Open defecation and childhood stunting in India: an ecological analysis of new data from 112 districts.

Poor sanitation remains a major public health concern linked to several important health outcomes; emerging evidence indicates a link to childhood stunting. In India over half of the population defecates in the open; the prevalence of stunting remains very high. Recently published data on levels of stunting in 112 districts of India provide an opportunity to explore the relationship between levels of open defecation and stunting within this population. We conducted an ecological regression analysis to assess the association between the prevalence of open defecation and stunting after adjustment for potential confounding factors. Data from the 2011 HUNGaMA survey was used for the outcome of interest, stunting; data from the 2011 Indian Census for the same districts was used for the exposure of interest, open defecation. After adjustment for various potential confounding factors--including socio-economic status, maternal education and calorie availability--a 10 percent increase in open defecation was associated with a 0.7 percentage point increase in both stunting and severe stunting. Differences in open defecation can statistically account for 35 to 55 percent of the average difference in stunting between districts identified as low-performing and high-performing in the HUNGaMA data. In addition, using a Monte Carlo simulation, we explored the effect on statistical power of the common practice of dichotomizing continuous height data into binary stunting indicators. Our simulation showed that dichotomization of height sacrifices statistical power, suggesting that our estimate of the association between open defecation and stunting may be a lower bound. Whilst our analysis is ecological and therefore vulnerable to residual confounding, these findings use the most recently collected large-scale data from India to add to a growing body of suggestive evidence for an effect of poor sanitation on human growth. New intervention studies, currently underway, may shed more light on this important issue

Exploring the equity of GP practice prescribing rates for selected coronary heart disease drugs: a multiple regression analysis with proxies of healthcare need

Background There is a small, but growing body of literature highlighting inequities in GP practice prescribing rates for many drug therapies. The aim of this paper is to further explore the equity of prescribing for five major CHD drug groups and to explain the amount of variation in GP practice prescribing rates that can be explained by a range of healthcare needs indicators (HCNIs). Methods The study involved a cross-sectional secondary analysis in four primary care trusts (PCTs 1–4) in the North West of England, including 132 GP practices. Prescribing rates (average daily quantities per registered patient aged over 35 years) and HCNIs were developed for all GP practices. Analysis was undertaken using multiple linear regression. Results Between 22–25% of the variation in prescribing rates for statins, beta-blockers and bendrofluazide was explained in the multiple regression models. Slightly more variation was explained for ACE inhibitors (31.6%) and considerably more for aspirin (51.2%). Prescribing rates were positively associated with CHD hospital diagnoses and procedures for all drug groups other than ACE inhibitors. The proportion of patients aged 55–74 years was positively related to all prescribing rates other than aspirin, where they were positively related to the proportion of patients aged >75 years. However, prescribing rates for statins and ACE inhibitors were negatively associated with the proportion of patients aged >75 years in addition to the proportion of patients from minority ethnic groups. Prescribing rates for aspirin, bendrofluazide and all CHD drugs combined were negatively associated with deprivation. Conclusion Although around 25–50% of the variation in prescribing rates was explained by HCNIs, this varied markedly between PCTs and drug groups. Prescribing rates were generally characterised by both positive and negative associations with HCNIs, suggesting possible inequities in prescribing rates on the basis of ethnicity, deprivation and the proportion of patients aged over 75 years (for statins and ACE inhibitors, but not for aspirin)

Cellular glycosylation affects Herceptin binding and sensitivity of breast cancer cells to doxorubicin and growth factors

Alterations in protein glycosylation are a key feature of oncogenesis and have been shown to affect cancer cell behaviour perturbing cell adhesion, favouring cell migration and metastasis. This study investigated the effect of N-linked glycosylation on the binding of Herceptin to HER2 protein in breast cancer and on the sensitivity of cancer cells to the chemotherapeutic agent doxorubicin (DXR) and growth factors (EGF and IGF-1). The interaction between Herceptin and recombinant HER2 protein and cancer cell surfaces (on-rate/off-rate) was assessed using a quartz crystal microbalance biosensor revealing an increase in the accessibility of HER2 to Herceptin following deglycosylation of cell membrane proteins (deglycosylated cells Bmax: 6.83 Hz; glycosylated cells Bmax: 7.35 Hz). The sensitivity of cells to DXR and to growth factors was evaluated using an MTT assay. Maintenance of SKBR-3 cells in tunicamycin (an inhibitor of N-linked glycosylation) resulted in an increase in sensitivity to DXR (0.1 µM DXR P<0.001) and a decrease in sensitivity to IGF-1 alone and to IGF-1 supplemented with EGF (P<0.001). This report illustrates the importance of N-linked glycosylation in modulating the response of cancer cells to chemotherapeutic and biological treatments and highlights the potential of glycosylation inhibitors as future combination treatments for breast cancer

Characterization and Separation Performance of a Novel Polyethersulfone Membrane Blended with Acacia Gum

Novel polyethersulfone (PES) membranes blended with 0.1–3.0 wt. % of Acacia gum (AG) as a pore-former and antifouling agent were fabricated using phase inversion technique. The effect of AG on the pore-size, porosity, surface morphology, surface charge, hydrophilicity, and mechanical properties of PES/AG membranes was studied by scanning electron microscopy (SEM), Raman spectroscopy, contact angle and zeta potential measurements. The antifouling -properties of PES/AG membranes were evaluated using Escherichia coli bacteria and bovine serum albumine (BSA). The use of AG as an additive to PES membranes was found to increase the surface charge, hydrophilicity (by 20%), porosity (by 77%) and permeate flux (by about 130%). Moreover, PES/AG membranes demonstrated higher antifouling and tensile stress (by 31%) when compared to pure PES membranes. It was shown that the prepared PES/AG membranes efficiently removed lead ions from aqueous solutions. Both the sieving mechanism of the membrane and chelation of lead with AG macromolecules incorporated in the membrane matrix contributed to lead removal. The obtained results indicated that AG can be used as a novel pore-former, hydrophilizing and antifouling agent, as well as an enhancer to the mechanical and rejection properties of the PES membranes

Association of HIV infection with distribution and viral load of HPV types in Kenya: a survey with 820 female sex workers

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) and HIV are each responsible for a considerable burden of disease. Interactions between these infections pose substantial public health challenges, especially where HIV prevalence is high and HPV vaccine coverage low.</p> <p>Methods</p> <p>Between July 2005 and January 2006, a cross-sectional community-based survey in Mombasa, Kenya, enrolled female sex workers using snowball sampling. After interview and a gynaecological examination, blood and cervical cytology samples were taken. Quantitative real-time PCR detected HPV types and viral load measures. Prevalence of high-risk HPV was compared between HIV-infected and -uninfected women, and in women with abnormal cervical cytology, measured using conventional Pap smears.</p> <p>Results</p> <p>Median age of the 820 participants was 28 years (inter-quartile range [IQR] = 24-36 years). One third of women were HIV infected (283/803; 35.2%) and these women were y more likely to have abnormal cervical cytology than HIV-negative women (27%, 73/269, versus 8%, 42/503; <it>P </it>< 0.001). Of HIV-infected women, 73.3% had high-risk HPV (200/273) and 35.5% had HPV 16 and/or 18 (97/273). Corresponding figures for HIV-negative women were 45.5% (229/503) and 15.7% (79/503). After adjusting for age, number of children and condom use, high-risk HPV was 3.6 fold more common in HIV-infected women (95%CI = 2.6-5.1). Prevalence of all 15 of the high-risk HPV types measured was higher among HIV-infected women, between 1.4 and 5.5 fold. Median total HPV viral load was 881 copies/cell in HIV-infected women (IQR = 33-12,110 copies/cell) and 48 copies/cell in HIV-uninfected women (IQR = 6-756 copies/cell; <it>P </it>< 0.001). HPV 16 and/or HPV 18 were identified in 42.7% of LSIL (32/75) and 42.3% of HSIL (11/26) lesions (<it>P </it>= 0.98). High-risk HPV types other than 16 and 18 were common in LSIL (74.7%; 56/75) and HSIL (84.6%; 22/26); even higher among HIV-infected women.</p> <p>Conclusions</p> <p>HIV-infected sex workers had almost four-fold higher prevalence of high-risk HPV, raised viral load and more precancerous lesions. HPV 16 and HPV 18, preventable with current vaccines, were associated with cervical disease, though other high-risk types were commoner. HIV-infected sex workers likely contribute disproportionately to HPV transmission dynamics in the general population. Current efforts to prevent HIV and HPV are inadequate. New interventions are required and improved implementation of existing strategies.</p

Genus Paracoccidioides: Species Recognition and Biogeographic Aspects

Background: Paracoccidioidomycosis is a systemic mycosis caused by Paracoccidioides brasiliensis (species S1, PS2, PS3), and Paracoccidioides lutzii. This work aimed to differentiate species within the genus Paracoccidioides, without applying multilocus sequencing, as well as to obtain knowledge of the possible speciation processes. Methodology/Principal Findings: Single nucleotide polymorphism analysis on GP43, ARF and PRP8 intein genes successfully distinguished isolates into four different species. Morphological evaluation indicated that elongated conidia were observed exclusively in P. lutzii isolates, while all other species (S1, PS2 and PS3) were indistinguishable. To evaluate the biogeographic events that led to the current geographic distribution of Paracoccidioides species and their sister species, Nested Clade and Likelihood Analysis of Geographic Range Evolution (LAGRANGE) analyses were applied. The radiation of Paracoccidioides started in northwest South America, around 11–32 million years ago, as calculated on the basis of ARF substitution rate, in the BEAST program. Vicariance was responsible for the divergence among S1, PS2 and P. lutzii and a recent dispersal generated the PS3 species, restricted to Colombia. Taking into account the ancestral areas revealed by the LAGRANGE analysis and the major geographic distribution of L. loboi in the Amazon basin, a region strongly affected by the Andes uplift and marine incursions in the Cenozoic era, we also speculate about the effect of these geological events on the vicariance between Paracoccidioides and L. loboi. Conclusions/Significance: The use of at least 3 SNPs, but not morphological criteria, as markers allows us to distinguish among the four cryptic species of the genus Paracoccidioides. The work also presents a biogeographic study speculating on how these species might have diverged in South America, thus contributing to elucidating evolutionary aspects of the genus Paracoccidioides

Regulation of inflammation in Japanese encephalitis

Uncontrolled inflammatory response of the central nervous system is a hallmark of severe Japanese encephalitis (JE). Although inflammation is necessary to mount an efficient immune response against virus infections, exacerbated inflammatory response is often detrimental. In this context, cells of the monocytic lineage appear to be important forces driving JE pathogenesis

Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating

The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly predominant over a. How genetic diversity is generated and maintained by this heterothallic fungus in a largely unisexual α population is unclear. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions generating both diploid intermediates and haploid recombinant progeny. Same-sex mating (α-α) also occurs in nature as evidenced by the existence of natural diploid αADα hybrids that arose by fusion between two α cells of different serotypes (A and D). How significantly this novel sexual style contributes to genetic diversity of the Cryptococcus population was unknown. In this study, ∼500 natural C. neoformans isolates were tested for ploidy and close to 8% were found to be diploid by fluorescence flow cytometry analysis. The majority of these diploids were serotype A isolates with two copies of the α MAT locus allele. Among those, several are intra-varietal allodiploid hybrids produced by fusion of two genetically distinct α cells through same-sex mating. The majority, however, are autodiploids that harbor two seemingly identical copies of the genome and arose via either endoreplication or clonal mating. The diploids identified were isolated from different geographic locations and varied genotypically and phenotypically, indicating independent non-clonal origins. The present study demonstrates that unisexual mating produces diploid isolates of C. neoformans in nature, giving rise to populations of hybrids and mixed ploidy. Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens