Are the Health of the Nation Outcome Scales (HoNOS) useful for measuring outcomes in older people's mental health services?
The Health of the Nation Outcome Scales (HoNOS) were developed to provide a single index in order to enable the government target 'to improve significantly the health and social functioning of mentally ill people' to be quantified. They were intended to be applicable to all adults (including older people), across a wide range of settings so that services in different localities could be compared and changes both within individuals and within services could be measured. In 1999 the HoNOS65+ was launched with a modified glossary for older people. The HoNOS has been formally adopted as the preferred outcome measure for adults of working age. There has been no such formal adoption of the HoNOS65+, or any other outcome measure, for mental health services for older people. This review summarises how the HoNOS was originally developed and validated. Studies with older people, which have used both the original definitions and those developed for the HoNOS65+ are reviewed focusing on data on the reliability and validity of the HoNOS and HoNOS65+ with older people. Finally the question of whether the HoNOS or HoNOS65+ is suitable as an outcome measure in routine clinical practice in services for older people is addressed.


Epiploic appendagitis with acute appendicitis.
A 28-year-old woman presented to accident and emergency department with a 1-day history of right-sided abdominal pain. She was afebrile, and haemodynamically stable, and the initial diagnosis was acute appendicitis. A transvaginal ultrasound scan was performed and was suggestive of appendicitis. The patient failed to improve with conservative management, and a laparosocopic appendicectomy was performed the next day to remove an inflamed, non-perforated appendix. Pelvic laparoscopy was performed, which noted normal ovaries and uterus, as well as a hard, swollen, discoloured epiploic appendage of the sigmoid colon. A decision was made not to remove the inflamed epiploic appendage. Postoperatively the patient complained of persisting pain, which settled over 2 days with analgesia and antibiotics. This case is an extremely unusual case of epiploic appendagitis and acute appendicitis. It demonstrates the importance of pelvic laparoscopy in all females with presumed appendicitis, even in the presence of an initial pathology.


Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes.
Many centers still admit children for several days to start the ketogenic diet. The exact incidence of adverse effects during the admission and their potential later impact on seizure reduction has not been widely studied. We performed a retrospective study of children with intractable epilepsy electively admitted for ketogenic diet initiation at our institution from 2011 to 2016. Charts were reviewed for adverse effects during the admission period and then examined for seizure reduction and compliance at three months. A rating scale (1 to 4) was created for severity of any adverse events. A total of 158 children were included, with the mean age 4.6 years. Potentially attributable adverse effects occurred in 126 (80%) children, most commonly emesis, food refusal, and hypoglycemia. Seventy-three (46%) children received some form of intervention by the medical team, most commonly the administration of juice (24%). Younger age was correlated with an increased likelihood of moderate to severe adverse effects during admission, often repeated hypoglycemia (3.6 versus 4.9 years, P = 0.04). Fasting was more likely to result in lethargy and a single blood glucose in the 30 to 40 mg/dL range, but it was not correlated with emesis, repeated hypoglycemia, or higher adverse effect scores. There was no statistically significant correlation between the severity of adverse effects and the three-month seizure reduction. Mild easily treated adverse effects occurred in most children admitted for the ketogenic diet. Younger children were at greater risk for significant difficulties and should be monitored closely. Because fasting led to more lethargy and hypoglycemia, it may be prudent to avoid this in younger children.


Alpha 4 beta 1 integrin-dependent cell adhesion is regulated by a low affinity receptor pool that is conformationally responsive to ligand.
alpha 4 beta 1 integrin (VLA-4) appears to be unique among the leukocyte integrins in that it can initiate the adhesion of circulating lymphocytes without cellular activation. It is not known how lymphocytes or other cell types maintain constitutive levels of alpha 4 beta 1 integrin activity. The current report describes a monoclonal antibody, 15/7, that recognizes a high affinity or ligand-occupied conformation of beta 1 integrin. Studies with 15/7 revealed that alpha 4 beta 1 integrin-dependent adhesion of leukocytic cell lines is mediated by a population of low affinity receptors that is conformationally responsive to ligand; the 15/7 epitope could be induced by nanomolar concentrations of soluble VCAM-1 or by micromolar concentrations of a peptide derived from the type III connecting segment domain of fibronectin (as ligands for alpha 4 beta 1 integrin). The same receptors were also responsive to adhesion activating reagents, such as Mn2+, activating anti-beta 1 integrin antibodies, and phorbol myristate acetate, which induced the 15/7 epitope directly and/or decreased the concentration of ligand required for epitope induction. In addition to the responsive receptor pool, cells expressed a second population of alpha 4 beta 1 integrin that was conformationally restrained, failing to respond to ligand or to any of the activating reagents. The relative size of the responsive and inactive receptor pools, as well as the affinity of the responsive receptors, represented a stable phenotype of different cell types and played important roles in defining the cells' adhesive capacity and ligand specificity. Similar receptor populations were measured on lymphocyte subsets in whole blood. These studies provide insight into how cells maintain different constitutive levels of alpha 4 beta 1 integrin activity, and how the activity of beta 1 integrin can be modulated by activators of cell adhesion.


Translational optical imaging in diagnosis and treatment of cancer.
In cancer imaging, many different modalities are used that each have their specific features, leading to the combined use of different techniques for the detection, staging and treatment evaluation of cancer. Optical imaging using near-infrared fluorescence light is a new imaging modality that has recently emerged in the field of cancer imaging. After extensive preclinical research, the first steps of translation to the clinical practice are currently being made. In this article, we discuss the preclinical and clinical results of near-infrared optical imaging for non-invasive detection and classification of tumors, therapy monitoring, sentinel lymph node procedures, and image-guided cancer surgery. Widespread availability of imaging systems and optical contrast agents will enable larger studies on their clinical benefit and can help establish a definitive role in clinical practice.


Vaccination of chickens against H5N1 avian influenza in the face of an outbreak interrupts virus transmission.
Vaccination of chickens with a commercially available killed H5N2 vaccine was being evaluated as an additional tool to enhanced biosecurity measures and intensive surveillance for control of highly pathogenic avian influenza subtype H5N1 disease in Hong Kong in 2002. In December 2002 to January 2003, there were outbreaks of H5N1 disease in waterfowl in two recreational parks, wild water birds, several poultry markets and five chicken farms. In addition to quarantine, depopulation of the affected sheds and increased biosecurity, vaccination of the unaffected sheds and surrounding unvaccinated farms was undertaken on three farms. In at least two farms, infection spread to the recently vaccinated sheds with low rates of H5N1 mortality in sheds when the chickens were between 9 and 18 days post-vaccination. However, after 18 days post-vaccination no more deaths from H5N1 avian influenza occurred and intensive monitoring by virus culture on these farms showed no evidence of asymptomatic shedding of the virus. This provides evidence that H5 vaccine can interrupt virus transmission in a field setting.


Hypothesis on the relationship between the change in intracellular pH and incidence of sporadic Alzheimer's disease or vascular dementia.
In order to perform their normal physiological functions, it is important that cells maintain the intracellular pH within the physiological range. Intracellular enzyme activity, cytoskeleton component integration, and cellular growth and differentiation rates are all closely associated with the intracellular pH. It has been demonstrated that in nervous system diseases, such as ischemic stroke, traumatic brain injury, epilepsy, Parkinson's disease, and Alzheimer's disease (AD), the common characteristics are decreased pH or acidosis at both tissular and cellular levels. Particularly, some AD-associated enzymes will have altered activities under acidic conditions. We inferred that aging or ischemia may cause intracellular acidification. This acidification not only induces apoptosis but also substantially alters enzyme activities and promotes the development of AD or vascular dementia. The hypothesis of an intracellular pH role in sporadic AD or vascular dementia will be discussed in this paper. If confirmed, this hypothesis may lead to the formulation of new pathogenesis and new therapeutic approaches to AD or vascular dementia.


Ferromagnetic Coupling in the Heterospin Bis-Catecholato-Manganese(IV) Complex with Pyridine Substituted by Nitronyl-nitroxide.
A new bis(3,6-di-tert-butyl-catecholato)manganese complex with two 4-NIT-Py ligands was synthesized and characterized [4-NIT-Py = pyridine substituted at position 4 with nitronyl-nitroxide radical, 2-(pyridin-4-yl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl]. X-ray diffraction indicated an octahedral environment of the manganese atom with a trans arrangement of ligands. Bonds lengths in the inner coordination core of the metal and in the chelate cycles that are representative of the charge distribution between the metal and ligands displayed a Mn(IV)(Cat2-)2 charge distribution. Variable-temperature magnetic susceptibility measurements detected intramolecular ferromagnetic coupling between the Mn(IV) S = 3/2 spins and spins of nitronyl-nitroxyls and intermolecular ferromagnetic interactions of spins of adjacent nitronyl-nitroxide fragments in a chain of molecules at low temperatures. The last phenomenon is revealed by short contacts between nitronyl-nitroxide radicals of adjacent complex molecules.


Assessment of phosphatic fertilizer production impact on occupational staff based on NAA of hair, nails, and inhald particles.
Neutron Activation Analysis (NAA) was performed for the determination of 25 elements in hair, toenails, and PM2.5 (particles smaller than 2.5 microm in aerodynamic diameter) to assess how human tissues of occupational staff and inhaled particles follow the industrial exposure of Gdansk Phosphatic fertilizer plant in Poland. Statistical analysis was used to elucidate this exposure. The results obtained were compared using box and whiskers plot and the parametric t-test and nonparametric Mann-Whitney U- test. The comparison showed a statistically significant difference between workers and control group concerning for example Br, Ca, Cl, La, Mn, Sm, U and V in hair, Cu, Dy, La, Sm, Ti and U in toenails and Al, As, Cl, I, K, La, Mg, Mn, Na, Sm and Zn in PM2.5 samples.


Diminutive and Small Colorectal Polyps: The Pathologist's Perspective.
Recent progress in advanced endoscopic imaging and electronic chromoendoscopy allows the real-time endoscopic estimation of the histologic type of polyps, mainly for the differentiation of adenomas from hyperplastic polyps. Accordingly, a "resect-and-discard" strategy applied to diminutive colorectal polyps is now one of the emerging issues among gastroenterologists. The strategy has a practical advantage in terms of the potential cost savings. However, it has a number of limitations in the medical, academic, and legal aspects. The major pitfalls include the endoscopic investigation of colorectal polyps with a wide variety of histogenetic origins, including serrated polyps, and the lack of a standardized method for polyp size measurement. Another issue is the importance of the pathologic diagnosis for legal purposes and medical research. Moreover, it is not certain whether the implementation of the strategy has economic benefit in countries with an undervalued reimbursement system for pathologic examination. There is no doubt that a highly confident optical diagnosis of polyp type is a novel valuable tool. It can provide a more steady symbiosis between gastroenterologists and pathologists to allow a more evident diagnosis and management of patients with colorectal polyps.


Microcirculation during surgery.
Throughout the long history of surgery, there has been great advancement in the hemodynamic management of surgical patients. Traditionally, hemodynamic management has focused on macrocirculatory monitoring and intervention to maintain appropriate oxygen delivery. However, even after optimization of macro-hemodynamic parameters, microcirculatory dysfunction, which is related to higher postoperative complications, occurs in some patients. Although the clinical significance of microcirculatory dysfunction has been well reported, little is known about interventions to recover microcirculation and prevent microcirculatory dysfunction. This may be at least partly caused by the fact that the feasibility of monitoring tools to evaluate microcirculation is still insufficient for use in routine clinical practice. However, considering recent advancements in these research fields, with more popular use of microcirculation monitoring and more clinical trials, clinicians may better understand and manage microcirculation in surgical patients in the future. In this review, we describe currently available methods for microcirculatory evaluation. The current knowledge on the clinical relevance of microcirculatory alterations has been summarized based on previous studies in various clinical settings. In the latter part, pharmacological and clinical interventions to improve or restore microcirculation are also presented.


Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians.
Insulin resistance is strongly associated with obesity, but even among obese subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone, resistin, was identified, shown to reduce insulin-mediated glucose uptake, and shown to be increased in obese mice. We used the chromosome 19 draft sequence to determine the genomic structure of human resistin and to screen the exons, introns, and flanking sequences for variation. We screened 44 subjects with type 2 diabetes and 20 nondiabetic family members who were at the extremes of insulin sensitivity. We identified eight noncoding single nucleotide polymorphisms (SNPs) and one GAT microsatellite repeat. Three SNPs, which were in incomplete linkage disequilibrium with each other and had allelic frequencies exceeding 5%, were selected for further study. No SNP was associated with type 2 diabetes, but the SNP in the promoter region was a significant determinant of insulin sensitivity index (P = 0.04) among nondiabetic family members who had undergone iv glucose tolerance tests. The three common SNPs showed statistical significance as determinants of insulin sensitivity index (P < 0.01) in interaction with body mass index. Noncoding SNPs in the resistin gene may influence insulin sensitivity in interaction with obesity, but this finding will need to be confirmed in other populations.


Inhibition of monoacylglycerol lipase and fatty acid amide hydrolase by analogues of 2-arachidonoylglycerol.
The pharmacology of monoacylglycerol lipase (MAGL) is not well understood. In consequence, the abilities of a series of analogues of 2-arachidonoylglycerol (2-AG) to inhibit cytosolic 2-oleoylglycerol and membrane-bound anandamide hydolysis by MAGL and fatty acid amide hydrolase (FAAH), respectively, have been investigated. 2-AG and its 1-regioisomer (1-AG) interacted with MAGL with similar affinities (IC(50) values 13 and 17 mum, respectively). Shorter homologues of 2-AG (2-linoleoylglycerol and 2-oleoylglycerol) had affinities for MAGL similar to 2-AG. This pattern was also seen when the arachidonoyl side chain of arachidonoyl trifluoromethylketone was replaced by an oleoyl side chain. Arachidonoyl serinol (IC(50) value 73 microM) was a weaker inhibitor of MAGL than 2-AG. The IC(50) values of noladin ether towards MAGL and FAAH were 36 and 3 microM, respectively. Arachidonoyl glycine interacted with FAAH (IC(50) value 4.9 microM) but only weakly interacted with MAGL (IC(50) value >100 microM). alpha-Methyl-1-AG had similar potencies towards MAGL and FAAH (IC(50) values of 11 and 33 microM, respectively). O-2203 (1-(20-cyano-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl) glycerol) and O-2204 (2-(20-hydroxy-16,16-dimethyl-eicosa-5,8,11,14-tetraenoyl) glycerol) were slightly less potent, but again affected both enzymes equally. alpha-Methyl-1-AG, O-2203 and O-2204 interacted only weakly with cannabinoid CB(1) receptors expressed in CHO cells (K(i) values 1.8, 3.7 and 3.2 microM, respectively, compared with 0.24 microM for 1-AG) and showed no evidence of central cannabinoid receptor activation in vivo at doses up to 30 mg kg(-1) i.v. It is concluded that compounds like alpha-Methyl-1-AG, O-2203 and O-2204 may be useful as leads for the discovery of selective MAGL inhibitors that lack direct effects upon cannabinoid receptors.


Histological support for the difference between malignant hyperthermia susceptible (MHS), equivocal (MHE) and negative (MHN) muscle biopsies.
The aim of this study was to find, using modern techniques, any histological differences in muscle biopsies between malignant hyperthermia (MH) susceptible (MHS), MH equivocal (MHE) and MH negative (MHN) patients. On the basis of the European MH contracture test carried out in 83 patients, 23 were shown to be MHS, nine MHE and 51 MHN. Four lesions were found with a significantly high frequency in MHS and MHE biopsies: muscle fibre hypertrophy and atrophy, internal nuclei and myofibrillar necrosis. These four lesions were observed together in 35% of MHS but in none of the MHE or MHN biopsies. Three of these lesions occurred together in 57% of MHS, 33% of MHE and 4% of MHN biopsies. Our results support a histological difference between MHE, MHS and MHN biopsies and attempt to contribute towards a better definition of MHE status.


Inhibition: its stability and correlates in sixteen- to forty-month-old children.
Inhibition was assessed in 144 Swedish children when they averaged 16 months of age using a composite measure tapping sociability toward strange adults, noninvolvement in peer play, and parental ratings of fearfulness. 91 children entered out-of-home care within 2 weeks of these initial assessments. Children were observed in this setting playing with peers; teachers and parents also rated children's adjustment to the out-of-home care settings. 1 and 2 years later, the children were assessed again, both at home and in the alternative care settings. Results showed that individual differences in inhibition were stable over the 2 years of the study. Inhibited children engaged in less high-quality peer play both at home and in the alternative care settings, and they were less able to play alone in their mothers' absence. On contemporaneous but not subsequent ratings, inhibited children had more difficulty adjusting to out-of-home care. Inhibition was not itself affected by out-of-home care experiences, and there were no sex differences in inhibition.


Mycobacterium leprae surface components intervene in the early phagosome-lysosome fusion inhibition event.
Bone marrow-derived cultured macrophages were infected with Mycobacterium leprae. The bacteria were either used as freshly isolated organisms or incubated with M. leprae antiserum (1:5) for 30 min prior to phagocytosis. Immediately after inoculation (1 to 4 h) and at 1 to 8 days later, macrophages were stained for acid phosphatase activity to assess fusions between phagosomes and lysosomes. Inhibition of fusions was essentially apparent as an early event, which was partially reversed by antiserum treatment of the bacteria, suggesting a role for M. leprae immunogenic surface components in this early phenomenon. Later incubation times (1 to 8 days) did not show any considerable difference between antiserum-treated and nontreated bacteria. The formation of an electron-transparent zone around phagocytized bacteria and its role in phagosome-lysosome fusion was investigated, and a direct relationship could not be established.


Autologous Fat Grafting Improves Facial Nerve Function.
We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman's technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function.


Multiparametric Imaging of Tumor Hypoxia and Perfusion with 18F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer.
Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with 18F-fluoromisonidazole (18F-FMISO) dynamic PET (dPET) in head and neck cancer. Methods: One hundred twenty head and neck cancer patients underwent 0- to 30-min 18F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 ± 6 and 160 ± 13 min after injection. A total of 248 lesions (≥2 cm3) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible 1-plasma 2-tissue-compartment model to calculate surrogate biomarkers of tumor hypoxia (k3), perfusion (K1), and 18F-FMISO distribution volume. The analysis was repeated with truncated dPET datasets. Results: Substantial inter- and intratumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound 18F-FMISO was rapid in all tumors. 18F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy between k3 maps and total 18F-FMISO uptake and reducing the dynamic range of total 18F-FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from a truncated 20-min dataset. Conclusion:18F-FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion, and radiotracer distribution volume. These data clarify the ambiguity in interpreting 18F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of 18F-FMISO dPET into the clinic.


Growth, body composition, and visceral organ mass and metabolism in lambs during and after metabolizable protein or net energy restrictions.
Three trials were conducted to assess effects of metabolizable protein and NE deficiencies on changes in body composition, organ mass and metabolism, and animal growth performance during restriction and realimentation. Growth of lambs was restricted to achieve no change in BW for periods of 5 to 6 wk by limiting intake of metabolizable protein or NE. In Trial 1, changes in body composition and visceral organ mass and metabolism during restriction were compared to unrestricted controls using 36 lambs. Trial 2 was designed to investigate changes in growth, body composition, and visceral organs during restriction and realimentation periods using 44 lambs. Trial 3 was limited to evaluation of differences in performance and carcass characteristics of previously restricted and unrestricted ram lambs (15 total). Results of Trial 1 indicated that liver weights were decreased with nutrient restrictions. Body protein mass was conserved in energy-restricted (ER) lambs and lost in protein-restricted (PR) lambs. Fat was mobilized at similar rates for PR and ER lambs. In Trial 2, liver and intestinal weights, as well as in vitro oxygen consumption by liver slices, were decreased with nutrient restrictions. The reductions persisted after 2 wk of realimentation, yet no compensatory growth was observed. Feed intakes were increased gradually during the first 2 wk of realimentation. Composition of gain during the realimentation period was similar to that of unrestricted lambs. In Trial 3, neither gain nor feed efficiency during realimentation was enhanced as a result of previous nutrient deficiencies. Absence of compensatory growth in Trial 3 is possibly attributable to differences in gastrointestinal fill. Lambs subjected to short-term PR and ER seem to have similar recuperative capacity.


[Experience with the glycerol lysis test in acid medium in diagnosis of hereditary spherocytosis].
The acidified glycerol lysis test (AGLT) is highly sensitive for hereditary spherocytosis (HS). In all 50 patients of the Children's Hospital of the Medical Academy Magdeburg suffering from HS the 50% lysis time was found to be pathological between 19 and 110 seconds. However, pathological results of this test were also found in autoimmune haemolytic anaemias. AGLT was negative in non-spherocytic haemolytic anaemias and normal controls. In conclusion, the AGLT is a rapid, simple and inexpensive screening procedure for spherocytes in blood.


Bone marrow transplantation temporarily improves pancreatic function in streptozotocin-induced diabetes: potential involvement of very small embryonic-like cells.
The role of bone marrow (BM)-derived cells in pancreatic beta-cell regeneration remains unresolved. We examined whether BM-derived cells are recruited to the site of moderate pancreatic injury and contribute to beta-cell regeneration. Low-dose streptozotocin (STZ) treatment was used to induce moderate pancreatic damage and hyperglycemia. Enhanced green fluorescent protein-positive (EGFP) BM chimeras were evaluated for beta-cell regeneration after STZ treatment. To test the hypothesis that pancreatic tissue injury induces a stromal cell-derived factor (SDF)-1 gradient to chemoattract the stem cells, we evaluated the expression of mRNA for SDF-1 in damaged pancreatic tissue. SDF-1 was significantly increased in the pancreas after damage, peaking at day 10. The majority of BM cells expressing mRNA for pancreatic development markers were detected in the subpopulation of CD45/Sca-1/Lin very small embryonic-like (VSEL) cells. VSEL cells mobilized from BM to peripheral blood in response to pancreatic damage, peaking in peripheral blood at day 5, and were enriched in the pancreas 10 to 15 days after STZ treatment. To confirm a role for BM-derived cells in pancreatic beta-cell regeneration, we prepared EGFP-->B6 chimeras. In the EGFP chimeras, EGFP cells were detected around duct and islets and were positive for insulin after STZ treatment. However, STZ-induced hyperglycemia was reduced only transiently (49-77 days) after pancreatic injury. These data suggest that VSEL cells are mobilized into injured pancreatic tissue and contribute to beta-cell regeneration. Transplantation of BM-derived cells improves the function of injured pancreas, although the response is not sufficient to restore sustained normoglycemia.


Perception of the tactile texture of raised-dot patterns: a multidimensional analysis.
An ALSCAL multidimensional scaling analysis in Euclidean space revealed that three orthogonal perceptual dimensions can account for the judged tactile dissimilarities of raised-dot patterns. Through magnitude estimates of various perceptual attributes, it was determined that the three dimensions consist of blur, roughness, and clarity. The only effect that selective adaptation of the Pacinian (P) channel had was to change the perceptual clarity of the raised dots against their background. Adaptation of the P channel with a 20 dB SL 250 Hz stimulus enhanced clarity. As indicated by magnitude estimates, adaptation of the P channel by the 250 Hz stimulus had no effect on the perceived roughness of the dot pattern but did cause the individual dots of the textured pattern to feel smoother. When the observer was required to estimate magnitude "overall roughness" defined as a combination of dot-pattern roughness and individual-dot roughness, adaptation of the P channel affected perceived roughness by reducing it. Taken as a whole, the results are consistent with the hypothesis that the NP channels and the P channel jointly influence the perception of textured surfaces.


Education and research in INFOBIOMED, the European Network of Excellence in Biomedical Informatics.
During the last three years several initiatives have been deployed within INFOBIOMED, the European Network of Excellence (NoE) in Biomedical Informatics, for promoting research and education. In the context of genomic medicine, four research pilots were designed. To address the informational complexities of such research problems, new educational approaches are needed.


X-Ray diffraction and mu-Raman investigation of the monoclinic-orthorhombic phase transition in Th(1-x)U(x)(C(2)O(4))(2).2H(2)O solid solutions.
A complete Th(1-x)U(x)(C(2)O(4))(2).2H(2)O solid solution was prepared by mild hydrothermal synthesis from a mixture of hydrochloric solutions containing cations and oxalic acid. The crystal structure has been solved from twinned single crystals for x = 0, 0.5, and 1 with monoclinic symmetry, space group C2/c, leading to unit cell parameters of a approximately 10.5 A, b approximately 8.5 A, and c approximately 9.6 A. The crystal structure consists of a two-dimensional arrangement of actinide centers connected through bis-bidentate oxalate ions forming squares. The actinide metal is coordinated by eight oxygen atoms from four oxalate entities and two water oxygen atoms forming a bicapped square antiprism. The connection between the layers is assumed by hydrogen bonds between the water molecules and the oxygen of oxalate of an adjacent layer. Under these conditions, the unit cell contains two independent oxalate ions. From high-temperature mu-Raman and X-ray diffraction studies, the compounds were found to undergo a transition to an orthorhombic form (space group Ccca). The major differences in the structural arrangement concern the symmetry of uranium, which decreases from C2 to D2, leading to a unique oxalate group. Consequently, the nu(s)(C-O) double band observed in the Raman spectra recorded at room temperature turned into a singlet. This transformation was then used to make the phase transition temperature more precise as a function of the uranium content of the sample.


Beyond the Two-Clause Sentence: Acquisition of Clause Chaining in Six Languages.
Clause chains are a special type of complex sentence, found in hundreds of languages outside Western Europe, in which clauses are dependent but not embedded, and dozens of clauses can be combined into a single sentential unit. Unlike English complex sentences, clause chains' distribution is partially predictable in that they can, most fundamentally, be linked to a particular semantic context: description of temporally sequential events or actions. This and the morphological simplicity of verb forms in clause chains may combine to accelerate their acquisition by children, relative to complex sentences in other languages. No previous cross-linguistic studies of the acquisition of complex sentences have investigated clause chaining. In this paper, we report insights from a survey of the acquisition of clause chaining in six languages of diverse stocks with child speech databases spanning 1;1 to 10 years. Overall, children acquiring clause chaining languages begin to produce 2-clause chains between around 1;11 and 2;6. An initial stage in which chains are limited to just two clauses in length is followed by a stage in which longer chains of 3-5 clauses are also produced. Children acquiring languages in which adults produce both same-subject and different-subject clause chains produce a similar mix from early on; for some languages, this involves morphological "switch-reference" marking that anticipates the identity of the subject of an upcoming clause. This survey broadens our understanding of the acquisition of complex sentences by adding new data on the acquisition timing, semantics, and reference continuity of early clause chains.


Effect of electrical and chemical stimulation of the raphe obscurus on phrenic nerve activity in the cat.
The effect of electrical and chemical (L-glutamate) stimulation of the raphe obscurus on phrenic nerve activity was examined in the cat. Phrenic nerve activity was recorded from a C5 nerve root in anesthetized, paralyzed and artificially ventilated cats. Neural discharge was quantitated by integrating the phrenic nerve activity. The respiratory frequency was determined from the integrated nerve signal. Focal electrical stimulation (18-144 microA; 5-40 Hz; 100 microseconds pulse duration) resulted in significant (P less than 0.05) increases in both integrated phrenic nerve (IPN) amplitude and respiratory frequency. These changes were dependent upon current intensity and frequency of stimulation. The largest increases in IPN amplitude and respiratory frequency were 47 +/- 17% and 146 +/- 8%, respectively. To insure that the changes in integrated phrenic nerve activity (IPNA) were the result of stimulation of cell bodies and not axons of passage, L-glutamate (100, 200 nmol) was microinjected (100 nl) into the raphe obscurus. Significant (P less than 0.05) dose-related changes occurred in integrated phrenic nerve amplitude with an increase of 44 +/- 13% at 100 nmol and 80 +/- 13% at 200 nmol L-glutamate. No significant increase in respiratory frequency was observed with L-glutamate microinjection. The results suggest that the raphe obscurus may be involved in respiratory control.


[First cases of cholera observed in children at the Befelatanana General Hospital--Antananarivo University Hospital Center (Madagascar)].
Ravages caused by cholera among children are well known. The disease invaded Madagascar in 1999 May. This retrospective study reported the first childhood cholera cases. The survey was carried out at the Befelatanana Hospital during the period of cholera outbreak from April 23th to July 31st. The purpose of the study was to specify clinical, epidemiological and bacteriological characteristics of the disease. 5 out of 178 suspected cholera cases were less than 15 years old. 2 young girls out these 5 children, inhabitants of Antananarivo-City were hospitalized for acute diarrhoea with serious dehydratation. Their disease was confirmed by bacteriology. Vibrio cholera O1 strain, serovar Ogawa was identified. Epidemiological investigation allowed to identify the contamination modal in the file no 1. The authors conclude that cholera is an important problem of public health in developing country like Madagascar. Disease control needs environmental sanitation and good individual hygiene practices.


Similar mycorrhizal fungal communities associated with epiphytic and lithophytic orchids of Coelogyne corymbosa.
Mycorrhizal fungi are essential for the growth and development of both epiphytic (growing on trees) and lithophytic (growing on rocks) orchids. Previous studies indicate that in lowland tropical areas, orchid mycorrhizal fungal compositions are correlated with the life form (i.e., epiphytic, lithophytic, or terrestrial) of their host plants. We therefore tested if a similar correlation exists in an orchid distributed at higher elevations. Coelogyne corymbosa is an endangered ornamental orchid species that can be found as a lithophyte and epiphyte in subtropical to subalpine areas. Based on high-throughput sequencing of the fungal internal transcribed spacer 2 (ITS2)-rDNA region of mycorrhizae of C. corymbosa, we detected 73 putative mycorrhizal fungal Operational Taxonomic Units (OTUs). The OTUs of two dominant lineages (Cantharellales and Sebacinales) detected from C. corymbosa are phylogenetically different from those of other species within the genus Coelogyne, indicating that different orchid species prefer specific mycorrhizal fungi. We also found that the Non-metric multidimensional scaling (NMDS) plots of orchid mycorrhizal fungi were not clustered with life form, the variations among orchid mycorrhizal fungal communities of different life forms were not significant, and most of the OTUs detected from epiphytic individuals were shared by the lithophytic plants, suggesting that orchid mycorrhizal associations of C. corymbosa were not affected by life form. These findings provide novel insights into mycorrhizal associations with endangered ornamental orchids.


[Survey of epidemic status of principal human parasites in Jiangxi Province in 2014].
To understand and analyze the epidemic status of principal human parasites in Jiangxi Province, so as to provide the evidence for formulating The 13rd Five-Year Project of Parasites Control. A survey was performed according to the scheme of The 3rd National Survey of Principal Human Parasites as well as the specific situation of Jiangxi Province. The survey of the soil-transmitted nematodes and intestinal protozoa were performed based on the ecological regions and stratified by economic and geographic situation. The survey of Clonorchis sinensis was performed along with the soil-transmitted nematodes in rural, and was performed by the sample method of random cluster in cities and towns. Totally 23 606 residents of 92 survey sites from 32 counties were surveyed, all of them were tested for the infection of soil-transmitted nematodes, in which 21,569 residents were tested for intestinal protozoa infection, and 1 486 children were tested for eggs of Enterobius vermicularis. Twenty kinds of intestinal parasites were found, with the total infection rate of 9.64%, and 4.296 millions of patients were reckoned in the whole Jiangxi Province. The infection rate of children of E. vermicularis was 13.73%. The infection rates of C. sinensis and intestinal protozoa were 0.58% and 1.42% respectively. The infection rate of Toxoplasma gondii was 7.50%. In Jiangxi Province, the infection rates of soil-transmitted nematodes are decreasing but the infection rate of C. sinensis is increasing in local areas, and the control work of parasites still should be strengthened.


Asterixis.
Asterixis is a type of negative myoclonus characterized by irregular lapses of posture of various body parts. It is an uncommon but important sign in clinical neurology. Initially described as a "liver flap," its utility encompasses a galaxy of neurological and nonneurological situations. Asterixis has a rich history. Despite being described over 70 years ago, its exact pathogenesis remains unknown. Its significance as a tool for the evaluation and prognosis of encephalopathies has been suggested. This review presents its history, clinical implications and its significance.


Plastoglobular protein 18 is involved in chloroplast function and thylakoid formation.
Plastoglobules are lipoprotein particles that are found in different types of plastids. They contain a very specific and specialized set of lipids and proteins. Plastoglobules are highly dynamic in size and shape, and are therefore thought to participate in adaptation processes during either abiotic or biotic stresses or transitions between developmental stages. They are suggested to function in thylakoid biogenesis, isoprenoid metabolism, and chlorophyll degradation. While several plastoglobular proteins contain identifiable domains, others provide no structural clues to their function. In this study, we investigate the role of plastoglobular protein 18 (PG18), which is conserved from cyanobacteria to higher plants. Analysis of a PG18 loss-of-function mutant in Arabidopsis thaliana demonstrated that PG18 plays an important role in thylakoid formation; the loss of PG18 results in impaired accumulation, assembly, and function of thylakoid membrane complexes. Interestingly, the mutant accumulated less chlorophyll and carotenoids, whereas xanthophyll cycle pigments were increased. Accumulation of photosynthetic complexes is similarly affected in both a Synechocystis and an Arabidopsis PG18 mutant. However, the ultrastructure of cyanobacterial thylakoids is not compromised by the lack of PG18, probably due to its less complex architecture.


Targets and non-targets in the aging brain: A go/nogo event-related potential study.
This study tested whether older adults show enhanced suppression of inappropriate processing of non-target information, as marked with the nogo-P3 event-related potential (ERP). Healthy younger and older adults were tested on a simple go/nogo task with visually presented numbers. Unlike in most of the previous studies, go and nogo stimuli were matched for frequency and conflict level in order to minimize the impact of task difficulty, probability monitoring, or conflict detection and resolution on the age-related ERP differences. Older adults showed slower go responses but a comparable accuracy to younger controls. The parietal go-P3 latency was also delayed with aging, while the central nogo-P3 was more pronounced in older adults than in younger controls. The amplitude of this component negatively correlated with go-RTs. In line with previous studies, this suggests that a partial response preparation to nogo events is strongly suppressed in older adults, especially faster ones.


Global lessons from Nigeria's ebolavirus control strategy.
The current Ebola virus disease outbreak challenged medical and public health systems in West Africa. In Nigeria, the existing infrastructure of the polio surveillance system was leveraged rapidly to contain the spread of Ebola virus. We highlight important lessons learnt from the successful implementation of Ebola virus disease surveillance strategies, which should be amplified further to prepare the ground for successful vaccination programs. Close collaboration between national and international stakeholders as well as public/private partnerships will be instrumental in future Ebola virus immunization strategies.


Interaction of tropomyosin-troponin with actin filaments.
The assembly of actin filaments with tropomyosin-troponin was investigated by means of light scattering. Binding curves of tropomyosin-troponin [consisting of all three subunits (holotroponin)] and of tropomyosin-troponin-T-I to actin filaments were analyzed by separating the affinity of tropomyosin-troponin for actin filaments and the affinity for the end-to-end contact of tropomyosin molecules. Under the experimental conditions (42.4 degrees C, 300 mM KCl), tropomyosin-holotroponin in the absence of calcium and tropomyosin-troponin-T-I had similar affinities for actin filaments whereas tropomyosin-holotroponin in the presence of calcium was found to bind more weakly. Tropomyosin-holotroponin and tropomyosin-troponin-T-I bound about 200-300-fold more strongly to binding sites with adjacent tropomyosin-troponin units than to isolated sites on actin filaments. The equilibrium constant for isolated association with actin filaments was more than 2-fold higher for tropomyosin-holotroponin in the absence of calcium (15 400 M-1) and tropomyosin-troponin-T-I (17 500 M-1) than for tropomyosin-holotroponin in the presence of calcium (6600 M-1). Binding curves of mixtures of tropomyosin-holotroponin in the presence of calcium and of tropomyosin-troponin-T-I were measured and analyzed on the basis of a model of cooperative binding of two types of large ligands to a one-dimensional homogeneous lattice. The results provided information on the strength of the end-to-end contacts of tropomyosin-troponin units in different positions on an actin filament. It was found that a tropomyosin-troponin unit binds adjacently to another unit in a different position on an actin filament about 2-fold more weakly than adjacent to a unit in the same position. With the aid of these results, it was possible to obtain information of the equilibrium distribution of tropomyosin-troponin in the two positions on actin filaments. Generation of a sequence of tropomyosin-troponin units in a different position on actin filaments was found to be 4-fold less favored than elongation of an existing sequence (cooperativity parameter sigma = 1/4). Shifting of tropomyosin-troponin on actin filaments appears to be accompanied by small free-energy changes in the various interactions of the components of actin-tropomyosin-troponin filaments and not to be an all-or-none reaction


Teratogenic effects of blue cohosh (Caulophyllum thalictroides) in Japanese medaka (Oryzias latipes) are probably mediated through GATA2/EDN1 signaling pathway.
Blue cohosh (Caulophyllum thalictroides) (BC) has been used widely to induce labor and to treat other uterine conditions. However, the safety and effectiveness of this herbal product has not yet been evaluated by the US Food and Drug Administration (FDA). Several conflicting reports indicated that the root extract of BC is a teratogen and, by some unknown mechanisms, is able to induce cardiovascular malfunctions in new-born babies. To understand the mechanism, we have used Japanese medaka (Oryzias latipes) embryo-larval development as the experimental model and the methanolic extract of BC root as the teratogen. The embryo mortality, hatching efficiency, and morphological abnormalities in craniofacial and cardiovascular systems are considered for the evaluation of BC toxicity. Our results indicate that BC is able to disrupt cardiovascular and craniofacial cartilage development in medaka embryo in a dose and developmental stage-specific manner. Moreover, embryos in precirculation are to some extent more resistant to BC than ones with circulation. By using subtractive hybridization, we have observed that gata2 mRNA was differentially expressed in the circulating embryos after BC treatment. As GATA-binding sequences are required for the expression of the endothelin1 (edn1) gene and edn1 expressed in blood vessels and craniofacial cartilages, we have extended our investigations to edn1 gene expression regulation by BC. We found that edn1, furin1, and endothelin receptor A (ednrA) genes are developmentally regulated; endothelin converting enzyme mRNA (ece1) maintained a steady-state level throughout development. Circulating medaka embryos (3 days post fertilization, dpf) exposed to BC (10 microg/mL) for 48 h have increased levels of gata2, ece1, and preproenodthelin (preproedn1) mRNA contents; however, other mRNAs (furin and ednrA) remained unaltered. Therefore, the enhanced expression of gata2 mRNA followed by ece1 and preproedn1 mRNA by BC might be able to induce vasoconstriction and cardiovascular defects and disrupt craniofacial cartilages in medaka embryos. We conclude that cardiovascular and craniofacial defects in medaka embryogenesis by BC are probably mediated through a GATA2-EDN1 signaling pathway.


[Penetrating aortic ulcer: a series of 15 cases with thoracic and thoraco-abdominal management].
Penetrating aortic ulcer (PAU) consists of an ulcer located in the aortic wall that can cause sudden-onset thoracic or thoraco-abdominal pain. Symptomatic PAU is a life-threatening emergency because of the high risk of aortic rupture. First described in 1934, PAU was for many years seen only at autopsy. Now, multislice CT is the diagnostic method of choice. We report the cases of 15 such patients. Ten patients were symptomatic, with severe sudden-onset thoracic or thoraco-abdominal pain (7 cases) or less acute pain (3 cases). Surgical treatment consisted of aortic stent-grafting in 13 cases, with one or more endoprostheses. Bypass surgery was also necessary in 6 cases, using a hybrid technique (ilio-hepatic bypass graft in 1 case, multiple visceral bypass grafts in 3 cases, carotid-carotid bypass graft in 1 case, and carotid left subclavian bypass graft in 1 case), or a combined technique (aneurysmectomy and infrarenal Dacron tube repair in 1 case). Open thoraco-abdominal aortic repair was performed in two cases, with proximal anastomosis at the thoracoabdominal level and distal anastomosis at the level of the aortic carre four (with the Crawford inclusion technique in one case). Perioperative results were satisfactory, but one patient died of multiple organ failure on postoperative day 14. Four patients died during follow-up (mean 16.2 months ; range 1-44 months), 1 of stroke, 1 of a complicated esophageal-aortic fistula, and 2 of unknown causes. Follow-up has been uneventful in the other 10 patients.


Primary bone lymphoma: a retrospective analysis.
The aim of this study was to retrospectively define those patients with unequivocal primary bone lymphoma presenting to the Sheffield Lymphoma Group and document patient and tumour characteristics and management strategies, and correlate these with survival. Thirty-seven patients were documented from a total of 3148 cases of non-Hodgkin's lymphoma seen over 34 years. There were 17 males and 20 females, with a mean age of 55.4 years (range, 27-78). Pain was the most commonly presented symptom (67.5%), and the pelvis was the most frequently presented site (21.3%). Grade 2 and diffuse large B cell lymphoma comprised the majority of histologies (78.7% and 70.3%, respectively). Treatment was most often with radiotherapy alone (41.8%) or combined with CHOP-like chemotherapy (37.9%). The overall response rate was 56.7%, and 5- and 10-year survival rates were 64.5% and 49.6%, respectively. Univariate analysis showed an age of <60 years and complete response to be favourable prognostic factors. There was a trend toward better survival with combined modality therapy involving CHOP-like chemotherapy. Bone lymphoma has a better survival than other extranodal lymphomas. Younger age and complete response are favourable predictive factors. Combined modality treatment is likely to be the treatment of choice but this remains to be confirmed in large prospective multicentre studies.


Arsenic speciation in human hair: a new perspective for epidemiological assessment in chronic arsenicism.
The analysis for arsenic in hair is commonly used in epidemiological studies to assess exposure to this toxic element. However, poor correlation between total arsenic concentration in hair and water sources have been found in previous studies. Exclusive determination of endogenous arsenic in the hair, excluding external contamination has become an analytical challenge. Arsenic speciation in hair appears as a new possibility for analytical assessing in As-exposure studies. This study applied a relative simple method for arsenic speciation in human hair based on water extraction and HPLC-HG-ICP-MS. The concentration of arsenic species in human hair was assessed in chronically As(V)-exposed populations from two villages (Esquiña and Illapata) of the Atacama Desert, Chile. The arsenic concentrations in drinking water are 0.075 and 1.25 mg L(-1), respectively, where As(V) represented between 92 and 99.5% of the total arsenic of the consumed waters. On average, the total arsenic concentrations in hair from individuals of Esquiña and Illapata were 0.7 and 6.1 microg g(-1), respectively. Four arsenic species, As(III), DMA(V), MMA(V) and As(V), were detected and quantified in the hair extracts. Assuming the found species in extracts represent the species in hair, more than 98% of the total arsenic in hair corresponded to inorganic As. On average, As(III) concentrations in hair were 0.25 and 3.75 microg g(-1) in Esquiña and Illapata, respectively; while, the As(V) average concentrations were 0.15 and 0.45 microg g(-1) in Esquiña and Illapata, respectively. Methylated species represent less than 2% of the extracted As (DMA(V)+ MMA(V)) in both populations. As(III) in hair shows the best correlation with chronic exposure to As(V) in comparison to other species and total arsenic. In fact, concentrations of As(total), As(III) and As(V) in hair samples are correlated with the age of the exposed individuals from Illapata (R= 0.65, 0.69, 0.57, respectively) and with the time of residence in this village (R= 0.54, 0.71 and 0.58, respectively).


Delays in Cancer Diagnostic Testing at a Quick Referral Unit in Spain during COVID-19.
Although COVID-19 has had dire consequences on diagnosis of cancer, little data assessing its impact on the whole range of diagnostic activity relevant to cancer are available. We examined trends in the provision of full diagnostic tests for consecutive patients with suspected cancer referred to an academic hospital-based Quick Diagnosis Unit from January 2019 to December 2020. As weekly volumes declined, waiting times for endoscopic, imaging and biopsy/cytology procedures increased steeply during the COVID-impacted period (26 February-28 April 2020). The average weekly increase compared with the same period in 2019 was substantial for invasive procedures requiring admission (200.70%), CT scans (171.20%), GI endoscopy (161.50%), PET/CT scans (152.50%), ultrasonography (148.40%), and ambulatory biopsy/cytology procedures (111.20%). Volumes and waiting times to other procedures showed similar trends. There was a remarkable downward trend in cancer diagnosis during the COVID-impacted period, with a 54.07% reduction compared with the same weeks in 2019. Despite a modest recovery in the following months, the decline in weekly activity and cancer rates persisted until 30 December. Providing insight into how COVID-19 changed the full spectrum of diagnostic activity for suspected cancer informs resilience-building interventions to guarantee access to fast and efficient diagnostics ahead of new threats.


Prospective Rates, Longitudinal Associations, and Factors Associated With Comorbid Insomnia Symptoms and Perceived Cognitive Impairment.
Insomnia and cognitive impairment are both common conditions experienced by people diagnosed with cancer. Individually, these conditions have negative impacts on functioning, but the combined burden has yet to be evaluated. The purpose of this research was to estimate rates of comorbid insomnia and perceived cognitive impairments, examine the longitudinal associations between these two conditions, and identify demographic and clinical factors associated with reporting both insomnia and perceived cognitive impairment. In this secondary analysis, a heterogeneous sample of 962 patients completed the Insomnia Severity Index (ISI) and the Cognitive Failures Questionnaire (CFQ) at the time of their cancer surgery (baseline; T1) and then again at 2 (T2), 6 (T3), 10 (T4), 14 (T5), and 18 (T6) months. Correlations and partial correlations, controlling for age and education level, were computed at each time point to assess the relationship between ISI and CFQ scores. Cross-lagged correlations assessed associations between ISI and CFQ scores over time. Proportions of patients with comorbid insomnia and cognitive impairments were calculated and logistic regressions investigated changes over time in these proportions. ANOVAs, logistic regressions, ordinal regressions, and multinomial regressions were used to identify risk factors of having comorbid insomnia and cognitive difficulties. Significant and bidirectional correlations between ISI and CFQ scores were observed at each time point and over time. The proportion of patients having both clinical levels of insomnia and perceived cognitive difficulties ranged from 18.73 to 25.84% across time points and this proportion was significantly greater at T1 and T2 than T4, T5, and T6. Participants who reported comorbid insomnia and cognitive impairment were more likely to be younger, female, not currently working, currently receiving chemotherapy, with clinical levels depression and anxiety, and using antidepressants or anxiolytics. Comorbid insomnia and perceived cognitive impairment affects around one in five patients and is more frequent at the beginning of the cancer care trajectory. The relationship between insomnia and cognitive impairment appears to be bidirectional. Insomnia may represent an important patient level vulnerability that when identified and treated can improve perception of cognitive function.


Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid).
Tilapia are a commonly aquacultured fish yet little is known about their normal physiology and response to disease. In this study we determined the results of complete hematologic (n=40) and plasma biochemical profiles (n=63) in production tilapia (Oreochromis hybrids). The fish were raised in recirculating systems with a high stocking density (120 g/L), and were in the middle of a 15-month production cycle. Blood was analyzed using standard techniques, and reference intervals were determined using nonparametric methods. Non-production tilapia (n=15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry results were compared to reference intervals from the fish raised in high-density tanks. Differences were noted in plasma protein, calcium and phosphorus concentrations, such that reference intervals for high-density production tilapia were not applicable to fish raised under different environmental and management conditions.


MicroRNAs Modulate the Pathogenesis of Alzheimer's Disease: An In Silico Analysis in the Human Brain.
MicroRNAs (miRNAs) are small RNAs involved in the post-transcriptional regulation of their target genes, causing a decrease in protein translation from the mRNA. Different miRNAs are found in the nervous system, where they are involved in its physiological functions, but altered miRNAs expression was also reported in neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by memory loss, cognitive function abnormalities, and various neuropsychiatric disturbances. AD hallmarks are amyloid β (Aβ) aggregates, called senile plaques, and neurofibrillary tangles (NFTs) formed by hyperphosphorylated Tau protein. In this study, we performed an in silico analysis to evaluate altered patterns of miRNAs expression in the brains of AD patients compared to healthy subjects. We found 12 miRNAs that were differentially expressed in AD compared to healthy individuals. These miRNAs have target genes involved in AD pathogenesis. In particular, some miRNAs influence Aβ production, having as target secretase and amyloid precursor protein (APP). Some miRNAs were reported to be involved in nervous system functions, and their alteration can cause neuronal dysfunction.


Visualization of ensemble activity patterns of mechanosensory afferents in the cricket cercal sensory system with calcium imaging.
The cercal sensory system of the cricket mediates the detection and analysis of low velocity air currents in the animal's immediate environment, and is implemented around an internal representation of air current direction that demonstrates the essential features of a continuous neural map. Previous neurophysiological and anatomical studies have yielded predictions of the global spatio-temporal patterns of activity that should be evoked in the sensory afferent map by air current stimuli of different directions. We tested those predictions by direct visualization of ensemble afferent activity patterns using Ca2+ -sensitive indicators. The AM ester of the fluorescent Ca2+ indicator (Oregon Green 488 BAPTA-1 AM) was injected under the sheath of a cercal sensory nerve containing all of the mechanosensory afferent axons from one cercus. Optical signals were recorded with a digital intensified CCD camera. Control experiments using direct electrical stimulation of stained and unstained nerves demonstrated that the observed Ca2+ signals within the terminal abdominal ganglion (TAG) were due to activation of the dye-loaded sensory afferent neurons. To visualize the spatial patterns of air-current-evoked ensemble activity, unidirectional air currents were applied repeatedly from eight different directions, and the optically recorded responses from each direction were averaged. The dispersion of the optical signals by the ganglion limited the spatial resolution with which these ensemble afferent activity patterns could be observed. However, resolution was adequate to demonstrate that different directional stimuli induced different spatial patterns of Ca2+ elevation in the terminal arbors of afferents within the TAG. These coarsely- resolved, optically-recorded patterns were consistent with the anatomy-based predictions.


Plasticity of fixation in patients with central vision loss.
The aim of this study was to explore the plasticity of fixation in patients with central vision loss. Most of these patients use preferred retinal loci (PRLs) in the healthy eccentric part of the retina to fixate, but fixation stability and retinal location are not always optimal for best visual performance. This study examined whether fixation stability and a new PRL location can be trained and whether these changes in ocular motor control transfer into better reading performance. Six patients with age-related macular degeneration participated in the study. Fixation stability measurements, microperimetry, and auditory biofeedback training were performed with the MP-1 microperimeter. The auditory biofeedback was used during five 1-h long training sessions to improve fixation and relocate the PRL. Fixation location and stability were recorded while viewing four different targets: a cross, a letter, a word, and a nine-cycle radial grating. Visual acuity was assessed with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and reading performance with the MNRead test. The results showed that all patients developed a new PRL in an optimal location for reading, and they were able to use it consistently while viewing different targets. Fixation stability improved 53% after training. Learning transferred to the old PRL even though fixation stability at this location was not trained. All these improvements in ocular motor control translated into better reading performance: reading speed improved 38% and reading acuity and critical print size gained two lines. We conclude that the ability of the ocular motor system to fixate is flexible in patients with central vision loss: a new PRL can be trained, fixation stability can be improved, and learning transfers to an untrained location. These gains in ocular motor control result in better visual performance. This property can be successfully used to optimize the residual vision of patients with central vision loss.


HBV Infection-Related PDZK1 Plays an Oncogenic Role by Regulating the PI3K-Akt Pathway and Fatty Acid Metabolism and Enhances Immunosuppression.
We compared differentially expressed genes (DGEs) in HBV-positive and -negative tumor samples and conducted a Spearman correlation study between the DGEs and HBV titers within The Cancer Genome Atlas (TCGA). Moreover, we validated the results of our in-house samples. In this study, we discovered a series of genes that correlated statistically with HBV infection based on the TCGA database. These genes were related to increased inflammation and some oncogenic signaling pathways via Gene Set Enrichment Analysis (GSEA). PDZK1 is an ideal gene, which mostly relates positively to HBV infection; moreover, it is overexpressed in human HCC, especially in those HBV-infected HCCs. After analyzing the TCGA data and performing a verification study using our own samples, PDZK1 expression was investigated to be significantly associated with PI3K-Akt signaling and fatty acid metabolism. Further, single-sample GSEA analysis of tumor immune cell infiltration gene sets revealed that high PDZK1expression in HCC tissues was significantly associated with increased tumor-associated macrophages (TAMs) and regulatory T cells(Tregs). PDZK1 is an HBV infection-related gene, which plays oncogenic roles, possibly due to enhancing PI3K-Akt, fatty acid usage in tumor cells and TAMs, and Treg-induced immunosuppression.


[The effect of population growth on the economic development of Japan].
The author reviews research supporting and opposing the Malthusian view that the effect of population growth on per capita income in Japan has been negative. Distinguishing between total population growth and the growth of the labor force, the author finds that "over the total period (1880-1970) population cum labor growth on average tended to make a positive contribution to per capita income growth." (summary in ENG)


The development of wearable-type artificial endocrine pancreas and its usefulness in glycaemic control of human diabetes mellitus.
We have succeeded in miniaturizing a glucose monitoring system into a needle-type which preserves the characteristics suitable for application in a wearable closed-loop control system. The wearable artificial endocrine pancreas (12 X 15 X 6 cm, 400 g) consists of the sensor, a microcomputer which calculates the insulin and glucagon infusion rates and of a 2-syringe driving system. The device succeeded in controlling glycaemia perfectly in depancreatized dogs for a period of 3 days, and with replacement of subcutaneously inserted sensor for up to 7 days. When glucose monitoring by a needle-type glucose sensor inserted into subcutaneous tissue of the forearm or abdomen of healthy and diabetic volunteers was attempted, the readings were about 10% lower than blood glucose concentrations, but good correlation between them was observed in the range of 60 to 400 mg/dl. Perfect glycaemic control was established by infusing insulin either intravenously or subcutaneously in response to measured glucose concentrations on a moment-to-moment basis in diabetics for a period of several days. These results might indicate the feasibility of long-term glycaemic control in ambulatory diabetic patients with a wearable closed-loop glycaemic control system.


Mercator: a pipeline for multi-method, unsupervised visualization and distance generation.
Unsupervised machine learning provides tools for researchers to uncover latent patterns in large-scale data, based on calculated distances between observations. Methods to visualize high-dimensional data based on these distances can elucidate subtypes and interactions within multi-dimensional and high-throughput data. However, researchers can select from a vast number of distance metrics and visualizations, each with their own strengths and weaknesses. The Mercator R package facilitates selection of a biologically meaningful distance from 10 metrics, together appropriate for binary, categorical and continuous data, and visualization with 5 standard and high-dimensional graphics tools. Mercator provides a user-friendly pipeline for informaticians or biologists to perform unsupervised analyses, from exploratory pattern recognition to production of publication-quality graphics. Mercator is freely available at the Comprehensive R Archive Network (https://cran.r-project.org/web/packages/Mercator/index.html).


One-Pot Synthesis of BiCuSO Nanosheets under Ambient Atmosphere as Broadband Spectrum Photocatalyst.
Cuprous based chalcogenides have attracted intensive research interest due to the potential applications in solar energy conversion. However, typical fabrications of these compounds are often carried out under severe conditions, such as inert gas protection, high vacuum, and/or extreme high temperature. Here we reported a one-pot process for cuprous based chalcogenides synthesis in aqueous solution. A strategy for BiCuSO nanosheets fabrication without toxic chemicals or rigorous reagents at pretty low temperatures under an ambient atmosphere was established, with the practicality of morphology controlling and the compatibility of multifarious precursors. Platelike BiCuSO with a thickness range from several to hundreds nanometers are fabricated by adjusting the alkali concentration, reaction time, and temperature. The positive effect of alkali hydroxide concentration is proposed cautiously based on the experimental results. The photocatalytic activities of BiCuSO nanosheet under UV, visible, and near-infrared irradiation were also investigated. BiCuSO obtained at room temperature with a thickness of 4.5 nm showed the most impressive efficiency to decompose organic contaminants. Our research presented a new way for cuprous sulfides fabrication, and might open up a new vista for large-scale synthesis of cuprous based materials as promising broadband spectrum light-absorbing materials.


Respiratory dyskinesia: review and case reports.
Respiratory dyskinesia, the respiratory manifestations of tardive dyskinesia, has been recognized recently by several investigators. The literature is reviewed, two new cases are described, and possible directions for future research are discussed. It was concluded that respiratory dyskinesia is infrequently recognized clinically; more importantly, it may be easily mistaken for other medical disorders.


Local production of the p40 subunit of interleukin 12 suppresses T-helper 1-mediated immune responses and prevents allogeneic myoblast rejection.
The p40 subunit of interleukin 12 (IL-12p40) has been known to act as an IL-12 antagonist in vitro. We here describe the immunosuppressive effect of IL-12p40 in vivo. A murine myoblast cell line, C2C12, was transduced with retro-virus vectors carrying the lacZ gene as a marker and the IL-12p40 gene. IL-12p40 secreted from the transfectant inhibited the IL-12-induced interferon gamma (IFN-gamma) production by splenocytes in vitro. Survival of C2C12 transplanted into allogeneic recipients was substantially prolonged when transduced with IL-12p40. Cytokine (IL-2 and IFN-gamma) production and cytotoxic T lymphocyte induction against allogeneic C2C12 were impaired in the recipients transplanted with the IL-12p40 transfectant. Delayed-type hypersensitivity response against C2C12 was also diminished in the IL-12p40 recipients. Furthermore, serum antibodies against beta-galactosidase of the T-helper 1-dependent isotypes (IgG2 and IgG3) were decreased in the IL-12p40 recipients. These results indicate that locally produced IL-12p40 exerts a potent immunosuppressive effect on T-helper 1-mediated immune responses that lead to allograft rejection. Therefore, IL-12p40 gene transduction would be useful for preventing the rejection of allografts and genetically modified own cells that are transduced with potentially antigenic molecules in gene therapy.


B(C6F5)3-Catalyzed C-Si/Si-H Cross-Metathesis of Hydrosilanes.
The substituent redistribution of hydrosilanes on silicon through C-Si and Si-H bond cleavage and reformation is of great interest and importance, but this transformation is usually difficult to achieve in a selective fashion. By using electron-rich aromatic hydrosilanes, we have achieved for the first time the selective C-Si/Si-H bond homo- and cross-metathesis of a series of hydrosilanes in the presence of a boron catalyst B(C6F5)3. This protocol features simple reaction conditions, high chemoselectivity, wide substrate scope, and high functionality tolerance, offering a new pathway for the synthesis of multisubstituted functional silanes.


Electronic Medical Records for (Visceral) Medicine: An Overview of the Current Status and Prospects.
Electronic medical records (EMRs) offer key advantages over analog documentation in healthcare. In addition to providing details about current and past treatments, EMRs enable clear and traceable documentation regardless of the location. This supports evidence-based, multi-professional treatment and leads to more efficient healthcare. However, there are still several challenges regarding the use of EMRs. Understanding these challenges is essential to improve healthcare. The aim of this article is to provide an overview of the current state of EMRs in the field of visceral medicine, to describe the future prospects in this field, and to highlight some of the challenges that need to be faced. The benefits of EMRs are manifold and particularly pronounced in the area of quality assurance and improvement of communication not only between different healthcare professionals but also between physicians and patients. Besides the danger of medical errors, the health consequences for the users (cognitive load) arise from poor usability or a system that does not fit into the real world. Involving users in the development of EMRs in the sense of participatory design can be helpful here. The use of EMRs in practice together with patients should be accompanied by training to ensure optimal outcomes in terms of shared decision-making. EMRs offer a variety of benefits. However, it is critical to consider user involvement, setting specificity, and user training during development, implementation, and use in order to minimize unintended consequences.


[The expression and significance of chemokines eotaxin and RANTES in the rat model of allergic rhinitis].
To explore the expression and significance of Eotaxin and RANTES in the rat model of allergic rhinitis (AR). 20 female SD rats in 6-7 weeks were randomly divided into control group and AR group (n = 10, respectively). AR rat model was made with ovalbumin stimulation. To detect pathological changes in mucosa and chemokine Eotaxin, RANTES in their nasal and lung tissues after execution. Compared with the control group, Lung EOS cell counted higher in AR group and the difference was significant (P < 0.01); the AR rats nasal mucosa and lung tissue of Eotaxin, RANTES expression was significantly increased (P < 0.01). There exist high expression of Eotaxin, RANTES, infiltration of eosinophils in nasal and lung tissue of model rats with allergic rhinitis, inferring that the upper and lower respiratory tract inflammatory response has obvious consistency.


Influence of short-term side effects on oral sleep appliance compliance among CPAP-intolerant patients: An objective monitoring of compliance.
To investigate the predictive value of side effects on usage times during the initial titration phase of oral appliance therapy for sleep apnoea. The secondary objective was to assess the correlation between subjective and objective usage times. A total of 21 subjects diagnosed with sleep apnoea and a history of non-compliance with CPAP therapy were enrolled in the 4-week clinical study. Objective compliance was assessed through an intra-oral compliance monitor embedded in a Thornton Adjustable Positioner. Subjective compliance was evaluated through self-reporting and questionnaire for side effects. Excess salivation, xerostomia and tooth discomfort were the most common side effects (61%-67%). Noises (OR = 10, 95% CI = 0.85-117.02, P = 0.067), jaw discomfort (OR = 15, 95% CI = 1.21-185.20, P = 0.035) and gum discomfort (OR = 8.86, 95% CI = 1.0-∞, P = 0.038) were highly predictive of non-compliance. Subjects with either "none" or "mild" side effects recorded a mean oral appliance usage time ≥5.5 hours/night, while subjects reporting "severe" side effects recorded a mean usage time ≤4 hours/night. The mean usage time was 5.49 hours/night, with nightly compliance (defined as >4 hours per night for 70% the nights per week) at 33%. Nonetheless, compliance increased from 26%-50% from week 1 to week 4. The subjective and objective usage times were highly correlated (r = 0.81). There was a high correlation between subjective and objective compliance reporting data. Moderate/severe side effects had the greatest effect on compliance.


Two components of exocytosis and endocytosis in phaeochromocytoma cells studied using caged Ca2+ compounds.
1. Changes in membrane capacitance evoked by the rapid photolysis of a caged Ca2+ compound, DM-nitrophen or nitrophenyl-EGTA, were investigated in undifferentiated PC12 cells. They were interpreted as representing exocytosis and endocytosis. 2. The Ca2+ jumps evoked two components of exocytosis. Slow exocytosis was selectively evoked with small increases in intracellular Ca2+ concentration between 5 and 10 microM, while fast exocytosis preceded the slow one at [Ca2+]i greater than 10 microM. 3. The release rates of the two components of exocytosis depended steeply on [Ca2+]i. A half-maximal release rate was achieved at 8 and 24 microM for the slow and fast exocytoses, respectively. 4. Prior Ca2+ rises did not augment the fast exocytosis. 5. The fast exocytosis was often followed by a rapid decrease in membrane capacitance, representing endocytosis, after a delay of 0.5-2 s. The speed and delay in the fast endocytosis were Ca2+ dependent. Amounts of the fast endocytosis tended to balance with those of the fast exocytosis evoked by the same Ca2+ jumps. 6. The slow exocytosis was followed by a sluggish endocytosis that was associated with large capacitance steps indicative of secretory processes involving large dense-core vesicles. The onset of the slow endocytosis exhibited a complex Ca2+ dependence. The amounts of the slow endocytosis appeared to parallel those of the slow exocytosis. Prior induction of the slow exocytosis gave rise to selective excess retrieval of membrane during the slow endocytosis. 7. These data indicate the existence of two distinct populations of secretory vesicles in PC12 cells. They seem to couple selectively with specific endocytotic mechanisms. Our data suggest that the two vesicles belong to two distinct secretory pathways.


Budget impact of rosuvastatin initiation in high-risk hyperlipidemic patients from a US managed care perspective.
Statins reduce low-density lipoprotein cholesterol (LDL-C) levels, which, when elevated, represent a significant risk factor for cardiovascular (CV) disease. Hyperlipidemic patients at risk of CV events initiated on simvastatin or atorvastatin may be less likely to meet LDL-C goals (defined in National Cholesterol Education Program guidelines) and more likely to experience CV events than patients initiated on rosuvastatin. A 3-year budget impact model was developed to estimate the clinical impact and cost to a US managed care organization (MCO) with 1 million members of initiating high-risk hyperlipidemic patients on rosuvastatin rather than simvastatin or atorvastatin. A total of 1000 adult patients were assumed to initiate statins. The average baseline LDL-C level was 189 mg/dL. In scenario 1, all patients were initiated on simvastatin or atorvastatin and titrated to a higher dose, or switched to atorvastatin (if initiated on simvastatin) or rosuvastatin; in scenario 2, 50% of the 520 high-risk patients were initiated on rosuvastatin. Drug acquisition and administration costs were considered. Product labeling, clinical trial results, national prescription claims data, and published literature were used to populate the model. Over 3 years, 75 additional patients reached their LDL-C goal in scenario 2, compared with scenario 1 (633 vs 558, respectively), at an increased cost of $240,628 ($1,415,516 vs $1,174,888, respectively). The additional per member per month (PMPM) cost of scenario 2 was $0.007. This analysis assumed that statin efficacy is the same in real life as in trials, and used titration and switching patterns not based on patients' goal attainment. However, sensitivity and scenario analyses showed that the model was less sensitive to these parameters than to cost-related parameters. Initiating high-risk hyperlipidemic patients on rosuvastatin may increase the number of patients reaching LDL-C goal at a relatively modest increase in PMPM cost to an MCO.


Tooth-Supporting Hard Tissue Regeneration Using Biopolymeric Material Fabrication Strategies.
The mineralized tissues (alveolar bone and cementum) are the major components of periodontal tissues and play a critical role to anchor periodontal ligament (PDL) to tooth-root surfaces. The integrated multiple tissues could generate biological or physiological responses to transmitted biomechanical forces by mastication or occlusion. However, due to periodontitis or traumatic injuries, affect destruction or progressive damage of periodontal hard tissues including PDL could be affected and consequently lead to tooth loss. Conventional tissue engineering approaches have been developed to regenerate or repair periodontium but, engineered periodontal tissue formation is still challenging because there are still limitations to control spatial compartmentalization for individual tissues and provide optimal 3D constructs for tooth-supporting tissue regeneration and maturation. Here, we present the recently developed strategies to induce osteogenesis and cementogenesis by the fabrication of 3D architectures or the chemical modifications of biopolymeric materials. These techniques in tooth-supporting hard tissue engineering are highly promising to promote the periodontal regeneration and advance the interfacial tissue formation for tissue integrations of PDL fibrous connective tissue bundles (alveolar bone-to-PDL or PDL-to-cementum) for functioning restorations of the periodontal complex.


Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting.
Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.


Elevated expression of HDAC6 in clinical peritoneal dialysis patients and its pathogenic role on peritoneal angiogenesis.
Peritoneal dialysis (PD) is an important renal replacement therapy for end-stage renal disease (ESRD) patients. However, its complications, such as peritoneal fibrosis (PF) and angiogenesis can cause ultrafiltration failure and PD termination. Histone deacetylase 6 (HDAC6) has been demonstrated to be involved in PF. However, its underlying role in peritoneal angiogenesis is still unknown and clinical value needs to be explored. In this study, we analyzed the expression of HDAC6 in the peritoneum from patients with non-PD and PD-related peritonitis and dialysis effluent from stable PD patients. Our study revealed that HDAC6 expressed highly in the peritoneum with peritonitis and co-stained with α-smooth muscle actin (α-SMA), a biomarker of the myofibroblast. And the level of HDAC6 in the dialysate increased with time and positively correlated with transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and negatively with cancer antigen 125 (CA125). In vitro, blockading HDAC6 with a selective inhibitor tubastatin A (TA) or silencing HDAC6 with a small interfering RNA (siRNA) prominently decreased IL-6-stimulated VEGF expression in cultured human peritoneal mesothelial cells (HPMCs), and inhibited proliferation and vasoformation of human umbilical vein endothelial cells (HUVECs). TA or HDAC6 siRNA also suppressed the expression of Wnt1, β-catenin, and the phosphorylation of STAT3 in IL-6-treated HPMCs. In summary, HDAC6 inhibition protects against PD-induced angiogenesis through suppression of IL-6/STAT3 and Wnt1/β-catenin signaling pathway, subsequently reducing the VEGF production and angiogenesis. It could become a new therapeutic target or forecast biomarker for PF, inflammation, and angiogenesis in the future.


Structure of the ask-asd operon and formation of aspartokinase subunits in the cephamycin producer 'Amycolatopsis lactamdurans'.
The first two genes of the lysine pathway are closely linked forming a transcriptional operon in the cephamycin producer 'Amycolatopsis lactamdurans'. The asd gene, encoding the enzyme aspartic semialdehyde dehydrogenase, has been cloned by complementation of Escherichia coli asd mutants. It encodes a protein of 355 aa with a deduced M(r) of 37109. The ask gene encoding the aspartokinase (Ask) is located upstream of the asd gene as shown by determination of Ask activity conferred to E. coli transformants. asd and ask are separated by 2 nt and are transcribed in a bicistronic 2.6 kb mRNA. As occurs in corynebacteria, the presence of a ribosome-binding site within the ask sequence suggests that this ORF encodes two overlapping proteins, Askalpha of 421 aa and M(r) 44108, and Askbeta of 172 aa and M(r) 18145. The formation of both subunits of Ask from a single gene (ask) was confirmed by using antibodies against the C-terminal end of Ask which is identical in both subunits. Ask activity of 'A. lactamdurans' is regulated by the concerted action of lysine plus threonine and this inhibition is abolished in E. coli transformants containing Ser(301) to Tyr, or Gly(345) to Asp mutations of the 'A. lactamdurans' ask gene.


Intrafamilial variable expressivity of osteogenesis imperfecta due to mosaicism for a lethal G382R substitution in the COL1A1 gene.
Fibroblasts from a 23 week old fetus affected with lethal (type II) osteogenesis imperfecta (OI) produced normal and abnormal type I procollagen molecules. The abnormal molecules were shown to contain pro alpha 1(I) chains in which the glycine at position 382 of the triple helical domain was substituted by arginine, as the result of a G-to-C transversion at nucleotide 1797 of the pro alpha (I) coding sequence. Also fibroblasts from the apparently normal father produced abnormal type I collagen but the overmodified alpha 1(I) chains tended to disappear with increasing passage number. We determined that the mutant allele accounted for approximately 36% of the COL1A1 alleles in the father's skin fibroblasts. Upon careful clinical reexamination, the man appeared to be very mildly affected with OI. The most plausible explanation for such a phenotypic variation is that the father is a mosaic for a mutation that is lethal in the heterozygous son. This finding confirms previous observations that somatic mosaicism for new dominant mutations is responsible for extreme intrafamilial variability and poses some caveats in genetic counselling.


Dental care in children with developmental disabilities: attention deficit disorder, intellectual disabilities, and autism.
The Federal government reports that 13% of Americans between birth and 18 years of old meet the definition of a child with special health care needs. These children and young adults present unique challenges for both pediatric and general dentists to provide access to the oral health care system--establishing a treatment plan for those with unique medical, behavioral and dental needs and maintaining oral health over the lifetime. The purpose of this article was to describe the characteristics of 3 common developmental disabilities and the challenges these issues present to the oral health care practitioner.


Psychosurgery: past, present, and future, including prefrontal lobotomy and Connecticut's contribution.
Psychosurgery, a subspecialty of functional neurosurgery, has been used in the treatment of psychiatric illness, intractable pain, and, controversially, as ameans to control and modify violent human behavior. Prefrontal lobotomy, a procedure developed in the 20th century, arose as a result of pioneering research, includingwork done atYaleUniversity in New Haven. Prominent clinicians throughout Connecticut contributed to the development of modern psychosurgery. Neuroethics or ethics of neuroscience is essential to the study and practice ofpsychosurgery. New technology has provided improved accuracy with less morbidity. The progressive replacement of ablative procedures with deep-brain stimulation and restorative neurosurgery offers new perspectives in the treatment of some psychiatric conditions.


The effect of anticoagulants on the size of platelets in blood smears in the course of time.
In this study we measured platelet size in blood smears using the Kontron Mop Videoplan (Kontron Electronic Group, Weesp, Holland). The blood smears were prepared at different times after phlebotomy; samples were collected in three different anticoagulants and 100 consecutive platelets were measured in each smear. A number of platelet parameters were determined, some of which were based on the log normal distribution of the platelet area. We found that the size of platelets in blood smears is also dependent on the time after phlebotomy and the anticoagulant used. This may be important for the comparison of platelet areas, a characteristic of various disorders. Our data indicate that the optimal interval after phlebotomy for preparation of blood smears is 2-5 min.


How Fast Is Too Fast? Boundaries to the Perception of Electrical Stimulation of Peripheral Nerves.
Transcutaneous electrical stimulation is a promising technique for providing prosthetic hand users with information about sensory events. However, questions remain over how to design the stimulation paradigms to provide users the best opportunity to discriminate these events. Here, we investigate if the refractory period influences how the amplitude of the applied stimulus is perceived. Twenty participants completed a two-alternative forced choice experiment. We delivered two stimuli spaced between 250 ms to 450 ms apart (inter-stimulus-interval, isi). The participants reported which stimulus they perceived as strongest. Each stimulus consisted of either a single or paired pulse delivered transcutaneously. The inter-pulse interval (ipi) for the paired pulse stimuli varied between 6 and 10 ms. We found paired pulses with an ipi of 6 ms were perceived stronger than a single pulse less often than paired pulses with an ipi of 8 ms (p = 0.001) or 10 ms (p < 0.0001). Additionally, we found when the isi was 250 ms, participants were less likely to identify the paired pulse as strongest, than when the isi was 350 or 450 ms. This study emphasizes the importance of basing stimulation paradigms on the underlying neural physiology. The results indicate there is an upper limit to the commonly accepted notion that higher stimulation frequencies lead to stronger perception. If frequency is to be used to encode sensory events, then the results suggest stimulus paradigms should be designed using frequencies below 125 Hz.


[The relationship between alteration of mitochondrial enzyme activities and mitochondrial function after cervical cord injury].
To investigate the relationship between mitochondrial enzyme activities and mitochondrial function after cervical cord injury, cervical cord model was prepared using Allen method in cats. Changes in mitochondrial Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase, superoxide dismutase (SOD) activities, contents of malondialdehyde (MDA) and mitochondrial function in cervical cord were observed by different biochemical methods. The results showed that mitochondrial Na+, K(+)-ATPase, CA2+, Mg(2+)-ATPase, SOD activities decreased; mitichondral respiratory control rate (RCR), P/O ratio and oxidative phosphorylation rate (OPR) were also depressed is compared with control group (P < 0.05), but MDA level significantly increased compared to control group (P < 0.01). The results demonstrate that there is close correlation, between mitochondrial ATPase. SOD activities and mitochondral function, suggesting that mitochondrial pathophysiological alteration plays important roles in the secondary damage after cervical cord injury.


Hearing loss in a memory disorders clinic. A specially vulnerable population.
To determine the prevalence and characteristics of hearing loss in patients undergoing examination because of a memory disorder, to determine whether currently used screening tools were adequate for use in this specific population, and to determine if patients with Alzheimer disease reliably report hearing problems. Case-control study. A consecutive sample of 52 patients: 30 patients who met the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer disease (group 1) and 22 patients with other forms of cognitive impairment (group 2). Patients underwent a hearing screening that included a case history, a visual inspection of the external ear canal and tympanic membrane, and pure tone audiometry. Patients and their caregivers completed a questionnaire intended to assess hearing impairment and perceived disability. Pass or fail on pure tone audiometry and pass or fail on a hearing impairment questionnaire. Of the 52 patients, 49 had significant hearing loss. No difference was found in the failure rate between patients in groups 1 and 2. In group 1, a significant discrepancy was found between the patient's self-report and that of their caregivers, whereas in group 2, the self-report was reliable. The prevalence of hearing loss in this population greatly exceeds the prevalence in healthy aged controls. The extraordinarily high prevalence of hearing loss in this selected population suggests that a hearing evaluation should be part of any assessment of cognitive function.


Human TRIM5alpha expression levels and reduced susceptibility to HIV-1 infection.
Human TRIM5alpha (TRIM5alphahu), a member of the tripartite motif protein family, displays some anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro, although it is substantially less potent than its rhesus monkey counterpart (TRIM5alpharh). The effects of levels of TRIM5alphahu on prevention or control of HIV-1 infection in vivo are unknown. We used a quantitative real-time polymerase chain reaction (PCR) assay to measure levels of TRIM5alphahu expression in peripheral blood mononuclear cells (PBMCs) obtained from a cohort of individuals at high risk for HIV-1 infection in Durban, South Africa. Samples were available from 38 infected subjects (with all these samples obtained within 1 year of infection) and from 57 uninfected persons. Matched preinfection and postinfection samples were available from 13 individuals. TRIM5alphahu messenger RNA levels were lower in the PBMCs of HIV-1-infected subjects than in those of uninfected subjects (P <.001). Seroconverters had lower preinfection levels of TRIM5alphahu than did nonseroconverters (P<.001). TRIM5alphahu levels did not change significantly after infection. There was no correlation between TRIM5alphahu levels and viral loads or CD4(+) T cell counts. High expression of TRIM5alphahu is associated with reduced susceptibility to HIV-1 infection. Furthermore, infection is not associated with disregulation of TRIM5alphahu. TRIM5alphahu expression levels do not contribute to the control of primary HIV-1 viremia.


Piezoresistive cantilever array sensor for consolidated bioprocess monitoring.
Cellulolytic microbes occur in diverse natural niches and are being screened for industrial modification and utility. A microbe for consolidated bioprocessing (CBP) development can rapidly degrade pure cellulose and then ferment the resulting sugars into fuels. To identify and screen for novel microbes for CBP, we have developed a piezoresistive cantilever array sensor which is capable of simultaneous monitoring of glucose and ethanol concentration changes in a phosphate buffer solution. 4-mercaptophenylboronic acid and polyethyleneglycol-thiol are employed to functionalize each piezoresistive cantilever for glucose and ethanol sensing, respectively. Successful concentration measurements of glucose and ethanol with minimal interferences are obtained with our cantilever array sensor.


Clot Meniscus Sign Is Associated With Thrombus Permeability and Choice of Mechanical Thrombectomy Technique in Acute Middle Cerebral Artery Occlusion.
The method of mechanical thrombectomy (MT) is related to vascular anatomy and stroke etiology. Meniscus sign and thrombus permeability as imaging markers may be instructive for the selection of MT. This study aims to clarify the relationship among meniscus sign, thrombus permeability, and choice of MT in patients with acute middle cerebral artery occlusion. A total of 111 patients with acute middle cerebral artery occlusion (MCAO) who underwent MT were retrospectively analyzed. Clot meniscus sign was defined as the appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots. The radiographic, clinical, and surgical data of patients with MCAO with or without meniscus sign were compared. The meniscus sign positive group (n = 26) has higher thrombus permeability (HUs) (26.92 ± 9.69 vs. 22.84 ± 7.88, p = 0.031) than those without it. Shorter puncture-to-recanalization (P2R) time (65.5 vs. 88, p = 0.012), higher complete recanalization rate (85.71 vs. 33.33%, p < 0.01), and better clinical outcome (p < 0.01) were obtained by selecting contact aspiration (CA) over stent retriever (SR) in patients with positive meniscus sign. In patients with negative meniscus sign, there was no significant difference in clinical outcome after receiving CA or SR. Patients with MCAO with positive meniscus sign have higher thrombus permeability and are more suitable for CA to acquire better clinical outcomes.