Harmful alcohol use among injured adult patients presenting to a Ghanaian emergency department.
We performed a nested convenience sample survey of harmful alcohol use among injured patients aged 18 years and older treated in the Komfo Anokye Teaching Hospital (Kumasi, Ghana) emergency department (ED). Data from the Alcohol Use Disorder Identification Test, alcohol breath or saliva tests, patient demographics and injury characteristics were collected from an administered survey and medical chart review. A total of 403 subjects were surveyed, and 107 (27%; 95% CI 22 to 31) reported harmful alcohol use. High rates of harmful alcohol use were found among males (35%), acutely alcohol-positive subjects (55%), drivers (32%), pedestrians (35%) and assault victims (43%). A substantial proportion of injured patients reported harmful alcohol use. The data obtained support routine screening of injured patients presenting to Ghanaian EDs for harmful alcohol use.


Anxiety, Depression, and Coping Skills Among Mexican School Children: A Comparison of Students With and Without Learning Disabilities.
The purpose of this study was to compare severity and risk status for anxiety and depression with coping skills among 130 Mexican school children with learning disabilities (LD) and 130 school children without LD. This research is the first to explore the emotional difficulties of Mexican children with LD. Children completed the Spanish version of the Spence Children's Anxiety Scale and Children's Depression Inventory, and the Cuestionario de Afrontamiento (Coping Skills Questionnaire). Results indicated that a higher percentage of children with LD were at risk for anxiety (22.3% vs. 11.5%) and depression (32% vs. 18%). No statistically significant differences were found for coping skills. Results support the idea that there is an increased awareness of comorbid depression and anxiety among students with LD and a need to promote early identification and intervention in schools. Efforts should focus on better understanding the relationship between social-emotional difficulties and academic achievement and on developing effective interventions to support children with LD.


Theoretical framework for analyzing structural compliance properties of proteins.
We propose methods for directly analyzing structural compliance (SC) properties of elastic network models of proteins, and we also propose methods for extracting information about motion properties from the SC properties. The analysis of SC properties involves describing the relationships between the applied forces and the deformations. When decomposing the motion according to the magnitude of SC (SC mode decomposition), we can obtain information about the motion properties under the assumption that the lower SC mode motions or the softer motions occur easily. For practical applications, the methods are formulated in a general form. The parts where forces are applied and those where deformations are evaluated are separated from each other for enabling the analyses of allosteric interactions between the specified parts. The parts are specified not only by the points but also by the groups of points (the groups are treated as flexible bodies). In addition, we propose methods for quantitatively evaluating the properties based on the screw theory and the considerations of the algebraic structures of the basic equations expressing the SC properties. These methods enable quantitative discussions about the relationships between the SC mode motions and the motions estimated from two different conformations; they also help identify the key parts that play important roles for the motions by comparing the SC properties with those of partially constrained models. As application examples, lactoferrin and ATCase are analyzed. The results show that we can understand their motion properties through their lower SC mode motions or the softer motions.


Systematic review of the effect of diet and exercise lifestyle interventions in the secondary prevention of coronary heart disease.
The effectiveness of lifestyle interventions within secondary prevention of coronary heart disease (CHD) remains unclear. This systematic review aimed to determine their effectiveness and included randomized controlled trials of lifestyle interventions, in primary care or community settings, with a minimum follow-up of three months, published since 1990. 21 trials with 10,799 patients were included; the interventions were multifactorial (10), educational (4), psychological (3), dietary (1), organisational (2), and exercise (1). The overall results for modifiable risk factors suggested improvements in dietary and exercise outcomes but no overall effect on smoking outcomes. In trials that examined mortality and morbidity, significant benefits were reported for total mortality (in 4 of 6 trials; overall risk ratio (RR) 0.75 (95% confidence intervals (CI) 0.65, 0.87)), cardiovascular mortality (3 of 8 trials; overall RR 0.63 (95% CI 0.47, 0.84)), and nonfatal cardiac events (5 of 9 trials; overall RR 0.68 (95% CI 0.55, 0.84)). The heterogeneity between trials and generally poor quality of trials make any concrete conclusions difficult. However, the beneficial effects observed in this review are encouraging and should stimulate further research.


Glucocorticoids increase osmotic water permeability (Pf) of neonatal rabbit renal brush border membrane vesicles.
During postnatal maturation, there is an increase in renal brush border membrane vesicle (BBMV) osmotic water permeability and a parallel increase in aquaporin-1 (AQP1) protein abundance. The mechanisms responsible for these changes remain unknown. Because serum glucocorticoid levels rise postnatally and have previously been linked to other maturational changes in renal function, we examined the effects of glucocorticoids on osmotic (Pf) and diffusional (P(DW)) water permeability and AQP1 protein abundance of renal BBMV. Neonatal rabbits were treated with dexamethasone (10 microg/100 g) for three days and compared with control neonates and adults. Pf and P(DW) were measured at 20 degrees C with a stopped-flow apparatus using light-scattering and aminonaphthalene trisulfonic acid (ANTS) fluorescence, respectively. Pf was significantly higher in BBMV from dexamethasone-treated neonates compared with vehicle-treated neonates, but remained lower than in BBMV from adults (P<0.05). P(DW) in dexamethasone and vehicle-treated neonatal BBMV was lower than in adult BBMV. Pf/P(DW) ratio increased from neonate (5.1+/-0.3) to dexamethasone (7.0+/-0.1) and adult BBMV (6.3+/-0.1). AQP1 expression was increased by dexamethasone treatment to adult levels. Membrane fluidity, which is inversely related to generalized polarization (GP) of steady-state laurdan fluorescence, was significantly higher in neonatal BBMV than both dexamethasone and adult BBMV (GP: neonate 0.285+/-0.002, dexamethasone treatment 0.302+/-0.006, and adult 0.300+/-0.005; P<0.05). These combined results show that dexamethasone-treatment during days 4-7 of life increases BBMV water permeability despite a decrease in membrane fluidity. This occurs by increasing channel-mediated water transport, as reflected in an increase in AQP1 protein abundance and a higher Pf/P(DW) ratio. This mimics the maturational changes and suggests a physiological role for glucocorticoids in maturation of proximal tubule water transport.


A comparison of bone mineral density between Caucasian, Asian and Afro-Caribbean women.
1. We analysed the lumbar spine (L2-L4) and femoral neck bone mineral density results of Caucasian (n = 2232), Asian (Indian sub-continent) (n = 153) and Afro-Caribbean (n = 102) women referred for bone densitometry over a 30 month period. To assess the risk of osteoporosis, the results of Caucasian and Asian women were compared with those of a reference Caucasian population supplied by Lunar. 2. Subject characteristics were similar in all three groups, other than expected ethnic differences in stature and weight. We found that lumbar spine and femoral neck bone mineral density in Caucasians was lower than in Afro-Caribbeans, but higher than in Asians. Consistent with this, bone mineral density was also lower in Asians as compared with the reference Caucasian population, both at the lumbar spine and femoral neck. As a consequence, a higher proportion of Asian women were classified as being at increased risk of osteoporosis than Caucasian women. 3. Since ethnic differences in skeletal size might influence bone mineral density, we also obtained values for bone mineral content in Caucasian and Asian women that were corrected for projected skeletal area, and weight and years since menopause, using regression equations derived from the Caucasian study population. After this analysis, the difference in bone mineral content between Caucasians and Asians at the lumbar spine disappeared, while that at the femoral neck persisted. 4. We conclude that the assessment of risk of osteoporosis in Asian women by comparing bone mineral density with a reference Caucasian population may have limited validity because of the influence of skeletal size on such measurements.


Metric learning for text documents.
Many algorithms in machine learning rely on being given a good distance metric over the input space. Rather than using a default metric such as the Euclidean metric, it is desirable to obtain a metric based on the provided data. We consider the problem of learning a Riemannian metric associated with a given differentiable manifold and a set of points. Our approach to the problem involves choosing a metric from a parametric family that is based on maximizing the inverse volume of a given data set of points. From a statistical perspective, it is related to maximum likelihood under a model that assigns probabilities inversely proportional to the Riemannian volume element. We discuss in detail learning a metric on the multinomial simplex where the metric candidates are pull-back metrics of the Fisher information under a Lie group of transformations. When applied to text document classification the resulting geodesic distance resemble, but outperform, the tfidf cosine similarity measure.


Leukocyte immunoglobulin-like receptors: novel innate receptors for human basophil activation and inhibition.
Basophils, recruited from the blood to tissues, have been implicated by their presence in diverse allergic disorders including bronchial asthma, allergic rhinitis, and cutaneous contact hypersensitivity. We hypothesized that like other leukocytes involved in inflammatory responses, basophils would express members of the leukocyte immunoglobulin-like receptor (LIR) family of immuno-regulatory molecules on their cell surface. We identified LIR7, an activating member coupled to the common Fc receptor gamma chain, and LIR3, an inhibitory member containing cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, on these cells from human peripheral blood. Cross-linking of LIR7 resulted in the concentration-dependent net release of histamine (29.8 +/- 10.8%) and cysteinyl leukotrienes (cysLTs) (31.4 +/- 8.7 ng/10(6) basophils) that were maximal at 30 minutes, and of interleukin-4 (IL-4) (410.2 +/- 61.6 pg/10(6) basophils) that was maximal at 4 hours and comparable with the response initiated by cross-linking of the high-affinity receptor for immunoglobulin E (FcepsilonRI). Coligation of LIR3 to LIR7 or to FcepsilonRI by means of a second monoclonal antibody significantly inhibited net histamine release, cysLT production, and IL-4 generation. That LIR3 is profoundly counter-regulatory for both adaptive and innate receptors suggests a broad role in containment of the inflammatory response.


Significance of the dimensional view for visualizing relevant aspects of a production system in a co-operative planning process.
Pictorial visualization is expected to facilitate communication between industrial professionals when planning working environments and production systems. This hypothesis was investigated by studying how 24 participants including managers, supervisors, machine operators, and occupational health and safety officials, judged three types of computer animated visualization varying in dimensional view (scale and scope of a production line): shop floor view/survey of shop floor; production unit view/semi-survey of production unit; and workplace view/close-up of workplace, in relation to a set of planning issues. The participants participated in a controlled 2-day planning workshop, redesigning a fictitious manufacturing process by means of computer graphics, and then responded to a questionnaire. It can be concluded that shop floor view as well as production unit view are significant for survey planning issues, while all 3-dimensional views are significant for close-up planning issues. Analogously, all dimensional views are significant for technocentric planning issues, whereas only the workplace view is valuable for anthropocentric planning issues.


A Comparison of Fecal Immunochemical and High-Sensitivity Guaiac Tests for Colorectal Cancer Screening.
Annual testing using either a high-sensitivity guaiac fecal occult blood test (HS-gFOBT) or a fecal immunochemical test (FIT) is recommended for screening average-risk people for colorectal cancer. We compared the performance characteristics of the HS-gFOBT Hemoccult II SENSA and two FITs (InSure FIT and OC FIT-CHEK) for detecting advanced colorectal neoplasia. The study included 1,006 asymptomatic patients, aged 50-75 years, who were scheduled to receive a screening colonoscopy at gastroenterology practices in the Minneapolis and Indianapolis metropolitan areas. Each participant was asked to complete all three stool tests before their colonoscopy. Each test's performance characteristics were evaluated using the screening colonoscopic results as the reference standard. Sensitivity for detecting advanced colorectal neoplasia was highest for InSure FIT (26.3%, 95% confidence interval (CI) 15.9-40.7), followed by OC FIT-CHEK (15.1%, 95% CI 6.7-26.1) and Hemoccult II SENSA (7.4%, 95% CI 1.9-17.0). InSure FIT was statistically significantly more sensitive than both OC FIT-CHEK (absolute difference in sensitivity=11.2%, 95% CI 0.4-24.2) and Hemoccult II SENSA (difference in sensitivity=18.9%, 95% CI 10.2-32.6). Specificities were relatively high for all tests (between 96.8% and 98.6%). Our results suggest that some FITs are more sensitive than the HS-gFOBT Hemoccult II SENSA, but these results need to be confirmed in larger asymptomatic populations. Comparisons between the FITs examined in this study and other FITs are needed to determine the best tests for population screening.


A Randomized, Double-blind, Active-controlled Phase III Trial of a Cell Culture-derived Quadrivalent Inactivated Influenza Vaccine in Healthy South Korean Children and Adolescents 6 Months to 18 Years of Age.
Cell culture-derived influenza vaccines have several important advantages over egg-based influenza vaccines. The quadrivalent influenza vaccine may offer broader protection against seasonal influenza than trivalent influenza vaccine by containing 1 more B strain. The purpose of this study was to evaluate the immunogenicity and safety of NBP607-QIV, a novel cell culture-derived inactivated quadrivalent influenza vaccine (cIIV4), in children and adolescents. This phase III, randomized, double-blind, multicenter trial in children/adolescents (6 mo to 18 yr) was conducted in South Korea during 2014-2015 season. Subjects were randomized 4:1 to receive either NBP607-QIV or control inactivated trivalent influenza vaccine. Hemagglutination inhibition antibody titers were assessed in prevaccination and 28 days postvaccination sera. Safety data were collected for up to 6 months postvaccination. A total of 454 participants completed the study. Three-hundred sixty-six subjects received cIIV4 and 88 subjects received inactivated trivalent influenza vaccine. Overall, NBP607-QIV met the immunogenicity criteria of Committee for Medicinal Products for Human Use for each of the 4 strains. Between the NBP607-QIV and control groups, immunogenicity endpoints were comparable. Participants younger than 3 years of age had lower immunologic responses to 2 influenza B strains in both NBP607-QIV and control group. No deaths, vaccine-related serious adverse events (AEs) or withdrawals because of AEs were reported. The solicited AEs reported were generally of mild intensity. NBP607-QIV, a novel cIIV4, showed good immunogenicity to all 4 influenza strains and had tolerable safety profiles in children and adolescents. Moreover, NBP607-QIV was more immunogenic against influenza B compared with the control, an egg-based subunit vaccine.


Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.
The tight junction protein claudin-2 is upregulated in disease. Although many studies have linked intestinal barrier loss to local and systemic disease, these have relied on macromolecular probes. In vitro analyses show, however, that these probes cannot be accommodated by size- and charge-selective claudin-2 channels. We sought to define the impact of claudin-2 channels on disease. Transgenic claudin-2 overexpression or IL-13-induced claudin-2 upregulation increased intestinal small cation permeability in vivo. IL-13 did not, however, affect permeability in claudin-2-knockout mice. Claudin-2 is therefore necessary and sufficient to effect size- and charge-selective permeability increases in vivo. In chronic disease, T cell transfer colitis severity was augmented or diminished in claudin-2-transgenic or -knockout mice, respectively. We translated the in vitro observation that casein kinase-2 (CK2) inhibition blocks claudin-2 channel function to prevent acute, IL-13-induced, claudin-2-mediated permeability increases in vivo. In chronic immune-mediated colitis, CK2 inhibition attenuated progression in claudin-2-sufficient, but not claudin-2-knockout, mice, i.e., the effect was claudin-2 dependent. Paracellular flux mediated by claudin-2 channels can therefore promote immune-mediated colitis progression. Although the mechanisms by which claudin-2 channels intensify disease remain to be defined, these data suggest that claudin-2 may be an accessible target in immune-mediated disorders, including inflammatory bowel disease.


Gene index analysis of the human genome estimates approximately 120,000 genes.
Although sequencing of the human genome will soon be completed, gene identification and annotation remains a challenge. Early estimates suggested that there might be 60,000-100,000 (ref. 1) human genes, but recent analyses of the available data from EST sequencing projects have estimated as few as 45,000 (ref. 2) or as many as 140, 000 (ref. 3) distinct genes. The Chromosome 22 Sequencing Consortium estimated a minimum of 45,000 genes based on their annotation of the complete chromosome, although their data suggests there may be additional genes. The nearly 2,000,000 human ESTs in dbEST provide an important resource for gene identification and genome annotation, but these single-pass sequences must be carefully analysed to remove contaminating sequences, including those from genomic DNA, spurious transcription, and vector and bacterial sequences. We have developed a highly refined and rigorously tested protocol for cleaning, clustering and assembling EST sequences to produce high-fidelity consensus sequences for the represented genes (F.L. et al., manuscript submitted) and used this to create the TIGR Gene Indices-databases of expressed genes for human, mouse, rat and other species (http://www.tigr.org/tdb/tgi.html). Using highly refined and tested algorithms for EST analysis, we have arrived at two independent estimates indicating the human genome contains approximately 120,000 genes.


Six types of tea reduce high-fat-diet-induced fat accumulation in mice by increasing lipid metabolism and suppressing inflammation.
A high-fat diet results in obesity because of white fat accumulation. Although tea extracts alleviate lipid metabolism disorders and decrease white fat accumulation, the mechanisms underlying the therapeutic actions of different types of Chinese tea are unclear. We established a murine model of obesity by feeding mice with a high-fat diet (HFD) and treating them with atorvastatin (positive control) or water extracts (WEATs) of different tea types. The food and water intake, body weight gain, white fat accumulation, and triglyceride (TG) and total cholesterol (TC) levels were evaluated to assess the effects of the WEATs on obesity. The levels of the lipid metabolism enzymes p-AMPK, CPT-1A and FAS and the pro-inflammatory factors iNOS and IL-6 were determined. The WEATs not only reduced the body weight and white fat accumulation in the HFD-induced obese mice, but also relieved hepatic steatosis. Comparing the effects of the six kinds of tea showed that white tea has the best anti-obesity effect. Yellow tea and raw pu-erh tea significantly up-regulated p-AMPK, green tea, white tea and raw pu-erh tea markedly inhibited FAS, and white tea, yellow tea and oolong tea up-regulated CPT-1. Therefore, it is possible that white tea, yellow tea and oolong tea inhibit obesity by increasing energy expenditure and fatty acid oxidation, while green tea, white tea and raw pu-erh tea exert their effects by inhibiting fatty acid synthesis. In addition, the WEATs also significantly decreased the levels of IL-6, while green tea, yellow tea and oolong tea significantly inhibited iNOS. Different types of tea have specific chemical compositions and can regulate different lipid metabolism related proteins. In conclusion, despite variations in its composition and mechanism of action, tea is a potent anti-obesity agent.


A systematic review of satisfaction with care at the end of life.
The objective of this study was to systematically review the literature to better understand the conceptualization of satisfaction with end-of-life care and the effectiveness of palliative care interventions on this outcome. Data sources included Medline and the Database of Reviews of Effects. The review included relevant qualitative studies and intervention studies using satisfaction as an outcome from 1990 to 2005. Reviewing 24,423 citations yielded 21 relevant qualitative studies, four systematic reviews, and eight additional intervention studies. The qualitative literature described the domains of accessibility and coordination; competence, including symptom management; communication and education; emotional support and personalization of care; and support of patients' decision-making. For collaboration and consultation interventions, eight of 13 studies showed a significant effect on satisfaction. A meta-analysis found that palliative care and hospice teams improved satisfaction, although most studies did not include satisfaction as an outcome. For other types of interventions, only two of six showed a significant effect. For heart failure coordination of care, only seven of 32 studies addressed this as an outcome; two of the three that compared satisfaction between groups showed a significant difference. Evaluations used many different measures, only one of which was designed for the end of life. In conclusion, researchers have conceptualized satisfaction in palliative care, and different types of palliative care interventions can improve satisfaction, but it is often not included as an outcome. More focus on these satisfaction elements might improve the effectiveness of end-of-life interventions and their evaluation.


Health education to school children in Okpatu, Nigeria: impact on onchocerciasis-related knowledge.
We assessed the influence of health education on the knowledge about onchocerciasis in school children in Okpatu, Nigeria. The children, aged between 11 and 17 y, received health education in both English and Igbo (local language) for three months on the transmission, clinical manifestations, treatment and prevention of onchocerciasis. Illustrated pictorial materials were used to support and enhance their understanding of the subject matter. Their level of knowledge was evaluated nine months later using a pre-tested personal interview administered questionnaire. A significantly higher proportion of these children knew about onchocerciasis (chi2=260.4, df=1, P<0.0001), and its causative agent (chi2=175.0, df=4, P<0. 0001), clinical manifestations (chi2=254.0, df=5, P<0.0001), diagnosis (chi2=123.9, df=2, P<0.0001), treatment (chi2=197.8, df=3, P<0.0001) and prevention (chi2=220.8, df=3, P<0.0001) in the post- than in the pre-educational intervention. It is therefore concluded that school-based health education showed an increase in knowledge about onchocerciasis and school children could provide a useful 'multiplier' resource for health education in the community.


Urinary tract infections in acute psychosis.
Schizophrenia is associated with increased infections across the lifespan. We previously found an association between urinary tract infection (UTI) and acute nonaffective psychosis. The aims of this study were to explore further the relationship between UTI and acute psychosis, including associated clinical features. We identified by chart review subjects aged 18-64 years who were hospitalized between January 2010 and April 2012 for an acute episode of DSM-IV nonaffective psychosis (schizophrenia, schizoaffective disorder, psychosis not otherwise specified, or delusional disorder; n =134), affective psychosis (bipolar or major depressive disorder with psychotic features; n = 101), or alcohol detoxification (n = 105), and we recruited healthy controls (n =39). Urinary tract infection was defined as positive leukocyte esterase and/or positive nitrites on urinalysis and ≥ 5-10 leukocytes/high-powered field on urine microscopy. The prevalence of UTI was 21% in nonaffective psychosis, 18% in affective psychosis, 12% in alcohol use disorders, and 3% in controls. After controlling for potential confounders, UTI was almost 11 times more likely in subjects with nonaffective psychosis than controls (OR = 10.7; 95% CI, 1.4-83.2; P =.02) and almost 9 times more likely in subjects with major depressive disorder with psychotic features than controls (OR = 8.9; 95% CI, 1.1-71.4; P = .04). There were no associations between clinical characteristics and UTI in acute psychosis. We replicated and extended an association between an UTI and acute psychosis. Findings suggest that infections appear relevant to the etiopathophysiology of relapse and increased premature mortality risk in the psychoses. The results also highlight the potential importance of monitoring for comorbid UTI in relevant patient populations.


Diet, physical activity, and sedentary behaviors as risk factors for childhood obesity: an urban and rural comparison.
The aim of this study was to examine the differences in diet, physical activity, and weight status among children living in rural and urban America and to study the roles of obesity-related behaviors in residence-based differences in childhood obesity. We performed cross-sectional analysis of the 1999-2006 National Health and Nutrition Examination Survey data, restricted to 14,332 children aged 2-19 years old (2771 rural, 13,766 urban). Residence was measured at the census tract level using Rural-Urban Commuting Areas. Age-specific questions were used to assess physical activity, and the 24-hour diet recall was used to measure dietary intake. Among 2- to 11-year-olds, rural children consumed 90 more kcal/day on average than urban children (p < 0.05) and were more likely to consume the recommended two to three cups of dairy per day (p < 0.05). More 2- to 11-year-old rural children also reported participating in exercise five or more times per week than urban children of the same age (79.7% vs. 73.8%). Among 12- to 19-year-olds, rural children were less likely to consume any fruit or meet the recommendation of two cups of fruit. Using measured height and weight data, proportionately more rural than urban children were overweight/obese (35.4% v. 29.3%) and obese (18.6% v. 15.1%). Rural children had 30% higher odds of being overweight and/or obese even after adjustment for sociodemographics, health, diet, and exercise behaviors. The persistently higher odds of overweight and obesity among rural children even after adjustment suggest that rural environments may be "obesogenic" in ways that a person-level analysis cannot discern. Future research should examine disparities in the accessibility and affordability of healthy food and beverage choices and safe physical activity locales in rural areas.


Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder.
Variation at the DAOA/G30 locus has been described to be associated with both schizophrenia and bipolar disorder, but there is little consistency between studies of the tested polymorphisms or variants showing association. To obtain a stringent replication of association in large samples of both disorders using consistent clinical and laboratory methods, and to test the hypothesis that association at DAOA/G30 identifies an underlying domain of psychopathological abnormalities that cuts across traditional diagnostic categories. A systematic study of polymorphisms at DAOA/G30 using genetic case-control association analysis. Subjects were unrelated and ascertained from general psychiatric inpatient and outpatient services. White persons from the United Kingdom meeting criteria for DSM-IV schizophrenia (n = 709) or bipolar I disorder (n = 706) and 1416 ethnically matched controls. Nine polymorphisms that tag common genetic variations at DAOA/G30 were genotyped in all of the individuals, and comparisons were made between affected and unaffected individuals. We identified significant association (P = .01-.047) between 3 single-nucleotide polymorphisms and bipolar disorder but failed to find association with schizophrenia. Analyses across the traditional diagnostic categories revealed significant evidence (P = .002-.02) for association with 4 single-nucleotide polymorphisms in the subset of cases (n = 818) in which episodes of major mood disorder had occurred (gene-wide P = .009). We found a similar pattern of association in bipolar cases and in schizophrenia cases in which individuals had experienced major mood disorder. In contrast, we found no evidence for association in the subset of cases (n = 1153) in which psychotic features occurred (all P>.08). Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis. Instead, our results imply that variation at the DAOA/G30 locus influences susceptibility to episodes of mood disorder across the traditional bipolar and schizophrenia categories.


The CXCL12gamma chemokine displays unprecedented structural and functional properties that make it a paradigm of chemoattractant proteins.
The CXCL12gamma chemokine arises by alternative splicing from Cxcl12, an essential gene during development. This protein binds CXCR4 and displays an exceptional degree of conservation (99%) in mammals. CXCL12gamma is formed by a protein core shared by all CXCL12 isoforms, extended by a highly cationic carboxy-terminal (C-ter) domain that encompass four overlapped BBXB heparan sulfate (HS)-binding motifs. We hypothesize that this unusual domain could critically determine the biological properties of CXCL12gamma through its interaction to, and regulation by extracellular glycosaminoglycans (GAG) and HS in particular. By both RT-PCR and immunohistochemistry, we mapped the localization of CXCL12gamma both in mouse and human tissues, where it showed discrete differential expression. As an unprecedented feature among chemokines, the secreted CXCL12gamma strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion. Affinity chromatography and surface plasmon resonance allowed us to determine for CXCL12gamma one of the higher affinity for HS (K(d) = 0.9 nM) ever reported for a protein. This property relies in the presence of four canonical HS-binding sites located at the C-ter domain but requires the collaboration of a HS-binding site located in the core of the protein. Interestingly, and despite reduced agonist potency on CXCR4, the sustained binding of CXCL12gamma to HS enabled it to promote in vivo intraperitoneal leukocyte accumulation and angiogenesis in matrigel plugs with much higher efficiency than CXCL12alpha. In good agreement, mutant CXCL12gamma chemokines selectively devoid of HS-binding capacity failed to promote in vivo significant cell recruitment. We conclude that CXCL12gamma features unique structural and functional properties among chemokines which rely on the presence of a distinctive C-ter domain. The unsurpassed capacity to bind to HS on the extracellular matrix would make CXCL12gamma the paradigm of haptotactic proteins, which regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells.


Cognitive functioning in children with and without Attention-deficit/Hyperactivity Disorder with and without comorbid learning disabilities.
This study attempted to determine whether children with the combined subtype of attention-deficit/hyperactivity disorder (ADHD) have impairments in cognitive functioning and motor skills. The specific effect of the comorbidity of learning disabilities (LD) was also investigated. A battery of cognitive tests was administered to 26 children with a clinical diagnosis of ADHD-combined subtype (ADHD/C), to 24 children with ADHD/C with a comorbid diagnosis of LD (ADHD/C+LD), and to 102 participants without disabilities, all between ages 7 and 10. The testing battery consisted of tasks assessing memory, visuospatial and verbal abilities, and fine motor skills. In general, the test results of children with ADHD/C were poorer than those of the control group but better than the results of children with a combined ADHD/C+LD diagnosis (with the exception of motor skills). The predictive accuracy of the testing battery tasks in children with ADHD/C and ADHD/C+LD was examined. The results of a standard procedure of discriminant function analyses revealed that the measures correctly classified 73.6% of the children.


T cells expressing specific V beta elements regulate immunoglobulin E production and airways responsiveness in vivo.
The role of T cells expressing specific V beta elements was examined in the regulation of allergen-specific immunoglobulin (Ig)E production and airways responsiveness (AR). In BALB/c mice, inhalation of the allergen ovalbumin (OVA) induced an IgE anti-OVA response, immediate cutaneous reactivity, and increased AR. These results were associated with an expansion of V beta 8.1/8.2 T cells in local draining lymph nodes of the airways and the lung. Transfer of V beta 8.1/8.2 T cells from sensitized mice stimulated an IgE anti-OVA response, immediate cutaneous hypersensitivity, and increased AR in naive syngeneic recipients. In contrast, OVA-reactive V beta 2 T cells inhibited these effects. These data demonstrate for the first time that T cells with different V beta specificities play a critical role in the in vivo regulation of allergen-specific IgE production and AR.


Loss of tumor-specific and idiotype-specific immunity with age.
The ultraviolet light-induced fibrosarcoma 1591 undergoes "first-set rejection" when transplanted into normal syngeneic mice. We found, however, that the primary resistance of normal mice decreases with age, beginning at 9--12 mo, equivalent to middle age for mice. Mice lose with age the capacity to mount both idiotypic and anti-idiotypic responses responsible for controlling the growth of tumor. This loss was correlated with quantitative as well as qualitative changes in the response, such as changes in specificity and clonotype. Normal young mice regularly expressed a dominant common anti-1591 "idiotype" as defined by an anti-idiotypic probe. The capability of normal mice to respond with lymphocytes of this dominant common idiotype began to decline at about 8 mo of age. At this time, animals still generated tumor-specific lymphocytes, but these lymphocytes appear to be idiotypically different lymphocyte clones. With further increase in age, animals responded with tumor-reactive lymphocytes that showed a marked cross-reactivity to other tumor target cell lines. Both in vivo and in vitro, the capability of normal mice to mount an immune response that was specific for the 1591 tumor cells decreased between 9 and 14 mo, which was the age individual mice became increasingly susceptible to a challenge with 1591 tumor cells. Thus, our data suggest that clones of tumor-specific T cells provide primary and early protection of young animals against challenge with malignant 1591 cells. However, the dominance of these tumor-specific T cell clones in a primary immune response is lost in middle-age. Because the ability of animals to mount anti-idiotypic immune response also declined in middle-aged animals, it is possible that the observed loss of clonal dominance of tumor-specific clones with increasing age is at least partially related to age-dependent changes in the anti-idiotypic compartment.


Indefinite survival of rat islet allografts following infusion of donor bone marrow without cytoablation.
We have tested the effect of donor bone marrow cell (DBMC) infusion on the survival of pancreatic islet allografts in the rat, without the use of cytoablative recipient conditioning. Lewis and diabetic Brown Norway rats were used as donors and recipients, respectively. Donor islets were placed beneath the left renal capsule. Infusion of DBMC and temporary immunosuppression followed by delayed islet transplantation resulted in indefinite survival of all islet grafts (MST > 180 days). Control animals demonstrated recurrent hyperglycemia (islet allografts rejection). Donor bone marrow derived cells were detected in the spleen and cervical lymph nodes of BN recipients of LEW bone marrow but not in the recipients of islet transplants alone. Second set full thickness skin grafts were performed in normal BN and in recipients of a previously successful ITX. Donor specific skin grafts were accepted in the animals that had received DBMC 40 days before the islet allograft, while animals receiving DBMC at the time of the islet allograft rejected the donor specific skin graft similarly to the controls. However, these animals did not reject a second set donor-specific islet transplant. The results indicate that radiation conditioning of the recipients was not necessary to induce microchimerism and graft acceptance in this rodent model of islet allotransplantation.


Characterization of aspercetin, a platelet aggregating component from the venom of the snake Bothrops asper which induces thrombocytopenia and potentiates metalloproteinase-induced hemorrhage.
Thrombocytopenia occurs in a number of patients bitten by Bothrops asper, a species responsible for the majority of snakebites in Central America and southern Mexico. In this work we describe the isolation of a new platelet-aggregating protein, named aspercetin, from the venom of B. asper, which induces thrombocytopenia in mice. Isolation was carried out by a combination of ion-exchange chromatography on DEAE-Sepharose and affinity chromatography on Affi-Gel Blue. Aspercetin is a disulfide-linked heterodimer, with a pI of 4.5 and a molecular mass of 29,759 Da, detemined by MALDI-ESI mass spectrometry. N-terminal sequence shows homology with a number of venom proteins which belong to the C-type lectin family. Aspercetin has functional similarities with botrocetin, from B. jararaca venom, since it induces platelet aggregation only in the presence of plasma or purified von Willebrand factor. Aspercetin-mediated platelet aggregation results from the interaction of von Willebrand factor with platelet receptor GPIb. Aspercetin lacks anticoagulant effect and does not agglutinate erythrocytes, in contrast with other representatives of the C-type lectin family isolated from snake venoms. Moreover, aspercetin is not lethal, nor does it induce myonecrosis, hemorrhage and edema. When injected intravenously or intramuscularly in mice it induces a rapid, dose-dependent drop in platelet counts and prolongs the bleeding time, suggesting that it may play a role in the thrombocytopenia that develops in a number of B. asper envenomations. Moreover, mice injected intravenously with aspercetin and then receiving an intradermal injection of B. asper hemorrhagic metalloproteinase BaP1 develop a larger hemorrhagic lesion than mice receiving only BaP1. This suggests that aspercetin, by reducing platelet numbers, may


Different spatiotemporal expression of DOC2 genes in the developing rat brain argues for an additional, nonsynaptic role of DOC2B in early development.
DOC2A and DOC2B are two homologous genes implicated in synaptic vesicle exocytosis. Their complementary, nonoverlapping expression patterns in adult rat brain suggest that they exert similar functions in different neurons. We have analysed the expression pattern of the two genes in the developing rat brain by in situ hybridization. Unexpectedly, we found no parallel expression of the two genes during development. DOC2B mRNA was highly expressed as early as embryonic day 12 (E12) throughout the neuroepithelium, long before synaptic transmission is functional, and the expression remained abundant from E12 onwards. In contrast, faint expression of DOC2A transcripts was first detected at E17 in ventral brain areas, and it extended gradually to other brain structures in the sequence of their ontology, i.e. structures that had formed first also expressed DOC2A first. At postnatal day 3, both genes were highly expressed throughout the brain. This overlapping expression diverged to the complementary distribution of the adult brain. The temporal and spatial differences in expression point to a functional divergence between these homologous genes during brain development: the pattern of DOC2A is consistent with its proposed synaptic function, whereas that of DOC2B suggests an additional, nonsynaptic role in proliferating cells.


aCGHViewer: a generic visualization tool for aCGH data.
Array-Comparative Genomic Hybridization (aCGH) is a powerful high throughput technology for detecting chromosomal copy number aberrations (CNAs) in cancer, aiming at identifying related critical genes from the affected genomic regions. However, advancing from a dataset with thousands of tabular lines to a few candidate genes can be an onerous and time-consuming process. To expedite the aCGH data analysis process, we have developed a user-friendly aCGH data viewer (aCGHViewer) as a conduit between the aCGH data tables and a genome browser. The data from a given aCGH analysis are displayed in a genomic view comprised of individual chromosome panels which can be rapidly scanned for interesting features. A chromosome panel containing a feature of interest can be selected to launch a detail window for that single chromosome. Selecting a data point of interest in the detail window launches a query to the UCSC or NCBI genome browser to allow the user to explore the gene content in the chromosomal region. Additionally, aCGHViewer can display aCGH and expression array data concurrently to visually correlate the two. aCGHViewer is a stand alone Java visualization application that should be used in conjunction with separate statistical programs. It operates on all major computer platforms and is freely available at http://falcon.roswellpark.org/aCGHview/.


Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species.
The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.


Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
We have established previously that minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (Δψm) exist within populations of mammary and colonic carcinoma cells and that these differences in Δψm are linked to tumorigenic phenotypes consistent with increased probability of participating in tumor progression. However, the mechanism(s) involved in generating and maintaining stable differences in intrinsic Δψm and how they are linked to phenotype are unclear. Because the mucin 1 (MUC1) oncoprotein is over-expressed in many cancers, with the cytoplasmic C-terminal fragment (MUC1 C-ter) and its integration into the outer mitochondrial membrane linked to tumorigenic phenotypes similar to those of cells with elevated intrinsic Δψm, we investigated whether endogenous differences in MUC1 levels were linked to stable differences in intrinsic Δψm and/or to the tumor phenotypes associated with the intrinsic Δψm. We report that levels of MUC1 are significantly higher in subpopulations of cells with elevated intrinsic Δψm derived from both mammary and colonic carcinoma cell lines. However, using siRNA we found that down-regulation of MUC1 failed to significantly affect either the intrinsic Δψm or the tumor phenotypes associated with increased intrinsic Δψm. Moreover, whereas pharmacologically mediated disruption of the Δψm was accompanied by attenuation of tumor phenotype, it had no impact on MUC1 levels. Therefore, while MUC1 over-expression is associated with subpopulations of cells with elevated intrinsic Δψm, it is not directly linked to the generation or maintenance of stable alterations in intrinsic Δψm, or to intrinsic Δψm associated tumor phenotypes. Since the Δψm is the focus of chemotherapeutic strategies, these data have important clinical implications in regard to effectively targeting those cells within a tumor cell population that exhibit stable elevations in intrinsic Δψm and are most likely to contribute to tumor progression.


Genetic Vulnerability to Experiencing Child Maltreatment.
Although biological factors may influence the risk of experiencing negative life events, the role of genes in the vulnerability to child victimization remains poorly understood. In a large population-based Finnish sample (N = 13,024), we retrospectively measured multiple experiences of child victimization and, in a subsample of twins (n = 9,562), we estimated the extent to which genetic and environmental factors influenced these experiences. In particular, we investigated whether genetic and environmental influences varied depending on the type of child victimization, the genetic relatedness with the perpetrator, and the sex of the victim. Our quantitative genetic analyses supported the presence of both genetic and environmental influences on the occurrence and co-occurrence of child abuse and neglect. We also identified one common etiological pathway underlying multiple child victimizations, and after accounting for this common etiology, we singled out risk factors specific to sexual abuse. Environmental factors shared and nonshared between twins raised together influenced the risk of victimization by genetically related and unrelated perpetrators, respectively. Furthermore, we estimated sex differences in the etiology of emotional and sexual victimization, including larger unshared environmental influences for men and sex-limited genetic effects for women. These findings can inform child protection as they contribute to explaining why certain individuals are at increased risk of experiencing one or more types of child maltreatment.


Anticerebral oedema therapy in Reye's syndrome.
Sixteen patients with Reye's syndrome were seen over a 3-year period and treated with conservative management with an overall mortality of 31%. 6 of the 16 had illness limited to stages II and III. Intensive therapy of suspected cerebral oedema, with careful monitoring of serum osmolarity, was associated with survival in 5 of 10 patients with stage IV disease. The risks of lumbar puncture in the presence of cerebral oedema (stages III-IV) are emphasized. A change in clinical status (usually a reversal to a less severe stage and an improved electroencephalogram) was seen within hours of starting anticerebral oedema therapy. Neurological sequelae (memory deficit, hemiparesis, hemiballismic movements, and delayed motor milestones) that were present in stage IV survivors at discharge were absent 12 months after discharge. Conservative supportive management emphasizing treatment of presumed cerebral oedema in severe cases of Reye's syndrome has a mortality comparable to that occurring in exchange transfusion or peritoneal dialysis. This form of therapy should be included in controlled trials to determine which form of therapy is optimal.


Anomalous absorption of TM electromagnetic waves by an ultrathin layer: optical analog of liquid friction.
A strong maximum of absorption (as much as 100%) of bulk TM electromagnetic waves by an ultrathin film with imaginary dielectric permittivity is shown to exist at some optimal film thickness. This typical thickness is usually much smaller than the wavelength and the wave penetration depth in the material of the film. The absorptivity maximum increases and the typical thickness decreases with increasing dielectric permittivity of the layer. An optical analog of linear (liquid) friction is discussed. A frictional contact approximation for TM electromagnetic waves is analyzed, and relevant boundary conditions with an optical coefficient of friction are derived.


Exogenous interferon-alpha and interferon-gamma increase lethality of murine inhalational anthrax.
Bacillus anthracis, the etiologic agent of inhalational anthrax, is a facultative intracellular pathogen. Despite appropriate antimicrobial therapy, the mortality from inhalational anthrax approaches 45%, underscoring the need for better adjuvant therapies. The variable latency between exposure and development of disease suggests an important role for the host's innate immune response. Type I and Type II Interferons (IFN) are prominent members of the host innate immune response and are required for control of intracellular pathogens. We have previously described a protective role for exogenous Type I and Type II IFNs in attenuating intracellular B.anthracis germination and macrophage cell death in vitro. We sought to extend these findings in an in vivo model of inhalational anthrax, utilizing the Sterne strain (34F2) of B.anthracis. Mice devoid of STAT1, a component of IFN-alpha and IFN-gamma signaling, had a trend towards increased mortality, bacterial germination and extrapulmonary spread of B.anthracis at 24 hrs. This was associated with impaired IL-6, IL-10 and IL-12 production. However, administration of exogenous IFN-gamma, and to a lesser extent IFN-alpha, at the time of infection, markedly increased lethality. While IFNs were able to reduce the fraction of germinated spores within the lung, they increased both the local and systemic inflammatory response manifest by increases in IL-12 and reductions in IL-10. This was associated with an increase in extrapulmonary dissemination. The mechanism of IFN mediated inflammation appears to be in part due to STAT1 independent signaling. In conclusion, while endogenous IFNs are essential for control of B.anthracis germination and lethality, administration of exogenous IFNs appear to increase the local inflammatory response, thereby increasing mortality.


Hydrogen sulphide removal by activated sludge diffusion.
Odours from wastewater treatment plants comprise a mixture of various gases, of which hydrogen sulphide (H2S) is the main constituent. Microorganisms commonly found in wastewater can degrade sulphurous compounds. Therefore, the use of activated sludge (AS) for odour control offers an alternative to traditional waste gas treatment processes, such as biofilters, bioscrubbers and biotrickling filters, both in practical terms (use of existing facilities) and economically (minimal capital cost). The performance of AS diffusion as a bioscrubber for removing H2S at concentrations at 25, 75 and 150 ppmv was evaluated. Pilot-scale trials were undertaken using parallel 60-L aeration tanks and 20-L clarifier reactors at the Bedford Sewage Treatment Works, Carington, UK. Olfactometry measurements were also carried out to determine whether there was any increase in odour concentration owing to H2S diffusion. Hydrogen sulphide removal rates of 100% were obtained, with no noticeable increase in odour concentration throughout the trials as measured by olfactometry. Odour concentration was highest at the beginning of the trials and lowest during the high H2S dosing period, with similar values being obtained for test and control. It was concluded that AS diffusion is an effective bioscrubber for the removal of H2S odour.


Vertebrate diapause preserves organisms long term through Polycomb complex members.
Diapause is a state of suspended development that helps organisms survive extreme environments. How diapause protects living organisms is largely unknown. Using the African turquoise killifish (Nothobranchius furzeri), we show that diapause preserves complex organisms for extremely long periods of time without trade-offs for subsequent adult growth, fertility, and life span. Transcriptome analyses indicate that diapause is an active state, with dynamic regulation of metabolism and organ development genes. The most up-regulated genes in diapause include Polycomb complex members. The chromatin mark regulated by Polycomb, H3K27me3, is maintained at key developmental genes in diapause, and the Polycomb member CBX7 mediates repression of metabolism and muscle genes in diapause. CBX7 is functionally required for muscle preservation and diapause maintenance. Thus, vertebrate diapause is a state of suspended life that is actively maintained by specific chromatin regulators, and this has implications for long-term organism preservation.


Tell me if you prefer bovine or poultry sectors and I'll tell you who you are: Characterization of Salmonella enterica subsp. enterica serovar Mbandaka in France.
In north-western France, Salmonella enterica susp. enterica serovar Mbandaka (S. Mbandaka) is most frequently isolated from bovine and dairy samples. While this serovar most often results in asymptomatic carriage, for a number of years it has caused episodes of abortions, which have serious economic consequences for the sector. Interestingly, this serovar is also isolated from Gallus gallus in the same geographic zone. Despite its prevalence in bovines in north-western France, S. Mbandaka has not been broadly studied at the genomic level, and its prevalence and host adaptation are still not fully understood. In this study, we analyzed the genomic diversity of 304 strains of S. Mbandaka isolated from the bovine and poultry sectors in this area over a period of 5 years. A phylogenetic analysis was carried out and two approaches were followed to identify conserved genes and mutations related to host associations. The first approach targeted the genes compiled in the MEGARESv2, Resfinder, VFDB and SPI databases. Plasmid and phage contents were also investigated. The second approach refers to an in-house algorithm developed for this study that computes sensitivity, specificity, and accuracy of accessory genes and core variants according to predefined genomes groups. All the analyzed strains belong to the multi-locus sequence type profile ST413, and the phylogenomic analysis revealed main clustering by host (bovine and poultry), emphasizing the circulation of 12 different major clones, of which seven circulate in poultry and five in the bovine sector in France and a likely food production chain adaptation of these clones. All strains present resistance determinants including heavy metals and biocides that could explain the ability of this serovar to survive and persist in the environment, within herds, and in food processing plants. To explore the wild animal contribution to the spread of this serovar in north-western France, we retrieved S. Mbandaka genomes isolated from wild birds from EnteroBase and included them in the phylogenomic analysis together with our collection. Lastly, screening of accessory genes and major variants allowed us to identify conserved specific mutations characteristic of each major cluster. These mutations could be used to design useful probes for food safety surveillance.


Genetic variants in ALDH1B1 and alcohol dependence risk in a British and Irish population: A bioinformatic and genetic study.
Alcohol is metabolized in the liver via the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Polymorphisms in the genes encoding these enzymes, which are common in East Asian populations, can alter enzyme kinetics and hence the risk of alcohol dependence and its sequelae. One of the most important genetic variants, in this regards, is the single nucleotide polymorphism (SNP) rs671 in ALDH2, the gene encoding the primary acetaldehyde metabolizing enzyme ALDH2. However, the protective allele of rs671 is absent in most Europeans although ALDH1B1, which shares significant sequence homology with ALDH2, contains several, potentially functional, missense SNPs that do occur in European populations. The aims of this study were: (i) to use bioinformatic techniques to characterize the possible effects of selected variants in ALDH1B1 on protein structure and function; and, (ii) to genotype three missense and one stop-gain, protein-altering, non-synonymous SNPs in 1478 alcohol dependent cases and 1254 controls of matched British and Irish ancestry. No significant allelic associations were observed between the three missense SNPs and alcohol dependence risk. The minor allele frequency of rs142427338 (Gln378Ter) was higher in alcohol dependent cases than in controls (allelic P = 0.19, OR = 2.98, [0.62-14.37]) but as this SNP is very rare the study was likely underpowered to detect an association with alcohol dependence risk. This potential association will needs to be further evaluated in other large, independent European populations.


Taking part in Nordic collaboration; nursing students' experiences and perceptions from a learning perspective: A qualitative study.
Nordic networking of different kinds has a long tradition aiming to increase collaboration and understanding between citizens in different countries. Cultural competence in relation to health care and nursing is important for clinical nurses and is a central issue in nurse education. To gain an understanding of what nurse students experienced and learned during an intensive course in diabetes together with students and nurse educators from Denmark, Finland, Iceland, Norway, Sweden and the Faroe Islands. In 2012, an intensive course within the Nordic network, Nordkvist, was conducted in Faroe Islands with the theme "Nursing - to live a good life with diabetes". To answer the objective of the study, 26 students conducted written reflections based on two questions. The data was analyzed using qualitative content analysis. Through meetings with nurse students and educators from the Nordic countries the intensive course strengthened the students' identification with the nursing profession. The students gained new perspectives on diabetes, such as how complex it can be to live with a chronic illness. Because of the difficulties in understanding one another and because of different mother tongues, the students gained a better understanding of patients' vulnerability in relation to hospital jargon and how it felt to be in an unfamiliar place. The intensive course increased the students' personal and professional growth, cross-cultural competence, and their identification with nursing. Students' understanding of health care in the Nordic countries improved as similarities and differences were recognized.


Radioprotective potential of ginseng.
A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.


Critical elements in the design of culturally appropriate interventions intended to reduce health disparities: immunization rates among Hispanic seniors in New Mexico.
The importance of immunization in protecting seniors against influenza and pneumonia has long been recognized. Nevertheless, immunization rates among Medicare beneficiaries continue to fall short of what is both desirable and achievable. The problem is even more acute among certain racial and ethnic groups in the United States within which rates are below the rate for the country as a whole. This is true in New Mexico where 40 percent of the population is estimated to be Hispanic. As part of its work on behalf of the Centers for Medicare & Medicaid Services (CMS), the New Mexico Medical Review Association (NMMRA) undertook a project aimed both at reducing the disparities that exist in immunization status between the Hispanic and non-Hispanic population in the state and attempting to increase overall rates in the state for all groups. Developing interventions to reduce disparaties in immunization rates between Hispanic seniors and the rest of the senior population requires more than a straightforward review of the literature and must take into account not only the cultural differences that exist between Hispanics and non-Hispanics but, certainly, in the case of New Mexico, it must attempt to understand the richness and diversity that exists within the Hispanic communities across the state. To do otherwise runs the risk of designing interventions that are at best ineffective and at worst culturally insensitive and potentially damaging to future efforts to improve health status. This article describes the process undertaken by NMMRA, a Medicare Quality Improvement Organization (QIO), to collect qualitative data from three culturally different groups of Hispanics in New Mexico. The data are used to design interventions that will increase immunization rates for all Hispanics in New Mexico.


Coinfection of Helicobacter pylori and Hepatitis C Virus in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.
The relationship between Helicobacter pylori (H. pylori) and hepatocellular carcinoma (HCC) was firstly proposed in 1994 after Ward et al demonstrated the role of Helicobacter hepaticus in the development of HCC in mice. Studies also investigated the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) coexisting with H. pylori in causing HCC. A causal relationship was never confirmed, and the relationship remains controversial. This meta-analysis aimed to summarize the research on this topic and investigate if a relationship exists between H. pylori infection and the development of HCC and if the presence of HCV and HBV along with H. pylori plays a role in liver carcinogenesis. Following PRISMA guidelines, we performed a systematic review of all relevant studies published in the literature using the keywords "Helicobacter pylori" and "hepatocellular carcinoma" on major literature databases, including PubMed, EMBASE, Web of Science, and Cochrane controlled trials register. A total of 656 research studies were identified between 1994 and 2020. Of those, 26 qualified under our selection criteria. Patients who were positive for HCC were classified as cases and those who did not have HCC were classified as controls. The H. pylori status and HCV status, if available, were identified for both groups. Statistical analysis was carried out by a biostatistician according to the Cochrane reviewer's handbook. Out of the 26 studies included in the final analysis, 13 were retrospective case-control studies, 11 were cross-sectional studies, and two were prospective case-control and cohort studies. Overall, the prevalence of H. pylori infection was 64.78% (561 of 866) amongst HCC cases and 47.92% (1,718 of 3,585) in the non-HCC control group. The summary odds ratio (OR) for the association of H. pylori infection with the risk for HCC (using the random-effects model, which accounted for the heterogeneity across the 26 studies) was determined to be 4.75 (95% confidence interval (CI): 3.06 - 7.37, I2 = 63%). We also performed a subgroup analysis to determine the odds of developing HCC in the presence of H. pylori and HCV coinfection. The summary OR of it was 12.76 (95% CI: 4.13 - 39.41, I2 = 78%). The summary OR for the risk of developing HCC in the presence of HCV infection without H. pylori infection was 2.21 (95% CI: 0.70 - 6.94, I2 = 79%). Whereas, the odds of developing HCC in the presence of only H. pylori infection without HCV was found to be 0.54 (95% CI: 0.11 - 2.63, I2 = 80%). There was inconsistency in the data presented in some studies regarding HCV infection status. Since data were extracted from different study designs, subgroup analysis by study design was performed which showed no significant difference between the study groups (P = 0.5705). This meta-analysis demonstrates a positive association between H. pylori infection and the development of HCC. There is a significantly higher risk of developing HCC in the presence of HCV infection along with H. pylori. Further prospective cohort studies are needed to prove the causal relationship, especially in cases of HBV and HCV coinfection, and cirrhotic patients.


[Breast abnormalities: a retrospective study of 208 patients].
Ectopic breast tissue occurs in 0.4-6% of the general population. Usually, these tissues develop along the embryonic milk line but other sites are reported in the literature. Accessory breasts are commonly axillary and may undergo hormonal changes. Some pathologies of normally positioned breasts can occur in ectopic breast tissue, including carcinoma, and therefore require traditional senological flow-charts and imaging strategies. Supernumerary nipples are generally asymptomatic but may sometimes be associated with urological malformations. In our 10-year experience, 208 patients were observed (138 polythelia and 70 polymastia) and 159 surgical procedures were performed, 97 for supernumerary nipple excision and 67 for accessory breast ablation. Five neoplastic lesions and 25 fibrocystic mastopathies were detected in specimens; normal nipple or breast tissue was found in 129. In view of the potentially malignant transformation of accessory breasts, thorough physician evaluation is needed. Surgery is currently suggested in cases of suspected malignancy, in symptomatic cases and for cosmetic problems.


Role of Transcription Factors in Steatohepatitis and Hypertension after Ethanol: The Epicenter of Metabolism.
Chronic alcohol consumption induces multi-organ damage, including alcoholic liver disease (ALD), pancreatitis and hypertension. Ethanol and ethanol metabolic products play a significant role in the manifestation of its toxicity. Ethanol metabolizes to acetaldehyde and produces reduced nicotinamide adenine dinucleotide (NADH) by cytosolic alcohol dehydrogenase. Ethanol metabolism mediated by cytochrome-P450 2E1 causes oxidative stress due to increased production of reactive oxygen species (ROS). Acetaldehyde, increased redox cellular state and ROS activate transcription factors, which in turn activate genes for lipid biosynthesis and offer protection of hepatocytes from alcohol toxicity. Sterol regulatory element binding proteins (SREBPs) and peroxisome proliferator activated-receptors (PPARs) are two key lipogenic transcription factors implicated in the development of fatty liver in alcoholic and non-alcoholic steatohepatitis. SREBP-1 is activated in the livers of chronic ethanol abusers. An increase in ROS activates nuclear factor erythroid-2-related factor-2 (Nrf2) and hypoxia inducible factor (HIF) to provide protection to hepatocytes from ethanol toxicity. Under ethanol exposure, due to increased gut permeability, there is release of gram-negative bacteria-derived lipopolysaccharide (LPS) from intestine causing activation of immune response. In addition, the metabolic product, acetaldehyde, modifies the proteins in hepatocyte, which become antigens inviting auto-immune response. LPS activates macrophages, especially the liver resident macrophages, Kupffer cells. These Kupffer cells and circulating macrophages secrete various cytokines. The level of tumor necrosis factor-α (TNFα), interleukin-1beta (IL-1β), IL-6, IL-8 and IL-12 have been found elevated among chronic alcoholics. In addition to elevation of these cytokines, the peripheral iron (Fe(2+)) is also mobilized. An increased level of hepatic iron has been observed among alcoholics. Increased ROS, IL-1β, acetaldehyde, and increased hepatic iron, all activate nuclear factor-kappa B (NF-κB) transcription factor. Resolution of increased reactive oxygen species requires increased expression of genes responsible for dismutation of increased ROS which is partially achieved by IL-6 mediated activation of signal transducers and activators of transcription 3 (STAT3). In addition to these transcription factors, activator protein-1 may also be activated in hepatocytes due to its association with resolution of increased ROS. These transcription factors are central to alcohol-mediated hepatotoxicity.


Human breast tissue disposition and bioactivity of limonene in women with early-stage breast cancer.
Limonene is a bioactive food component found in citrus peel oil that has shown chemopreventive and chemotherapeutic activities in preclinical studies. We conducted an open-label pilot clinical study to determine the human breast tissue disposition of limonene and its associated bioactivity. We recruited 43 women with newly diagnosed operable breast cancer electing to undergo surgical excision to take 2 grams of limonene daily for two to six weeks before surgery. Blood and breast tissue were collected to determine drug/metabolite concentrations and limonene-induced changes in systemic and tissue biomarkers of breast cancer risk or carcinogenesis. Limonene was found to preferentially concentrate in the breast tissue, reaching high tissue concentration (mean = 41.3 μg/g tissue), whereas the major active circulating metabolite, perillic acid, did not concentrate in the breast tissue. Limonene intervention resulted in a 22% reduction in cyclin D1 expression (P = 0.002) in tumor tissue but minimal changes in tissue Ki67 and cleaved caspase-3 expression. No significant changes in serum leptin, adiponectin, TGF-β1, insulin-like growth factor binding protein-3 (IGFBP-3), and interleukin-6 (IL-6) levels were observed following limonene intervention. There was a small but statistically significant postintervention increase in insulin-like growth factor I (IGF-I) levels. We conclude that limonene distributed extensively to human breast tissue and reduced breast tumor cyclin D1 expression that may lead to cell-cycle arrest and reduced cell proliferation. Furthermore, placebo-controlled clinical trials and translational research are warranted to establish limonene's role for breast cancer prevention or treatment.


Brain structures differ between musicians and non-musicians.
From an early age, musicians learn complex motor and auditory skills (e.g., the translation of visually perceived musical symbols into motor commands with simultaneous auditory monitoring of output), which they practice extensively from childhood throughout their entire careers. Using a voxel-by-voxel morphometric technique, we found gray matter volume differences in motor, auditory, and visual-spatial brain regions when comparing professional musicians (keyboard players) with a matched group of amateur musicians and non-musicians. Although some of these multiregional differences could be attributable to innate predisposition, we believe they may represent structural adaptations in response to long-term skill acquisition and the repetitive rehearsal of those skills. This hypothesis is supported by the strong association we found between structural differences, musician status, and practice intensity, as well as the wealth of supporting animal data showing structural changes in response to long-term motor training. However, only future experiments can determine the relative contribution of predisposition and practice.


Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.
To evaluate the clinical and cost-effectiveness of new and emerging technologies for early, localised prostate cancer. Electronic databases, reference lists of relevant articles and various health services research-related resources. A list of new and emerging technologies was identified and agreed. A systematic review was undertaken and selected studies were reviewed against a set of criteria. An economic model was developed and used to compare the specified newer treatments with the traditional approaches. For neoadjuvant hormonal therapy, no evidence of benefit was seen in terms of biochemical disease-free survival. For adjuvant hormonal therapy, there was no evidence of benefit in terms of survival, but some conflicting evidence that higher risk patients may benefit. The largest number of studies reported results for brachytherapy, where some evidence suggested that it may be more effective than standard treatments for lower risk patients, although less effective for intermediate- and high-risk patients, in terms of biochemical disease-free survival. Lower quality evidence reported fewer complications than for standard treatments. Higher quality evidence suggested that disease-specific quality of life (QoL) for brachytherapy patients was lower than for patients receiving standard treatments. The review of three-dimensional conformal radiotherapy (3D-CRT) considered treatment-related morbidity, where significantly fewer gastrointestinal complications occurred than with standard radiotherapy. It was suggested that higher radiation doses achieved better disease control, although patient characteristics were often reported as independent indicators of control. The review of intensity-modulated conformal radiotherapy suggested that late gastrointestinal toxicity may be reduced compared with 3D-CRT. For cryotherapy, high rates of impotence were reported. Owing to the paucity and poor quality of evidence identified for other interventions, conclusions regarding their clinical effectiveness cannot be drawn. Cost-effectiveness estimates were based on the impact of adverse events on quality-adjusted life-years and the assessment was restricted to brachytherapy, 3D-CRT and cryotherapy compared with standard treatments. Of the new treatments included, only cryotherapy appeared not to be potentially cost-effective compared with traditional treatments, owing to the associated high incidence of impotence. The results of the clinical effectiveness review should be viewed in the context of the quality of the available evidence. Very few randomised controlled trials (RCTs) were identified, with the majority of included studies being descriptive case series, open to patient selection bias and measuring surrogate end-points with short-term follow-up. It is difficult therefore to draw conclusions on the relative benefits or otherwise of the newer technologies owing to the lack of substantive evidence of any quality and the lack of comparisons between the newer technologies and with standard treatments. Given the lack of high-quality clinical evidence with long-term follow-up and the uncertainty surrounding the assumptions in the economic analysis, the following areas are recommended for further research: RCTs with sufficient follow-up to measure benefits in terms of overall survival to include QoL measurement to establish trade-offs between potential adverse events and benefits of treatment; the identification of prognostic risk factors among men diagnosed with early prostate cancer; QoL studies to compare the utility of health states among patients on active monitoring, patients receiving treatment and the comparable healthy population; the relationship between surrogate end-points and survival; and the adoption of standard definitions for adverse events.


Hepatitis C virus replication and potential targets for direct-acting agents.
We finally stand at the brink of novel, oral, direct-acting antivirals for the treatment of hepatitis C virus (HCV) infection. Basic science research has lead to a greater understanding of the viral life cycle and identified numerous potential targets for therapy. Early compounds were plagued by inconsistent in vivo activity and side effects that led to discontinuation of investigational efforts. However, several agents have now progressed to phase 2 human studies and two protease inhibitors have completed enrolment for their phase 3 clinical trials and look promising. Thus, while it appears that protease inhibitors will likely be the next available drugs for the treatment of HCV infection, the quest for additional therapeutic agents will continue. The future of HCV therapy lies in multidrug cocktails of several agents targeted against a variety of targets. In the near future these agents will be added to the current standard therapy consisting of pegylated interferon and ribavirin; however, the ultimate and probably realistic goal will be to develop multidrug oral regiments to replace the need for interferon.


Multicompartmental Pharmacokinetic Model of Tenofovir Delivery to the Rectal Mucosa by an Enema.
Rectal enemas that contain prophylactic levels of anti-HIV microbicides such as tenofovir have emerged as a promising dosage form to prevent sexually transmitted HIV infections. The enema vehicle is promising due to its likely ability to deliver a large amount of drug along the length of the rectal canal. Computational models of microbicide drug delivery by enemas can help their design process by determining key factors governing drug transport and, more specifically, the time history and degree of protection. They can also inform interpretations of experimental pharmacokinetic measures such as drug concentrations in biopsies. The present work begins rectal microbicide PK modeling, for enema vehicles. Results here show that a paramount factor in drug transport is the time of enema retention; direct connectivity between enema fluid and the fluid within rectal crypts is also important. Computations of the percentage of stromal volume protected by a single enema dose indicate that even with only a minute of enema retention, protection of 100% can be achieved after around 14 minutes post dose. Concentrations in biopsies are dependent on biopsy thickness; and control and/or knowledge of thickness could improve accuracy and decrease variability in biopsy measurements. Results here provide evidence that enemas are a promising dosage form for rectal microbicide delivery, and offer insights into their rational design.


Health benefits from large-scale ozone reduction in the United States.
Exposure to ozone has been associated with adverse health effects, including premature mortality and cardiopulmonary and respiratory morbidity. In 2008, the U.S. Environmental Protection Agency (EPA) lowered the primary (health-based) National Ambient Air Quality Standard (NAAQS) for ozone to 75 ppb, expressed as the fourth-highest daily maximum 8-hr average over a 24-hr period. Based on recent monitoring data, U.S. ozone levels still exceed this standard in numerous locations, resulting in avoidable adverse health consequences. We sought to quantify the potential human health benefits from achieving the current primary NAAQS standard of 75 ppb and two alternative standard levels, 70 and 60 ppb, which represent the range recommended by the U.S. EPA Clean Air Scientific Advisory Committee (CASAC). We applied health impact assessment methodology to estimate numbers of deaths and other adverse health outcomes that would have been avoided during 2005, 2006, and 2007 if the current (or lower) NAAQS ozone standards had been met. Estimated reductions in ozone concentrations were interpolated according to geographic area and year, and concentration-response functions were obtained or derived from the epidemiological literature. We estimated that annual numbers of avoided ozone-related premature deaths would have ranged from 1,410 to 2,480 at 75 ppb to 2,450 to 4,130 at 70 ppb, and 5,210 to 7,990 at 60 ppb. Acute respiratory symptoms would have been reduced by 3 million cases and school-loss days by 1 million cases annually if the current 75-ppb standard had been attained. Substantially greater health benefits would have resulted if the CASAC-recommended range of standards (70-60 ppb) had been met. Attaining a more stringent primary ozone standard would significantly reduce ozone-related premature mortality and morbidity.


A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein.
CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size. This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.


The social and functional consequences of stroke for elderly patients.
This study sought to answer questions about the social and functional consequences of stroke for elderly patients (greater than or equal to 65 years of age). Survivors of acute stroke were retrospectively identified, and hospital records were reviewed. One year after discharge, follow-up interviews were conducted with families of surviving patients. Most patients were discharged to home (82%) and remained there. Independent functional status was the single predictor of discharge to home (p less than 0.01). By the time of followup, less than half of the surviving patients were functionally independent (42%). Stroke is an important cause of functional dependence among the elderly. Attention should be focused on minimizing the effects of persisting dysfunction on them and their families.


Metal complexes as a promising source for new antibiotics.
There is a dire need for new antimicrobial compounds to combat the growing threat of widespread antibiotic resistance. With a currently very scarce drug pipeline, consisting mostly of derivatives of known antibiotics, new classes of antibiotics are urgently required. Metal complexes are currently in clinical development for the treatment of cancer, malaria and neurodegenerative diseases. However, only little attention has been paid to their application as potential antimicrobial compounds. We report the evaluation of 906 metal-containing compounds that have been screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD) for antimicrobial activity. Metal-bearing compounds display a significantly higher hit-rate (9.9%) when compared to the purely organic molecules (0.87%) in the CO-ADD database. Out of 906 compounds, 88 show activity against at least one of the tested strains, including fungi, while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties. Herein, we highlight the structures of the 30 compounds with activity against Gram-positive and/or Gram-negative bacteria containing Mn, Co, Zn, Ru, Ag, Eu, Ir and Pt, with activities down to the nanomolar range against methicillin resistant S. aureus (MRSA). 23 of these complexes have not been reported for their antimicrobial properties before. This work reveals the vast diversity that metal-containing compounds can bring to antimicrobial research. It is important to raise awareness of these types of compounds for the design of truly novel antibiotics with potential for combatting antimicrobial resistance.


Genetic and environmental influences on serum lipid tracking: a population-based, longitudinal Chinese twin study.
We conducted cross-sectional and longitudinal twin analysis to explore genetic and environmental contribution to serum lipid tracking during childhood and adolescence. The study sample was part of a population-based twin cohort that was recruited in the rural areas of the Anhui Province of China. The baseline recruitment of twins was carried out from 1998 through 2000 and the follow-up from 2005 through 2007. Serum lipids showed significant tracking during childhood and adolescence. Participants with lipids at the highest tertile at the baseline tended to remain high at follow-up across ages and Tanner stages, whereas subjects with lipids at the lowest tertile at the baseline tended to remain low at follow-up. Using twin modeling, we showed that genetic and environmental factors contributed to individual variations in lipid levels and tracking from the baseline to the follow-up visit. The estimated tracking correlations for total cholesterol, triglyceride, and LDL cholesterol were in the range of 0.25-0.53 and were predominantly influenced by genetic factors. In contrast, the phenotypic tracking of HDL cholesterol was influenced by both genetic and environmental factors. Our study underscores the importance of considering both environmental and genetic factors in studying the etiology of dyslipidemia.


Expectant Fathers, Abortion, and Embryos.
One thread of abortion criticism, arguing that gender equality requires that men be allowed to terminate legal parental status and obligations, has reinforced the stereotype of men as uninterested in fatherhood. As courts facing disputes over stored pre-embryos weigh the equities of allowing implantation of the pre-embryos, this same gender stereotype has been increasingly incorporated into a legal balancing test, leading to troubling implications for ART and family law.


Spectrum of Disease and Prescription Pattern for Outpatients with Neurological Disorders: An Empirical Pilot Study in Bangladesh.
Neurological disorders represent one of the most prominent causes of morbidity and mortality that adversely affect the lifestyle of patients and a major percentage of these diseases exists in developing countries. The objective of this study was to examine the prevalence and prescription pattern for outpatients with neurological disorders in Bangladesh. The study was conducted on 1,684 patients in 6 hospitals (National Institute of Neurosciences and Hospital, Dhaka Medical College and Hospital, Bangabandhu Sheikh Mujib Medical University, Shaheed Suhrawardy Medical College, Sir Salimullah Medical College, and Apollo Hospitals Dhaka) of the Dhaka City from March 2014 to June 2015. Data were collected through a predesigned questionnaire from the patients that contain information about gender, age, marital status, occupation, residential status, affected disease, self-medicated medicines, and prescribed medicines. Out of 1,684 patients, 28.38% patients were aged 51-60 years and male, 57.19% predominance. The study exposed headache and migraine for 29.75% patients, followed by stroke for 23.93% patients and seizure for 7.07% patients. Genetic reason for the neurological disorders was seen only among 12.35% patients. In this study, 16.98% patients had been affected by neurological disorders for more than 2 years and 19% of patients for less than 6 months. Most extensively prescribed medicines were multivitamins and multiminerals used by 17.89% of patients followed by nonsteroidal anti-inflammatory drugs and other analgesic by 14.84%; afterwards antiulcerants were used by 12.62%, subsequently anticoagulants were used by 11.61% followed by antihyperlipidemic medicines by 10.26% and antiepileptic drugs by 8.08% of patients. The crucial reasons for the selection of prescribed medicines were the confidence that patients had with the physician's prescribed medicines, which was shown for 40.97% patients and knowledge of the medicines was reported for 35.04% patients. The period of prescribed medicine usage was 1-3 months for 39.73% patients and 3-6 months for 29.16% patients. The patient's compliance for prescribed medicines was satisfactory for 34.56% patients, good for 28.15% patients, and side effects were reported for 23.22% patients. In Bangladesh, it is not surprising to note that neurological diseases are more prevalent than other different diseases among different age groups and genders. Headache and migraine, stroke and seizure are most frequently encountered neurological disorders here. Treatment procedure of these disorders is not quite suitable due to the anomalies of health care management systems. Appropriate management of the health care system, especially the placement of hospital and community pharmacy can overcome the existing inconsistencies as well as increase the knowledge, awareness, and perception of the patients about health and neurological disorders.


Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center.
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P=0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.


Chemoselective imaging of mouse brain tissue via multiplex CARS microscopy.
The fast and reliable characterization of pathological tissue is a debated topic in the application of vibrational spectroscopy in medicine. In the present work we apply multiplex coherent anti-Stokes Raman scattering (MCARS) to the investigation of fresh mouse brain tissue. The combination of imaginary part extraction followed by principal component analysis led to color contrast between grey and white matter as well as layers of granule and Purkinje cells. Additional quantitative information was obtained by using a decomposition algorithm. The results perfectly agree with HE stained references slides prepared separately making multiplex CARS an ideal approach for chemoselective imaging.


Composition, variation, expression and evolution of low-molecular-weight glutenin subunit genes in Triticum urartu.
Wheat (AABBDD, 2n = 6x = 42) is a major dietary component for many populations across the world. Bread-making quality of wheat is mainly determined by glutenin subunits, but it remains challenging to elucidate the composition and variation of low-molecular-weight glutenin subunits (LMW-GS) genes, the major components for glutenin subunits in hexaploid wheat. This problem, however, can be greatly simplified by characterizing the LMW-GS genes in Triticum urartu, the A-genome donor of hexaploid wheat. In the present study, we exploited the high-throughput molecular marker system, gene cloning, proteomic methods and molecular evolutionary genetic analysis to reveal the composition, variation, expression and evolution of LMW-GS genes in a T. urartu population from the Fertile Crescent region. Eight LMW-GS genes, including four m-type, one s-type and three i-type, were characterized in the T. urartu population. Six or seven genes, the highest number at the Glu-A3 locus, were detected in each accession. Three i-type genes, each containing more than six allelic variants, were tightly linked because of their co-segregation in every accession. Only 2-3 allelic variants were detected for each m- and s-type gene. The m-type gene, TuA3-385, for which homologs were previously characterized only at Glu-D3 locus in common wheat and Aegilops tauschii, was detected at Glu-A3 locus in T. urartu. TuA3-460 was the first s-type gene identified at Glu-A3 locus. Proteomic analysis showed 1-4 genes, mainly i-type, expressed in individual accessions. About 62% accessions had three active i-type genes, rather than one or two in common wheat. Southeastern Turkey might be the center of origin and diversity for T. urartu due to its abundance of LMW-GS genes/genotypes. Phylogenetic reconstruction demonstrated that the characterized T. urartu might be the direct donor of the Glu-A3 locus in common wheat varieties. Compared with the Glu-A3 locus in common wheat, a large number of highly diverse LMW-GS genes and active genes were characterized in T. urartu, demonstrating that this progenitor might provide valuable genetic resources for LMW-GS genes to improve the quality of common wheat. The phylogenetic analysis provided molecular evidence and confirmed that T. urartu was the A-genome donor of hexaploid wheat.