Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Prevalence and Factors Associated with Hypertension among Adolescents in Malaysia

Introduction: Evidence has shown an increase in paediatric hypertension globally and this could give rise to increase prevalence of adult hypertension. The purpose of this paper was to determine the prevalence of hypertension among adolescents in Malaysia as well as the association between hypertension and lifestyle factors selected based on published literature. Methods: Adolescents aged 13-17 years old were selected randomly from two secondary schools to have their blood pressure measured. Their lifestyle information was obtained through completed bilingual questionnaires based on validated instruments, as well as anthropometry measurements. The relationship between hypertension and lifestyle factors was determined through statistical analysis. Results: A total of 273 students were included in the study with 120 (44%) males and 153 (56%) females. The prevalence of hypertension was 24.5% among the respondents with the highest being recorded among Malays (28.7%). Generally, hypertension was associated with an increased Body Mass Index (BMI) (AOR=4.053, 95%CI=1.677-9.795, p=0.002) and waist circumference (WC) (AOR=2.918, 95%CI=1.171-7.269, p=0.021) in all respondents. Similar associations were noted in females (BMI: AOR=7.707, 95%CI=2.043-29.072, p=0.003; WC: AOR=3.690, 95%CI=1.011-13.464, p=0.048) but not in males. Conclusion: Hypertension recorded high prevalence among Malaysian adolescents in our study. The strong association between elevated body weight, BMI and WC with hypertension may require further study to evaluate the need for screenin

A human PrM antibody that recognizes a novel cryptic epitope on dengue E glycoprotein

10.1371/journal.pone.0033451PLoS ONE74

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

Cognitive function, social integration and mortality in a U.S. national cohort study of older adults

<p>Abstract</p> <p>Background</p> <p>Prior research suggests an interaction between social networks and Alzheimer's disease pathology and cognitive function, all predictors of survival in the elderly. We test the hypotheses that both social integration and cognitive function are independently associated with subsequent mortality and there is an interaction between social integration and cognitive function as related to mortality in a national cohort of older persons.</p> <p>Methods</p> <p>Data were analyzed from a longitudinal follow-up study of 5,908 American men and women aged 60 years and over examined in 1988–1994 followed an average 8.5 yr. Measurements at baseline included self-reported social integration, socio-demographics, health, body mass index, C-reactive protein and a short index of cognitive function (SICF).</p> <p>Results</p> <p>Death during follow-up occurred in 2,431. In bivariate analyses indicators of greater social integration were associated with higher cognitive function. Among persons with SICF score of 17, 22% died compared to 54% of those with SICF score of 0–11 (p < 0.0001). After adjusting for confounding by baseline socio-demographics and health status, the hazards ratio (HR) (95% confidence limits) for low SICF score was 1.43 (1.13–1.80, p < 0.001). After controlling for health behaviors, blood pressure and body mass, C-reactive protein and social integration, the HR was 1.36 (1.06–1.76, p = 0.02). Further low compared to high social integration was also independently associated with increased risk of mortality: HR 1.24 (1.02–1.52, p = 0.02).</p> <p>Conclusion</p> <p>In a cohort of older Americans, analyses demonstrated a higher risk of death independent of confounders among those with low cognitive function and low social integration with no significant interaction between them.</p

Replacement of α-galactosidase A in Fabry disease: effect on fibroblast cultures compared with biopsied tissues of treated patients

The function and intracellular delivery of enzyme therapeutics for Fabry disease were studied in cultured fibroblasts and in the biopsied tissues of two male patients to show diversity of affected cells in response to treatment. In the mutant fibroblasts cultures, the final cellular level of endocytosed recombinant α-galactosidases A (agalsidases, FabrazymeTM, and ReplagalTM) exceeded, by several fold, the amount in control fibroblasts and led to efficient direct intra-lysosomal hydrolysis of (3H)Gb3Cer. In contrast, in the samples from the heart and some other tissues biopsied after several months of enzyme replacement therapy (ERT) with FabrazymeTM, only the endothelial cells were free of storage. Persistent Gb3Cer storage was found in cardiocytes (accompanied by increase of lipopigment), smooth muscle cells, fibroblasts, sweat glands, and skeletal muscle. Immunohistochemistry of cardiocytes demonstrated, for the first time, the presence of a considerable amount of the active enzyme in intimate contact with the storage compartment. Factors responsible for the limited ERT effectiveness are discussed, namely post-mitotic status of storage cells preventing their replacement by enzyme supplied precursors, modification of the lysosomal system by longstanding storage, and possible relative lack of Sap B. These observations support the strategy of early treatment for prevention of lysosomal storage

Household Possession and Use of Insecticide-Treated Mosquito Nets in Sierra Leone 6 Months after a National Mass-Distribution Campaign

BACKGROUND: In November 2010, Sierra Leone distributed over three million long-lasting insecticide-treated nets (LLINs) with the objective of providing protection from malaria to individuals in all households in the country. METHODS: We conducted a nationally representative survey six months after the mass distribution campaign to evaluate its impact on household insecticide-treated net (ITN) ownership and use. We examined factors associated with household ITN possession and use with logistic regression models. RESULTS: The survey included 4,620 households with equal representation in each of the 14 districts. Six months after the campaign, 87.6% of households own at least one ITN, which represents an increase of 137% over the most recent estimate of 37% in 2008. Thirty-six percent of households possess at least one ITN per two household members; rural households were more likely than urban households to have ≥ 1:2 ITN to household members, but there was no difference by socio-economic status or household head education. Among individuals in households possessing ≥ 1 ITN, 76.5% slept under an ITN the night preceding the survey. Individuals in households where the household head had heard malaria messaging, had correct knowledge of malaria transmission, and where at least one ITN was hanging, were more likely to have slept under an ITN. CONCLUSIONS: The mass distribution campaign was effective at achieving high coverage levels across the population, notably so among rural households where the malaria burden is higher. These important gains in equitable access to malaria prevention will need to be maintained to produce long-term reductions in the malaria burden

Heterogeneity of Glia in the Retina and Optic Nerve of Birds and Mammals

We have recently described a novel type of glial cell that is scattered across the inner layers of the avian retina [1]. These cells are stimulated by insulin-like growth factor 1 (IGF1) to proliferate, migrate distally into the retina, and up-regulate the nestin-related intermediate filament transitin. These changes in glial activity correspond with increased susceptibility of neurons to excitotoxic damage. This novel cell-type has been termed the Non-astrocytic Inner Retinal Glia-like (NIRG) cells. The purpose of the study was to investigate whether the retinas of non-avian species contain cells that resemble NIRG cells. We assayed for NIRG cells by probing for the expression of Sox2, Sox9, Nkx2.2, vimentin and nestin. NIRG cells were distinguished from astrocytes by a lack of expression for Glial Fibrilliary Acidic Protein (GFAP). We examined the retinas of adult mice, guinea pigs, dogs and monkeys (Macaca fasicularis). In the mouse retina and optic nerve head, we identified numerous astrocytes that expressed GFAP, S100β, Sox2 and Sox9; however, we found no evidence for NIRG-like cells that were positive for Nkx2.2, nestin, and negative for GFAP. In the guinea pig retina, we did not find astrocytes or NIRG cells in the retina, whereas we identified astrocytes in the optic nerve. In the eyes of dogs and monkeys, we found astrocytes and NIRG-like cells scattered across inner layers of the retina and within the optic nerve. We conclude that NIRG-like cells are present in the retinas of canines and non-human primates, whereas the retinas of mice and guinea pigs do not contain NIRG cells

Women's Status and Violence against Young Married Women in Rural Nepal

<p>Abstract</p> <p>Background</p> <p>Studies conducted around the world consistently show the existence of violence against women. Despite the increasing number of studies being conducted on violence against young married women elsewhere, this subject has received little attention from researchers and policy makers in Nepal. This paper assesses the prevalence of violence among young married women in rural Nepal. Specifically, it examines [factors related to] women's status in order to better understand the risk of violence.</p> <p>Methods</p> <p>A cross-sectional study was conducted in 2009 among 1,296 young married women aged 15-24 years in four major ethnic groups. Bivariate analysis and multivariate logistic regression were used to examine the association between selected risk factors and violence.</p> <p>Results</p> <p>More than half the women (51.9%) reported having experienced some form of violence in their lifetime. One-fourth (25.3%) reported physical violence and nearly half (46.2%) reported sexual violence. Likewise, one-third (35.8%) of women reported experiencing some form of violence in the past 12 months. No or little inter-spousal communication and low autonomy of women significantly increases the odds of experiencing violence among married women.</p> <p>Conclusions</p> <p>The violence against women is quite common among young married women in rural Nepal. Although the Domestic Violence and Punishment Act 2066 has been enacted, equal attention needs to be given to increasing women's autonomy and activities that encourage inter-spousal communication. Furthermore, more research is required in Nepal that examines dynamics of violence perpetrated by husbands.</p