Hearing function in a hyperbaric environment.
Navy divers' hearing function was assessed as part of three saturation deep dives to 1,000 feet of sea water (fsw) to determine explanations for threshold shifts observed under hyperbaric conditions. Across the three deep dives, different aspects of the ear were evaluated, including air- and bone-conduction pure-tone thresholds, real ear probe microphone measurements, auditory evoked potentials, and central auditory processing assessments. Attempts to measure middle ear function and cochlear function (through otoacoustic emissions) were unsuccessful. Baseline measurements were obtained at 0 fsw in air before and after the saturation deep dives. Results showed that some aspects of hearing function remained unchanged with increases in depth. In general, audiometric thresholds at depth were similar to those measured on the surface at 500, 1,000, 2,000, 3,000, and 4,000 Hz. However, hearing sensitivity actually improved at depth at 6,000 and 8,000 Hz. The use of a specially designed sound booth for a pressurized heliox environment yielded significantly lower ambient noise levels and improved the accuracy of threshold measurement. Auditory evoked potential measurements and central auditory processing function were relatively unaffected by changes in depth. Significant changes at depth were seen in ear canal resonance which shifted up in frequency; this finding was attributed to the effect of helium on the hearing mechanism. Because objective measurement of middle ear and inner ear function were not methodologically possible, questions still remain regarding the interpretation of middle and inner ear function at depth. Nonetheless, our overall findings suggest that most aspects of hearing functioning are similar under high atmospheric pressures and in heliox as they are on the surface, with the exception of shifts in ear canal resonance and improvements in audiometric thresholds at high frequencies.


Morning glory disc anomaly in childhood - a population-based study.
To report prevalence, ocular characteristics and coexisting neurological, behavioural, somatic and neuroradiological abnormalities in children and adolescents with morning glory disc anomaly (MGDA). In a cross-sectional population-based study, 12 patients with MGDA, aged 2-20 years, were identified. All 12 agreed to ophthalmological assessments including visual functions, refraction, fundus photography, optical coherence tomography (OCT) and ocular motor score (OMS). Neurological examinations and behavioural/developmental screening were carried out. Data from previous or new neuroradiological investigations were collected. The prevalence of MGDA was 2.6/100 000. MGDA was unilateral in 11/12 patients with a best-corrected visual acuity (BCVA) in the MGDA eye ranging from hand motion to 0.65 (median 0.06). Severe microphthalmus prevented unilaterality to be determined in one adolescent. All patients had a binocular BCVA of ≥0.5. OMS showed abnormalities in pupil response, vestibulo-ocular reflex, stereo visual acuity, strabismus and convergence. OCT revealed peripapillary or macular oedema in 5/8 patients and foveal aplasia in 3/8 patients. Three patients had extensive capillary hemangiomas, of which one had PHACES syndrome and one had additional cerebrovascular anomalies and corpus callosum agenesis. Neuroradiology showed craniovascular anomalies in two patients. Neurology was mostly normal. Behavioural/developmental screening showed attention deficit hyperactivity disorder in one patient. The prevalence data, previously not reported, of morning glory disc anomaly was 2.6/100 000. Coexisting retinal peripapillary or macular oedema was common, as were cerebral abnormalities and/or cutaneous vascular malformations. The associated findings may not be discovered through routine ophthalmological examination why OCT and neuroimaging are called for.


Acute Stroke Despite Dabigatran Anticoagulation Treated with Idarucizumab and Intravenous Tissue Plasminogen Activator.
Dabigatran is a direct thrombin inhibitor used to reduce the risk of stroke in patients with nonvalvular atrial fibrillation. For patients who present with an acute stroke despite dabigatran therapy, clinical data on the use of intravenous tissue plasminogen activator (IV-tPA) is limited. There is an anticipated increased risk of symptomatic intracranial hemorrhage (sICH) when using IV-tPA in patients on dabigatran therapy. In 2015, the humanized monoclonal antibody fragment idarucizumab was approved for rapid (minutes) reversal of anticoagulant effects of dabigatran. Dabigatran reversal with idarucizumab before administration of IV-tPA might reduce the risk of sICH. We report a case of a 69-year-old stroke patient on dabigatran for paroxysmal atrial fibrillation who presented with an initial National Institutes of Health Stroke Scale (NIHSS) of 12. There was no early evidence of ischemic stroke or hemorrhage on head computed tomography, and coagulation studies implied therapeutic dabigatran levels. After controlling blood pressure, dabigatran was reversed with idarucizumab, and IV-tPA was administrated beginning 197 minutes after he was last seen at his baseline. Subsequent brain magnetic resonance imaging showed 2 punctate infarcts in the left temporal lobe and occipital lobe with no evidence of hemorrhage. The patient was discharged with an NIHSS of 1. Telephone follow-up 2 months later indicated that he was at his prestroke baseline, except for a complaint of worsened short-term memory. Idarucizumab reversal of dabigatran may reduce the risk of sICH and should be considered for acute stroke patients arriving in the IV-tPA time window.


Accessibility and utilization patterns of a mobile medical clinic among vulnerable populations.
We mapped mobile medical clinic (MMC) clients for spatial distribution of their self-reported locations and travel behaviors to better understand health-seeking and utilization patterns of medically vulnerable populations in Connecticut. Contrary to distance decay literature, we found that a small but significant proportion of clients was traveling substantial distances to receive repeat care at the MMC. Of 8404 total clients, 90.2% lived within 5 miles of a MMC site, yet mean utilization was highest (5.3 visits per client) among those living 11-20 miles of MMCs, primarily for those with substance use disorders. Of clients making >20 visits, 15.0% traveled >10 miles, suggesting that a significant minority of clients traveled to MMC sites because of their need-specific healthcare services, which are not only free but available at an acceptable and accommodating environment. The findings of this study contribute to the important research on healthcare utilization among vulnerable population by focusing on broader dimensions of accessibility in a setting where both mobile and fixed healthcare services coexist.


Evaluation of the sustainability of contrasted pig farming systems: integrated evaluation.
The aim of this paper is to present an approach for an integrated evaluation of the sustainability of pig farming systems, taking into account the three classical pillars: economy, environment and society. Eight sustainability themes were considered: Animal Welfare (AW), Animal Health (AH), Breeding Programmes (BP), Environment (EN), Meat Safety (MS), Market Conformity (MC), Economy (EC) and Working Conditions (WC). A total of 37 primary indicators were identified and used for the evaluation of 15 much contrasted pig farming systems in five EU countries. The results show that the eight themes were not redundant and all contributed to the observed variation between systems. The tool was very robust for highlighting the strengths and weaknesses of the systems along the eight themes that were considered. The number of primary indicators could be reduced from 37 to 18 with limited impact on the strengths/weaknesses profile of the individual systems. Integrating the eight theme evaluations into a single sustainability score is based on hypotheses or presumptions on the relative weights that should be given to the eight themes, which are very dependent on the context and on the purpose of the users of the tool. Therefore, the present paper does not have the ambition to provide a ready-for-use tool, rather to suggest an approach for the integrated evaluation of the sustainability of pig farming systems.


[Effect of haloperidol, diazepam and sodium oxybutyrate on the antinociceptive activity of opioid agonists administered via the theca medullaris spinalis].
At intrathecal administration the antinociceptive effect of morphine and DADL significantly exceeds the antinociceptive effect of pentazocine (ED50 in tail flick test were 1.1, 1.64, 75.0 nmol per mouse and in "writhing" test 0.0064, 0.0047, 24.53 nmol per mouse, respectively). All the agonists tested exhibited significantly higher activity at chemical stimulation than at thermal one. During the analysis of pA2 of naloxone during the interaction with morphine, DADL and pentazocine under thermal and chemical stimulation a pronounced mu-receptor component in the effect of DADL and pentazocine was suggested. A preliminary subcutaneous injection of sodium oxybutyrate (150 mg/kg) fails to change the activity of opioids administered intrathecally. Diazepam (5 mg/kg, subcutaneously) enhances the antinociceptive activity of DADL only at chemical stimulation. Haloperidol (2 mg/kg) increases the antinociceptive effect of morphine and DADL at pain stimulation of both types but exerts no influence on the analgesic effect of pentazocine. Haloperidol produces the most pronounced enhancement of the spinal component of delta-agonist DADL antinociceptive action. The enhancing effect of haloperidol is realized at the supraspinal level.


The Relationship Between BMI and Work-Related Musculoskeletal (MSK) Injury Rates is Modified by Job-Associated Level of MSK Injury Risk.
The aim of this study was to examine the relationship between body mass index (BMI) and occupational musculoskeletal (MSK) injury rates, and the statistical interaction between BMI and occupational exposure to MSK hazards (measured by level of MSK injury risk based on job category). Using 17 years of data from 38,214 university and health system employees, multivariate Poisson regression modeled the interaction between BMI and MSK injury risk on injury rates. A significant interaction between BMI and MSK injury risk was observed. Although the effect of BMI was strongest for 'low' MSK injury risk occupations, absolute MSK injury rates for 'mid'/'high' MSK injury risk occupations remained larger. To address the occupational MSK injury burden, initiatives focused on optimal measures of workers' BMI are important but should not be prioritized over (or used in lieu of) interventions targeting job-specific MSK injury hazards.


Differential Responses of Vanilla Accessions to Root Rot and Colonization by Fusarium oxysporum f. sp. radicis-vanillae.
Root and stem rot (RSR) disease caused by Fusarium oxysporum f. sp. radicis-vanillae (Forv) is the most damaging disease of vanilla (Vanilla planifolia and V. × tahitensis, Orchidaceae). Breeding programs aimed at developing resistant vanilla varieties are hampered by the scarcity of sources of resistance to RSR and insufficient knowledge about the histopathology of Forv. In this work we have (i) identified new genetic resources resistant to RSR including V. planifolia inbreds and vanilla relatives, (ii) thoroughly described the colonization pattern of Forv into selected vanilla accessions, confirming its necrotic non-vascular behavior in roots, and (iii) evidenced the key role played by hypodermis, and particularly lignin deposition onto hypodermal cell walls, for resistance to Forv in two highly resistant vanilla accessions. Two hundred and fifty-four vanilla accessions were evaluated in the field under natural conditions of infection and in controlled conditions using in vitro plants root-dip inoculated by the highly pathogenic isolate Fo072. For the 26 accessions evaluated in both conditions, a high correlation was observed between field evaluation and in vitro assay. The root infection process and plant response of one susceptible and two resistant accessions challenged with Fo072 were studied using wide field and multiphoton microscopy. In susceptible V. planifolia, hyphae penetrated directly into the rhizodermis in the hairy root region then invaded the cortex through the passage cells where it induced plasmolysis, but never reached the vascular region. In the case of the resistant accessions, the penetration was stopped at the hypodermal layer. Anatomical and histochemical observations coupled with spectral analysis of the hypodermis suggested the role of lignin deposition in the resistance to Forv. The thickness of lignin constitutively deposited onto outer cell walls of hypodermis was highly correlated with the level of resistance for 21 accessions tested. The accumulation of p-coumaric and sinapic acids, two phenolic precursors of lignin, was observed in the resistant plants inoculated with Fo072, but not in the susceptible one. Altogether, our analyses enlightened the mechanisms at work in RSR resistant genotypes and should enhance the development of novel breeding strategies aimed at improving the genetic control of RSR of vanilla.


Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.
Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.


Geographic and temporal genetic patterns of Aedes aegypti populations in Rio de Janeiro, Brazil.
Rio de Janeiro is considered as the most important entry point for dengue viruses in Brazil. Using isoenzyme markers, we investigated the genetic structure of the mosquito vector Aedes aegypti sampled at three-month intervals in 14 districts in Rio de Janeiro from December 2002 to December 2003. We detected high levels of genetic differentiation (i.e. high F(ST) values and significant P values), which tended to persist throughout the year. The species does not take advantage of routes and railways to disperse. Genetic structuring was higher in the rainy season, suggesting low dispersion of Ae. aegypti at this time of year when all dengue epidemics have been reported in the city.


Spatially structured eco-evolutionary dynamics in a host-pathogen interaction render isolated populations vulnerable to disease.
While the negative effects that pathogens have on their hosts are well-documented in humans and agricultural systems, direct evidence of pathogen-driven impacts in wild host populations is scarce and mixed. Here, to determine how the strength of pathogen-imposed selection depends on spatial structure, we analyze growth rates across approximately 4000 host populations of a perennial plant through time coupled with data on pathogen presence-absence. We find that infection decreases growth more in the isolated than well-connected host populations. Our inoculation study reveals isolated populations to be highly susceptible to disease while connected host populations support the highest levels of resistance diversity, regardless of their disease history. A spatial eco-evolutionary model predicts that non-linearity in the costs to resistance may be critical in determining this pattern. Overall, evolutionary feedbacks define the ecological impacts of disease in spatially structured systems with host gene flow being more important than disease history in determining the outcome.


Researching Aboriginal health: experience from a study of urban young people's health and well-being.
European colonisation had a devastating effect on the health and well-being of indigenous people in Australia. The history of Aboriginal health research has reflected the history of colonisation; research has understandably been viewed with distrust. The need for accurate statistics and improved understanding of health problems is clear, but obtaining them is not easy. In this paper we describe the first stage of a study of the health and well-being of urban young people that was initiated and carried out by the Victorian Aboriginal Health Service (VAHS), a community controlled organisation. This longitudinal study aims to describe the prevalence and incidence of a range of health problems, to explore their interrelated determinants, and to increase the capacity of the VAHS to carry out research. The process of planning and carrying out this study raised a number of interesting ethical, cultural and methodological issues. These issues include the establishment of an appropriate and properly constituted local ethics committee, the difficulty of obtaining a representative sample, the need for ongoing negotiation, attention to language, the use of a subject-generated identity code, and the need to recruit a wide range of peer interviewers. Achievements include a series of community reports of the findings, the establishment of a cohort of young people for a longitudinal study; a shift in attitudes toward research; a strengthened network of young Kooris; increased use of the health service by young people and the establishment of an after-hours clinic service and meeting place for young people. The aim of this analysis of our achievements and constraints is to assist others planning similar research, and to demonstrate the value for process and outcomes of research conducted under Aboriginal community control.


[Pathogens and drug resistance of nosocomial pneumonia after intracranial surgery].
To determine the antimicrobial resistance and bacterial distribution of nosocomial pneumonia in neurosurgical patients. We analyzed and counted the result of sputum culture, drug sensibilities test, and the rate of nosocomial pneumonia after intracranial surgery of all the patients in the Department of in Neurosurgery our hospital in 2002. The rate of nosocomial pneumonia after intracranial surgery was 6.2%. The first 5 strains were pseudomonas aeruginosa, acinetobacter, enterobacteriaceae, klebsiella, and staphylococcus epidermidis. Statistics of drug sensibility test suggested:the rate of ampicillin and cefuroxime resistance was over 83%. Gram-negative bacterium was the first sensitive to sulperazon and imipenem. Gram-positive bacterium was the first sensitive to vancomycin, ampicillin/sulbactam and rifampicin. The rate of neurosurgical infection was high. The most common pathogens were gram-negative bacteria. Drug resistance was serious.


Childhood-onset schizophrenia: brain MRI rescan after 2 years of clozapine maintenance treatment.
The effect of clozapine on striatal morphology was examined in adolescents with childhood-onset schizophrenia. Eight adolescent patients with onset of psychosis before age 12 and eight matched comparison subjects had initial and 2-year follow-up brain magnetic resonance imaging scans. Basal ganglia and lateral ventricle volumes were measured. The patients were on a clozapine regimen during the 2-year interim. Caudate volume was larger in the patients at the initial scanning, decreased in the patients between scans, and did not differ significantly between the patients and the comparison subjects at the second scanning. Caudate enlargement in patients with childhood-onset schizophrenia who are taking typical neuroleptics appears to be secondary to medication exposure. Rescanning to examine basal ganglia morphology is indicated for these patients when they are taking an atypical neuroleptic.


Bilirubin and urobilins in germfree, ex-germfree, and conventional rats.
No urobilinogens are present in the feces or urine of germfree rats. After contamination of germfree animals with feces from conventional animals the exgermfree rats produced urobilins to the same extent as conventional animals on the same diet. The negative urobilin test turned positive in germfree animals infected with a single Clostridium-like microorganism isolated from the intestinal contents of rats with urobilins in the feces. The output increased in these monoinfected animals after superinfection with a strain of E. coli but never reached the values of conventional animals.


Allergy epidemiology in the St. Louis, Missouri, area: II grasses.
3219 patients for seven species of grass pollen extracts and mixtures of these grasses in the St. Louis, Missouri, metropolitan area exhibited specific levels of allergenicity to different grasses, as well as a degree of cross-reactivity among all species tested. Adult patient reactions to these extracts generally were similar to those of the pediatric patients tested. Mixed grass pollen preparations proved to be inadequate as a gauge of patient allergenicity to individual species. Intersection of the prick skin testing method and the intracutaneous technique was found at specific concentrations. For the first time phylogenetic and taxonomic conclusions regarding the grass family are supported by immunological data.


Energy loss of a charged particle in a magnetized quantum plasma.
This paper investigates the stopping power of a weakly coupled magnetized plasma. The effect of the Larmor rotation of the heavy charged test particle is carefully analyzed. The dielectric formalism is employed to obtain a general expression for the stopping power. A quantum mechanical form of the random-phase approximation dielectric function is used so that an arbitrary cutoff procedure is not required. Simple analytical expressions for the stopping power have been found for the cases of high and low projectile velocity of the test particle. The dependence of the stopping power on the angle of incidence is studied. A comparison with numerical solutions is given. It is found that in general a magnetic field reduces the stopping power of the plasma at high velocities, while it increases the stopping power at low velocities.


Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk.
In the human colon, arachidonic acid is metabolized primarily by cyclooxygenase (COX) and arachidonate lipoxygenase (ALOX) to bioactive lipids, which are implicated in colon cancer risk. Several polymorphisms in ALOX and COX genes have been identified, including G-1752A, G-1699A and Glu254Lys in ALOX5; Gln261Arg in ALOX12; Leu237Met and Val481Ile in COX1; and C-645T and Val511Ala in COX2. Because of the significant role of arachidonic acid metabolism in colon cancer, we hypothesized that these polymorphisms could influence susceptibility to colon cancer. We addressed this hypothesis in African-Americans and Caucasians using colon cancer cases (n = 293) and hospital- (n = 229) and population-based (n = 304) control groups. Polymorphisms did not differ between the control groups (P > 0.05); thus, they are combined for all analyses presented. ALOX5 Glu254Lys and COX2 C-645T and Val511Ala allele frequencies differed between Caucasians and African-American controls (P < 0.001). The ALOX5 -1752 and -1699 polymorphisms were in linkage disequilibrium (P < 0.001) and associated with a decreased risk in Caucasians in ALOX5 haplotype analyses (P = 0.03). Furthermore, an inverse association was observed between A alleles at positions -1752 and -1699 of ALOX5 and colon cancer risk in Caucasians, but not in African-Americans. Caucasians with A alleles at ALOX5 -1752 had a reduced odds of colon cancer versus those with G alleles [odds ratio (OR) (GA versus GG), 0.63; 95% confidence interval (CI), 0.39-1.01; OR (AA versus GG), 0.33; 95% CI, 0.07-1.65, P(trend) = 0.02]. Similar results were observed for ALOX5 G-1699A [OR (GA versus GG), 0.59, 95% CI, 0.37-0.94; OR (AA versus GG), 0.27, 95% CI, 0.06-1.32, P(trend) = 0.01]. Statistically significant associations with colon cancer were not observed for the other polymorphisms investigated. We have shown for the first time that a haplotype containing ALOX5 G-1752A and G-1699A in a negative regulatory region of the promoter may influence colon cancer risk in Caucasians.


Double-blind placebo and active (caffeine) controlled study to examine the effects of the herbal nutritional supplement beverage "Wake up" on vigilance and function after lunch.
Post-lunch dip is a well-known phenomenon that results in a substantial deterioration in function and productivity after lunch. To assess whether a new herbal-based potentially wake-promoting beverage is effective in counteracting somnolence and reduced post-lunch performance. Thirty healthy volunteers were studied on three different days at the sleep clinic. On each visit they ate a standard lunch at noontime, followed by a drink of "Wake up," 50 mg caffeine, or a placebo in a cross-over double-blind regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests to determine the effects of the beverage. These included: a) a subjective assessment of alertness and performance based on a visual analog scale, and b) objective function tests: the immediate word recall test, the digit symbol substitution test (DSST), and hemodynamic measurements. The results of the three visits were compared using one-way analysis of variance, with P < 0.05 considered statistically significant. In all performance tests, subjective vigilance and effectiveness assessment, both Wake up and caffeine were significantly superior to placebo 30 minutes after lunch. However, at 2 hours after lunch, performance had deteriorated in those who drank the caffeine-containing drink, while Wake up was superior to both caffeine and placebo. Blood pressure and pulse were higher 2 hours after caffeine ingestion, compared to both Wake up and placebo. These results suggest that a single dose of Wake up is effective in counteracting the somnolence and reduced performance during the post-lunch hours. In the current study it had no adverse hemodynamic consequences.


Free jejunal transfer for pharyngo-esophageal reconstruction.
During the course of head and neck surgery for cancer the reconstructive surgeon is involved in replacement of pharyngeal mucosal defects. Siedenberg (7) first reported free transplantation in 1959 using a segment of jejunum, Roberts (5) using jejunum, Nakayama (3) using colon and Jurkiewicz (4) using ileum and jejunum. Green (2) in 1966 using microsurgical techniques demonstrated 100% survival of free transfers of jejunum and also patches of jejunum in dogs. We have used free interposing iso-peristaltic jejunal loop transfer in 30 patients to bridge the cervical esophagus defects for advanced cancer of hypopharynx, larynx and cervical esophagus after ablative cancer surgery. The major complication rate was 13% (4/30 cases) including total flap failure and loss of interposed jejunal segment. The minor complication rate was 36% (11/30 cases) including postoperative hypothyroidism in 2 patients. Intra-abdominal hemorrhage or peri-operative mortality was not observed in any of our cases. Total post-operative average hospital stay was 15 days, and median swallowing time was 10 days. Complication rates and success of early functional and social restoration have been analyzed.


Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA).
Cartilage-derived retinoic acid sensitive protein (CD-RAP) also known as melanoma inhibitory activity (MIA) has already been established as a marker for chondrocyte differentiation and a number of cancerous conditions in humans. Studies have also shown that CD-RAP/MIA is a potential marker of joint disease. The objective of this study was to characterize the equine CD-RAP/MIA gene and thus make it available as a marker in cartilage research and clinical studies. Gene analysis revealed that the equine gene (GenBank accession no. EF679787) consists of four exons and three introns, and the homology to the human gene is 90% for the translated region. The upstream sequence includes regulatory elements and putative transcription factor binding sites previously described in the human and murine promoter regions. The deduced amino acid sequence consists of 130 aa including a signal peptide of 23 aa, and has a 91% identity to the human protein. Using radiation hybrid mapping, the CD-RAP/MIA gene was localized to the p arm of equine chromosome 10 (ECA10p), which is in accordance with prediction based on the current human-equine comparative map. Gene expression studies showed expression of CD-RAP/MIA mRNA in articular cartilage and chondrocytes from horses with no signs of joint disease. The expression decreased as the cells dedifferentiated in monolayer culture. We also identified an equine CD-RAP/MIA splice variant similar to that reported in humans. The CD-RAP/MIA protein was detected in equine synovial fluid, serum and culture medium from chondrocyte cultures. In conclusion, CD-RAP/MIA is expressed in equine cartilage and chondrocytes, and the protein can be detected in equine serum, synovial fluid and in culture medium from chondrocyte cultures. The equine gene and resulting protein share great homology with the human gene, making future studies on CD-RAP/MIAs potential as a marker in joint disease possible using the equine joint as a model.


Evidence against the existence of acetylated Sudan Black B.
The nature of acetylated Sudan Black B (aSBB) has been investigated, and it has been found, by thin layer chromatography, that each fraction of aSBB has an Rf which is the same as that of a similar fraction of Sudan Black B (SBB). However, aSBB has been found to have fewer fractions, 9-12 than SBB, 14-16. The two major fractions from aSBB and SBB were examined, and a great similarity was found between the absorption spectra of the respective fractions of aSBB and SBB. The major fraction of aSBB was investigated by mass spectroscopy and found to have a similar molecular weight to that expected of SBB. This demonstrates that aSBB is not in fact acetylated, and that the components of aSBB are chemically no different from the corresponding components of SBB.


Synthesis and in vitro properties of dexamethasone 21-sulfate sodium as a colon-specific prodrug of dexamethasone.
We synthesized dexamethasone 21-sulfate sodium (DS) as a colon-specific prodrug of dexamethasone and investigated its properties. Introduction of a sulfate group to dexamethasone lowered the apparent partition coefficient from 52.5 to 0.27 in 1-octanol/pH 6.8 phosphate buffer at 37 degrees C. DS was stable on incubation with buffer solutions of varied pH or with the upper intestinal contents of rats at 37 degrees C for 24 h. On incubation with the cecal contents, DS was hydrolyzed by producing dexamethasone over 80% of the dose at 10 h. When DS was incubated with the cecal contents collected from trinitrobenzenesulfonic acid (TNBS)-induced colitic rats, the degree of prodrug hydrolysis and production of dexamethasone amounted to 70% of healthy rats. In comparison with prednisolone, hydrocortisone, and cortisone, dexamethasone was stable against bioinactivation by the cecal contents, a desirable property for the development of a colon-specific prodrug. These results demonstrated that DS might be delivered specifically to the colon as an intact form to produce dexamethasone in high yield, suggesting DS as a potential colon-specific prodrug of dexamethasone.


Construction and structural modeling of a single-chain Fv-asparaginase fusion protein resistant to proteolysis.
In this study, we construct a fusion protein composed of L-asparaginase (ASNase; from Escherichia coli AS 1.357) and a protective single-chain Fv (scFv), which was selected from a phage-display scFv library from our previous studies. The antibody moiety of the fusion protein was fused to the N-terminus of the enzyme moiety via a linker peptide, (Gly(4)Ser)(6). Recombinant plasmid pET-SLA was constructed to express scFv-ASNase fusion to high levels in E. coli and the expressed product was found to form inclusion bodies. We obtained a soluble fusion protein by refolding and purification. The soluble fusion protein exhibited about 82% of the enzymatic activity of the native ASNase at the same molar concentration, and had a K(m) value similar to that of the native enzyme for the substrate L-asparagine. Importantly, the fusion protein was more stable than native ASNase. In addition: (1) following treatment with trypsin, alpha-chymotrypsin, and rennet, at 37 degrees C for 30 min, scFv-ASNase fusion retained 94.0%, 88.8%, and 84.5% of its original activity, respectively, whereas native ASNase became inactive; and (2) ScFv-ASNase fusion had a much longer in vitro half-life (9 h) in serum than the native enzyme (2 h). The three-dimensional structure of the fusion protein was obtained by modeling with the Homology and Discover modules of the INSIGHT II software package. On the basis of the structural evidence and biochemical properties, we propose that the scFv moiety of the fusion protein may confer ASNase moiety resistance to proteolysis as a result of both steric hindrance and a change in the electrostatic surface of the enzyme.


Dietary betaine reduces plasma homocysteine concentrations and improves bone strength in laying hens.
1. This study tested the hypothesis that the methyl-donor properties of betaine could reduce homocysteine concentrations, which has been recognised in a previous genetics study to be linked to bone quality. This was combined with phytase treatment, as phosphorus is critical for bone mineralisation.2. Using a 2 × 2 factorial arrangement, a total of 1920 Lohmann LSL-lite chickens housed as 24 replicates of 20 chickens were fed one of four diets containing dietary betaine (0 or 1000 mg/kg) and phytase (300 or 1000 FTU/kg) from one day old until end-of-lay. Blood and bone samples were collected at 45 and 70 weeks of age.3. Hens fed betaine had lower plasma homocysteine level (P < 0.05), higher tibia breaking strength (P < 0.05) and higher tibia bone density (P < 0.05).4. Egg production and quality was excellent throughout the study and were not affected by the dietary treatments.5. The addition of dietary betaine was successful at reducing plasma homocysteine concentrations and improving bone strength in laying hens, which could be used as an intervention to alleviate welfare concerns.


Experience Affects Critical Period Plasticity in the Visual Cortex through an Epigenetic Regulation of Histone Post-Translational Modifications.
During an early phase of enhanced sensitivity called the critical period (CP), monocular deprivation causes a shift in the response of visual cortex binocular neurons in favor of the nondeprived eye, a process named ocular dominance (OD) plasticity. While the time course of the CP for OD plasticity can be modulated by genetic/pharmacological interventions targeting GABAergic inhibition, whether an increased sensory-motor experience can affect this major plastic phenomenon is not known. We report that exposure to environmental enrichment (EE) accelerated the closure of the CP for OD plasticity in the rat visual cortex. Histone H3 acetylation was developmentally regulated in primary visual cortex, with enhanced levels being detectable early in enriched pups, and chromatin immunoprecipitation revealed an increase at the level of the BDNF P3 promoter. Administration of the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to animals reared in a standard cage mimicked the increase in H3 acetylation observed in the visual cortex and resulted in an accelerated decay of OD plasticity. Finally, exposure to EE in adulthood upregulated H3 acetylation and was paralleled by a reopening of the CP. These findings demonstrate a critical involvement of the epigenetic machinery as a mediator of visual cortex developmental plasticity and of the impact of EE on OD plasticity. While it is known that an epigenetic remodeling of chromatin structure controls developmental plasticity in the visual cortex, three main questions have remained open. Which is the physiological time course of histone modifications? Is it possible, by manipulating the chromatin epigenetic state, to modulate plasticity levels during the critical period? How can we regulate histone acetylation in the adult brain in a noninvasive manner? We show that the early exposure of rat pups to enriching environmental conditions accelerates the critical period for plasticity in the primary visual cortex, linking this effect to increased histone acetylation, specifically at the BDNF gene level. Moreover, we report that the exposure of adult animals to environmental enrichment enhances histone acetylation and reopens juvenile-like plasticity.


Hypothyroidism and bipolar affective disorder: is there a connection?
Hypothalamic-pituitary-thyroid axis dysfunction in the pathophysiology of bipolar disorder has received less attention as compared with that in depressive disorder. To study the prevalence of hypothyroidism in patients diagnosed with bipolar disorder and compare it with a population norm. The setting was the psychiatry inpatient unit of a tertiary care hospital. The design was retrospective and observational. A retrospective observational study was performed, referring to the case records of 84 cases of bipolar disorder admitted to the Department of Psychiatry in a Tertiary Referral Center during the year 2010-2012. The prevalence of hypothyroidism both subclinical as demonstrated by elevated thyroid stimulating hormone (TSH) levels (cut-off value 4.2 μU/ml) and overt hypothyroidism (fasting T4 <0.92 ng/dl and TSH >4.2 μU/ml) was calculated. This was compared with the population prevalence of hypothyroidism as determined by an epidemiological study carried out in the year 2009, in the same region. The correlation between hypothyroidism, gender, lithium prophylaxis and family history of mood disorder was computed. Percentage prevalence of hypothyroidism in the sample was calculated and compared to a population norm. The correlation between hypothyroidism, gender, lithium prophylaxis and family history of mood disorder was computed using the odds ratio (OR). The total prevalence of hypothyroidism in both males and females in the bipolar group was comparable with that in the general population. There is a significant association between family history of mood disorder in first degree relatives and patients having hypothyroidism (OR 5.504 and P = 0.012). There were no statistically significant associations between thyroid abnormalities and age, duration of illness and lithium prophylaxis. There is no significant association between hypothyroidism and bipolar disorder. Family history of mood disorder and hypothyroidism show significant association. (OR -5.504 AND P = 0.012).


Experiences and concerns among patients being treated for atypical chest pain.
Many patients who are discharged from the hospital without receiving a clear-cut diagnosis of their chest pain continue to consume health care because of disabling physical and psychological symptoms. By identifying their experiences and concerns following hospitalization, an empirical basis for discussions on ways of improving the care of these particular patients will be obtained. A qualitative analysis of semi-structured interviews with 38 patients with a diagnosis of unspecified chest pain was carried out. Two-thirds of the respondents had unanswered questions and concerns that had not been addressed. They found it difficult to understand why they had not undergone more tests. They requested an explanation for their chest pain, at the very least, or were worried about the future. Some respondents accepted the fact that they had not been given a sufficient amount of time and information. They referred to the stressful working situation of the physicians, the view that their admission could be regarded as unnecessary or that physicians at the hospital could not be expected to do more than exclude serious diseases. Health professionals should address their patients' questions and fears properly and provide them with the most probable explanation for their symptoms. When taking the harmlessness of their symptoms or the situation of their caregivers into account, patients may find it inappropriate to impose further demands on care.


Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis.
The soluble interleukin 2 receptor (sIL-2R) has been proposed as a marker of disease activity in patients with sarcoidosis. However, no studies have evaluated whether serum sIL-2R measurement is of use in establishing the diagnosis of sarcoidosis in patients who are suspected of sarcoidosis among other diseases. A cohort study was conducted, consisting of new patients who visited the immunology outpatient clinic and whose serum sIL-2R levels were available before a definitive diagnosis was established between February 2011 and February 2016. All patients underwent standard diagnostic testing for sarcoidosis (e.g. laboratory tests, radiographic and/or nuclear imaging and/or affected site biopsy). This resulted either in the diagnosis of sarcoidosis or the exclusion of sarcoidosis with the diagnosis of another disease. Results of sIL-2R and angiotensin-converting enzyme (ACE) levels, radiographic and nuclear imaging and histology results were collected and definitive diagnoses were recorded. Sensitivity, specificity, the concordance statistic from the receiver operating characteristic curve and Youden's Index were calculated to assess the performance of sIL-2R in the diagnosis of sarcoidosis and were compared to ACE, currently one of the most used diagnostic biomarkers in the diagnosis of sarcoidosis. In total 983 patients were screened for inclusion, of which 189 patients met the inclusion criteria. A total of 101 patients were diagnosed with sarcoidosis after diagnostic workup, of whom 79 were biopsy-proven. In 88 patients a diagnosis other than sarcoidosis was made. The sensitivity and specificity of serum soluble interleukin 2 receptor levels to detect sarcoidosis were 88% and 85%. The sensitivity and specificity of ACE were 62% and 76%. Receiver operating characteristic curve analysis revealed that sIL-2R receptor is superior to ACE (p<0.0001). Serum sIL-2R is a sensitive biomarker and superior to ACE in establishing the diagnosis of sarcoidosis and can be used to rule out sarcoidosis in patients suspected of sarcoidosis.


"It's not smoke. It's not tar. It's not 4000 chemicals. Case closed": Exploring attitudes, beliefs, and perceived social norms of e-cigarette use among adult users.
Electronic cigarette (e-cigarette) use is rapidly increasing among adults in the U.S. The purpose of this qualitative study was to explore consumer perceptions about e-cigarettes, including knowledge, attitudes, beliefs and perceived social norms. A total of 14 focus groups (N=116) were conducted with current adult e-cigarette users in five U.S. cities from March through May, 2014. Focus groups were segmented by age (young adults aged 18-29 and older adults aged 30 and older) as well as by e-cigarette use status (exclusive e-cigarette users and non-exclusive e-cigarette users). Focus group discussions lasted approximately 60-min and were audio-recorded and transcribed; data were analyzed using a phenomenological approach. Participants expressed many positive attitudes towards e-cigarettes and simultaneously reported a lack of information and knowledge about the products. Focus group participants overwhelmingly felt as though the ingredients of e-cigarettes were likely less harmful than conventional cigarettes. Additionally, many described positive reactions from family and friends, especially when e-cigarettes were used in place of conventional cigarettes. Findings from this qualitative study provide insight into consumer knowledge, attitudes and beliefs about e-cigarettes increasing our understanding of why and how they are being used. Such information will help provide insight into the potential public health impact of these emerging products.


[Ethmoid sinus osteoma with orbital invasion: report of three cases and review of the literature].
We report three rare cases of ethmoid osteoma extending to the medial quadrant of the orbit that had singular particularities, such as occurring in women, at an unusual age group, and complaint of epiphora. The radiographic images were typical of this condition. Patients were submitted to surgery with complete resolution of the disease.


Small-molecule inhibitor LF3 restrains the development of pulmonary hypertension through the Wnt/β-catenin pathway.
Pulmonary hypertension (PH) associated with congenital heart disease is a progressive hemodynamic disease that can lead to increased pulmonary vascular resistance, vascular remodeling, and even right heart failure and death. LF3 is a novel inhibitor of the reporter gene activity of β-catenin/TCF4 interaction in the Wnt/β-catenin signal pathway. However, whether this action of LF3 can prevent PH development remains unclear. In this study, we investigated the therapeutic effect of LF3 in rat primary pulmonary artery smooth muscle cells (PASMCs) of the PH model. We found that LF3 inhibited the decrease in pulmonary artery acceleration time and ejection time by ultra-high-resolution ultrasound imaging and blocked the increase of pulmonary artery systolic pressure by using the BL420 biological function experimental system and right ventricular hypertrophy index by the electronic scales. Simultaneously, it prevented the increase of α-smooth muscle actin and fibronectin and the decrease of elastin in pulmonary arteries of rats in the PH group, as revealed by an immunohistochemical analysis. Moreover, cell proliferation and migration assays showed that LF3 significantly reduced the proliferation and migration of PASMCs. Western blotting and quantitative real-time polymerase chain reaction analyses revealed that LF3 suppressed the expression of proliferating cell nuclear antigens and Bcl-2 and increased the expression of Bax but did not alter the expressions of β-catenin and TCF4. Taken together, LF3 can reduce the migration and proliferation of PASMCs and induce their apoptosis to prevent the development of PH. It would be worthwhile to explore the potential use of LF3 in the treatment of PH.


Ultrafast spin transport as key to femtosecond demagnetization.
Irradiating a ferromagnet with a femtosecond laser pulse is known to induce an ultrafast demagnetization within a few hundred femtoseconds. Here we demonstrate that direct laser irradiation is in fact not essential for ultrafast demagnetization, and that electron cascades caused by hot electron currents accomplish it very efficiently. We optically excite a Au/Ni layered structure in which the 30 nm Au capping layer absorbs the incident laser pump pulse and subsequently use the X-ray magnetic circular dichroism technique to probe the femtosecond demagnetization of the adjacent 15 nm Ni layer. A demagnetization effect corresponding to the scenario in which the laser directly excites the Ni film is observed, but with a slight temporal delay. We explain this unexpected observation by means of the demagnetizing effect of a superdiffusive current of non-equilibrium, non-spin-polarized electrons generated in the Au layer.


Rare Occurrence of an Intraocular Choroidal Solitary Fibrous Tumor/Hemangiopericytoma.
Tumors previously diagnosed as solitary fibrous tumors (SFT) and hemangiopericytomas (HPC) are characterized by the NAB2-STAT6 fusion gene, leading to nuclear STAT6 expression, and are now considered part of one SFT/HPC tumor entity by the 2016 World Health Organization Classification of Tumors of the Central Nervous System. We present the first primary choroidal SFT/HPC with the diagnosis confirmed by STAT6 expression. A 51-year-old man underwent enucleation for a choroidal mass, which revealed a spindle cell neoplasm involving the optic nerve, without extrascleral extension. Immunohistochemical stains for S-100, melan-A, tyrosinase, and HMB45 were all negative; however, detection of monosomy 3 by FISH favored a choroidal spindle cell melanoma. Four years later, he presented with hepatic metastases of a spindle cell tumor, and a year later with an epithelioid malignancy involving the calvarium. The calvarial tumor showed nuclear STAT6 immunoreactivity, supporting the diagnosis of SFT/HPC. Retrospectively, the choroidal and hepatic masses were also found to demonstrate nuclear STAT6 expression, supporting the diagnosis of a primary choroidal SFT/HPC with metachronous metastases to the liver and calvarium. This case highlights the significance of considering SFT/HPC in the diagnosis of intraocular spindle cell tumors and the importance of STAT6 immunohistochemistry in the evaluation of such tumors.


Evaluation of Performance of Introduced Yam Bean (Pachyrhizus spp.) in Three Agro-Ecological Zones of Rwanda.
The yam bean (Pachyrizhus spp) was recently introduced as a root crop with high-yield potential, considerable protein and micro-nutrient concentration to investigate its potential for food production in Rwanda. Except for Chuin types (Pachyrizhus tuberosus) which have high storage root dry matter (RDM) (26 to 36%), most accessions are consumed raw and are reported to have low RDM. The present study aimed to evaluate and identify adapted high yielding yam bean accessions in major agro-ecological zones of Rwanda. Field experiments with 22 accessions were conducted in 2012 at three research sites representing the major agro-ecologies of Rwanda. Strict reproductive pruning was followed to enhance fresh storage root yields. Across locations, ANOVA indicated highly significant differences (p < 0.01) for genotypes (G), locations (L), seasons (S) and G x L effects for storage root yield, vine yield and harvest index and accounted for 21.88%, 43.41%, 1.43% and 13.25% of the treatment sum of squares, respectively. The GGE bi-plot revealed that EC209018 is high yielding but unstable. However, genotypes, AC209034, AC209035 and EC209046, were outstanding in terms of adaptation and relative stability across the 3 locations, suggesting consistent root yields irrespective of location and environmental conditions. The GGE scatter plot showed that all genotypes formed one mega-environment for storage root yield (Karama, Musanze and Rubona) and two mega-environments for biomass yield (Karama and Rubona as one mega-environment and Musanze the second one). This study revealed that Karama is the most suitable environment for evaluation and selection of yam bean for yield components in Rwanda.


Limtongozyma siamensis gen. nov., sp. nov., a yeast species in the Saccharomycetales and reassignment of Candida cylindracea to the genus Limtongozyma.
Two yeast strains, DMKU-WBL1-3 and DMKU GT3-16, were obtained from grease samples collected from grease traps at the Kasetsart University canteen, Thailand. Pairwise sequence analysis indicated that the strains were closely related to Candida cylindracea NRRL Y-17506T, but differed by 11 and 35 nucleotide substitutions in the D1/D2 domain of the large subunit (LSU) rRNA gene and the ITS region, respectively. Based on sequence divergences, the novel species was distinguished from C. cylindracea. The results of phylogenetic analysis based on the concatenated sequences from small subunit rRNA, ITS region and LSU rRNA genes showed that the two strains and C. cylindracea NRRL Y-17506T formed a distinct lineage related to the genus Babjeviella. A novel genus, Limtongozyma, is proposed to accommodate these clade members. Hence, Candida cylindracea NRRL Y-17506T is transferred to this genus and assigned as the type species of the genus. The holotype of Limtongozyma siamensis is DMKU-WBL1-3.


Comprehensive mapping of the human papillomavirus (HPV) DNA integration sites in cervical carcinomas by HPV capture technology.
Integration of human papillomavirus (HPV) DNA into the host genome can be a driver mutation in cervical carcinoma. Identification of HPV integration at base resolution has been a longstanding technical challenge, largely due to sensitivity masking by HPV in episomes or concatenated forms. The aim was to enhance the understanding of the precise localization of HPV integration sites using an innovative strategy. Using HPV capture technology combined with next generation sequencing, HPV prevalence and the exact integration sites of the HPV DNA in 47 primary cervical cancer samples and 2 cell lines were investigated. A total of 117 unique HPV integration sites were identified, including HPV16 (n = 101), HPV18 (n = 7), and HPV58 (n = 9). We observed that the HPV16 integration sites were broadly located across the whole viral genome. In addition, either single or multiple integration events could occur frequently for HPV16, ranging from 1 to 19 per sample. The viral integration sites were distributed across almost all the chromosomes, except chromosome 22. All the cervical cancer cases harboring more than four HPV16 integration sites showed clinical diagnosis of stage III carcinoma. A significant enrichment of overlapping nucleotides shared between the human genome and HPV genome at integration breakpoints was observed, indicating that it may play an important role in the HPV integration process. The results expand on knowledge from previous findings on HPV16 and HPV18 integration sites and allow a better understanding of the molecular basis of the pathogenesis of cervical carcinoma.


Analysis of Key Genes Involved in Potato Anthocyanin Biosynthesis Based on Genomics and Transcriptomics Data.
The accumulation of secondary metabolites, such as anthocyanins, in cells plays an important role in colored plants. The synthesis and accumulation of anthocyanins are regulated by multiple genes, of which the R2R3-MYB transcription factor gene family plays an important role. Based on the genomic data in the Potato Genome Sequencing Consortium database (PGSC) and the transcriptome data in the SRA, this study used potato as a model plant to comprehensively analyze the plant anthocyanin accumulation process. The results indicated that the most critical step in the synthesis of potato anthocyanins was the formation of p-coumaroyl-CoA to enter the flavonoid biosynthetic pathway. The up-regulated expression of the CHS gene and the down-regulated expression of HCT significantly promoted this process. At the same time, the anthocyanins in the potato were gradually synthesized during the process from leaf transport to tubers. New transcripts of stAN1 and PAL were cloned and named stAN1-like and PAL-like, respectively, but the functions of these two new transcripts still need further study. In addition, the sequence characteristics of amino acids in the R2-MYB and R3-MYB domains of potato were preliminarily identified. The aims of this study are to identify the crucial major genes that affect anthocyanin biosynthesis through multi-omics joint analysis and to transform quantitative traits into quality traits, which provides a basis and reference for the regulation of plant anthocyanin biosynthesis. Simultaneously, this study provides the basis for improving the anthocyanin content in potato tubers and the cultivation of new potato varieties with high anthocyanin content.


Effects of hatha yoga exercises on spine flexibility in women over 50 years old.
[Purpose] The aim of this study was to access the flexibility of the spine in women practicing yoga as a part of the "University for Health" project. [Subjects and Methods] The study included 56 women ranging in age between 50-79 and attending 90 minutes hatha yoga sessions once a week. The measurements were performed twice-at the beginning of the project and after its completion, i.e., after 20 weeks of classes. The range of spine mobility in three planes was measured using a Rippstein plurimeter. The range of motion in the sagittal and frontal planes was measured in a standing position with the feet hip-width apart. The torsional range of motion of the subjects was measured with the trunk bent at a right angle and the legs apart. The flexibility ranges of the spine and hamstrings were also measured by the toe-touch test in a standing position. [Results] This study showed that the applied yoga exercises increased spinal mobility and flexibility of the hamstring muscles regardless of age. [Conclusion] Yoga exercises should be recommended to the elderly to make their muscles more flexible and to increase the range of motion in the joints, which is particularly important for improving their life quality.


A Laser Time-of-Flight Range Scanner for Robotic Vision.
The requirements of three-dimensional scene analysis in support of vision driven robotic manipulation are such that direct range finding capabilities can greatly reduce the computational burden (time and complexity) for reliable determination of the placement and spatial extent of objects in the scene. This paper describes a laser time-of-flight range scanner capable of acquiring a reasonable rangepic of 64 × 64 spatial resolution in 4 s. However, at the current state of development, 100 samples/point are required to achieve a range accuracy of approxi-mately ±¿ cm, with a scan time of 40 s. Returned signal amplitude de-pendency is also apparent in the range determination, the dynamic range of intensity being considerable. Improved accuracy can be traded for tine. The vision/robotics laboratory environment within which the range scanner operates is briefly touched upon and some preliminary rangepic results presented.


Association of socioeconomic position with maternal pregnancy and infant health outcomes in birth cohort studies from Brazil and the UK.
Socioeconomic inequalities in health outcomes are dynamic and vary over time. Differences between countries can provide useful insights into the causes of health inequalities. The study aims to compare the associations between two measures of socioeconomic position (SEP)-maternal education and family income-and maternal and infant health outcomes between ALSPAC and Pelotas cohorts. Birth cohort studies were started in Avon, UK, in 1991 (ALSPAC) and in the city of Pelotas, Brazil, in 1982, 1993 and 2004. Maternal outcomes included smoking during pregnancy, caesarean section and delivery not attended by a doctor. Infant outcomes were preterm birth, intra-uterine growth restriction (IUGR) and breast feeding for <3 months. The relative index of inequality was used for each measure of SEP so that results were comparable between cohorts. An inverse association (higher prevalence among the poorest and less educated) was observed for almost all outcomes, with the exception of caesarean sections where a positive association was found. Stronger income-related inequalities for smoking and education-related inequalities for breast feeding were found in the ALSPAC study. However, greater inequalities in caesarean section and education-related inequalities in preterm birth were observed in the Pelotas cohorts. Mothers and infants have more adverse health outcomes if they are from poorer and less well-educated socioeconomic backgrounds in both Brazil and the UK. However, our findings demonstrate the dynamic nature of the association between SEP and health outcomes. Examining differential socioeconomic patterning of maternal and infant health outcomes might help understanding of mechanisms underlying such inequalities.


[Multiple myeloma: evaluation of invasiveness by magnetic resonance imaging].
The paper presents a case history of multiple myeloma in a female patient. Its diagnosis was established only 10 years after the onset of the disease, which results in severe invalidity (she was treated with calcium preparations in accordance with the diagnosis of generalized osteoporosis. Persistent therapy with calcium preparations was ineffective; the number of pathological fractures increased. Further bone study and current instrumental imaging methods could make a precise diagnosis and use etiotropic treatment, which yielded a positive clinical effect. The data on high-technology studies, body magnetic resonance imaging used in the diagnosis of the diseases accompanied by bone destructive changes are given. The problems in the diagnosis of multiple myeloma are outlined.


Birth defects and exposure to video display terminals during pregnancy. A Finnish case-referent study.
In a test of the widely publicized allegation that exposure to video display terminals causes birth defects, interview forms of mothers of 1 475 children reported consecutively to the Finnish Register of Congenital Malformations to have defects of the central nervous system, orofacial clefts, skeletal defects, or cardiovascular malformations and the forms of the same number of their paired referents were studied. The scrutiny revealed 490 mothers with occupational titles indicating potential exposure to video display terminals. Of the 490, 235 were case mothers and 255 were referents. Then, unaware of the case-referent status, three members of the research team perused the mothers' interview descriptions of workday activities for information indicating exposure to video display terminals. Work with such terminals during the first trimester of pregnancy was ascertained for 111 mothers. Of these, 51 were case mothers and 60 were referents. The comparison of the mothers exposed to video display terminals during the first trimester with those not exposed at all showed a crude odds-ratio point estimate of 0.9 with 95% confidence limits of 0.6 and 1.2. Adjustment for potential confounders by multivariate logistic regression methods did not materially affect the risk estimates. The results did not indicate a teratogenic risk for operators of video display terminals.


TolC2 is required for the resistance, colonization and virulence of Actinobacillus pleuropneumoniae.
Purpose. To colonize and cause infection in the host, pathogens must be well equipped to respond to and survive in several hostile conditions. TolC, an outer membrane channel component used by multidrug efflux pumps and type I secretion systems, is considered to be largely involved in bacterial physiology and virulence. In this study, we attempted to investigate the possible roles of TolC2, a homologue of TolC, in the pathogenesis of Actinobacillus pleuropneumoniae.Methodology. The cell viability was investigated under stress conditions (oxidative, thermal, acid and osmotic). Virulence was assessed by lethal intraperitoneal injection of mice. The underlying mechanisms of the attenuation were further explored by serum bactericidal, in vivo phagocytosis and organ burden assays.Results/Key findings. The deletion of tolC2 caused increased sensitivity to oxidative, thermal and acid challenges, indicating a critical role of TolC2 in A. pleuropneumoniae survival under stress conditions. The intraperitoneal injection of mice showed that the ΔtolC2 mutant caused significantly decreased mortality, suggesting the involvement of TolC2 in the virulence of A. pleuropneumoniae. In the serum-killing assays, the ΔtolC2 mutant showed significantly reduced survival ability when exposed to fresh serum. By the in vivo phagocytosis assays, we found that the loss of tolC2 rendered the mutant susceptible to phagocytosis by macrophages. Finally, the organ burden assays revealed decreased colonization of ΔtolC2 in lungs, indicating a higher bacterial clearance rate in mice in the absence of TolC2.Conclusion. Our findings demonstrate that TolC2 contributes to the virulence of A. pleuropneumoniae by helping survival and maximal colonization in the host.


Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA.
Application of the WHO fracture prediction algorithm in conjunction with an updated US economic analysis indicates that osteoporosis treatment is cost-effective in patients with fragility fractures or osteoporosis, in older individuals at average risk and in younger persons with additional clinical risk factors for fracture, supporting existing practice recommendations. The new WHO fracture prediction algorithm was combined with an updated economic analysis to evaluate existing NOF guidance for osteoporosis prevention and treatment. The WHO fracture prediction algorithm was calibrated to the US population using national age-, sex- and race-specific death rates and age- and sex-specific hip fracture incidence rates from the largely white population of Olmsted County, MN. Fracture incidence for other races was estimated by ratios to white women and men. The WHO algorithm estimated the probability (%) of a hip fracture (or a major osteoporotic fracture) over 10 years, given specific age, gender, race and clinical profiles. The updated economic model suggested that osteoporosis treatment was cost-effective when the 10-year probability of hip fracture reached 3%. It is cost-effective to treat patients with a fragility fracture and those with osteoporosis by WHO criteria, as well as older individuals at average risk and osteopenic patients with additional risk factors. However, the estimated 10-year fracture probability was lower in men and nonwhite women compared to postmenopausal white women. This analysis generally endorsed existing clinical practice recommendations, but specific treatment decisions must be individualized. An estimate of the patient's 10-year fracture risk should facilitate shared decision-making.


The use of principal component analysis in studying physical, chemical and biological soil properties in southern caspian forests (North of Iran).
This research was conducted in Khanikan forests located in lowland of Mazandaran province (North of Iran). Eighteen profiles were dug and several chemical, physical and biological soil properties were investigated. The soil properties evaluated were soil pH, bulk density, saturation moisture content, electrical conductivity, organic carbon, total nitrogen, cation exchangeable capacity, available phosphorous, soil texture, calcium carbonate content, number and biomass of earthworms, litter carbon and litter nitrogen. Principal Component Analysis (PCA) was used to identify the variation of soil properties. PCA, a technique which reduces the dimensionality of multivariate data by removing Interco relations among variables, has a number of useful applications in forest researches. The results showed significant relationships between some soil factors with PC1 and PC2 axes, also, among different soil factors, the distribution of forest types was most strongly controlled with some soil characteristics such as acidity, bulk density, texture, phosphorous, organic carbon, total nitrogen and cation exchangeable capacity.


MAPPING CHILDREN'S POLITICS: SPATIAL STORIES, DIALOGIC RELATIONS AND POLITICAL FORMATION.
This article confronts a persistent challenge in research on children's geographies and politics: the difficulty of recognizing forms of political agency and practice that by definition fall outside of existing political theory. Children are effectively "always already" positioned outside most of the structures and ideals of modernist democratic theory, such as the public sphere and abstracted notions of communicative action or "rational" speech. Recent emphases on embodied tactics of everyday life have offered important ways to recognize children's political agency and practice. However, we argue here that a focus on spatial practices and critical knowledge alone cannot capture the full range of children's politics, and show how representational and dialogic practices remain a critical element of their politics in everyday life. Drawing on de Certeau's notion of spatial stories, and Bakhtin's concept of dialogic relations, we argue that children's representations and dialogues comprise a significant space of their political agency and formation, in which they can make and negotiate social meanings, subjectivities, and relationships. We develop these arguments with evidence from an after-school activity programme we conducted with 10-13 year olds in Seattle, Washington, in which participants explored, mapped, wrote and spoke about the spaces and experiences of their everyday lives. Within these practices, children negotiate autonomy and self-determination, and forward ideas, representations, and expressions of agreement or disagreement that are critical to their formation as political actors.


Effects of photostimulatory light intensity on ovarian morphology and carcass traits at sexual maturity in modern and antique egg-type pullets.
The effects of light intensity during sexual maturation on ovarian and carcass morphology at first oviposition [sexual maturity (SM)] were examined in two Single Comb White Leghorn (SCWL) strains. A modern commercial layer strain (COMM; Shaver Starcross 288) and an antique randombred control strain (ANT) were used to compare the effects of changes in laying stock on their response to varying light intensities from photostimulation (PS) until SM. Two hundred pullets from each strain were reared following COMM breeder guidelines. At 18 wk of age, 32 COMM and 32 ANT pullets were individually caged in individually lit cages and photostimulated with light intensities of 1, 5, 50, and 500 lx. Each bird was processed when it reached SM, and carcass and ovarian morphology were assessed. The ANT birds came into production 9.1 d later than the COMM birds, on average. The ANT pullets consumed 7.0% more feed per day than COMM pullets but gained at a slower rate (ANT = 12.9 g/d; COMM = 15.0 g/d). The ANT birds reached SM at a greater weight and with a smaller ovary than did COMM birds. Although the number of large yellow follicles (LYF) was similar between strains (mean = 6.72), both LYF weight and first egg weight were lower in ANT birds than in COMM birds. The COMM layer strain was more growth efficient and had a greater emphasis on ovary maintenance. Light intensity had no effect on the timing of SM or on BW at SM, indicating that all intensities used were effectively able to stimulate the sexual maturation process. However, ovary weight and number of LYF exhibited an increasing dose response to light intensity, particularly in the COMM birds. Overall, the birds photostimulated with 1 lx of light had reduced ovary development and were heavier than their counterparts exposed to 50 and 500 lx. Within the ANT strain, LYF numbers were not significantly affected by light intensities, whereas, within the COMM strain, LYF numbers were 4.88, 6.63, 7.88, and 8.13 for the 1-, 5-, 50-, and 500-lx intensity groups, respectively. Although light intensity did not affect the rate of sexual maturation, it altered ovarian morphology and carcass lipid stores. A light intensity of 1 lx was limiting to ovarian follicle formation and caused increased carcass weight compared with birds on higher light intensity treatments. The COMM birds were more negatively affected by low light intensity than were the ANT birds, indicating that light intensity may be a more critical environmental factor with modern, highly efficient SCWL strains than has previously been thought. Light intensity can affect the reproductive development and likely the associated egg production potential of modern layer stocks.


Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy.
Systemic rheumatoid vasculitis (SRV) is a rare but potentially serious systemic disease manifestation of rheumatoid arthritis (RA) characterized by the development of necrotizing vasculitis. The incidence of SRV appears to be decreasing possibly reflecting progress in RA treatment. The aims of this study were to review the clinical manifestations of SRV in a stable well-defined population during 2001-10 and to compare with our previous cohort (1988-2000) and also a cohort from 1975 to 1981. Using Norfolk Vasculitis Register, a prospective register of patients with systemic vasculitis since 1988, all patients with a diagnosis of SRV from 1 January 2001 until 31 December 2010 were identified. SRV was defined according to the Scott and Bacon criteria (1984). Clinical features were obtained by retrospective case note review. Eighteen patients with SRV were identified (10 male), median age at diagnosis was 72 years and average disease duration 15.6 years. The average annual incidence for 2001-10 was 3.9 per million. One-year mortality was 12% and 5-year mortality 60%. The clinical manifestations were similar apart from systemic and cutaneous features which were more common in the earlier cohorts. The incidence of SRV has declined significantly in the last 40 years; but the clinical manifestations remain similar. Systemic symptoms, and cutaneous manifestations such as infarcts and nodules, are slightly less common in the recent cohort. Despite modern immunosuppressive therapy the prognosis remains poor.


Alternative tricortical methods of screw implantation for anterior cervical plate fixation: a preliminary report.
An experience with 26 cases of anterior cervical interbody plate fixation with an alternative method of screw implantation is described. The follow up ranges from 15 to 51 months. The screws are placed obliquely such that they engage the anterior cortex of the body and traverse through the cortices adjoining the disc space. By this method the screws not only hold the plate firmly with a tricortical purchase, but also, by virtue of their course, stabilise the two adjoining vertebral bodies by themselves. In five of these cases only tricortical screws without the metal plate were used for fixation. Cortico-cancellous iliac crest bone graft shredded into small pieces is placed between the vertebral bodies after adequately preparing the bed. A 100% bony union rate was achieved, with no morbidity or instrument fatigue or failure. The described technique of plate fixation appears to be biomechanically stronger. It provided a rigid segmental internal fixation permitting early mobilisation of the patient with minimal external support.


[The use of an optical polarization method for the evaluation of oculomotor muscle function in vertical deviation].
The state of oculomotor muscles in vertical deviation has been studied by means of polarioptic method. A control group included 62 healthy persons, of them 24 (48 eyes) with orthophoria, 19 (38 eyes) with esophoria and 19 (38 eyes) with exophoria. A group of patients with vertical deviation included 39 (78 eyes) with concomitant convergent squint with a vertical component and 9 children (18 eyes) with concomitant vertical squint without a horizontal component. In patients with vertical squint, the polarioptic method revealed high frequency of functional muscular imbalance and anatomic asymmetry of muscles of both horizontal and vertical action. It is shown that in case of convergent squint with a vertical action, not only the frequency is higher, but to a much greater degree increases the value of anatomic asymmetry in the position of horizontal muscles.


Predictive Factors for the Evolution of Reactive Arthritis to Ankylosing Spondylitis.
The goal of this study is to identify the predictive factors involved in the evolution of the reactive arthritis to ankylosing spondylitis by following the presence and degree of sacroiliitis and also the appeareance of acute anterior uveitis. The study was performed between 01.01.2011- 31.12.2014 on 112 patients, aged between 17 and 47 years old, in evidence of the Rheumatology Clinic of the Clinical Hospital Emergency Craiova. The patients were divided in 2 lots according to the radiological criteria: the first lot included 52 patients diagnosed with reactive arthritis, with the determination of the pathogen agent involved and the demonstration of sacroiliitis first degree by Nuclear Magnetic Resonance (IRM). The second lot included a number of 60 patients diagnosed with reactive arthritis, without presenting significant changes in the sacroiliac joints and at the cervico-dorsal- lumbar spine. In the first batch, the performance of the IRM and monitoring the patients every 6 months over 3 years revealed the progression of sacroiliitis from first degree in which it was at the moment of diagnosing at second degree in a 6 month period. Three years after initiation of therapy for reactive arthritis, the patients from the second batch responded favorably to treatment, the performance of imaging not revealing signs of sacroiliitis. Association of sacroiliitis at baseline proved to be a negative prognostic factor in reactive arthritis, which can suggest the evolution to ankylosing spondylitis, monitoring these patients being necessary for at least 3 years from the point of diagnosing.


Evaluation of the lymphocyte trafficking drug FTY720 in SHIVSF162P3-infected rhesus macaques.
FTY720 causes retention of lymphocytes in lymphatic tissues. Previous studies revealed that FTY720 can decrease or eliminate chronic viral infections of mice. We address here whether therapeutic use of FTY720 in simian human immunodeficiency virus (SHIV)-infected rhesus macaques could also decrease viraemia. FTY720 was administered intravenously to three SHIV(SF162P3)-infected macaques at 39, 7 or 6 weeks of infection; three control macaques (47, 48 or 6 weeks of infection) did not receive drug. FTY720 was given at 0.004 mg/kg on days 0, 1, 2, 14, 15 and 16, followed by 0.1 mg/kg on days 28, 29, 30, 42, 43 and 44. Blood was collected seven times throughout and four times during 47 days of follow-up. Only the 0.1 mg/kg dose resulted in a reduction in mean blood CD4+ T cells and B cells (to 33% and 27% of pre-drug levels, P=0.0024 and 0.003, respectively). FTY720 treatment did not lead to significant deviations from the natural pattern of viral control. Plasma viraemia progressed from a range of 10(4)-10(2) copies/mL before treatment to 10(4)-temporarily undetectable levels on the last day of treatment. SHIV(SF162P3) was not eliminated, however, as plasma viraemia and proviral DNA persisted during the follow-up. No significant alterations in T cell activity were noted throughout the drug course. FTY720 administration had no detectable therapeutic effect at the doses and schedules outlined here, although blood CD4+ T cells and B cells were effectively reduced. Future work might reveal whether FTY720 could be beneficial in more pathogenic SHIV, simian immunodeficiency virus or HIV infections.


Bateman's principle and immunity in a sex-role reversed pipefish.
In diverse animal species, from insects to mammals, females display a more efficient immune defence than males. Bateman's principle posits that males maximize their fitness by increasing mating frequency whereas females gain fitness benefits by maximizing their lifespan. As a longer lifespan requires a more efficient immune system, these implications of Bateman's principle may explain widespread immune dimorphism among animals. Because in most extant animals, the provisioning of eggs and a higher parental investment are attributes of the female sex, sex-role reversed species provide a unique opportunity to assess whether or not immune dimorphism depends on life history and not on sex per se. In the broad-nosed pipefish Syngnathus typhle, males brood and nourish the eggs in a ventral pouch and thus invest more into reproduction than females. We found males to have a more active immune response both in field data from four populations and also in an experiment under controlled laboratory conditions. This applied to different measures of immunocompetence using innate as well as adaptive immune system traits. We further determined the specificity of immune response initiation after a fully factorial primary and secondary exposure to a common marine pathogen Vibrio spp. Males not only had a more active but also a more specific immune defence than females. Our results thus indeed suggest that the sex that invests more into the offspring has the stronger immune defence.


Predicting the activity phase of a follower neuron with A-current in an inhibitory network.
The transient potassium A-current is present in most neurons and plays an important role in determining the timing of action potentials. We examine the role of the A-current in the activity phase of a follower neuron in a rhythmic feed-forward inhibitory network with a reduced three-variable model and conduct experiments to verify the usefulness of our model. Using geometric analysis of dynamical systems, we explore the factors that determine the onset of activity in a follower neuron following release from inhibition. We first analyze the behavior of the follower neuron in a single cycle and find that the phase plane structure of the model can be used to predict the potential behaviors of the follower neuron following release from inhibition. We show that, depending on the relative scales of the inactivation time constant of the A-current and the time constant of the recovery variable, the follower neuron may or may not reach its active state following inhibition. Our simple model is used to derive a recursive set of equations to predict the contribution of the A-current parameters in determining the activity phase of a follower neuron as a function of the duration and frequency of the inhibitory input it receives. These equations can be used to demonstrate the dependence of activity phase on the period and duty cycle of the periodic inhibition, as seen by comparing the predictions of the model with the activity of the pyloric constrictor (PY) neurons in the crustacean pyloric network.


Polyglutamylation and polyglycylation of alpha- and beta-tubulins during in vitro ciliated cell differentiation of human respiratory epithelial cells.
Tubulins are the major proteins within centriolar and axonemal structures. In all cell types studied so far, numerous alpha- and beta-tubulin isoforms are generated both by expression of a multigenic family and various post-translational modifications. We have developed a primary culture of human nasal epithelial cells where the ciliated cell differentiation process has been observed and quantified. We have used this system to study several properties concerning polyglutamylation and polyglycylation of tubulin. GT335, a monoclonal antibody directed against glutamylated tubulins, stained the centriole/basal bodies and the axonemes of ciliated cells, and the centrioles of non-ciliated cells. By contrast, axonemal but not centriolar tubulins were polyglycylated. Several polyglutamylated and polyglycylated tubulin isotypes were detected by two-dimensional electrophoresis, using GT335 and a specific monoclonal antibody (TAP952) directed against short polyglycyl chains. Immunoelectron microscopy experiments revealed that polyglycylation only affected axonemal tubulin. Using the same technical approach, polyglutamylation was shown to be an early event in the centriole assembly process, as gold particles were detected in fibrogranular material corresponding to the first cytoplasmic structures involved in centriologenesis. In a functional assay, GT335 and TAP952 had a dose-dependent inhibitory effect on ciliary beat frequency. TAP952 had only a weak effect while GT335 treatment led to a total arrest of beating. These results strongly suggest that in human ciliated epithelial cells, tubulin polyglycylation has only a structural role in cilia axonemes, while polyglutamylation may have a function both in centriole assembly and in cilia activity.


Neuronal insulin signaling and resistance: a balancing act of kinases and phosphatases.
Insulin signaling cascade in peripheral insulin-sensitive tissues regulates whole-body glucose metabolism. Any deregulation in this pathway leads to insulin resistance, ultimately leading to metabolic diseases like type 1 diabetes, type 2 diabetes, and obesity. Insulin signaling in the brain has also been studied for many decades and associated with many primary functions like maintenance of synaptic plasticity, regulation of cognition, and circadian rhythm. Importantly, neuronal insulin signaling has also been associated with the regulation of neuronal glucose uptake. Any impairment in neuronal insulin signaling affecting neuronal glucose uptake has been associated with neurodegenerative disorders like Alzheimer's disease, the process now being termed as type 3 diabetes. Since the criticality lies in proper signaling cascade, determining important points of deregulation is important. In this review, we have discussed some critical points of such deregulation, dividing them into two classes of enzymes: kinases and phosphatases. We have highlighted their individual roles in neuronal insulin signaling, along with their possible implications in neuronal insulin resistance. Future strategies targeting these nodes in neuronal insulin signaling might be helpful in exploring potential therapeutic opportunities to overcome neuronal insulin resistance and related neurodegenerative diseases.


Mechanical circulatory devices for the treatment of heart failure.
During the last four decades substantial efforts have been made in the development of effective mechanical circulatory devices. Since the first clinical utilization in the 1960s, the field has gone from the stage of clinical experimentation to that of a valid and effective heart failure treatment alternative. Experience gained during the short-term use of these devices, typically as a bridge to cardiac transplantation, has led to increased expectations of devices capable of long-term or permanent support to be used as a permanent treatment for end-stage heart failure patients. This article reviews the history, current state of the art, and future of the field of mechanical circulatory devices. Mechanical circulatory devices can be classified into three major categories: (1) total artificial hearts, (2) pulsatile ventricular assist devices, and (3) nonpulsatile ventricular assist devices. The most widely used devices have been the pulsatile ventricular assist devices with more than 5,800 reported cases, whereas the use of total artificial hearts has been limited to less than 350 reported cases. Nonpulsatile devices have been used clinically, but only in short-term cases (i.e., hours and days), whereas the pulsatile devices have been used in the long-term application, with patients supported for weeks, months, and in a small number of cases, years. The technological evolution of these devices has gone from large, extracorporeal systems designed to keep the patient alive in the intensive care unit (ICU) until a donor organ could be found, to portable devices that allow the patient to be mobilized outside of the hospital setting. The clinical experience with mechanical circulatory devices as a bridge to cardiac transplantation has saved the lives of thousands of patients. Exciting new research discoveries related to recovery of native heart function during extended circulatory support have provided new hope for many more patients. Additional research efforts currently underway are being tested at various laboratories around the world and will soon provide the next generation of systems. These new systems will offer the recipients an unparalleled quality of life with minimal limitations on daily activities. The progress in this field has reached the point where circulatory support will soon be considered a valid long-term or permanent therapy and an elective to transplantation.


Bioactive dammarane-type saponins from Operculina turpethum.
Four new dammarane-type saponins, operculinosides A-D (1-4), were isolated from the aerial parts of Operculina turpethum, of which 1 and 2 are the first two dammarane-type triterpenoids having an oxymethyl group at C-24. Their structures were determined by spectroscopic analysis and acid hydrolysis. The absolute configuration of operculinoside A (1) was confirmed by X-ray crystallography. Compounds 1 and 3 showed significant protective activities against d-galactosamine-induced toxicity in L-02 human hepatic cells.


What Is Case Management? A Scoping and Mapping Review.
The description of case management in research and clinical practice is highly variable which impedes quality analysis, policy and planning. Case management makes a unique contribution towards the integration of health care, social services and other sector services and supports for people with complex health conditions. There are multiple components and variations of case management depending on the context and client population. This paper aims to scope and map case management in the literature to identify how case management is described in the literature for key complex health conditions (e.g., brain injury, diabetes, mental health, spinal cord injury). Following literature searches in multiple databases, grey literature and exclusion by health condition, community-based and adequate description, there were 661 potential papers for data extraction. Data from 79 papers (1988-2013) were analysed to the point of saturation (no new information) and mapped to the model, components and activities. The results included 22 definitions, five models, with 69 activities or tasks of case managers mapped to 17 key components (interventions). The results confirm the significant terminological variance in case management which produces role confusion, ambiguity and hinders comparability across different health conditions and contexts. There is an urgent need for an internationally agreed taxonomy for the coordination, navigation and management of care.


A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein.
We have identified and purified a platelet integral membrane protein (140,000 mol wt), using the KC4 monoclonal antibody specific for activated platelets, that is internal in resting platelets but exposed on activated platelets (Hsu-Lin S.-C., C.L. Berman, B.C. Furie, D. August, and B. Furie, 1984, J. Biol. Chem. 259: 9121-9126.). The expression of the protein on the platelet surface is secretion-dependent. This protein has been named platelet activation-dependent granule-external membrane (PADGEM) protein. PADGEM protein is distinct from the surface glycoproteins of resting platelets, but identical to the S12 antigen, GMP-140. Using immunofluorescent staining, resting platelets failed to stain for PADGEM protein with the KC4 antibody, but after permeabilization showed a punctate staining of the cell interior. Thrombin-stimulated intact platelets stained with a peripheral rim pattern thus demonstrating the translocation of PADGEM protein from an internal location to the cell surface. PADGEM protein expression on the platelet surface at varying thrombin concentrations correlated with alpha granule release, as measured by the secretion of platelet factor 4. Further evidence for an alpha granule localization of PADGEM protein was provided by nitrogen cavitation of resting platelets followed by metrizamide density gradient centrifugation; PADGEM protein codistributed with platelet factor 4. Using immunoelectron microscopy, the protein was localized to the alpha granule in frozen ultrathin sections of resting platelets labeled using rabbit anti-PADGEM protein antibodies, whereas in thrombin-activated platelets, the plasma membrane was labeled. These studies indicate that PADGEM protein is a component of the alpha granule membrane of resting platelets and is incorporated into the plasma membrane upon activation and secretion.


Synthetic quorum sensing in model microcapsule colonies.
Biological quorum sensing refers to the ability of cells to gauge their population density and collectively initiate a new behavior once a critical density is reached. Designing synthetic materials systems that exhibit quorum sensing-like behavior could enable the fabrication of devices with both self-recognition and self-regulating functionality. Herein, we develop models for a colony of synthetic microcapsules that communicate by producing and releasing signaling molecules. Production of the chemicals is regulated by a biomimetic negative feedback loop, the "repressilator" network. Through theory and simulation, we show that the chemical behavior of such capsules is sensitive to both the density and number of capsules in the colony. For example, decreasing the spacing between a fixed number of capsules can trigger a transition in chemical activity from the steady, repressed state to large-amplitude oscillations in chemical production. Alternatively, for a fixed density, an increase in the number of capsules in the colony can also promote a transition into the oscillatory state. This configuration-dependent behavior of the capsule colony exemplifies quorum-sensing behavior. Using our theoretical model, we predict the transitions from the steady state to oscillatory behavior as a function of the colony size and capsule density.


Alternative strategies for increasing employment.
As states reform their welfare systems to emphasize work and self-sufficiency, they can draw on significant past experience with efforts to promote employment. Work and training programs for welfare recipients and other disadvantaged individuals have been operating in every state for nearly 30 years. This article summarizes findings from key evaluations of strategies to increase the employment and earnings of individuals. The article also reviews lessons about program design and management drawn from studies of program outcomes and implementation. Evaluations of net impact typically measure outcomes for randomly selected individuals who participated in programs, and compare those with outcomes for individuals who did not receive the treatment. Studies of program outcome and implementation analyze the effectiveness of entire programs in real-world operational settings. The evidence from net-impact evaluations shows that programs that encourage, help, or require welfare recipients to find jobs or participate in training or work-related activities can increase employment and earnings and in some cases reduce welfare costs. Even the most successful programs, however, yield only small gains in earnings that do not move most former welfare recipients out of poverty. The article also discusses critical policy and implementation issues that influence the effectiveness of welfare-to-work programs overall. It focuses on strategies for increasing rates of participation in the programs, for improving implementation, and for strengthening links with the local labor market, which ultimately determines the success or failure of any welfare-to-work program.


Patterns of usual care for schizophrenia: initial results from the Schizophrenia Patient Outcomes Research Team (PORT) Client Survey.
To examine the conformance of current patterns of usual care for persons with schizophrenia to the Schizophrenia Patient Outcomes Research Team (PORT) Treatment Recommendations, the PORT surveyed a stratified random sample of 719 persons diagnosed with schizophrenia in two States. The types of treatment settings surveyed included acute inpatient programs and continuing outpatient programs in urban and rural locales. Using data from medical record reviews and patient interviews, the PORT assessed the conformance of current care with 12 of the Treatment Recommendations. The rates at which patients' treatment conformed to the recommendations were modest at best, generally below 50 percent. Conformance rates were higher for pharmacological than for psychosocial treatments and in rural areas than in urban ones. Rates of Treatment Recommendation conformance for minority patients were lower than those for Caucasians, and patterns of care varied between the two States. The findings indicate that current usual treatment practices likely fall substantially short of what would be recommended based on the best evidence on treatment efficacy. This disparity underscores the need for greater efforts to ensure that treatment research results are translated into practice.


Evaluating fMRI-Based Estimation of Eye Gaze During Naturalistic Viewing.
The collection of eye gaze information during functional magnetic resonance imaging (fMRI) is important for monitoring variations in attention and task compliance, particularly for naturalistic viewing paradigms (e.g., movies). However, the complexity and setup requirements of current in-scanner eye tracking solutions can preclude many researchers from accessing such information. Predictive eye estimation regression (PEER) is a previously developed support vector regression-based method for retrospectively estimating eye gaze from the fMRI signal in the eye's orbit using a 1.5-min calibration scan. Here, we provide confirmatory validation of the PEER method's ability to infer eye gaze on a TR-by-TR basis during movie viewing, using simultaneously acquired eye tracking data in five individuals (median angular deviation < 2°). Then, we examine variations in the predictive validity of PEER models across individuals in a subset of data (n = 448) from the Child Mind Institute Healthy Brain Network Biobank, identifying head motion as a primary determinant. Finally, we accurately classify which of the two movies is being watched based on the predicted eye gaze patterns (area under the curve = 0.90 ± 0.02) and map the neural correlates of eye movements derived from PEER. PEER is a freely available and easy-to-use tool for determining eye fixations during naturalistic viewing.