related conditions that include systemic lupus erythematosus (SLE) and the antiphospholipid (Hughes) syndrome, scleroderma, myositis and Sjögren's syndrome. They are characterized by autoantibody production and other immune-mediated dysfunction. There are common clinical and serological features with some patients having multiple overlapping connective tissue disorders. The latest advances include new approaches to therapy, including more focused utilization of existing therapies and the introduction of biological therapies in SLE, more precise protocols for assessment of severe disease manifestations such as in interstitial lung disease and pulmonary artery hypertension in scleroderma, new antibodies for disease characterization in myositis and new approaches to patient assessment in Sjögren's syndrome. B cells have a critical role in most, if not all of these disorders such that B-cell depletion or suppression of B-cell activating cytokines improves disease in many patients. In particular, the introduction of rituximab, a monoclonal antibody targeting the CD20 molecule on B cells, into clinical practice for rheumatoid arthritis and B-cell lymphoma has been a key driver of experimental approaches to therapy in connective tissue disorders. Genetic studies also suggest a role for the innate immune system in disease pathogenesis, suggesting further future targets for biological therapies over the next few years.
Rao, Vijay
Visual Impairment, Including Blindness
... faces and the subtleties of expression, what different things look like and how big they are, and the physical environments where we live and move, including approaching hazards. When a child has a ...
Asthma and Mood Disorders.
The high rate of comorbidity of asthma and mood disorders would imply the possibility of potential shared pathophysiologic factors. Proposed links between asthma and mood disorders include a vulnerability (trait) and state connection. Vulnerability for both asthma and mood disorders may involve genetic and early developmental factors. State-related connections may include obstructive factors, inflammatory factors, sleep impairment, psychological reactions to chronic medical illness, as well as exacerbation of asthma in individuals with chronic stress. Treatment for asthma may also exacerbate mood disorders. New research suggests involvement of the central nervous system in asthma and allergy. Further characterization of clinical, psychological, cellular and molecular interconnections between asthma and mood disorders is needed to better evaluate and treat these patients. A close collaboration between mental health professionals and allergists could result in improved symptom control, quality of life, overall functioning and ultimately, decreased mortality. PMID:19180246
Kewalramani, Anupama; Bollinger, Mary E; Postolache, Teodor T
Asthma and Mood Disorders
The high rate of comorbidity of asthma and mood disorders would imply the possibility of potential shared pathophysiologic factors. Proposed links between asthma and mood disorders include a vulnerability (trait) and state connection. Vulnerability for both asthma and mood disorders may involve genetic and early developmental factors. State-related connections may include obstructive factors, inflammatory factors, sleep impairment, psychological reactions to chronic medical illness, as well as exacerbation of asthma in individuals with chronic stress. Treatment for asthma may also exacerbate mood disorders. New research suggests involvement of the central nervous system in asthma and allergy. Further characterization of clinical, psychological, cellular and molecular interconnections between asthma and mood disorders is needed to better evaluate and treat these patients. A close collaboration between mental health professionals and allergists could result in improved symptom control, quality of life, overall functioning and ultimately, decreased mortality.
Kewalramani, Anupama; Bollinger, Mary E.; Postolache, Teodor T.
Eating disorders.
The main forms of eating disorders are anorexia and bulimia nervosa and obesity. The clinical features, aetiology, treatment and prognosis of anorexia and bulimia nervosa are described to highlight the similarities and differences between these two conditions. Both conditions affect predominantly the young female population with body image disturbance as one of the core symptoms. Whilst the body weight of anorexics are by definition low, most bulimics have normal or near normal body weight. Sufferers of anorexia nervosa tend to deny their illness while those with bulimia are often miserable and acutely aware of their eating difficulties. The aetiological factors in both conditions overlap to a large extent. The outcome of treatment for bulimia is reportedly better than that of anorexia nervosa. Obese people often become depressed and anxious as a result of low self-esteem causing them to seek psychiatric treatment. The severely obese who are placed on very low calorie diets may develop adverse emotional disturbances whilst weight gain may follow a major depressive illness or develop as a side effect of psychotropic medications. A subgroup of the obese population engage in frequent binge eating and preliminary criteria are being developed for this condition called "binge eating disorder". Behaviour therapy is the treatment of choice for obesity. Other forms of treatment include individual and group psychotherapy, use of appetite suppressants and in the severely obese, surgical methods. PMID:7761892
Low, B L
Difference or Disorder? Cultural Issues in Understanding Neurodevelopmental Disorders
Developmental disorders, such as autism spectrum disorder and specific language impairment, are biologically based disorders that currently rely on behaviorally defined criteria for diagnosis and treatment. Specific behaviors that are included in diagnostic frameworks and the point at which individual differences in behavior constitute abnormality…
Norbury, Courtenay Frazier; Sparks, Alison
Primary Immune Deficiency Disorders Presenting as Autoimmune Diseases: IPEX and APECED
Background Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune\\u000a dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders\\u000a (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting\\u000a in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and
D. Moraes-Vasconcelos; B. T. Costa-Carvalho; T. R. Torgerson; H. D. Ochs
Choline transporter gene variation is associated with attention-deficit hyperactivity disorder
The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning\\u000a and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer's Disease, addiction,\\u000a schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during
Brett A. English; Maureen K. Hahn; Ian R. Gizer; Michelle Mazei-Robison; Angela Steele; Daniel M. Kurnik; Mark A. Stein; Irwin D. Waldman; Randy D. Blakely
Metabolic Disorders
... energy in your body tissues, such as your liver, muscles, and body fat. A metabolic disorder occurs ... metabolic disorder when some organs, such as your liver or pancreas, become diseased or do not function ...
Bipolar Disorder
... with spouses and family members. Thus, people undergoing treatment for bipolar disorder sometimes benefit from psychotherapy, in which the ... learn to be an active part of the treatment. Parent's Medication Guide to Treating Bipolar Disorder (APA nd AACAP)
Panic Disorder
Panic disorder is a type of anxiety disorder. It causes panic attacks, which are sudden feelings of terror when ... or a cold chill Tingly or numb hands Panic attacks can happen anytime, anywhere, and without warning. ...
Bleeding disorders
Bleeding disorders are a group of conditions in which there is a problem with the body's blood ... These disorders can lead to heavy and prolonged bleeding after an injury. Bleeding can also begin on ...
Movement Disorders
... t want them to. If you have a movement disorder, you experience these kinds of impaired movement. Dyskinesia ... movement and is a common symptom of many movement disorders. Tremors are a type of dyskinesia. Nerve diseases ...
Learning Disorders
... new information. People with learning disorders may have problems Listening or paying attention Speaking Reading or writing ... around them can make them less of a problem. NIH: National Institute of Neurological Disorders and Stroke
... People who have a history of physical or sexual abuse are more likely to have this disorder. However, ... depend on what symptoms you have. A psychological evaluation is performed to identify related disorders. If, after ...
... 8-10 Bipolar disorder also co-occurs with attention deficit hyperactivity disorder (ADHD), which has some symptoms that overlap with bipolar ... levels of testosterone (a male hormone) in teenage girls and lead to polycystic ovary syndrome (PCOS) in ...
Growth Disorders
... because their parents are. But some children have growth disorders. Growth disorders are problems that prevent children from developing normal ... grow too much. In adults, it can cause acromegaly, which makes the hands, feet and face larger ...
Pituitary Disorders
... functions of other glands in the body. With pituitary disorders, you often have too much or too little of one of your hormones. Injuries can cause pituitary disorders, but the most common cause is a pituitary ...
Child Behavior Disorders
... a death in the family may cause a child to act out. Behavior disorders are more serious. ... The behavior is also not appropriate for the child's age. Warning signs can include Harming or threatening ...
Testing the role of circadian genes in conferring risk for psychiatric disorders.
Disturbed sleep and disrupted circadian rhythms are a common feature of psychiatric disorders, and many groups have postulated an association between genetic variants in circadian clock genes and psychiatric disorders. Using summary data from the association analyses of the Psychiatric Genomics Consortia (PGC) for schizophrenia, bipolar disorder and major depressive disorder, we evaluated the evidence that common SNPs in genes encoding components of the molecular clock influence risk to psychiatric disorders. Initially, gene-based and SNP P-values were analyzed for 21 core circadian genes. Subsequently, an expanded list of genes linked to control of circadian rhythms was analyzed. After correcting for multiple comparisons, none of the circadian genes were significantly associated with any of the three disorders. Several genes previously implicated in the etiology of psychiatric disorders harbored no SNPs significant at the nominal level of P?0.05, and none of the the variants identified in candidate studies of clock genes that were included in the PGC datasets were significant after correction for multiple testing. There was no evidence of an enrichment of associations in genes linked to control of circadian rhythms in human cells. Our results suggest that genes encoding components of the molecular clock are not good candidates for harboring common variants that increase risk to bipolar disorder, schizophrenia, or major depressive disorder. © 2014 Wiley Periodicals, Inc. PMID:24687905
Byrne, Enda M; Heath, Andrew C; Madden, Pamela A F; Pergadia, Michele L; Hickie, Ian B; Montgomery, Grant W; Martin, Nicholas G; Wray, Naomi R
Gender differences in a clinical sample of patients with borderline personality disorder.
The aim of the study was to investigate gender differences and similarities in patients with borderline personality disorder (BPD) with respect to Axis I comorbidity, Axis II comorbidity, general psychopathology (Symptom Checklist 90-Revised), and dimensional personality traits (NEO-Personality-Inventory Revised [NEO-PI-R] and the Dimensional Assessment of Personality Profile Basic questionnaire [DAPP-BQ]). Fifty-seven men and 114 women with BPD were included in the study. Regarding Axis I and II disorders in an exploratory analysis, men with BPD more often fulfilled the diagnostic criteria for binge eating disorder, antisocial personality disorder, narcissistic personality disorder, and conduct disorder in childhood, whereas women had higher frequencies of bulimia nervosa, posttraumatic stress disorder, and panic disorder with agoraphobia. After correcting for multiple tests, only the gender differences in narcissistic and antisocial personality disorder remained significant. In the SCL-90-R profile, no significant gender differences could be identified. In the exploratory analysis of the dimensional personality traits, women showed higher rates on the NEO-PI-R main factors (Neuroticism and Agreeableness) compared to men. In the DAPP-BQ profile, men reached higher sores on the main factor, Dissocial Behavior. When correcting for multiple tests, gender differences still existed for Neuroticism and Dissocial Behavior. Our results argue for gender differences in Axis I and II comorbidity and dimensional personality traits in BPD. However, in general, more similarities than differences were shown in this study. PMID:22686225
Banzhaf, Anke; Ritter, Kathrin; Merkl, Angela; Schulte-Herbrüggen, Olaf; Lammers, Claas-Hinrich; Roepke, Stefan
Gender Differences in a Clinical Sample of Patients with Borderline Personality Disorder.
The aim of the study was to investigate gender differences and similarities in patients with borderline personality disorder (BPD) with respect to Axis I comorbidity, Axis II comorbidity, general psychopathology (Symptom Checklist 90-Revised), and dimensional personality traits (NEO-Personality-Inventory Revised [NEO-PI-R] and the Dimensional Assessment of Personality Profile Basic questionnaire [DAPP-BQ]). Fifty-seven men and 114 women with BPD were included in the study. Regarding Axis I and II disorders in an exploratory analysis, men with BPD more often fulfilled the diagnostic criteria for binge eating disorder, antisocial personality disorder, narcissistic personality disorder, and conduct disorder in childhood, whereas women had higher frequencies of bulimia nervosa, posttraumatic stress disorder, and panic disorder with agoraphobia. After correcting for multiple tests, only the gender differences in narcissistic and antisocial personality disorder remained significant. In the SCL-90-R profile, no significant gender differences could be identified. In the exploratory analysis of the dimensional personality traits, women showed higher rates on the NEO-PI-R main factors (Neuroticism and Agreeableness) compared to men. In the DAPP-BQ profile, men reached higher sores on the main factor, Dissocial Behavior. When correcting for multiple tests, gender differences still existed for Neuroticism and Dissocial Behavior. Our results argue for gender differences in Axis I and II comorbidity and dimensional personality traits in BPD. However, in general, more similarities than differences were shown in this study. PMID:22494170
Multiple phases in the system MgF2Nb2O5 an electron microscope study of intergrowths, defects, and disordered crystals
Mixtures of MgF2.xNb2O5 with x = 7 and 14 have, on annealing at high temperatures yielded a wide variety of block structures in which MgF2 has replaced MeO2 (Me = Ti4+, Nb4+). With F- stabilizing the formation of large blocks, numerous defect structures have been characterized by direct lattice resolution electron microscopy. Features thus observed include planar faults, intergrowths, segregated
J. L. Hutchison; F. J. Lincoln; J. S. Anderson
Multiple pterygium syndrome.
The multiple pterygium syndrome is a rare autosomal recessive condition characterised by arthrogryposis multiplex congenita, pterygia of the neck, fingers, and antecubital, popliteal, and intercrural areas, growth retardation, and facial, vertebral, and genital anomalies. We present two unrelated patients of 17 and 6 years of age, respectively, affected with this condition. We describe the natural history of their disorder since birth and review the spectrum of phenotypic variation of the multiple pterygium syndrome in 25 published cases. Images
Penchaszadeh, V B; Salszberg, B
... you have bipolar disorder. Some people who have bipolar disorder don't want to get treatment. Often, they don't realize how much it ... give you the best chance at getting helpful treatment. Read about bipolar disorder and tell your family what you learn. ...
Bipolar Disorder.
Bipolar disorder, a brain disorder that causes unusual shifts in a person's mood, affects approximately one percent of the population. It commonly occurs in late adolescence and is often unrecognized. The diagnosis of bipolar disorder is made on the basis of symptoms, course of illness, and when possible, family history. Thoughts of suicide are…
Spearing, Melissa
Bipolar disorder
Bipolar disorder is a pathological disturbance of mood, characterized by waxing and waning manic, depressive and, sometimes distinctly mixed states. A diagnosis of bipolar disorder can only be made with certainty when the manic syndrome declares itself. Most individuals who are diagnosed with this disorder will experience both poles of the illness recurrently, but depressive episodes are the commonest cause
Gérard Emilien; Lucia Septien; Claudine Brisard; Emmanuelle Corruble; Michel Bourin
Sleep Disorders and Fibromyalgia
Disordered sleep is such a prominent symptom in fibromyalgia that the American College of Rheumatology included symptoms such\\u000a as waking unrefreshed, fatigue, tiredness, and insomnia in the 2010 diagnostic criteria for fibromyalgia. Even though sleep\\u000a recording is not part of the routine evaluation, polysomnography may disclose primary sleep disorders in patients with fibromyalgia,\\u000a including obstructive sleep apnea and restless leg
Suely Roizenblatt; Nilton Salles Rosa Neto; Sergio Tufik
Primary headache disorders.
Primary headache disorders include migraine, tension-type headaches, and the trigeminal autonomic cephalgias (TACs). "Primary" refers to a lack of clear underlying causative pathology, trauma, or systemic disease. The TACs include cluster headache, paroxysmal hemicrania, and short-lasting neuralgiform headache attacks with conjunctival injection and tearing; hemicrania continua, although classified separately by the International Headache Society, shares many features of both migraine and the TACs. This article describes the features and treatment of these disorders. PMID:23809307
Benoliel, Rafael; Eliav, Eli
[Pervasive developmental disorders].
Pervasive developmental disorders (PDD-ICD10), covering roughly the same entity as the autism spectrum disorders (ASD DSM-IVTR and DSM-V) include a heterogeneous clinical reality. PDD develop in childhood and are characterized by alterations in socialization, communication and behavior disorders with stereotypies and repetitive movements. Autism is included in PDD and has led to many debates in France and to the publication of recommendations and government plans, in recent years. We propose in this article to review the current knowledge of this topic. PMID:24855782
Ferreri, Mélanie
Substance use disorders in schizophrenia
Substance use disorders occur in approximately 40 to 50% of individuals with schizophrenia. Clinically, substance use disorders are associated with a variety of negative outcomes in schizophrenia, including incarceration, homelessness, violence, and suicide. An understanding of the reasons for such high rates of substance use disorders may yield insights into the treatment of this comorbidity in schizophrenia. This review summarizes
Jack J Blanchard; Seth A Brown; William P Horan; Andrea R Sherwood
Comorbidity in Hoarding Disorder
Hoarding Disorder (HD) is currently under consideration for inclusion as a distinct disorder in DSM-5 (1). Few studies have examined comorbidity patterns in people who hoard, and the ones that have suffer from serious methodological shortcomings including drawing from populations already diagnosed with obsessive compulsive disorder (OCD), using outdated definitions of hoarding, and relying on inadequate assessments of hoarding. The present study is the first large-scale study (n=217) of comorbidity in a sample of people meeting recently proposed criteria for hoarding disorder (1) and relying on validated assessment procedures. The HD sample was compared to 96 participants meeting criteria for OCD without HD. High comorbidity rates were observed for major depressive disorder (MDD) as well as acquisition-related impulse control disorders (compulsive buying, kleptomania, and acquiring free things). Fewer than 20% of HD participants met criteria for OCD, and the rate of OCD in HD was higher for men than women. Rates of MDD and acquisition-related impulse control disorders were higher among HD than OCD participants. No specific anxiety disorder was more frequent in HD, but social phobia was more frequent among men with HD than among men with OCD. Inattentive ADHD was diagnosed in 28% of HD participants and was significantly more frequent than among OCD participants (3%). These findings form important base rates for developing research and treatments for hoarding disorder.
Frost, Randy O.; Steketee, Gail; Tolin, David F.
Listening to Include
This paper attempts to make important connections between listening and inclusive education and the refusal to listen and exclusion. Two lines of argument are advanced. First, if educators and learners are to include each other within their educational institutions as unique individuals, then they will need to listen attentively to each other.…
Veck, Wayne
Eating Disorders: Disorders of Under and Overnutrition
\\u000a \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Eating disorder diagnoses consist of anorexia nervosa (restricting type and binge-eating\\/purging type); bulimia nervosa (purging\\u000a and nonpurging types); and eating disorder, not otherwise specified (including binge-eating disorder, night eating syndrome,\\u000a and purging disorder).\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Physical complications of anorexia nervosa affect most major systems in the body and are caused by starvation and the effects\\u000a of purging. Most physical complications
Kelly C. Allison
Immunologic Endocrine Disorders
Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies.
Michels, Aaron W.; Eisenbarth, George S.
Stages of Plasma Cell Neoplasms (Including Multiple Myeloma)
... Neoplasms for more information. High-dose chemotherapy with stem cell transplant This treatment is a way of giving ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...
Diagnosis and management of acute movement disorders.
Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders.Drug-induced movement disorders are mainly caused by dopamine-receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief. Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased. Neuroleptic Malignant Syndrome is a rare, but life-threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial. Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non-Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer. Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied by dysarthria and dystonia and usually respond to phenytoin. In Type 2 they can last for several hours, may be accompanied by vertigo, headache and malaise and usually respond to acetazolamide. Symptomatic episodic ataxias can occur in a number of metabolic disorders, but also in multiple sclerosis and Behcet's disease. PMID:16208529
Dressler, D; Benecke, R
MENU Return to Web version Multiple Sclerosis Overview What is multiple sclerosis (MS)? Multiple sclerosis is an autoimmune disease that affects the nervous system. Normally, antibodies produced by ...
Childhood functional gastrointestinal disorders
This is the first attempt at defining criteria for functional gastrointestinal disorders (FGIDs) in infancy, childhood, and adolescence. The decision-making process was as for adults and consisted of arriving at consensus, based on clinical experience. This paper is intended to be a quick reference. The classification system selected differs from the one used in the adult population in that it is organized according to main complaints instead of being organ-targeted. Because the child is still developing, some disorders such as toddler's diarrhea (or functional diarrhea) are linked to certain physiologic stages; others may result from behavioral responses to sphincter function acquisition such as fecal retention; others will only be recognizable after the child is cognitively mature enough to report the symptoms (e.g., dyspepsia). Infant regurgitation, rumination, and cyclic vomiting constitute the vomiting disorders. Abdominal pain disorders are classified as: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain, abdominal migraine, and aerophagia. Disorders of defecation include: infant dyschezia, functional constipation, functional fecal retention, and functional non-retentive fecal soiling. Some disorders, such as IBS and dyspepsia and functional abdominal pain, are exact replications of the adult criteria because there are enough data to confirm that they represent specific and similar disorders in pediatrics. Other disorders not included in the pediatric classification, such as functional biliary disorders, do occur in children; however, existing data are insufficient to warrant including them at the present time. For these disorders, it is suggested that, for the time being, clinicians refer to the criteria established for the adult population.???Keywords: infant vomiting; cyclic vomiting syndrome; functional dyspepsia in children; irritable bowel syndrome in children; functional abdominal pain in children; functional diarrhea in children; functional constipation in children; Rome II
Rasquin-Weber, A; Hyman, P; Cucchiara, S; Fleisher, D; Hyams, J; Milla, P; Staiano, A
Supportive Therapy Including Nutrition
Modern head and neck cancer treatment, including accelerated and hyperfractionated fractionation schedules, are known to increase\\u000a acute side effects to radiation. Furthermore, concurrent chemoradiation aggravates acute mucosal reaction (Brizel et al. 1998),\\u000a which now has become the limiting factor in radical head and neck cancer treatment. For this reason, supportive care strategies\\u000a are necessary to prevent, treat, and alleviate discomfort
JřRGEN Johansen; JřRN Herrstedt
Neuropsychopathological comorbidities in learning disorders
Background Learning Disorders (LD) are complex diseases that affect about 2-10% of the school-age population. We performed neuropsychological and psychopathological evaluation, in order to investigate comorbidity in children with LD. Methods Our sample consisted of 448 patients from 7 to 16 years of age with a diagnosis of LD, divided in two subgroups: Specific Learning Disorders (SLD), including reading, writing, mathematics disorders, and Learning Disorders Not Otherwise Specified (LD NOS). Results Comorbidity with neuropsychopathologies was found in 62.2% of the total sample. In the LSD subgroup, ADHD was present in 33%, Anxiety Disorder in 28.8%, Developmental Coordination Disorder in 17.8%, Language Disorder in 11% and Mood Disorder in 9.4% of patients. In LD NOS subgroup, Language Disorder was present in 28.6%, Developmental Coordination Disorder in 27.5%, ADHD in 25.4%, Anxiety Disorder in 16.4%, Mood Disorder in 2.1% of patients. A statistically significant presence was respectively found for Language and Developmental Coordination Disorder comorbidity in LD NOS and for ADHD, mood and anxiety disorder comorbidity in SLD subgroup. Conclusions The different findings emerging in this study suggested to promote further investigations to better define the difference between SLD and LD NOS, in order to improve specific interventions to reduce the long range consequences.
Immunopathogenesis of multiple sclerosis
Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by autoimmune inflammation, demyelination, and axonal damage. MS etiology remains unknown, but disease phenotype is most likely the result of an interaction between complex genetic factors and environmental influences. The better understanding of the mechanisms involved in the immunopathogenesis of MS has led to the development of
Manuel Comabella; Samia J. Khoury
[DSM-5: OCD and related disorders].
DSM-5 moved OCD out from under the Anxiety Disorder section, into a new category: Obsessive Compulsive and Related Disorders and added two new specifiers. Specifically a modification of one specifier (insight) and the addition of a new tic specifier. DSM-5 redefined obsessions and recognizes the importance of avoidance and thought stopping beyond compulsions as other strategies to deal with obsessions. OCD related disorders include: Trichotillomania, Hoarding Disorder, Skin Picking Disorder, and Body Dysmorphic Disorder. PMID:24887372
Toro-Martínez, Esteban
Attention deficit hyperactivity disorder.
Over the last two decades, there have been numerous technical and methodological advances available to clinicians and researchers to better understand attention deficit hyperactivity disorder (ADHD) and its etiology. Despite the growing body of literature investigating the disorder's pathophysiology, ADHD remains a complex psychiatric disorder to characterize. This chapter will briefly review the literature on ADHD, with a focus on its history, the current genetic insights, neurophysiologic theories, and the use of neuroimaging to further understand the etiology. We address some of the major concerns that remain unclear about ADHD, including subtype instability, heterogeneity, and the underlying neural correlates that define the disorder. We highlight that the field of ADHD is rapidly evolving; the descriptions provided here will hopefully provide a sturdy foundation for which to build and improve our understanding of the disorder. PMID:24214656
Matthews, Marguerite; Nigg, Joel T; Fair, Damien A
Body dysmorphic disorder
Body dysmorphic disorder (BDD) is a relatively common disorder that consists of a distressing or impairing preoccupation with imagined or slight defects in appearance. BDD is commonly considered to be an obsessivecompulsive spectrum disorder, based on similarities it has with obsessive-compulsive disorder. It is important to recognize and appropriately treat BDD, as this disorder is associated with marked impairment in psychosocial functioning, notably poor quality of life, and high suicidality rates. In this review, we provide an overview of research findings on BDD, including its epidemiology, clinical features, course of illness, comorbidity, psychosocial functioning, and suicidality We also briefly review recent research on neural substrates and cognitive processing. Finally, we discuss treatment approaches that appear efficacious for BDD, with a focus on serotonin-reuptake inhibitors and cognitive-behavioral therapy.
Bjornsson, Andri S.; Didie, Elizabeth R.; Phillips, Katharine A.
Body dysmorphic disorder.
Body dysmorphic disorder (BDD) is a relatively common disorder that consists of a distressing or impairing preoccupation with imagined or slight defects in appearance. BDD is commonly considered to be an obsessive-compulsive spectrum disorder, based on similarities it has with obsessive-compulsive disorder. It is important to recognize and appropriately treat BDD, as this disorder is associated with marked impairment in psychosocial functioning, notably poor quality of life, and high suicidality rates. In this review, we provide an overview of research findings on BDD, including its epidemiology, clinical features, course of illness, comorbidity, psychosocial functioning, and suicidality. We also briefly review recent research on neural substrates and cognitive processing. Finally, we discuss treatment approaches that appear efficacious for BDD, with a focus on serotonin-reuptake inhibitors and cognitive-behavioral therapy. PMID:20623926
Bjornsson, Andri S; Didie, Elizabeth R; Phillips, Katharine A
Correlations between predicted protein disorder and post-translational modifications in plants
Motivation: Protein structural research in plants lags behind that in animal and bacterial species. This lag concerns both the structural analysis of individual proteins and the proteome-wide characterization of structure-related properties. Until now, no systematic study concerning the relationships between protein disorder and multiple post-translational modifications (PTMs) in plants has been presented. Results: In this work, we calculated the global degree of intrinsic disorder in the complete proteomes of eight typical monocotyledonous and dicotyledonous plant species. We further predicted multiple sites for phosphorylation, glycosylation, acetylation and methylation and examined the correlations of protein disorder with the presence of the predicted PTM sites. It was found that phosphorylation, acetylation and O-glycosylation displayed a clear preference for occurrence in disordered regions of plant proteins. In contrast, methylation tended to avoid disordered sequence, whereas N-glycosylation did not show a universal structural preference in monocotyledonous and dicotyledonous plants. In addition, the analysis performed revealed significant differences between the integral characteristics of monocot and dicot proteomes. They included elevated disorder degree, increased rate of O-glycosylation and R-methylation, decreased rate of N-glycosylation, K-acetylation and K-methylation in monocotyledonous plant species, as compared with dicotyledonous species. Altogether, our study provides the most compelling evidence so far for the connection between protein disorder and multiple PTMs in plants. Contact: firstname.lastname@example.com or firstname.lastname@example.com Supplementary information: Supplementary data are available at Bioinformatics online.
Kurotani, Atsushi; Tokmakov, Alexander A.; Kuroda, Yutaka; Fukami, Yasuo; Shinozaki, Kazuo; Sakurai, Tetsuya
Is multiple sclerosis a mitochondrial disease?
Multiple sclerosis (MS) is a relatively common and etiologically unknown disease with no cure treatment. It is the leading cause of neurological disability in young adults, affecting over two million people worldwide. Traditionally, MS has been considered a chronic, inflammatory disorder of the central white matter in which ensuing demyelination results in physical disability. Recently, MS has become increasingly viewed as a neurodegenerative disorder in which axonal injury, neuronal loss, and atrophy of the central nervous system lead to permanent neurological and clinical disability. In this article, we discuss the latest developments on MS research, including etiology, pathology, genetic association, EAE animal models, mechanisms of neuronal injury and axonal transport and therapeutics. In this article, we also focus on the mechanisms of mitochondrial dysfunction that are involved in MS, including mitochondrial DNA defects, and mitochondrial structural/functional changes.
Mao, Peizhong; Reddy, P. Hemachandra
Should Relational Aggression Be Included in DSM-V?
The study examines whether relational aggression should be included in DSM-V disruptive behavior disorders. The results conclude that some additional information is gathered from assessing relational aggression but not enough to be included in DSM-V.
Keenan, Kate; Coyne, Claire; Lahey, Benjamin B.
Evidence for genetic association of RORB with bipolar disorder
Background Bipolar disorder, particularly in children, is characterized by rapid cycling and switching, making circadian clock genes plausible molecular underpinnings for bipolar disorder. We previously reported work establishing mice lacking the clock gene D-box binding protein (DBP) as a stress-reactive genetic animal model of bipolar disorder. Microarray studies revealed that expression of two closely related clock genes, RAR-related orphan receptors alpha (RORA) and beta (RORB), was altered in these mice. These retinoid-related receptors are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. Here we report association studies between bipolar disorder and single-nucleotide polymorphisms (SNPs) in RORA and RORB. Methods We genotyped 355 RORA and RORB SNPs in a pediatric cohort consisting of a family-based sample of 153 trios and an independent, non-overlapping case-control sample of 152 cases and 140 controls. Bipolar disorder in children and adolescents is characterized by increased stress reactivity and frequent episodes of shorter duration; thus our cohort provides a potentially enriched sample for identifying genes involved in cycling and switching. Results We report that four intronic RORB SNPs showed positive associations with the pediatric bipolar phenotype that survived Bonferroni correction for multiple comparisons in the case-control sample. Three RORB haplotype blocks implicating an additional 11 SNPs were also associated with the disease in the case-control sample. However, these significant associations were not replicated in the sample of trios. There was no evidence for association between pediatric bipolar disorder and any RORA SNPs or haplotype blocks after multiple-test correction. In addition, we found no strong evidence for association between the age-at-onset of bipolar disorder with any RORA or RORB SNPs. Conclusion Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder.
[Schizophrenia-like personality disorders].
According to DSM-IV the cluster A personality disorders include paranoid, schizoid, and schizotypal personality disorders. There exists a phenomenological similarity between the experience and behaviour of the so-called odd or eccentric personality disorders and the symptoms of schizophrenia. Evidence of common etiological factors is still the best for the schizotypal personality disorder. The cluster A personality disorders are among the less common personality disorders with a high co-occurrence. Present findings about the neurobiological substrate of the schizotypal personality disorder are discussed also taking neuropsychological results into consideration. A central prerequisite of psychotherapeutic and pharmacological treatment of cluster A personality disorders is a strong therapeutic patient relationship. PMID:19011827
Suslow, T; Arolt, V
This chapter focuses on the eating disorders that draw the attention of most clinicians and researchers: anorexia nervosa,\\u000a bulimia nervosa, and eating disorders not otherwise specified. For information about other, less well-known eating problems\\u000a in adolescents, and about the medical and nutritional effects of eating disorders in adolescents, see Lask and Bryant-Waugh\\u000a (2000) and Fisher et al. (1995).
Michael P. Levine; Niva Piran
\\u000a Eating disorders are serious mental health conditions that are more common among women and present with well-documented physical\\u000a manifestations and psychiatric comorbidities. An estimated 5–10 million females are affected with some form of eating disorder\\u000a (Gordon 1990; Crowther et al. 1992; Fairburn et al. 1995; Hoek 2002). The American College of Physicians lists eating disorders\\u000a as one of the nine
Rita DeBate; Heather Blunt; Marion Ann Becker
Treatment of Bipolar Disorder: The Evolving Role of Atypical Antipsychotics
Management of bipolar disorder (BPD) may require multiple medications, including lithi- um, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs—olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole—are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for
Roy H. Perlis
The Relationship Between Bipolar Disorder, Seasonality, and Premenstrual Symptoms
Cyclical mood disorders characterized by shifting affective states include bipolar disorder, seasonal affective disorder, and premenstrual syndrome/premenstrual dysphoric disorder. In this article, we explore the relationship between these disorders and bring the reader up to date on the advances made in the past year in understanding the relationship between bipolar disorder, seasonality, and premenstrual symptoms.
Czarkowski, Kathryn A.; Epperson, C. Neill
Mental, Emotional and Behavior Disorders in Children and Adolescents. Factsheet.
This factsheet describes the different mental, emotional, and behavior problems that can occur during childhood and adolescence. The incidence and symptoms of the following disorders are discussed: (1) anxiety disorders (including phobia, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder);…
Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Mental Health Services.
Movement disorders in children: Tourette syndrome.
Movement disorders in childhood are rare, but their occurrence is dramatic and frightening. Differential diagnosis depends primarily on a detailed evaluation of the history and an analysis of the characteristics of the movements. Tics are the most common movement disorder in childhood, ranging in severity for simple transient tics to the complex Tourette syndrome, which may be associated with many bizarre behaviors. Minimal defining characteristics of Tourette syndrome are the presence of multiple motor and vocal tics. Associated features may include echolalia, coprolalia, complex stereotyped movements, and compulsive behavior. There is a prominent familial occurrence of Tourette syndrome. Stimulant drugs may cause exacerbation of symptoms. The only consistency useful medication is haloperidol, but its use is associated with side effects in approximately 50% of the patients treated. PMID:6961138
Golden, G S
The Role of Ghrelin, Salivary Secretions, and Dental Care in Eating Disorders
Eating disorders, including anorexia and bulimia nervosa, are potentially life-threatening syndromes characterized by severe disturbances in eating behavior. An effective treatment strategy for these conditions remains to be established, as patients with eating disorders tend to suffer from multiple relapses. Because ghrelin was originally discovered in the stomach mucosa, it has been widely studied over the past decade in an effort to uncover its potential roles; these studies have shed light on the mechanism by which ghrelin regulates food intake. Thus, studying ghrelin in the context of eating disorders could improve our understanding of the pathogenesis of eating disorders, possibly resulting in a promising new pharmacological treatment strategy for these patients. In addition, early detection and treatment of eating disorders are critical for ensuring recovery of young patients. Oral symptoms, including mucosal, dental, and saliva abnormalities, are typically observed in the early stages of eating disorders. Although oral care is not directly related to the treatment of eating disorders, knowledge of the oral manifestations of eating disorder patients may aid in early detection, resulting in earlier treatment; thus, oral care might contribute to overall patient management and prognosis. Moreover, ghrelin has also been found in saliva, which may be responsible for oral hygiene and digestion-related functions. This review discusses the pharmacological potential of ghrelin in regulating food-intake and the role of saliva and oral care in young patients with eating disorders.
Yagi, Takakazu; Ueda, Hirotaka; Amitani, Haruka; Asakawa, Akihiro; Miyawaki, Shouichi; Inui, Akio
Ghrelin and Eating Disorders
There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders.
Atalayer, Deniz; Gibson, Charlisa; Konopacka, Alexandra; Geliebter, Allan
Ghrelin and eating disorders.
There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders. PMID:22960103
Recent advancements in stem cell and gene therapies for neurological disorders and intractable epilepsy
The potential applications of stem cell therapies for treating neurological disorders are enormous. Many laboratories are focusing on stem cell treatments for CNS diseases, including spinal cord injury, Amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, stroke, traumatic brain injury, and epilepsy. Among the many stem cell types under testing for neurological treatments, the most common are fetal and
Janice R. Naegele; Xu Maisano; Jia Yang; Sara Royston; Efrain Ribeiro
Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death
Oxidative stress has been implicated in both normal aging and in various neurodegenerative disorders and may be a common mechanism underlying various forms of cell death including necrosis, apoptosis, and excitotoxicity. In this review, we develop the hypothesis that oxidative stress-mediated neuronal loss may be initiated by a decline in the antioxidant molecule glutathione (GSH). GSH plays multiple roles in
Jaswinder S Bains; Christopher A Shaw
The Effects of Covert Audio Coaching on Teaching Clerical Skills to Adolescents with Autism Spectrum Disorder
Employment instruction for secondary students with autism spectrum disorder (ASD) has received very little attention in the professional literature. However, adults with ASD usually have difficulty maintaining employment for a variety of reasons, including problems with performing work tasks. This study used a multiple baseline design across…
Bennett, Kyle D.; Ramasamy, Rangasamy; Honsberger, Toby
Brief Report: Disordered Eating and Psychosocial Factors in Adolescent Females with Type 1 Diabetes Mellitus
Objective To evaluate whether insulin pump therapy (continuous subcutaneous insulin infusion (CSII)) is associated with a lower frequency of disordered eating, better glycemic control, and improved quality of life and self-efficacy compared to multiple daily injections (MDI) in adolescent females with type 1 diabetes mellitus (T1DM). Methods This cross- sectional study included 22 adolescent females using CSII and 47 adolescent
Marissa R. Battaglia; Ramin Alemzadeh; Heidi Katte
Common Pediatric Urological Disorders
The clinical and radiological presentations of 12 pediatric urological disorders are described. The described disorders include pyelonephritis, vesicoureteral reflux, ureteropelvic obstruction, ureterovesical obstruction, ectopic ureterocele, posterior urethral valves, multicystic dysplastic kidney, polycystic kidney disease, ectopic kidney, staghorn calculi, urethral diverticulum, and urethral meatal stenosis. ImagesFigure 1-2Figure 3Figure 3Figure 4Figure 5Figure 6-7Figure 8-9Figure 10Figure 11-12
Robson, Wm. Lane M.; Leung, Alexander K.C.; Boag, Graham S.
First ray disorders in athletes.
Athletes who participate in contact sports (American football, soccer, rugby) or who are involved in high-impact sports (dancing, running, gymnastics) are susceptible to first ray forefoot injuries. Common first ray disorders in athletes include hallux rigidus, turf toe, sand toe, sesamoid disorders, and fractures. First ray disorders in athletes frequently are treated by nonoperative methods including relative rest, ice, elevation, activity modification, shoe modification, and insoles. PMID:19680112
Nihal, Aneel; Trepman, Elly; Nag, David
Knowledge of Social Anxiety Disorder Relative to Attention Deficit Hyperactivity Disorder Among Educational Professionals
Social anxiety disorder (SAD), the 3rd most common psychiatric disorder in the United States, follows a chronic and unremitting course, often resulting in severe im- pairments in multiple areas of functioning. Despite a typical age of onset in early ado- lescence, the disorder is rarely recognized and treated in adolescent populations. Given its early age of onset, school professionals are
James D. Herbert; Kia Crittenden; Kristy L. Dalrymple
Efficacy of Cognitive-Behavioral Therapy for Comorbid Panic Disorder with Agoraphobia and Generalized Anxiety Disorder
The goal of this study was to evaluate the efficacy of cognitive-behavioral therapy for comorbid panic disorder with agoraphobia (PDA) and generalized anxiety disorder (GAD) by combining treatment strategies for both disorders. A single-case, multiple-baseline design across participants was used. Three participants with primary PDA and secondary…
Labrecque, Joane; Marchand, Andre; Dugas, Michel J.; Letarte, Andree
Retinal Disorders - Multiple Languages: MedlinePlus
... Hindi (??????) Japanese (???) Korean (???) Portuguese (portuguęs) Russian (???????) Somali (af Soomaali) Spanish (espańol) Vietnamese ( ... PDF Health Information Translations Return to top Portuguese (portuguęs) Retinal Tears and Detachment Ruptura e descolamento de ...
Joint Disorders - Multiple Languages: MedlinePlus
... Hindi (??????) Japanese (???) Korean (???) Portuguese (portuguęs) Russian (???????) Somali (af Soomaali) Spanish (espańol) Tagalog ( ... PDF Health Information Translations Return to top Portuguese (portuguęs) Home Care After Total Joint Replacement Cuidados em ...
Heritable disorders of the bile ducts
Diseases of the bile ducts encompass a wide range of disorders. These include those disorders primarily affecting extra and intrahepatic bile ducts and those that may be classified as panbiliary. A simple classification of bile duct disorders is represented in Box 1. This discussion focuses on heritable disorders of the bile ducts. For a discussion of so-called ''isolated'' or ''sporadic''
Binita M. Kamath; David A. Piccoli
Mitochondrial involvement in psychiatric disorders
Recent findings of mitochondrial abnormalities in brains from subjects with neurological disorders have led to a renewed search for mitochondrial abnormalities in psychiatric disorders. A growing body of evidence suggests that there is mitochondrial dysfunction in schizophrenia, bipolar disorder, and major depressive disorder, including evidence from electron microscopy, imaging, gene expression, genotyping, and sequencing studies. Specific evidence of dysfunction such as increased common deletion and decreased gene expression in mitochondria in psychiatric illnesses suggests that direct examination of mitochondrial DNA from postmortem brain cells may provide further details of mitochondrial alterations in psychiatric disorders.
Shao, Ling; Martin, Maureen V.; Watson, Stanley J.; Schatzberg, Alan; Akil, Huda; Myers, Richard M.; Jones, Edward G.; Bunney, William E.; Vawter, Marquis P.
Depressive Disorders During Pregnancy
OBJECTIVE To estimate the prevalence of major and minor depression, panic disorder, and suicidal ideation during pregnancy while also identifying factors independently associated with antenatal depressive disorders. METHODS In this prospective study, participants were 1,888 women receiving ongoing prenatal care at a university obstetric clinic from January 2004 through January 2009. Prevalence of psychiatric disorders was measured using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria based on the Patient Health Questionnaire. Multiple logistic regression identified factors associated with probable major depressive disorder and any depressive disorder. RESULTS Antenatal depressive disorders were present in 9.9% with 5.1% (97) meeting criteria for probable major depression and 4.8% (90) meeting criteria for probable minor depression. Panic disorder was present in 3.2% (61), and current suicidal ideation was reported by 2.6% (49). Among patients with probable major depression, 29.5% (28) reported current suicidal ideation. Psychosocial stress (odds ratio [OR], 1.29; 95% confidence interval [CI], 1.21–1.36), domestic violence (OR 3.45; 95% CI 1.46–8.12), chronic medical conditions (OR 3.05; 95% CI 1.63–5.69), and race (Asian: OR 5.81; 95% CI 2.55–13.23; or African American: OR 2.98; 95% CI 1.24–7.18) each significantly increased the odds of probable antepartum major depressive disorder, whereas older age (OR 0.92; 95% CI 0.88–0.97) decreased the odds. Factors associated with odds of any depression were similar overall except that Hispanic ethnicity (OR 2.50; 95% CI 1.09–5.72) also independently increased the odds of any depression. CONCLUSION Antenatal major and minor depressive disorders are common and significantly associated with clinically relevant and identifiable risk factors. By understanding the high point prevalence and associated factors, clinicians can potentially improve the diagnosis and treatment rates of serious depressive disorders in pregnant women.
Melville, Jennifer L.; Gavin, Amelia; Guo, Yuqing; Fan, Ming-Yu; Katon, Wayne J.
Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders
The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson's disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new "omics" techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives.
Constantinescu, Radu; Mondello, Stefania
Achilles tendon disorders.
Achilles tendon disorders include tendinosis, paratenonitis, insertional tendinitis, retrocalcaneal bursitis, and frank rupture. Patients present with pain and swelling in the posterior aspect of the ankle. Magnetic resonance imaging and ultrasound are helpful in confirming the diagnosis and guiding treatment. Nonsurgical management of Achilles tendon disorders includes nonsteroidal anti-inflammatory drugs, physical therapy, bracing, and footwear modification. Surgical treatment includes debridement of the diseased area of the tendon with direct repair. Tendon transfer may be necessary to augment the strength of the Achilles tendon. PMID:24559878
Weinfeld, Steven B
... Doctors Treat It? Although there's no cure for bipolar disorder, treatment can help stabilize moods and help the person ... will watch the symptoms closely and offer additional treatment advice if necessary. Living With Bipolar Disorder Teens normally face ups and downs with ...
... org 3803 N. Fairfax Drive, Suite 100, Arlington, Va. 22203 1 What is panic disorder? Panic disorder is characterized ... SHEET NAMI • The National Alliance on Mental Illness • 1 (800) 950-NAMI • www.nami.org 3803 N. Fairfax Drive, Suite 100, Arlington, Va. 22203 2 can cause panic attacks. People who ...
... org 3803 N. Fairfax Drive, Suite 100, Arlington, Va. 22203 1 What is bipolar disorder? Bipolar disorder is a ... SHEET NAMI • The National Alliance on Mental Illness • 1 (800) 950-NAMI • www.nami.org 3803 N. Fairfax Drive, Suite 100, Arlington, Va. 22203 2 • A long period of feeling hopeless, ...
Eating Disorders.
An eating disorder is an illness that causes serious disturbances to your everyday diet, such as eating extremely small amounts of food or severely overeating. A person with an eating disorder may have started out just eating smaller or larger amounts of ...
Adjustment disorders
Adjustment disorder (AD) is a common condition, with a prevalence of between 12% and 23% in psychiatric outpatient and liaison psychiatry settings. It is usually characterized by mild depressive symptoms, anxiety symptoms, traumatic stress symptoms or a combination of these. AD is often self-limiting but between 20% and 50% of AD sufferers are diagnosed with a more serious psychiatric disorder
Divya Sakhuja
Multiple Sexual Victimizations among Adolescent Boys and Girls: Prevalence and Associations with Eating Behaviors and Psychological Health
The purpose of this study was to assess the prevalence of sexual abuse, including multiple victimizations, among adolescents and to examine associations among history of sexual abuse, disordered eating behaviors and psychological health. The sample included 81,247 students (40,946 girls and 40,301 boys) in 9th and 12th grades in Minnesota public…
Ackard, Diann M.; Neumark-Sztainer, Dianne
Multiplication Fun
Play to following games to pracitce your muliplicaiton tables. Hit a Home Run! Start with Multiplication Baseball (Easy). Once your have beat this team try to beat Multiplication Baseball (Medium). When you beat the first two teams try to beat this challanging team Multiplication Baseball (Hard) Learn your multiplication facts by playing Multiplication Flash Fun ...
Young, Mrs.
Multiplication 2
Try some harder multiplication activities! Missing Factor Meteor Blasting Complete the Missing Step Batter s Up Multiplication Sum Sense Multiplication Challenge a Friend to Grand Prix Multiplication Double Digit Multiplication https://embed.espresso.co.uk/espresso/embed/images/logo_espresso.gif ) no-repeat center center"
Lerdahl, Miss
Combination therapy for bipolar disorder
US Patent & Trademark Office Database
Treatment regimens for mood disorders that include administration of buprenorphine, alone or in combination with additional pharmacological agents are described. Specifically, treatment regimens that alleviate racing thoughts associated with bipolar disorder, and pharmaceutical compositions and kits for use therein are described. Dosing regimens, compositions, and kits including buprenorphine for treating mania associated with opioid withdrawal are also described.
Psychological management of mood disorders
Evidence-based psychological treatments for adults with unipolar depressive disorder and bipolar disorder are reviewed. There is most empirical evidence for cognitive behavioural therapy (CBT), which is examined in terms of what it is and its evidence base in unipolar depression, including severe, chronic, and treatment-resistant cases. The evidence base for the combination of CBT plus antidepressant treatment, including where continuation
Richard K. Morriss; Jan Scott
Viruses, schizophrenia, and bipolar disorder.
The hypothesis that viruses or other infectious agents may cause schizophrenia or bipolar disorder dates to the 19th century but has recently been revived. It could explain many clinical, genetic, and epidemiologic aspects of these diseases, including the winter-spring birth seasonality, regional differences, urban birth, household crowding, having an older sibling, and prenatal exposure to influenza as risk factors. It could also explain observed immunological changes such as abnormalities of lymphocytes, proteins, autoantibodies, and cytokines. However, direct studies of viral infections in individuals with these psychiatric diseases have been predominantly negative. Most studies have examined antibodies in blood or cerebrospinal fluid, and relatively few studies have been done on viral antigens, genomes, cytopathic effect on cell culture, and animal transmission experiments. Viral research on schizophrenia and bipolar disorder is thus comparable to viral research on multiple sclerosis and Parkinson's disease: an attractive hypothesis with scattered interesting findings but no clear proof. The application of molecular biological techniques may allow the identification of novel infectious agents and the associations of these novel agents with serious mental diseases.
Yolken, R H; Torrey, E F
Emerging Pharmacotherapies for Neurodevelopmental Disorders
A growing and interdisciplinary translational neuroscience research effort for neurodevelopmental disorders (NDDs) is investigating the mechanisms of dysfunction and testing effective treatment strategies in animal models and, when possible, in the clinic. NDDs with a genetic basis have received particular attention. Transgenic animals that mimic genetic insults responsible for disease in man have provided insight about mechanisms of dysfunction, and, surprisingly, have shown that cognitive deficits can be addressed in adult animals. This review will present recent translational research based on animal models of genetic NDDs, as well as pharmacotherapeutic strategies under development to address deficits of brain function for Down syndrome, fragile X syndrome, Rett syndrome, neurofibromatosis-1, tuberous sclerosis, and autism. Although these disorders vary in underlying causes and clinical presentation, common pathways and mechanisms for dysfunction have been observed. These include abnormal gene dosage, imbalance among neurotransmitter systems, and deficits in the development, maintenance and plasticity of neuronal circuits. NDDs affect multiple brain systems and behaviors that may be amenable to drug therapies that target distinct deficits. A primary goal of translational research is to replace symptomatic and supportive drug therapies with pharmacotherapies based on a principled understanding of the causes of dysfunction. Based on this principle, several recently developed therapeutic strategies offer clear promise for clinical development in man.
Wetmore, Daniel Z.; Garner, Craig C.
Fracturing Highly Disordered Materials
We investigate the role of disorder on the fracturing process of heterogeneous materials by means of a two-dimensional fuse network model. Our results in the extreme disorder limit reveal that the backbone of the fracture at collapse, namely, the subset of the largest fracture that effectively halts the global current, has a fractal dimension of 1.22±0.01. This exponent value is compatible with the universality class of several other physical models, including optimal paths under strong disorder, disordered polymers, watersheds and optimal path cracks on uncorrelated substrates, hulls of explosive percolation clusters, and strands of invasion percolation fronts. Moreover, we find that the fractal dimension of the largest fracture under extreme disorder, df=1.86±0.01, is outside the statistical error bar of standard percolation. This discrepancy is due to the appearance of trapped regions or cavities of all sizes that remain intact till the entire collapse of the fuse network, but are always accessible in the case of standard percolation. Finally, we quantify the role of disorder on the structure of the largest cluster, as well as on the backbone of the fracture, in terms of a distinctive transition from weak to strong disorder characterized by a new crossover exponent.
Moreira, A. A.; Oliveira, C. L. N.; Hansen, A.; Araújo, N. A. M.; Herrmann, H. J.; Andrade, J. S., Jr.
Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. Much of what is known about MS has been learned from an animal model of the disease, experimental allergic encephalomyelitis. PMID:24381825
Gaby, Alan
Multiple sclerosis
Introduction Multiple sclerosis is the most common cause of neurological disability in young adults. Irreversible disability can occur, but life expectancy is generally not affected. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions aimed at reducing relapse rates and disability in people with multiple sclerosis? What are the effects of interventions to improve symptoms during acute relapse? What are the effects of treatments for fatigue, spasticity, and multidisciplinary care on disability in people with multiple sclerosis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 68 systematic reviews, RCTs, and observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following key interventions: amantadine, azathioprine, behaviour modification, botulinum toxin, corticosteroids, exercise, gabapentin, inpatient or outpatient rehabilitation, interferon beta, intrathecal baclofen, intravenous immunoglobulin, methotrexate, mitoxantrone, modafinil, natalizumab, oral drug treatments, parenteral glatiramer acetate, physiotherapy, and plasma exchange.
Plasma Cell Disorders
... Blood Disorders > Plasma Cell Disorders 4 Overview of Plasma Cell Disorders (Dysproteinemias; Monoclonal Gammopathies; Paraproteinemias; Plasma Cell Dyscrasias) Plasma cell disorders are uncommon. They ...
Multiplication table
Help learn First learn go over your Learn The Multiplication table now get some extra help Learn The Multiplication table have fun Learn The multiplication table with games good luck practice test pre test pre test final test ...
Mastering Multiplication
Play the following games to practice your multiplication. Take a swing at Multplication Baseball! (Set with hard) Use your multiplication knowledge and defeat the Mayan Math Monster! (Set to hard) Quick! Stop the Multiplication Invader before it is too late! ...
Jackson, Ms.
Infranuclear ocular motor disorders.
This chapter covers the very large number of possible disorders that can affect the three ocular motor nerves, the neuromuscular junction, or the extraocular muscles. Conditions affecting the nerves are discussed under two major headings: those in which the site of damage can be anatomically localized (e.g., fascicular lesions and lesions occurring in the subarachnoid space, the cavernous sinus, the superior orbital fissure, or the orbit) and those in which the site of the lesion is either nonspecific or variable (e.g., vascular lesions, tumors, "ophthalmoplegic migraine," and congenital disorders). Specific comments on the diagnosis and management of disorders of each of the three nerves follow. Ocular motor synkineses (including Duane's retraction syndrome and aberrant regeneration) and disorders resulting in paroxysms of excess activity (e.g., neuromyotonia) are then covered, followed by myasthenia gravis and other disorders that affect the neuromuscular junction. A final section discusses disorders of the extraocular muscles themselves, including thyroid disease, orbital myositis, mitochondrial disease, and the muscular dystrophies. PMID:21601071
Lueck, Christian J
Paranoid personality disorder.
Paranoid personality disorder (PPD) is currently included in DSM-IV's "odd cluster" or "cluster A." In the present article, the authors review available information pertaining to the psychometric properties of PPD, as derived from the relevant literature and from databases of personality disorder study groups. There is comparatively little published evidence for the reliability and validity of PPD, and researchers by and large have tended not to study the disorder, either because of investigators' difficulty recruiting individuals with PPD into research studies, or (as seems more likely) because the trait-paranoia from which many psychiatric patients suffer has seemed better explained by other DSM-IV disorders on Axis I and/or Axis II than by PPD. Given the scant empirical evidence on PPD, it seems reasonable to remove it as an independent diagnosis from the next edition of DSM, and instead to encourage clinicians to code trait-paranoia using a dimensional approach. PMID:22928850
Triebwasser, Joseph; Chemerinski, Eran; Roussos, Panos; Siever, Larry J
Disorders of visual perception.
Visual perceptual disorders are often presented as a disparate group of neurological deficits with little consideration given to the wide range of visual symptoms found in psychiatric and neurodevelopmental disease. Here, the authors attempt a functional anatomical classification of all disorders linked to visual perception, whatever the clinical context in which they arise, including those disorders that bridge vision, emotion, memory, language and action. Guided by clinical and neuroimaging evidence, visual perceptual disorders are classified by the functional anatomical networks likely to be involved and the class of underlying dysfunction, whether topological (a localised deficit or region of hyperfunction) or hodological (a disconnection or hyperconnection). The wider perspective forces us to consider what visual functions underlie a range of symptoms sidelined by previous classificatory schemes and helps generate novel hypotheses for further research in the area. PMID:20972204
Ffytche, Dominic H; Blom, J D; Catani, M
Multiple Co-occurring Behaviours among Gamblers in Treatment: Implications and Assessment
A substantial portion of gamblers in treatment may have co-occurring mental health disorders including substance use disorders, especially alcohol dependency, personality disorders, affective disorders, anxiety disorders and impulse control disorders. Co-occurring mental health disorders affect treatment seeking, the treatment process and its outcome, quality of life and functioning in many mental health disorders. Participants in this study were 78 adults
James R. Westphal; Lera Joyce Johnson
Multimethod Investigation of Interpersonal Functioning in Borderline Personality Disorder
Even though interpersonal functioning is of great clinical importance for patients with borderline personality disorder (BPD), the comparative validity of different assessment methods for interpersonal dysfunction has not yet been tested. This study examined multiple methods of assessing interpersonal functioning, including self- and other-reports, clinical ratings, electronic diaries, and social cognitions in three groups of psychiatric patients (N=138): patients with (1) BPD, (2) another personality disorder, and (3) Axis I psychopathology only. Using dominance analysis, we examined the predictive validity of each method in detecting changes in symptom distress and social functioning six months later. Across multiple methods, the BPD group often reported higher interpersonal dysfunction scores compared to other groups. Predictive validity results demonstrated that self-report and electronic diary ratings were the most important predictors of distress and social functioning. Our findings suggest that self-report scores and electronic diary ratings have high clinical utility, as these methods appear most sensitive to change.
Stepp, Stephanie D.; Hallquist, Michael N.; Morse, Jennifer Q.; Pilkonis, Paul A.
[CNS disorders caused by metabolic disorders].
A guideline for early diagnosis of metabolic disorders affecting central nervous system during neonatal and early infancy was presented. Clinical manifestations associated with inborn errors of metabolism in the neonatal period are poor feeding, vomiting, diarrhea, abnormalities in muscle tonus, dyspnea, convulsion, coma and so on, and these are not specific to each disorder. However, such symptoms or signs as described below have often intimate relation to metabolic disorders: (1) previous children died of undetermined causes during early infancy; (2) complicat