A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke.
Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.


[Changes in the EEG in the course of therapy with lithium salts].
The effect of lithium during chronic treatment on the EEG. has been studied in 21 subbjects affected by manic-depressive psychosis. The relation between lithiemic values and EEG. modification has been discussed from varius points of view, considering records of what has been observed in the present research and what reported in literature. The mean hematic lithium level has been considered insufficient to obtein the essential informations. The determination of the intracellular lithium concentration may be a more informative one.


Neu-P11, a novel MT1/MT2 agonist, reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axis in rats.
Excessive glucocorticoid (GC) in type 2 diabetes mellitus (T2DM) reduces insulin sensitivity, impairs β-cell function, increases gluconeogenesis and glycogenolysis, impairs glucose uptake and metabolism, and reduces the insulinotropic effects of glucagon-like peptide 1. Melatonin, which serves as a physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis, has been suggested to have anti-diabetic effects. The objective of the present study was to investigate the effect of the MT1/MT2 melatonin agonist Neu-P11 on glucose and lipid metabolism in T2DM rats induced by a high fat diet combined with low doses of streptozotocin. T2DM rats were intragastrically administered melatonin (20mg/kg), Neu-P11 (20, 10, 5mg/kg), or a vehicle for 4 weeks. The results showed that the increased food intake, water consumption, hyperglycemia, glucose intolerance, and insulin resistance in T2DM rats were all improved by Neu-P11 treatment. Neu-P11 increased GC receptor expression and suppressed 11β-hydroxysteroid dehydrogenase 1 activity in the hippocampus by enhancing GC sensitivity and HPA feedback, thus decreasing the high GC levels. Transcript levels of the glucose metabolism-related genes peroxisome proliferator-activated receptor-γ, glucose transporter type-4, and adiponectin in adipose tissue were significantly increased after Neu-P11 treatment, while leptin mRNA was significantly decreased. Furthermore, MT1 and MT2 protein levels were enhanced by Neu-P11. These data suggest that normalization of the hyperactivated HPA axis by melatonin and Neu-P11 in T2DM regulates metabolic profiles and insulin sensitivity, which may attenuate insulin resistance and glucose homeostasis. Because Neu-P11 has superior pharmacokinetics and a longer half-life than melatonin, it might be beneficial in treating obesity and T2DM.


Enhanced optical properties of TiO2 nanoceramic films by oxygen atmosphere.
TiO2 nanoceramic films were deposited on glasses by rf magnetron sputtering and corresponded to nanocrystalline anatase. The porosity and surface roughness decreased with the oxygen pressure. The optical transmission of TiO2 nanoceramic films obviously increased with the decrease of film thickness or the increase of oxygen pressure, especially in the visible region. Moiré deflectometry was used to measure the nonlinear refractive indices of TiO2 films deposited in a mixed Ar-O2 atmosphere. The nonlinear refractive index was measured to be of the order of 10(-8) cm2 W(-1) and the change in refractive index was of the order of 10(-5). As the oxygen pressure increased, the transparent TiO2 film exhibited a high linear refractive index, a low stress and a low stress-optical coefficient.


Localisation of alphafetoprotein (AFP) in murine teratocarcinoma.
Solid tumours with histopathological characteristics of teratocarcinoma (generally presenting the structures of nervous origin) were induced in the mouse by subcutaneous inoculation with murine embryonal carcinoma (EC) cells of line PCC4-azal. An indirect immunoperoxidase technique using anti-mouse AFP antibodies was applied for the localization of the protein on paraffin sections of tissue fixed with acetic acid-ethanol. The PCC4-azal EC cells were AFP negative in vitro. In the solid tumours, the immature embryonal or fetal components (i. e. tubes or cysts mimicking the development of the neural tube) and the groups of neuroepithelial cells arranged in more or less differentiating structures (pseudotubes, cluters) were AFP positive; on the contrary, cells of the same differentiated neuroepithelial type, but lacking recognizable tissue architecture, were AFP negative. Mature, adult components were AFP negative. Undifferentiated cancer components, whether structured or not, were AFP negative. These results suggest that the intracellular presence of AFP requires a minimum degree of both cell differentiation and tissue organization.


Molecular cloning and characterization of cDNAs for the gamma- and epsilon-subunits of mitochondrial F1F0 ATP synthase from the sweet potato.
Mitochondrial F1F0 ATP synthases purified from dicotyledonous plants contain six different subunits named alpha, beta, gamma, delta, delta', and epsilon. Our previous N-terminal amino acid sequence analyses indicated that the gamma- and epsilon-subunits of the sweet potato mitochondrial F1 correspond to the gamma- and epsilon-subunits of animal mitochondrial F1, respectively (Kimura, T., Nakamura, K., Kajiura, H., Hattori, H., Nelson, N., and Asahi, T. (1989) J. Biol. Chem. 264, 3183-3186). A cDNA clone for the gamma-subunit of the sweet potato mitochondrial F1 was identified by oligonucleotide hybridization selection of a cDNA library, and a cDNA clone for the epsilon-subunit was isolated by reverse polymerase chain reaction and hybridization selection of a cDNA library by the polymerase chain reaction product. The 1.4-kilobase long cDNA for the gamma-subunit contained a 978-base pair open reading frame coding for a precursor for the gamma-subunit. The mature gamma-subunit is composed of 281 amino acids, and its sequence showed significantly higher similarities with the gamma-subunit of animal mitochondrial F1 and bacterial F1 compared with the gamma-subunit of chloroplast CF1 from plants. The precursor for the gamma-subunit contained N-terminal presequence of 45 amino acid residues. By contrast, the 0.46-kilobase long cDNA for the epsilon-subunit contained a coding sequence of 207-base pairs for the mature epsilon-subunit of 69 amino acid residues that is preceded by an ATG codon suggesting that the epsilon-subunit is synthesized without the cleavable presequence for mitochondrial import. The amino acid sequence of the epsilon-subunit of sweet potato mitochondrial F1 showed similarities of 25 and 36% amino acid positional identity with the epsilon-subunits of mitochondrial F1 from yeast and bovine, respectively.


Development of the caruncular and intercaruncular regions in the bovine endometrium.
Uterine specimens from fetal and postnatal heifers were examined by various types of microscopy to determine when the endometrium differentiated into caruncular and intercaruncular regions and changes in the cell types as the uterus developed. The luminal surface of the fetal uterus was formed into prominent pedunculated or mushroom-shaped nodules. Glandular development was first observed at about 250 days of gestation as short invaginations of the epithelium of the internodular surface adjacent to nodular stalks. The basal profile of each epithelial cell in the deeper portions of developing glands formed cytoplasmic processes which extended into the stroma. Between birth and 3 months of age there was a tremendous increase in the glandular epithelium. Concurrent thickening of the connective tissue component caused expansion of the nodular peduncle and a gradual flattening of the nodule until, by 1 year of age, only slight elevations remained, with a discrete caruncle visible on each. By following the development of the glandular component it was concluded that only the apical portion of each fetal nodule will develop into a caruncle and the sides of the nodule, together with the internodular portion, are destined to be the intercaruncular region.


Content validity of the comprehensive international classification of functioning, disability and health (ICF) core set for low back pain from the perspective of physicians: a Delphi survey.
The 'Comprehensive ICF Core Set for low back pain (LBP)' is an application of the International Classification of Functioning, Disability and Health (ICF) and represents the typical spectrum of problems in functioning of patients with LBP. The objective of this study was to validate this ICF Core Set from the perspective of physicians. Physicians experienced in the treatment of LBP were asked about the patients' problems, patients' resources and aspects of environment that physicians take care of in a three-round survey using the Delphi technique. Responses were linked to the ICF. Seventy-one physicians in 36 countries named 707 concepts that covered all ICF components. One hundred ninety-three ICF categories were linked to these answers. Three ICF categories were not represented in the Comprehensive ICF Core Set for LBP although at least 75% of the participants have rated them as important. Twenty-six concepts were linked to the not yet developed ICF component personal factors and 21 issues were not covered by the ICF. The high percentage of ICF categories represented in the ICF Core Set for LBP indicates good content validity from the perspective of the physicians. However, some issues were raised that were not covered and need to be investigated further.


Autologously up-regulated Fc receptor expression and action in airway smooth muscle mediates its altered responsiveness in the atopic asthmatic sensitized state.
To elucidate the role of IgE-dependent mechanisms in inducing altered airway responsiveness in the atopic asthmatic state, the expression and actions of Fc receptor activation were examined in isolated rabbit tracheal smooth muscle (TSM) tissue and cultured cells passively sensitized with sera from atopic asthmatic patients or nonatopic/nonasthmatic (control) subjects. Relative to control tissues, the atopic asthmatic-sensitized TSM exhibited significantly increased maximal isometric contractility to acetylcholine (P < 0. 01) and attenuated maximal relaxation responses and sensitivity (i.e.,-log ED50) to isoproterenol (P < 0.005). These changes in agonist responsiveness in atopic sensitized TSM were ablated by pretreating the tissues with a blocking mAb to the low affinity receptor for IgE, FcepsilonRII (i.e., CD23) or by depleting the sensitizing serum of its immune complexes. Moreover, in complimentary experiments, exogenous administration of IgE immune complexes to naive TSM produced changes in agonist responsiveness that were qualitatively similar to those obtained in the atopic asthmatic-sensitized state. Extended studies further demonstrated that, in contrast to their respective controls, atopic asthmatic serum-sensitized human and rabbit TSM tissue and cultured cells exhibited markedly induced mRNA and cell surface expression of FcepsilonRII, whereas constitutive expression of the IgG receptor subtype, FcgammaRIII, was unaltered. Finally, the up-regulated mRNA expression of FcepsilonRII observed following exposure of TSM to atopic asthmatic serum or to exogenously administered IgE immune complexes was significantly inhibited by pretreating the tissues or cells with anti-CD23 mAb. Collectively, these observations provide evidence demonstrating that the altered agonist responsiveness in atopic asthmatic sensitized airway smooth muscle is largely attributed to IgE-mediated induction of the autologous expression and activation of FcepsilonRII receptors in the airway smooth muscle itself.


Discoid lateral meniscus in a young child: case report and review of the literature.
Management of discoid lateral meniscus in a 6-month-old child is discussed. The patient presented with a lateral knee mass and an associated popping sound of the joint during flexion and extension. The diagnosis, which the authors believe to be the youngest presentation of this entity, was confirmed by arthrography. Computed tomographic features and magnetic resonance images of the discoid meniscus are presented. Management and theories of etiology of the discoid lateral meniscus are discussed.


Prediction of the severity of allergic reactions to foods.
There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. The study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B = 0.30, P < .001), eliciting dose (B = -0.09, P < .001), level of specific immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = -0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P < .001), history of atopic dermatitis (B = -0.47, P = .006), and severity of DBPCFC reaction (B = 0.12, P = .003). The severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.


Molecular mechanisms of memory formation.
Studies with neonate chicks, trained on a passive avoidance task, suggest that at least two shorter-term memory stages precede long-term, protein synthesis-dependent memory consolidation. Posttetanic neuronal hyperpolarization arising from two distinct mechanisms is postulated to underlie formation of these two early memory stages. Maintenance of the second of these stages may involve a prolonged period of hyperpolarization brought about by phosphorylation of particular proteins. A triggering mechanism for long-term consolidation is postulated to occur at a specific time during the second stage, and may involve reinforcement-contingent release of neuronal noradrenaline stimulating cAMP-dependent intracellular processes. The possibility that astroglia may have a critical role to play in these early stages of memory processing is raised.


Reversible pancytopenia and immunodeficiency in a patient with hereditary folate malabsorption.
Mutations in SLC46A1 result in a defect of the proton coupled folate transporter (PCFT) and are the basis of hereditary folate malabsorption (HFM). Patients with HFM frequently present with neurodevelopmental delay and megaloblastic anemia. Some cases may be complicated by additional lymphopenia and immunodeficiency. We report a patient with a new homozygous mutation in the SLC46A1 gene. The boy presented with early-onset pancytopenia and secondary immunodeficiency. We provide clinical and molecular observations that extend the phenotypic description of HFM and highlight diagnostic as well as therapeutic pitfalls in this rare condition.


The interaction of asbestos and smoking in lung cancer: a modified measure of effect.
The ratio of the relative risk of lung cancer due to asbestos exposure in non-smokers to that in smokers has been termed the relative asbestos effect (RAE). In a review, Liddell [Liddell FDK (2001) Ann Occup Hyg; 45: 341-56] estimated that the RAE was approximately 2. This measure is satisfactory when there is an appreciable relative risk due to asbestos but does not generalize to lower levels of exposure. A modified measure is proposed to overcome this difficulty. The modified measure, RAEm, is defined as the ratio of the excess relative risk (RR - 1) in non-smokers to that in smokers. The cohort studies combined in Liddell's 2001 analysis have been used to give a combined estimate of the modified measure. The combined value of RAEm is 3.19 with 95% confidence interval 1.67-6.13. The excess relative risk of lung cancer from asbestos exposure is about three times higher in non-smokers than in smokers. The modified measure has been placed within a more versatile model of interaction. If interaction is present the relative risk from asbestos exposure changes only slightly between light and heavy smokers, but is higher in very light smokers and non-smokers. The relative risk estimated from epidemiological studies of a mixed population of non-smokers and smokers applies to smokers.


Microbiological Sealing Analysis of a Tapered Connection and External Hexagon System.
Considering the variety of implant connection systems available in the market and the contrasting literature regarding tapered connection systems in terms of bacterial leakage, the aim of this in vitro study was to compare the effectiveness of the bacterial seal at the implant/abutment interface between an external hexagon and a tapered connection system. Twelve sets of indexed tapered connection components and twelve sets of external hexagon connection components were used for microbiological analysis. In addition, for each model, an implant with its respective prosthetic abutment was used as a negative control and another as a positive control of microbial contamination. Failure of the abutment/implant interface seal was observed via turbidity or presence of deposits in the culture. Descriptive analysis of the data and relative frequency (percentage) as well as Fisher's exact test were used at a significance level of 5%. Two of ten (20%) external hexagon specimens showed contamination against 0/10 (0%) tapered connection implants. In conclusion, both implant/abutment connections were able to prevent bacterial leakage in vitro.


The hyoid, laryngeal and pharyngeal regions of bathyergid and other selected rodents.
The morphology of the hyoid, laryngeal and pharyngeal regions of the following rodent genera was studied: Cryptomys, Bathyergus, Georychus, Heliophobius, Heterocephalus, Ctenomys, Petromus, Thryonomys, Geomys, Cannomys, and Tachyoryctes. A number of morphological conditions unique to bathyergids, and associated with the use of the head and lower incisors in burrowing are described. The conditions include the formation of functional complexes of MM. sterno-geniohyoideus and omo-mylohyoideus, the presence of a unique deep oblique part of M. transversus mandibulae and a strong separate slip of M. platysma myoides pars mentalis. The hyoid skeleton is modified to allow the muscle complexes to act independently of the basihyal bone, and to allow the unusually protrusible tongue to be withdrawn. The nerves of the jugular foramen do not form a true pharyngeal plexus, and their configuration is influenced by the absence of a well developed internal carotid artery in hystricognaths. The morphology of the regions studied indicates a natural grouping of bathyergids, but one in which Heterocephalus is somewhat separate from the remaining bathyergid genera. The grouping of bathyergids and New and Old World hystricognath rodents into a suborder Hystricognatha is supported.


Simple model of intra-extracellular potassium kinetics and removal applied to constant and potassium-profiled dialysis.
The incidence rate for sudden death in hemodialysis patients ranges between 2% and 7%. This phenomenon is frequently due to cardiac arrhythmias. In particular, the process of potassium (K(+)) depuration performed during hemodialysis has been found to be related to arrhythmia onset. The main aim of this study was to introduce a simple double-pool mathematical model of K(+) kinetics to investigate the effects of dialysate K(+) concentration on intracellular and extracellular K(+) removal. The secondary aim was to evaluate the K(+) removed from the different body pools in 2 different types of K(+) dialysate: constant and profiled. Our model evaluated K(+) removal and body water in the intracellular and extracellular spaces using plasma, erythrocytes and spent dialysate K(+) concentration, and intracellular and extracellular volume (t=0) in 6 patients (4 females and 2 males). All patients were treated with acetate-free biofiltration with a constant K(+) dialysate concentration (AFB) and with a profiled one (AFB-K). Moreover, the electrolyte concentration (sodium, calcium and bicarbonate) and pH were analyzed in all sessions. A similar total potassium removal was evaluated by the model, starting from a similar final K(+) plasma reduction. At 10 minutes, the model assessed a higher K(+) removal in the extracellular space during AFB (26.6% vs. 7.7%, p<0.001) involving a lower K(+) concentration (5.0 +/- 0.5 in AFB and 5.2 +/- 0.6 in AFB-K, p<0.05) and consequently a higher cell hyperpolarization (-73.4 +/- 3.9 mV vs. -72.1 +/- 2.4 mV, p=0.05). No differences in pH, intracellular and extracellular Na+ or plasma Ca(2+) were highlighted between AFB and AFB-K. The model we developed allows us to evaluate K(+) removal and body water in the intracellular and extracellular spaces during treatment. The assessment of this information may have a relevant role toward an understanding of the causes of the Nernst potential changes during hemodialysis that are often related to the onset of arrhythmias.


Case of generalised myasthenia gravis with membranous nephropathy.
We report a 40-year old woman with bilateral partial ptosis, complete external ophthalmoplegia, and weakness and fatiguability of upper limbs. She was on treatment for hypertension for 5 months at the time of admission. She was found to have generalised myasthenia gravis and membranous nephropathy with end-stage renal disease. Her symptoms and signs improved within 2 months on treatment with neostigmine and prednisolone. It is postulated that either thymic hyperplasia or the subclinical stage of a thymoma may be the underlying aetiological factor in this patient.


A single short stretch of homology between adenoviral vector and packaging cell line can give rise to cytopathic effect-inducing, helper-dependent E1-positive particles.
An undesirable byproduct from recombinant adenoviral vectors is the emergence of replication competent adenovirus (RCA) that result from rare homologous recombination events between the viral E1-containing (permissive) mammalian host cell genome and the virus itself, restoring the E1 gene to the viral genome. To reduce or eliminate the problem of RCA, we evaluated production of a first generation Ad5 vector (Ad5FGF4) in the cell line PER.C6. This E1-transformed human cell line contains only Ad5 nucleotides 459-3510, which precludes double crossover-type homologous recombination because the Ad5FGF-4 only contains 5' Ad5 sequence up to nucleotide 453. The Ad5FGF4 vector does, however, retain 177 nucleotides of the 3' end of the E1B-55K gene that are also present in PER.C6. With only this single region of homology between vector and cell line, we were surprised to detect virus-specific cytopathic effects (CPE) in our cell-based assay for RCA. This CPE-inducing agent was amplified in nonpermissive A549 cells but also supported amplification of the parental Ad5FGF-4. Because we were unable to isolate the CPE-inducing agent in pure form we first identified it as atypical RCA. Polymerase chain reaction (PCR) and Southern blot experiments identified viral DNA segments in which recombination had occurred between the 177 nucleotides of E1B present in both Ad5FGF-4 and PER.C6. The atypical RCA genomes contain a copy of the original (PGK promoter-E1 gene carrying) plasmid used in the construction of the PER.C6 cell line and they retained the parental FGF-4 transgene. However, significant deletions occurred within the recombined genomes in compensation for the large insertion from PER.C6 sequences and resulted in the loss of essential viral genes. This deletion renders these recombinant viruses replication defective, requiring helper functions from remaining parental Ad5FGF-4 for amplification. These atypical RCA entities may be more properly designated as helper-dependent E1-positive particles (HDEPs). This finding shows the importance of avoiding the use of "nonmatched" vectors where any overlap exists between the recombinant vector and E1 sequences in the packaging cell line. The cloning of the FGF-4 transgene into an adenoviral vector specifically "matched" for PER.C6 (lacking the 177 nucleotide region of homology) has allowed extensive virus propagation (Ad5.1FGF-4) with no CPE- or HDEP-like events yet detected.


Knockdown of GATAD2A suppresses cell proliferation in thyroid cancer in vitro.
GATAD2A (GATA zinc finger domain containing 2A), is a subunit of NuRP (nucleosome remodeling and histone deacetylation) which plays key roles in tumor growth inhibition and embryonic development. However, its role in thyroid cancer remains unclear. In our study, we established two thyroid cancer cell lines by lentivirus-delivered short hairpin (shRNA) to knockdown the expression of GATAD2A. Then loss-of-function assays indicated that knockdown of GATAD2A decreased the ability of cell proliferation and colony formation in thyroid cancer cells by MTT and colony formation assay, respectively. Moreover, cell cycle assay by flow cytometry revealed that the percentage of cells in G0/G1 phase was significantly decreased in GATAD2A knockdown cells accompanied by increase of cells in G2/M phase. Furthermore, inhibition of GATAD2A promoted cell apoptosis via elevating the expression of caspase-3 and PARP cleavage using Annexin V/7-AAD double staining and western blotting. In conclusion, GATAD2A is an essential factor in thyroid cancer cell growth and apoptosis, and may be a potential therapeutic biomarker in thyroid cancer.


What is the role of the clinical microbiology laboratory in the care of diagnostically challenging OPAT patients? Illustrative cases and literature review.
Optimal care of patients requiring long-term outpatient parenteral or oral antimicrobial therapy by infectious diseases (ID) specialists is facilitated by an accurate microbiologic diagnosis. Close collaboration between ID specialists and the clinical microbiology laboratory for routine or specialized molecular testing can result in more accurate diagnoses, streamlined antimicrobial regimens, and improved patient outcomes.


Electronic and geometric structure of cationic and neutral chromium and molybdenum ammonia complexes.
High level quantum chemical approaches are used to study the geometric and electronic structures of M(NH3)n and M(NH3)n + (M = Cr, Mo for n = 1-6). These complexes possess a dual shell electronic structure of the inner metal (3d or 4d) orbitals and the outer diffuse orbitals surrounding the periphery of the complex. Electronic excitations reveal these two shells to be virtually independent of the other. Molybdenum and chromium ammonia complexes are found to differ significantly in geometry with the former adopting an octahedral geometry and the latter a Jahn-Teller distorted octahedral structure where only the axial distortion is stable. The hexa-coordinated complexes and the tetra-coordinated complexes with two ammonia molecules in the second solvation shell are found to be energetically competitive. Electronic excitation energies and computed IR spectra are provided to allow the two isomers to be experimentally distinguished. This work is a component of an ongoing effort to study the periodic trends of transition metal solvated electron precursors.


Fast algorithm to identify minimal patterns of synchrony through fibration symmetries in large directed networks.
Recent studies have revealed the interplay between the structure of network circuits with fibration symmetries and the functionality of biological networks within which they have been identified. The presence of these symmetries in complex networks predicts the phenomenon of cluster synchronization, which produces patterns of a synchronized group of nodes. Here, we present a fast, and memory efficient, algorithm to identify fibration symmetries in networks. The algorithm is particularly suitable for large networks since it has a runtime of complexity O(MlogN) and requires O(M+N) of memory resources, where N and M are the number of nodes and edges in the network, respectively. The algorithm is a modification of the so-called refinement paradigm to identify circuits that are symmetrical to information flow (i.e., fibers) by finding the coarsest refinement partition over the network. Finally, we show that the algorithm provides an optimal procedure for identifying fibers, overcoming current approaches used in the literature.


A Hepatitis C Virus-Associated Cirrhotic Patient Developing Interstitial Pneumonia during the Course of Antiviral Therapy with Ombitasvir/Paritaprevir/Ritonavir.
Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the first agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent therapy for HCV genotype 1b. Among the adverse events associated with these oral DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have already been reported in a postmarketing surveillance. Recently, we have encountered a HCV-associated genotype 1b cirrhosis patient who developed interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir and who recovered after drug discontinuation without corticosteroid therapy. Interstitial pneumonia was confirmed by chest x-ray and chest computed tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration of the drug administration was 7 weeks, and she achieved SVR24. This is the first detailed report in the literature on the development of interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared in the treatment with DAAs, chest computed tomography and the evaluation of serum KL-6 level were recommended.


Epigenetic Marks at the Ribosomal DNA Promoter in Skeletal Muscle Are Negatively Associated With Degree of Impairment in Cerebral Palsy.
Introduction: Cerebral palsy (CP) is the most common motor impairment in children. Skeletal muscles in individuals with CP are typically weak, thin, and stiff. Whether epigenetic changes at the ribosomal DNA (rDNA) promoter are involved in this dysregulation remains unknown. Methods: Skeletal muscle samples were collected from 19 children with CP and 10 typically developed (TD) control children. Methylation of the rDNA promoter was analyzed using the Agena Epityper Mass array and gene expression by qRT-PCR. Results: Biceps brachii muscle ribosome biogenesis was suppressed in CP as compared to TD. Average methylation of the rDNA promoter was not different between CP and TD but negatively correlated to elbow flexor contracture in the CP group. Discussions: We observed a negative correlation between rDNA promoter methylation and degree of muscle contracture in the CP group. Children with CP with more severe motor impairment had less methylation of the rDNA promoter compared to less affected children. This finding suggests the importance of neural input and voluntary muscle movements for promoter methylation to occur in the biceps muscle.


All the world's a stage.
Whenever an actor describes their job as hard work, I have been known to guffaw ungenerously. But I have had to eat humble pie.


Preliminary analysis of a trial of pulse cyclophosphamide in IFN-beta-resistant active MS.
This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFN-beta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone (MP) once monthly for 6 months then followed for an additional 18 months. All patients received IFN-beta1a for the 24-month study period. The primary endpoint was mean change from baseline in the number of gadolinium-enhancing (Gd+) lesions. Secondary endpoints included the percentage of patients with Gd+ lesions, change in T2 lesion burden, change in brain parenchymal fraction (BPF), time to treatment failure, and cumulative probability of relapse. Safety was assessed by the incidence of adverse events and the results of blood and urine testing. A higher number of patients completed the study in the pulse cyclophosphamide group because approximately half as many of these patients became treatment failures (26% vs. 52%, p = 0.03). During the infusion phase, the mean number of Gd+ lesions declined 70-80% from baseline in the CY group vs. a small increase in MP (p = 0.02 and 0.04 at 3 and 6 months). We conclude that pulse cyclophosphamide appears to be well tolerated in combination with IFN-beta1a. Pulse cyclophosphamide decreases the number of Gd+ lesions in patients with active disease on IFN-beta compared to pulse methylprednisolone alone. Six doses of pulse cyclophosphamide in combination with IFN-beta1a both prevent and delay clinical disease activity in patients with previously active disease on IFN-beta alone. Pulse cyclophosphamide is a therapeutic option as rescue therapy for patients thought to be interferon non-responders.


Validation of a food quantification picture book and portion sizes estimation applying perception and memory methods.
We tested the applicability of EPIC-SOFT food picture series used in the context of a Hungarian food consumption survey gathering data for exposure assessment, and investigated errors in food portion estimation resulted from the visual perception and conceptualisation-memory. Sixty-two participants in three age groups (10 to <74 years) were presented with three different portion sizes of five foods. The results were considered acceptable if the relative difference between average estimated and actual weight obtained through the perception method was ≤25%, and the relative standard deviation of the individual weight estimates was <30% after compensating the effect of potential outliers with winsorisation. Picture series for all five food items were rated acceptable. Small portion sizes were tended to be overestimated, large ones were tended to be underestimated. Portions of boiled potato and creamed spinach were all over- and underestimated, respectively. Recalling the portion sizes resulted in overestimation with larger differences (up to 60.7%).


Cancer control planners' perceptions and use of evidence-based programs.
The Cancer Prevention and Control Research Network surveyed 282 cancer control planners to inform its efforts to increase the use of evidence-based cancer control programs (EBPs; programs that have been scientifically tested and have successfully changed behavior). Respondents included planners from organizations in state Comprehensive Cancer Control coalitions as well as other governmental and nongovernmental organizations and community-based coalitions. Respondents provided information about personal and organizational characteristics, their cancer control programs, their attitudes toward EBPs, and their awareness and use of Web-based resources for EBPs. Although findings showed strong preferences for cancer control programs that have been shown to work, less than half of respondents (48%) had ever used EBP resources. Regardless of whether they had used EBP resources, almost all respondents (97%) indicated that further training would help them and their organizations adopt and adapt EBPs for use in their communities. The most frequently endorsed training needs were finding and securing additional resources (such as funding and technical assistance), followed by adapting EBPs for cultural appropriateness. The Cancer Prevention and Control Research Network consortium is using these findings to develop a Web-based interactive training and decision support tool that is responsive to the needs identified by the survey respondents.


Proteinase-activated receptor-2 exerts protective and pathogenic cell type-specific effects in Alzheimer's disease.
The proteinase-activated receptors (PARs) are a novel family of G protein-coupled receptors, and their effects in neurodegenerative diseases remain uncertain. Alzheimer's disease (AD) is a neurodegenerative disorder defined by misfolded protein accumulation with concurrent neuroinflammation and neuronal death. We report suppression of proteinase-activated receptor-2 (PAR2) expression in neurons of brains from AD patients, whereas PAR2 expression was increased in proximate glial cells, together with up-regulation of proinflammatory cytokines and chemokines and reduced IL-4 expression (p < 0.05). Glial PAR2 activation increased expression of formyl peptide receptor-2 (p < 0.01), a cognate receptor for a fibrillar 42-aa form of beta-amyloid (Abeta(1-42)), enhanced microglia-mediated proinflammatory responses, and suppressed astrocytic IL-4 expression, resulting in neuronal death (p < 0.05). Conversely, neuronal PAR2 activation protected human neurons against the toxic effects of Abeta(1-42) (p < 0.05), a key component of AD neuropathogenesis. Amyloid precursor protein-transgenic mice, displayed glial fibrillary acidic protein and IL-4 induction (p < 0.05) in the absence of proinflammatory gene up-regulation and neuronal injury, whereas PAR2 was up-regulated at this early stage of disease progression. PAR2-deficient mice, after hippocampal Abeta(1-42) implantation, exhibited enhanced IL-4 induction and less neuroinflammation (p < 0.05), together with improved neurobehavioral outcomes (p < 0.05). Thus, PAR2 exerted protective properties in neurons, but its activation in glia was pathogenic with secretion of neurotoxic factors and suppression of astrocytic anti-inflammatory mechanisms contributing to Abeta(1-42)-mediated neurodegeneration.


The duct system of the avian salt gland as a transporting epithelium: structure and morphometry in the duck Anas platyrhynchos.
The duct system of the nasal salt gland of the duck comprises central central canals, secondary ducts and main ducts. The secondary and main ducts consist of a layer of columnar cells overlying a layer of small cuboidal cells. The columnar cells have complex intercellular spaces showing evidence of Na+K+-ATPase at the apical regions. Approximately 70% of surface area of the duct system is external to the gland. During adaptation to salt water the duct system increases in size as does the gland. Although the components of the gland of adapted ducks, including the duct system within the gland, increase in size compared with normal ducks, the percentage volume densities of the components remain similar in both categories of ducks, i.e. the duct system increases in size in proportion to the glandular tissue. The volume of the duct system external to the gland is six to seven times larger than the volume within the gland. Thus, if ductal modification of secreted fluid occurs, it will be most likely to take place in the ducts external to the gland. Total surface areas of the duct system were measured from serial sections of glands and ducts from one normal and one adapted duck. These were used to calculate possible flux rates of water and sodium across the duct epithelium, assuming the occurrence of either water reabsorption of sodium secretion. Although these flux rates are high it is shown that they are similar to calculated flux rates across the luminal surface of the secretory tubules.


Awareness during general anesthesia: analysis of contributing causes aided by automatic data capture.
The cause of the awareness under general anesthesia often cannot be definitely determined from retrospective reviews of handwritten records, examinations of equipment, or interviews with clinicians. Failure to deliver the intended concentrations of anesthetic agents to the patient is one possible contributing cause for awareness. An advantage of an automated Anesthesia Information Management System (AIMS) is its ability to electronically capture and preserve case data that might otherwise be lost. We reviewed the AIMS records of 3 anesthetics in which intraoperative awareness was felt to have probably occurred. The details of the reported awareness event were temporally correlated with the anesthetic gas concentrations in an effort to determine if low concentrations were contributing factors. The data captured by the AIMS revealed low levels of inspired or expired inhalation agents during the intervals correlating with apparent patient recall. The findings suggest that failure to deliver sufficient concentrations of anesthetic gases permitted awareness events in these cases. Thus data from automated anesthesia information management in the operating room may help identify causes of awareness, and means to prevent awareness can be instituted.


Influence of Trapezoidal Cavity on the Wettability of Hydrophobic Surface: A Molecular Dynamics Study.
In this study, the behaviors of water droplets on hydrophobic surfaces with different cavities are studied by molecular dynamics. Hydrophobic surfaces with different cavities are designed and simulated: trapezoidal cavity with the same lower width, upside down trapezoidal cavity with the same lower width, and so on. The results show that the influence of the upper width and the depth of the cavity on the contact state and contact angle is different for different trapezoidal cavities. For example, for the trapezoidal cavity with the same lower width, the upper width decreases with the increase of the cavity depth. In such a scenario, the upper width and depth of the cavity collectively promote the droplet transition into the Cassie state from the Wenzel state, but the effect of the upper width and depth on the contact angle is opposite, and the decrease of the upper width of the cavity is the dominant factor, which leads to a decrease in the contact angle. Then, we have built trapezoidal cavities with different base angles. The influence of different base angles on wettability is also discussed, and it is found that an increase in base angle can significantly delay the transition from Cassie state into the Wenzel state.


A simple cell for the analysis of nanoelectromechanical systems under gas pressure.
A simple yet versatile apparatus for optical microscopy investigations of solid-state devices under high gas pressures is presented. Interchangeable high-grade sapphire windows with different thicknesses allow variable choice of trade-off between the maximum operating pressure and maximum spatial resolution. The capabilities of this compact chamber were tested by performing stroboscopic optical interferometry on nanoelectromechanical systems (NEMSs) under capacitive excitation. With a 1.7 mm thick sapphire window, the cell is safe to operate at pressures ranging from vacuum to 5 MPa. Minimal optical wavefront distortion allows NEMSs with linear dimensions of 0.1x1.6 microm(2) to be explored. For a sapphire window with a maximum thickness of 6 mm, the safe operating pressure increases up to an estimated 60 MPa; however, the increasing distortions inhibit signal from NEMSs smaller than approximately 0.5x1 microm(2). The cell can be used for confocal microscopy, microphotoluminescence and electroluminescence, light scattering spectroscopy, and reflectivity. The light weight and compact design of the chamber allow mounting on a precision piezomotion control stage or inside a volume tight apparatus such as cryostats.


Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin as a single injection for Pasteurellaceae respiratory infections in cattle using population pharmacokinetics and Monte Carlo simulations.
Population pharmacokinetic of marbofloxacin was investigated with 52 plasma concentration-time profiles obtained after intramuscular administration of Forcyl® in cattle. Animal's status, pre-ruminant, ruminant, or dairy cow, was retained as a relevant covariate for clearance. Monte Carlo simulations were performed using a stratification by status, and 1000 virtual disposition curves were generated in each bovine subpopulation for the recommended dosage regimen of 10 mg/kg as a single injection. The probability of target attainment (PTA) of pharmacokinetic/pharmacodynamic (PK/PD) ratios associated with clinical efficacy and prevention of resistance was determined in each simulated subpopulation. The cumulative fraction of response (CFR) of animals achieving a PK/PD ratio predictive of positive clinical outcome was then calculated for the simulated dosage regimen, taking into account the minimum inhibitory concentration (MIC) distribution of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni. When considering a ratio of AUC0-24 hr /MIC (area under the curve/minimum inhibitory concentration) greater than 125 hr, CFRs ranging from 85% to 100% against the three Pasteurellaceae in each bovine subpopulation were achieved. The PTA of the PK/PD threshold reflecting the prevention of resistances was greater than 90% up to MPC (mutant prevention concentration) values of 1 μg/ml in pre-ruminants and ruminants and 0.5 μg/ml in dairy cows.


[Expression of CD56, as a potential diagnostic marker, in small cell carcinoma].
Small cell carcinoma is a rare malignant disease with high mortality, which is pathologically diagnosed by using routine neuroendocrinal markers, such as neuron-specific enolase (NSE), synaptophysin (SYN), chromogranin A (CgA). This study was to investigate the expression of CD56, a neural cell adhesion molecule (NCAM), in small cell carcinoma tissues, and to explore the possibility of CD56 as a diagnostic marker of small cell carcinoma. Eighty samples of small cell carcinoma were collected, including 42 samples of small cell lung carcinoma (with 20 cases of lymph node metastases), 21 samples of small cell esophageal carcinoma, and 17 samples of small cell colorectal carcinoma. Thirty-eight samples of non-small cell lung cancer (with 28 cases of lymph node metastases), including 26 samples of squamous cell carcinoma and 12 samples of adenocarcinoma, were used as control. All samples were detected using markers of CD56, NSE, SYN, CgA, cytokeratin (CK), and epithelial membrane antigen (EMA) immunohistochemically. Positive rate of CD56 was significantly higher in either small cell lung carcinoma or their metastatic lymph nodes than in either non-small cell lung carcinoma or their metastatic lymph nodes [90.5% (38/42) vs. 7.8% (3/38), 90.0% (18/20) vs. 3.5% (1/28); H=85.731, P<0.001]. Positive rate of CD56 in small cell carcinoma samples (86.3%, 69/80) were significantly higher than those of SYN (78.8%, 63/80), CgA (73.8%, 59/80), EMA (66.3%, 53/80), CK (61.3%, 49/80), and NSE (56.3%, 45/80) (H=38.871, P<0.001). Positive rate of CD56 in small cell lung carcinoma (90.5%, 38/42) was similar to those in small cell esophageal carcinoma (81.0%, 17/21) and small cell colorectal carcinoma (82.4%, 14/17) (H=1.651, P=0.438). CD56 is highly expressed in either small cell carcinoma or their metastatic lymph nodes without organ-specificity. It could serve as a potential diagnostic marker of small cell carcinoma.


Reproductive genetic testing from an international perspective: impact on women in underdeveloped countries.
The impact of reproductive genetic testing (preconceptional and prenatal screening for genetic diseases) on women in the third world must take into account the many aspects that characterize underdevelopment: poverty; little access to education; housing; adequate nutrition; health services, and other. In these countries women usually suffer from male domination in a number of aspects of their lives, including reproduction. Illiteracy is high, particularly among women. Infant mortality and fertility rates are high, and the primary causes of death are infectious diseases and malnutrition. Health services are poorly organized, and family planning and prenatal care programs are deficient. Although abortions are illegal, they outnumber live births 3:1. Maternal mortality is 10-100 times higher than in industrialized nations, and complications of illegal abortions are one of its main causes. This description applies to the majority of the population and contrasts with that of the small segment of well-to-do upper classes, who have access to education, housing and health services that include family planning, prenatal care and reproductive genetic testing. By and large, all main cities count with clinical genetic centers. The illegality of abortion, however, makes prenatal testing in the public sector a difficult task, while in the private sector quality control is an unheard concept and the patients frequently fall victims of the entrepreneurial and commercial goals of the providers. For the majority of the population, the impact of reproductive genetic testing is almost nil, simply because the services are not available.(ABSTRACT TRUNCATED AT 250 WORDS)


Staphylococcus aureus Bacteraemia presenting as Sternoclavicular Arthritis.
Two brief patients' histories are presented to increase clinicians' awareness of the possible presentation of staphylococcus aureus bacteraemia as a metastatic infection of the sternal joints, without endocarditis and possibly without fever or a potential portal of entry. Referred shoulder pain often mimics a benign, chronic shoulder condition, with dangerous diagnostic delays. However, common point-tenderness over the sternoclavicular joint, and increased WBC and C-reactive protein will suggest the correct diagnosis to the practitioner, confirmed by CT imaging, even before results of blood cultures are received.


Formaldehyde fixation contributes to detoxification for growth of a nonmethylotroph, Burkholderia cepacia TM1, on vanillic acid.
During bacterial degradation of methoxylated lignin monomers, such as vanillin and vanillic acid, formaldehyde is released through the reaction catalyzed by vanillic acid demethylase. When Burkholderia cepacia TM1 was grown on vanillin or vanillic acid as the sole carbon source, the enzymes 3-hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI) were induced. These enzymes were also expressed during growth on Luria-Bertani medium containing formaldehyde. To understand the roles of these enzymes, the hps and phi genes from a methylotrophic bacterium, Methylomonas aminofaciens 77a, were introduced into B. cepacia TM1. The transformant strain constitutively expressed the genes for HPS and PHI, and these activities were two- or threefold higher than the activities in the wild strain. Incorporation of [14C]formaldehyde into the cell constituents was increased by overexpression of the genes. Furthermore, the degradation of vanillic acid and the growth yield were significantly improved at a high concentration of vanillic acid (60 mM) in the transformant strain. These results suggest that HPS and PHI play significant roles in the detoxification and assimilation of formaldehyde. This is the first report that enhancement of the HPS/PHI pathway could improve the degradation of vanillic acid in nonmethylotrophic bacteria.


Trends in prostate cancer incidence and mortality in Canada during the era of prostate-specific antigen screening.
Widespread use of prostate-specific antigen (PSA) to screen for prostate cancer began in the early 1990s. Advocates for screening assert that this has caused a decrease in prostate cancer mortality. We sought to describe secular changes in prostate cancer incidence and mortality in Canada in relation to the onset of PSA screening. Age-standardized and age-specific prostate cancer incidence (1969-2007) and mortality (1969-2009) from Public Health Agency of Canada databases were analyzed by joinpoint regression. Changes in incidence and mortality were related to introduction of PSA screening. Prior to PSA screening, prostate cancer incidence increased from 54.2 to 99.8 per 100 000 between 1969 and 1990. Thereafter, incidence increased sharply (12.8% per year) to peak at 140.8/100 000 in 1993. After decreasing in all age groups between 1993 and 1996, incidence continued to increase for men aged less than 70 years, but decreased for older men. Age-standardized mortality was stable from 1969 to 1977, increased 1.4% per year to peak in 1995 and subsequently decreased at 3.3% per year; the decline started from 1987 in younger men (age < 60 yr). Incidence was increasing before PSA screening occurred, but rose further after it was introduced. Reductions in prostate cancer mortality began before PSA screening was widely used and were larger than could be anticipated from screening alone. These findings suggest that screening caused artifactual increase in incidence, but no more than a part of reductions in prostate cancer mortality. The reduction may be due to changing treatment or certification of death.


[Erectile dysfunction among Norwegian men over 40 years of age].
Erectile dysfunction (ED) is prevalent and often associated with chronic diseases and previous operations on the prostate. Our aims were to investigate the prevalence of ED among males seeking general practitioners and to register known risk factors. During a short period in late 1998, 49 Norwegian general practitioners in the county of Østfold asked all their male patients over 40 years of age to anonymously fill in a questionnaire. 1,182 men completed the study. 20% stated that they had moderate ED, while 13% had complete ED. The prevalence of ED increased with age. Complete ED was found in 2% of those between 40 and 50, 5% between 50 and 60, 16% between 60 and 70, and in 37% of those above 70 years of age. The corresponding values for moderate ED was 6, 16, 32 and 28%. Moderate/complete ED was increased in the subgroups with hypertension, depression, diabetes, > one concomitant disease, and post prostate surgery. Physically "very active" individuals had less ED than the "non-active". No significant association was found with alcohol or tobacco. Most patients with ED wanted to discuss the problem with their general practitioners, but only 6% received treatment.


Imaging of tuberous sclerosis complex: a pictorial review.
Tuberous sclerosis complex (TSC) is a genetically determined hamartomatous neurocutaneous disease with high phenotypic variability. TSC is characterized by widespread hamartomas and benign, or rarely malignant, neoplasms distributed in several organs throughout the body, especially in the brain, skin, retina, kidney, heart, and lung. Common manifestations include cortical tubers, subependymal nodules, white matter abnormalities, retinal abnormalities, cardiac rhabdomyoma, lymphangioleiomyomatosis, renal angiomyolipoma, and skin lesions. The wide range of organs affected by the disease implies that TSC1 and TSC2 genes play important roles in the regulation of cell proliferation and differentiation. Although recent advances in treatment have improved morbidity, the prognosis remains quite poor and nearly 40% of patients die by the age of 35 years. Imaging is important in the evaluation of TSC because of its role not only in presumptive diagnosis, but also in defining the full extent of involvement. This information allows a better understanding of the behavioural phenotype, as related to lesion location. Imaging also contributes to treatment planning. This pictorial review describes common and uncommon imaging manifestations of TSC.


mVisualizer: Easily Accessible Data Exploration for Clinicians.
In medical research and clinical work, having direct access to a large knowledge base of information about patients is very useful. Software for information visualisation can help the user browse, analyse and learn from such knowledge, thus providing new insights and accelerating research. However, when introducing new software to clinicians, who may have limited computer knowledge, adoption can be hindered by the complexity of the applications and the time investments necessary to learn them. By involving clinicians directly in the design process, we have developed mVisualizer, an application that provides a hands-on workspace to visualise and explore patient data. mVisualizer was designed for accessibility and simplicity, and to encourage users to explore the data in order to make discoveries and pose new questions relevant for knowledge gathering and research. The user-centered approach helped ensure that mVisualizer is understandable and easy to learn for clinicians. The application is in use by clinicians today, and its use has led to new discoveries and theories that will be the subject of future medical research. This leads to the conclusion that information visualisation software for exploring patient data can help clinicians and researchers by making the data more accessible, which stimulates research and learning.


Neural cell adhesion molecule-associated polysialic acid inhibits NR2B-containing N-methyl-D-aspartate receptors and prevents glutamate-induced cell death.
The neural cell adhesion molecule (NCAM) and its associated glycan polysialic acid play important roles in the development of the nervous system and N-methyl-D-aspartate(NMDA)receptor-dependent synaptic plasticity in the adult. Here, we investigated the influence of polysialic acid on NMDA receptor activity. We found that glutamate-elicited NMDA receptor currents in cultured hippocampal neurons were reduced by approximately 30% with the application of polysialic acid or polysialylated NCAM but not by the sialic acid monomer, chondroitin sulfate, or non-polysialylated NCAM. Polysialic acid inhibited NMDA receptor currents elicited by 3 microm glutamate but not by 30 microm glutamate, suggesting that polysialic acid acts as a competitive antagonist, possibly at the glutamate binding site. The polysialic acid induced effects were mimicked and fully occluded by the NR2B subunit specific antagonist, ifenprodil. Recordings from single synaptosomal NMDA receptors reconstituted in lipid bilayers revealed that polysialic acid reduced open probability but not the conductance of NR2B-containing NMDA receptors in a polysialic acid and glutamate concentration-dependent manner. The activity of single NR2B-lacking synaptosomal NMDA receptors was not affected by polysialic acid. Application of polysialic acid to hippocampal cultures reduced excitotoxic cell death induced by low micromolar concentration of glutamate via activation of NR2B-containing NMDA receptors, whereas enzymatic removal of polysialic acid resulted in increased cell death that occluded glutamate-induced excitotoxicity. These observations indicate that the cell adhesion molecule-associated glycan polysialic acid is able to prevent excitotoxicity via inhibition of NR2B subunit-containing NMDA receptors.


Macroporous polymer from core-shell particle-stabilized Pickering emulsions.
Poly(styrene-co-N-isopropylacrylamide) (PS-co-PNIPAM) core-shell particles were synthesized and used as particulate emulsifiers in the preparation of particle-stabilized (Pickering) emulsions. Highly concentrated oil-in-water emulsions with an internal phase up to 80 vol % can be produced using PS-co-PNIPAM core-shell particles along as the emulsifiers in emulsions. The core-shell particles are adsorbed at the liquid interface, acting as a barrier against oil droplet coalescence. In addition, it is likely that excess particles simultaneously form a gel in the continuous phase to trap oil droplets in the gel matrix, in turn inhibiting creaming and phase inversion. Evaporation in air of such a core-shell particle-stabilized emulsion directly leads to porous membranes in the absence of chemical reactions. The pore walls of the final structures are densely packed with layers of the core-shell particles. This provides great flexibility to prepare functionalized porous materials for opening up new applications.


Genomic islands of Pseudomonas aeruginosa.
Key to Pseudomonas aeruginosa's ability to thrive in a diversity of niches is the presence of numerous genomic islands that confer adaptive traits upon individual strains. We reasoned that P. aeruginosa strains capable of surviving in the harsh environments of multiple hosts would therefore represent rich sources of genomic islands. To this end, we identified a strain, PSE9, that was virulent in both animals and plants. Subtractive hybridization was used to compare the genome of PSE9 with the less virulent strain PAO1. Nine genomic islands were identified in PSE9 that were absent in PAO1; seven of these had not been described previously. One of these seven islands, designated P. aeruginosa genomic island (PAGI)-5, has already been shown to carry numerous interesting ORFs, including several required for virulence in mammals. Here we describe the remaining six genomic islands, PAGI-6, -7, -8, -9, -10, and -11, which include a prophage element and two Rhs elements.


Anti-proliferative and cytotoxic effects of Strychnos nux-vomica root extract on human multiple myeloma cell line - RPMI 8226.
Multiple myeloma (MM) is an incurable hematological malignancy with high incidence in the elderly. The currently used chemotherapeutic drugs show severe side effects, dose-limiting toxicity and development of resistance. In search of novel plant derived anti-cancer agents, Strychnos nux-vomica L. (SN) root extract was screened using the human MM-cell line, RPMI 8226. SN-extract exhibited anti-proliferative activity in a dose and time dependent manner. The morphological assessment of SN-extract treated cells showed significant features associated with apoptosis. Cell cycle analysis using flow cytometry of cells stained with propidium iodide revealed accumulation of cells at sub-G(0)/G(1) phase. In addition, disruption of mitochondrial membrane potential and subsequent leakage of mitochondrial cytochrome c was observed in SN-extract treated myeloma cells. The anti-proliferative and cytotoxic activity could be due to the alkaloids strychnine and brucine, which have been identified by LC-mass spectral analysis of the SN-extract in comparison to the reference standards analyzed under identical conditions.


Novel isoform of insulin receptor substrate p53/p58 is generated by alternative splicing in the CRIB/SH3-binding region.
Insulin receptor substrate p53/p58 (IRSp53) is involved in cytoskeletal dynamics and is a candidate disease sensor in polyglutamine expansion neurodegeneration. It is widely expressed throughout the body, but its levels are dramatically elevated in forebrain regions. IRSp53 functions as a signal transducing adaptor between activated Rho family GTPases and their effectors. There are four known alternatively spliced isoforms of IRSp53 that vary by the identity of the 3'-terminal exon. We report here that there is a fifth alternatively spliced isoform, IRSp53-B, which lacks 40 amino acids abutting the CRIB/SH3 (Cdc42/Rac-interactive binding/Src homology 3)-binding site. We speculate that the novel form has an altered function related to the mechanism of autoinactivation. IRSp53-B has an odd history in the mammalian lineage, which may complicate the use of rodent models to study cytoskeletal reorganization.


[Assessing quality of life in Parkinson's disease using the PDQ-39. A pilot study].
The aim of this pilot study was to analyze an adaptation of the PDQ-39, a Parkinson's disease (PD) quality of life questionnaire, for use in Spanish. Fifty patients were enrolled. Patient characteristics and medical histories were recorded, including scores on the following scales: Hoehn and Yahr (HY), PD unified (UPDRS), Schwab and England (SE), Intermediate Scale for Assessment of PD (ISAPD). Barthel Index (BI), Pfeiffer's SPMSQ, Global Deterioration Scale (GDS), Geriatric Depression Scale (GDS). Hospital Depression and Anxiety Scale (HDA) and the PDQ-39. Descríptive statistics were recorded, as well as Spearman's r and ANOVA results. The dimensions that correlated well with PD scale scores were mobility, daily life activities and cognitive deterioration. The dimension stigma correlated with complications on the UPDRS and the ISAPD. Emotional well-being correlated with subscale I of the UPDRS, the GDS and the HDA (r = 0.39-0.79, p < 0.01-0.001). Physical discomfort correlated only with depression and anxiety. Stage of disease and level of depression influenced most dimensions assessed by the PDQ-39. Some psychosocial factors that are important components of well-being are scarcely reflected by the clinical scales usually applied.


Response to change is facilitated by a three-neuron disinhibitory pathway in the tiger salamander retina.
Most retinal ganglion cells respond only transiently, for approximately 150 msec at the onset and termination of a light flash. The responses are transient because it has been shown that bipolar-to-ganglion cell transmission is truncated after 150 msec by a feedback inhibition to bipolar cell terminals. The feedback inhibition itself must be delayed by approximately 150 msec to allow the initial bipolar-ganglion cell transmission. This study identifies a three-component serial synaptic pathway from glycinergic amacrine cells to GABAergic amacrine cells to bipolar cell terminals as one source of this delay. We used perforated and whole-cell patch-clamp recordings to measure the timing of light responses in amacrine, bipolar, and ganglion cells under control and glycine and GABA receptor-blocked conditions. Our results suggest that, after a light flash, a population of glycinergic amacrine cells responds first, inhibiting a population of GABAergic amacrine cells for approximately 150 msec. The GABAergic amacrine cells feed back to bipolar terminals, but only after the 150 msec delay, allowing the bipolar terminals to excite ganglion cells for the first 150 msec. Blocking the glycinergic amacrine cell activity with strychnine allows the GABAergic system to become active earlier. GABAergic amacrine cells then inhibit release from bipolar cells earlier. Under these conditions, the ganglion cell response to change would be decreased.


Dynamic cleft maxillary orthopedics and periosteoplasty: benefit or detriment?
In 1990, Drs Millard and Latham published their initial experience with dynamic maxillary appliances (DMAs) and periosteoplasty for children with cleft lip and palate. The technique provided for alveolar alignment and consolidation, with elimination of oronasal fistulas. Opponents to this approach speculated about impairments to facial growth. To date no longitudinal studies have been published. Over the last 10 years, 35 unilateral and 10 bilateral complete clefts have been treated with this technique. All patients have been followed and documented clinically, orthodontically, and radiographically. Cephalometric analyses were performed on children after the age of 6 years. The children have excellent facial aesthetics with well-balanced lips and noses. Radiographs demonstrate bone within the repaired alveolar clefts. Articulated impressions show anterior and lateral crossbites in the unilateral patients that improve over time and appear to be correctable orthodontically. The bilateral patients have satisfactory occlusions and arch forms. Cephalometric analyses confirmed no evidence of skeletal crossbites or midfacial growth retardation. This is a work in progress that will continue as the children grow. Although definite and final conclusions would be premature, it can be stated that to date all patients are following consistent and favorable growth patterns. Our team is confident in proceeding with this technique.


Chlamydomonas-Methylobacterium oryzae cooperation leads to increased biomass, nitrogen removal and hydrogen production.
In the context of algal wastewater bioremediation, this study has identified a novel consortium formed by the bacterium Methylobacterium oryzae and the microalga Chlamydomonas reinhardtii that greatly increase biomass generation (1.22 g L-1·d-1), inorganic nitrogen removal (>99%), and hydrogen production (33 mL·L-1) when incubated in media containing ethanol and methanol. The key metabolic aspect of this relationship relied on the bacterial oxidation of ethanol to acetate, which supported heterotrophic algal growth. However, in the bacterial monocultures the acetate accumulation inhibited bacterial growth. Moreover, in the absence of methanol, ethanol was an unsuitable carbon source and its incomplete oxidation to acetaldehyde had a toxic effect on both the alga and the bacterium. In cocultures, both alcohols were used as carbon sources by the bacteria, the inhibitory effects were overcome and both microorganisms mutually benefited. Potential biotechnological applications in wastewater treatment, biomass generation and hydrogen production are discussed.


Disorder of Selfhood in Schizophrenia: A Symptom or a Gestalt?
The concept of schizophrenia (SCZ) was originally associated with a disorder of formal strata of the self. During the last two decades, empirical studies have demonstrated a selective hyper-aggregation of self-disorders in the SCZ spectrum. As with other scientific research areas, the role of self-disturbances in SCZ has been up for debate in various disciplines including cognitive sciences, philosophy of mind, and psychopathology. Several philosophical papers have used the psychopathological phenomena of "thought insertion" as an alleged example of a complete loss of minimal selfhood. In the field of psychopathology, it has been claimed that self-disorders may comprise a transdiagnostic phenotype. Common to these approaches is the underlying assumption that self-disorders reflect well-delineated and isolated symptoms akin to the notion of symptom in the medical model. The aim of this paper was to argue that the clinical manifestation of self-disturbances is to be seen as aspects of a Gestalt of disturbed experiential selfhood. Seven videotaped interviews of patients with SCZ who were emblematic of very diverse symptomatological constellations were selected and jointly watched and discussed by the authors, who reached a consensus assessment. The interviews were semi-structured and narrative in nature in order to obtain faithful self-descriptions according to the standards of phenomenologically oriented interviews. For the purpose of this article, we chose 4 videos from which excerpts were verbatim transcribed and translated from Danish into English. The patients describe unique combinations of various psychopathological phenomena such as diminished sense of embodied self-presence, loss of ego boundaries, diminished sense of self, alienation and objectification of the experiential processes, mirror-phenomena, and Schneiderian passivity phenomena. Through an interweaving of the four vignettes and their subsequent psychopathological discussions, we argue that the invariant commonality across the different symptomatic expressions in these patients resides in a Gestalt of pervasive disturbance of self-experience. From a phenomenological perspective, these self-disturbances target a basic structure of phenomenal consciousness, namely, the first-person givenness of experience. We conclude that self-disorders reflect a trait-instability in the most basic structures of consciousness in SCZ and that its clinical manifestations are to be seen as aspects of a particular Gestalt rather than appearing as separate and well-delineated symptoms.


Prevalence of arsenic-related skin lesions in 53 widely-scattered villages of Bangladesh: an ecological survey.
A survey was carried out to provide a representative assessment of prevalence and risk of arsenic-related skin lesions in relation to geographical distribution of arsenic in wells of rural Bangladesh as a necessary background for research into effects in pregnancy and cancer risks. A systematic random sample of 53 villages in four divisions of Bangladesh served by Gonoshasthaya Kendra was selected, and all women aged 18 years or more (n=16,740) were listed. Trained paramedics recorded the presence of skin thickening and nodules on the palms and soles, together with information on tubewell use. The prevalence was related to the mean concentration of arsenic for the district as indicated by data from the British Geological Survey and to the date the first well in the village was installed. Overall, the observed prevalence was 176 cases (1.3%) in 13,705 women examined, varying from 0% in 26 villages to 23% in one; lesions were observed more frequently on hands than on feet. The estimate doubled with concentrations of arsenic from 11 to < or =50 microg/L and increased more than 20 times at >50 microg/L. In the absence of further information, priority for control measures should be directed at areas where the average concentrations of arsenic are above 50 microg/L, especially in villages where skin lesions have been identified.


Vanadium procatalysts bearing chelating aryloxides: structure-activity trends in ethylene polymerisation.
High-valent vanadium complexes bearing a variety of chelating aryloxides including di- and linear tri-phenolates, C/N-capped tripods, phenoxyimines and calixarenes type ligands, when used in combination with dialkylaluminium halides as co-catalyst and a reactivator, are found to act as highly active catalytic systems for alpha-olefin polymerisation. Pro-catalyst structure-catalytic activity trends can be identified for the various ligand families employed.


New N(3)S donor ligand small peptide analogues of the N-mercaptoacetyl-glycylglycylglycine ligand in the clinically used Tc-99m renal imaging agent: evidence for unusual amide oxygen coordination by two new ligands.
Three new X-ray structurally characterized Re(V)O complexes, ReO(MEG(3)H(2)) (10), ReClO(MAEG(2)H(3)) (11), and [ReO(MECG(2)H(2))](2) (12), were prepared from protected forms of three new ligands, mercaptoethyl-glycylglycylglycine (MEG(3)H(5)), mercaptoacetamide-ethyl-glycylglycine (MAEG(2)H(5)), and mercaptoethyl-carbamoylmethyl-glycylglycine (MECG(2)H(5)). (Subscript on H indicates the number of dissociable protons.) Mercaptoacetyltriglycine (MAG(3)H(5)) is the ligand precursor for the clinically used Tc-99m renal imaging agent. The new potentially N(3)S donor ligands have a glycylglycine carboxyl end as in MAG(3)H(5), but a secondary amine (sp(3) N) replaces one amide (sp(2) N) of MAG(3)H(5). ReO(MEG(3)H(2)) (10) is a typical five-coordinate pseudo-square-pyramidal complex with the oxo ligand at the apex and the trianionic form of MEG(3)H(5) coordinated in the basal plane via N(3)S. In the other complexes, the quadridentate ligand has N(2)OS ligation, with the carbonyl oxygen of the glycyl amide group coordinated trans to the oxo ligand. This unusual ligation mode, which is facilitated by the preferred endo configuration of the ligated glycyl sp(3) N, leaves a vacant basal coordination site. In 11, the chloro ligand completes the equatorial plane, whereas, in 12, a glycine carboxylate oxygen of the ligand on the partner Re completes the equatorial plane. Both complexes thus possess an unexpected pseudo-octahedral geometry. For 10, 11, and 12, the (1)H NMR spectra, monitored from high to low pH, exhibited changes only when the pH was lowered below 6. This finding indicates that at physiological pH these complexes possess the desirable characteristic of existing as one monomeric species having only one ionization state, with the coordinated sp(3) N deprotonated. Below pH 6 and above pH approximately 4, changes in the (1)H NMR shifts indicate that this sp(3) N has become protonated. Thus, the N(3)S ligands in all three complexes exhibit normal coordination above pH approximately 4. However, X-ray data for 11 and 12 and some NMR evidence for 11 indicate that the ligands of the two complexes rearrange at low pH (<3). The striking differences between the solution- and solid-state structures reinforce the caveat that solution structural studies conducted at physiological pH are necessary in order to gain insight into the nature of radiopharmaceuticals.


Nasal and sinus pain: current diagnosis and treatment.
Intranasal and sinus disease may result in disabling head and facial pain and serious complications. Awareness of the symptoms of acute and chronic sinusitis and their various presentations will enhance diagnostic accuracy and improve patient outcome. It is important to remember that the nasal mucosa is under autonomic control. Sinus symptomatology, whether from anatomic abnormality or chronic inflammation, may occur with and will typically be exacerbated by increased parasympathetic outflow or reduced sympathetic tone. Thus, the possibility of underlying intranasal or sinus disease must be considered in patients with atypical migraine or vascular instability headaches. A new appreciation of the impact of sinusitis on facial and head pain syndromes is developing among otolaryngologists because of the improved diagnostic capabilities afforded by combined intranasal endoscopy and modified CT. In the past, patients with nasal complaints and facial pain who had normal plain radiographs were often passed off as "chronic nasal complainers" and given decongestants or the recommendation to see a psychiatrist. On the other hand, patients with symptoms and radiologic abnormalities often underwent radical surgery aimed at the maxillary or frontal sinus, sometimes with persistence or worsening of their complaints. Now, however, underlying causes for these problems can often be found in the ostiomeatal complex and corrected with minimally invasive surgery. In general, the major sinuses appear to be more sensitive to pain before the development of chronic mucosal changes. Minor disease in critical locations within the ostiomeatal complex may therefore give rise to greater symptomatology than diffuse disease in less critical sites. Although head CT may be a routine part of the neurologist's examination in patients with headache or facial pain, routine CT techniques are inadequate to evaluate fully the ostiomeatal complex and sinuses and must be modified to rule out adequately pain of sinus origin. Nasal endoscopic examination provides a noninvasive examination by which patients may be selected for sinus CT and is a necessary part of a complete evaluation. Close cooperation between the neurologist and otolaryngologist-head and neck surgeon is therefore essential for the accurate diagnosis of this often puzzling group of patients.


Magnetic-optical nanohybrids for targeted detection, separation, and photothermal ablation of drug-resistant pathogens.
A rapid, sensitive and quantitative immunoassay for the targeted detection and decontamination of E. coli based on Fe3O4 magnetic nanoparticles (MNPs) and plasmonic popcorn-shaped gold nanostructure attached single-walled carbon nanotubes (AuNP@SWCNT) is presented. The MNPs were synthesized as the support for a monoclonal antibody (mAb@MNP). E. coli (49979) was captured and rapidly preconcentrated from the sample with the mAb@MNP, followed by binding with Raman-tagged concanavalin A-AuNP@SWCNTs (Con A-AuNP@SWCNTs) as detector nanoprobes. A Raman tag 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) generated a Raman signal upon 670 nm laser excitation enabling the detection and quantification of E. coli concentration with a limit of detection of 10(2) CFU mL(-1) and a linear logarithmic response range of 1.0 × 10(2) to 1.0 × 10(7) CFU mL(-1). The mAb@MNP could remove more than 98% of E. coli (initial concentration of 1.3 × 10(4) CFU mL(-1)) from water. The potential of the immunoassay to detect E. coli bacteria in real water samples was investigated and the results were compared with the experimental results from the classical count method. There was no statistically significant difference between the two methods (p > 0.05). Furthermore, the MNP/AuNP@SWCNT hybrid system exhibits an enhanced photothermal killing effect. The sandwich-like immunoassay possesses potential for rapid bioanalysis and the simultaneous biosensing of multiple pathogenic agents.


The nurse endoscopist: reality or fiction?
In this article, the author describes a study conducted to determine whether advanced practice registered nurses (APRNs) should perform endoscopic procedures, such as colonoscopy and esophagogastroduodenoscopy. Questionnaires were mailed to APRNs belonging to the Society of Gastroenterology Nurses and Associates. Questionnaire items pertained to demographics, current activities, interest in performing GI endoscopic procedures, and barriers to performing GI endoscopic procedures. Over 70% of respondents approved of nurses performing diagnostic endoscopic procedures, yet 80.6% did not think that nurses should perform therapeutic endoscopic procedures. Training opportunities were limited. The barriers to performing endoscopic procedures included liability, third-party reimbursement, lack of physician support, lack of policies, and lack of education. APRNs should develop policies and establish acceptable training guidelines and competency rates in performing GI endoscopic procedures.


Estimation of frontal-plane cardiac vectors in heart disease.
Frontal-plane vector angle and magnitude values were clinically estimated in 100 patients with cardiac disease. Maximal deviations from isopotential in standard limb leads I and II were summed and mathematically transformed into estimated vector magnitudes (mV) and estimated angles (degrees). These values were then compared against reference vectors (previously shown to be excellent standards) defined from the same QRS complexes. The estimated magnitude values reached a degree of accuracy of +/- .25 mV in 78% of the cases, and the estimated angle values reached a degree of accuracy of +/- 15 degrees in 80% of the cases. The lowest estimate errors occurred in the infarct group, whereas the largest errors occurred in the chamber-enlargement and axis-deviation groups.


Clam ileoplasty bladder augmentation and renal transplantation.
In our patient, with a small contacted bladder and end stage renal failure, bladder augmentation (clam ileocystoplasty) was done in conjunction with renal transplantation. Our patient has stable renal and bladder function 46 months after kidney transplantation.


Rhodosporidium toruloides - A potential red yeast chassis for lipids and beyond.
The red yeast Rhodosporidium toruloides naturally produces microbial lipids and carotenoids. In the past decade or so, many studies demonstrated R. toruloides as a promising platform for lipid production owing to its diverse substrate appetites, robust stress resistance and other favorable features. Also, significant progresses have been made in genome sequencing, multi-omic analysis and genome-scale modeling, thus illuminating the molecular basis behind its physiology, metabolism and response to environmental stresses. At the same time, genetic parts and tools are continuously being developed to manipulate this distinctive organism. Engineered R. toruloides strains are emerging for enhanced production of conventional lipids, functional lipids as well as other interesting metabolites. This review updates those progresses and highlights future directions for advanced biotechnological applications.


Globularia alypum aqueous extract decreases hypertriglyceridemia and ameliorates oxidative status of the muscle, kidney, and heart in rats fed a high-fructose diet.
Fructose is widely used as a food ingredient and has potential to increase oxidative stress. Moreover, the beneficial health effects of plant polyphenols are frequently attributed to their potent antioxidant effects. We hypothesized that administration of Globularia alypum (Ga) aqueous extract would reduce metabolic disorders and oxidative stress induced in rats fed a high-fructose diet. Male Wistar rats (n = 24) weighing 242 ± 13 g were divided into 4 groups and fed, during 14 week, diets containing 20% casein and 61% cornstarch (control diet, or C) or fructose (F), and Ga supplementation (0.5%; CGa and FGa). Compared with control group, rats fed a high-fructose diet increased plasma triglycerides (TG; +48%) and very low-density lipoprotein-TG (+45%) levels. In addition, thiobarbituric acid reactive substances were increased in the liver (+31%), heart (+55%), and muscle (+58%). Moreover, activities of superoxide dismutase in the liver and heart, catalase in liver and glutathione peroxidase in the heart were diminished. In the FGa group, a hypertriglyceridemic effect was observed concomitantly with a low level of TG in very low-density lipoprotein and high-density lipoprotein 2, compared with the F group. Thiobarbituric acid reactive substance concentrations were reduced in the kidney (-42%)and muscle (-76%), and antioxidant enzymes activity was increased for superoxide dismutase in the muscle (+81%) and heart (+28%), and for glutathione peroxidase, in the kidney (+70%) and heart (+30%). In conclusion, the Ga extract has a beneficial effect on plasma TG and gives a promising perspective for hypertriglyceridemia treatment. Moreover, in the muscle and kidney, Ga is effective by lowering lipid peroxidation and improves antioxidant enzymes.


Ophthalmoplegia associated with lung adenocarcinoma in a patient with the Lambert-Eaton myasthenic syndrome: A case report.
The Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disease; its unique symptoms of LEMS include dry mouth with a metallic taste, constipation, and erectile dysfunction. As it is quite rare, isolated ocular muscle impairment associated with LEMS east to ignore. A 65-year-old man presented with alternating ptosis and diplopia. Isolated ocular muscle impairment had lasted for 6 years, and the patient was initially diagnosed with ocular myasthenia gravis (MG). Treatment with azathioprine only slightly improved symptoms over the first 2 months; long-term treatment was not effective. Dynamic observation of chest computed tomography images revealed a slowly progressing nodule in the lower lobe of the left lung. The subsequent pathologic examination following mass resection confirmed a diagnosis of lung adenocarcinoma. The patient was ultimately diagnosed with the Lambert-Eaton myasthenic syndrome associated with pulmonary adenocarcinoma. Resection of the lung tumor relieved all symptoms. Other causes of ocular MG symptoms should be considered when standard MG therapy is ineffective, especially the Lambert-Eaton myasthenic syndrome.


Prosthetic joint infection-a devastating complication of hemiarthroplasty for hip fracture.
Background and purpose - Hemiarthroplasty is the most common treatment in elderly patients with displaced femoral neck fracture. Prosthetic joint infection (PJI) is a feared complication. The infection rate varies in the literature, and there are limited descriptive data available. We investigated the characteristics and outcome of PJI following hemiarthroplasty over a 15-year period. Patients and methods - Patients with PJI were identified among 519 patients treated with hemiarthroplasty for a femoral neck fracture at Oslo University Hospital between 1998 and 2012. We used prospectively registered data from previous studies, and recorded additional data from the patients' charts when needed. Results - Of the 519 patients, we identified 37 patients (6%) with early PJI. 20 of these 37 patients became free of infection. Soft tissue debridement and retention of implant was performed in 35 patients, 15 of whom became free of infection with an intact arthroplasty. The 1-year mortality rate was 15/37. We found an association between 1-year mortality and treatment failure (p = 0.001). Staphylococcus aureus and polymicrobial infection were the most common microbiological findings, each accounting for 14 of the 37 infections. Enterococcus spp. was found in 9 infections, 8 of which were polymicrobial. There was an association between polymicrobial infection and treatment failure, and between polymicrobial infection and 1-year mortality. Interpretation - PJI following hemiarthroplasty due to femoral neck fracture is a devastating complication in the elderly. We found a high rate of polymicrobial PJIs frequently including Enterococcus spp, which is different from what is common in PJI after elective total hip arthroplasty.


Preincubation-dependent and long-lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug-drug interactions.
Preincubation with cyclosporin A (CsA), a potent inhibitor of organic anion transporting polypeptide 1B1 (OATP1B1) and OATP1B3, enhanced its inhibitory effects on these transporters in vitro. A similar effect was observed upon preincubation with some other inhibitors. Removing these from the incubation media did not readily reverse the inhibition on OATP1B1 and OATP1B3. This preincubation-dependent long-lasting inhibition appeared to be related to CsA concentration in the cells in addition to that in the incubation media. Thus, we hypothesized that CsA inhibits OATP1B1 and OATP1B3 from inside (trans-inhibition) as well as outside (cis-inhibition) the cells and constructed the cis- and trans-inhibition model. The enhanced inhibitory effect of CsA on OATP1B1 observed after preincubation was quantitatively described using Ki,out and Ki,in as inhibition constants for cis- and trans-inhibitions, respectively. In addition, a long-lasting inhibition was also described by this model. Additional factors taken into consideration when simulating in vivo pharmacokinetic alterations by CsA are potential inhibition by AM1, a major metabolite of CsA, which has been reported to inhibit OATP1B1 and OATP1B3. Based on the physiologically based pharmacokinetic model incorporating trans- and cis-inhibition of OATP1B1 by CsA, the simulation showed that OATP1B1-mediated drug-drug interaction with CsA was suggested to be time-dependent also in vivo although further clinical studies are required for confirmation.


[Alcoholic delirium--a potentially life-threatening condition].
Full-blown alcoholic delirium is characterised by the symptoms of an exogenous psychosis and signs of vegetative dysregulation. Organic brain disease may initiate its development. The pathogenesis of the condition remains hypothetical. Therapeutic drugs of first choice have long been clomethiazole and benzodiazepines. Basic sedative treatment may be usefully supplemented by highly potent neuroleptic agents. This, together with improvements in intensive medical care, has reduced the mortality rate to 3 to 8%. Concomitant organic diseases may complicate and prolong the condition. A defective state is a possible outcome.


Comparison of three competitive immunoassays for measurement of TSH receptor antibodies in patients with Graves' disease.
Thyrotropin (TSH) receptor antibodies (TRAb) mediate the hyperthyroidism of Graves' disease (GD). The aim of the study was to compare the diagnostic performance and assay agreement between three immunoassays for the measurement of TRAb in patients with newly diagnosed GD. TRAb was measured with three different assays [H-TRAb (BRAHMS Diagnostica), M22-Man (RSR Limited) and M22-Aut (Roche Diagnostics)] in 387 participants who were recruited from two Danish population-based studies and diagnosed with GD (n = 101), multinodular toxic goitre (n = 88), primary autoimmune hypothyroidism (n = 100) or included as controls (n = 98). Coefficient of variation for duplicate measurements with each of the three assays were H-TRAb: 3.6%, M22-Man: 9.4%, M22-Aut: 7.7%. Frequency of TRAb positivity in patients with GD were H-TRAb: 95%, M22-Man: 94%, M22-Aut: 96%. Receiver operating characteristic analysis revealed a high sensitivity (H-TRAb: 95%, M22-Man: 93%, M22-Aut: 95%) and specificity (H-TRAb: 99%, M22-Man: 99%, M22-Aut: 97%) for the diagnosis of GD with all assays. Comparison of TRAb levels showed inter-assay variability and values were considerably lower with the M22-Man assay. All TRAb assays showed a high diagnostic performance for GD, but a high inter-assay variability was observed limiting the use of different assays in clinical monitoring of patients with GD.


Morphological aspects of gastrointestinal tract invasion by Candida albicans in the infant mouse.
The infant mouse has proved to be a useful model for examination of various aspects of gastrointestinal and systemic candidosis. Oral-intragastric inoculation of 5-6-day-old mice with yeast of a virulent strain of Candida albicans (CA30) resulted in systemic spread within 30 min after challenge. Histological examinations of the gastrointestinal (GI) tract have shown that the highest frequency of invasion of the mucosa by yeast cells occurred in the region of the jejunum 1-3 h after inoculation. Results of ultrastructural examinations of sites where the fungus invaded the bowel wall suggested that C. albicans yeast cells are capable of progressive extracellular digestion of the intestinal mucus barrier and microvillus layer, followed by intracellular invasion of columnar epithelial cells. Minimal disruption of cytoplasmic contents of the host epithelial cells appears to result from invasion and transmigration of the pathogen. The infant mouse model is suggested to be well suited for localization of extracellular products of C. albicans yeast in vivo which may play pivotal roles in the invasion of host tissue during GI candidosis.


Short toxic methamphetamine schedule impairs object recognition task in male rats.
Performance on object recognition and object placement memory tasks was evaluated after a short-dosing model of methamphetamine (MA) regime and monoamines and metabolites were measured post-testing. Adult male rats received three injections of 10 mg/kg at 2-h intervals. In striatum DA and 5-HT were depleted by 65% and 79%, respectively, no significant changes were found in pre-frontal cortex, hippocampus, ventral tegmental area (VTA) or substantia nigra. The experimental group also showed less exploratory activity in the open field and the sample trials of both object recognition and object placement tasks. MA groups also showed decreased performance in the object recognition trial (1-h and 2-h inter-trial delays). Less exploration of the objects in the sample trial by the MA group might indicate deficits in general exploratory drive and/or to initiate actions. Nevertheless, in the spatial version of the recognition test (object placement task) the experimental group performed as well as the control group in two of the three delays (2 h and 4 h) even with significantly lower total exploration times in the sample trial. Our results demonstrate that a short toxic schedule induced profound changes in neurochemistry (comparable to classic acute toxic models of MA: four injections of 10 mg/kg) but selective declines in behavioral tasks.


A feasibility study of municipal solid waste incineration fly ash utilisation in Estonia.
The purpose of this paper is to discuss the alternative environmental management options for the utilisation of municipal solid waste (MSW) incineration fly ash (FA), which is generated at Iru Power Plant where MSW is incinerated in Estonia. To determine sustainable and economically feasible environmental management options for MSW incineration FA in Estonia, CO2 sequestration with a further carbonation process was examined. A partial Cost & Benefit Analysis has been conducted to compare the carbonation process to the current situation. Two carbonation options were developed. Option 1 is to use carbonated FA in any other processes based on the waste-to-product principle. Option 2 is to send carbonated FA to the non-hazardous landfill in Tallinn, Estonia. Important parameters, such as Net Present Value (NPV), Internal Rate of Return (IRR), Benefit-Cost Ratio (BCR) and Break Even Point (BEP), have been calculated for carbonation options and the current case. In addition, a sensitivity analysis has been conducted to examine its robustness. The results showed that the best option is carbonation Option 1 with NPV of 9,209,662 EUR, IRR of 43%, BCR of 2.63 and BEP between 2018 and 2019. Both Options 1 and 2 constitute more sustainable and environmentally friendly management options compared to the current situation. It can be concluded that this preliminary feasibility study showed that running a carbonation plant may be profitable and sustainable for Estonia. Currently, there is no treatment technology for MSW incineration FA in Estonia and FA is sent to a neighbouring country for further utilisation. This is the first study to demonstrate FA management options with economic and environmental benefits.