A New Antifungal Antibiotic from Bacillus sp. KM5 Isolated from Rice Rhizospheric Soil

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Bacterial strain, Bacillus sp. KM5 was recently isolated and characterized by strong antifungal activities...     

Technique of flap elevation for robot assisted selective neck dissection via retroauricular approach: a surgeon’s guide

Journal of Robotic Surgery - The retroauricular approach is being increasingly used in surgeries of head and neck in an attempt to avoid a disfiguring scar over the face or neck. The elevation of...     

Adding pharmacists to primary care teams reduces predicted long‐term risk of cardiovascular events in Type 2 diabetic patients without established cardiovascular disease: results from a randomized trial

Aim To determine the impact of adding pharmacists to primary care teams on predicted 10‐year risk of cardiovascular events in patients with Type 2 diabetes without established cardiovascular disease. Methods This was a pre‐specified secondary analysis of randomized trial data. The main study found that, compared with usual care, addition of a pharmacist resulted in improvements in blood pressure, dyslipidaemia, and hyperglycaemia for primary care patients with Type 2 diabetes. In this sub‐study, predicted 10‐year risk of cardiovascular events at baseline and 1 year were calculated for patients free of cardiovascular disease at enrolment. The primary outcome was change in UK Prospective Diabetes Study (UKPDS) risk score; change in Framingham risk score was a secondary outcome. Results Baseline characteristics were similar between the 102 intervention patients and 93 control subjects: 59% women, median (interquartile range) age 57 (50–64) years, diabetes duration 3 (1–6.5) years, systolic blood pressure 128 (120–140) mmHg, total cholesterol 4.34 (3.75–5.04) mmol/l and HbA_1c 54 mmol/mol (48–64 mmol/mol) [7.1% (6.5–8.0%)]. Median baseline UKPDS risk score was 10.2% (6.0–16.7%) for intervention patients and 9.5% (5.8–15.1%) for control subjects (P = 0.80). One‐year post‐randomization, the median absolute reduction in UKPDS risk score was 1.0% greater for intervention patients compared with control subjects (P = 0.032). Similar changes were seen with the Framingham risk score (median reduction 1.2% greater for intervention patients compared with control subjects, P = 0.048). The two risk scores were highly correlated (rho = 0.83; P < 0.001). Conclusion Adding pharmacists to primary care teams for 1 year significantly reduced the predicted 10‐year risk of cardiovascular events for patients with Type 2 diabetes without established cardiovascular disease.     

Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica infection in Bangladeshi children

BACKGROUND: The association of antibody responses with both innate and acquired immunity to amebiasis indicate that CD4+ T cells play a role in protection against Entamoeba histolytica infection. To test this hypothesis, we compared the genotype frequencies of human leukocyte antigen (HLA) class II alleles in a cohort of Bangladeshi children intensively monitored for E. histolytica infection for a 3-year period. METHODS: Using logistic regression, we calculated the odds of disease by genotype and by haplotype. RESULTS: The DQB1*0601 heterozygous and homozygous genotypes were found in 55% of E. histolytica-negative children but in only 34% of E. histolytica-positive children (overall odds ratio, 2.39; 95% confidence interval [CI], 1.26-4.54). Children who were heterozygous for the DQB1*0601/DRB1*1501 haplotype were 10.1 times (95% CI, 2.02-50.6) more likely to be both E. histolytica negative and serum anti-lectin immunoglobulin G negative at baseline. Other DQB1 and DRB1 alleles (DQB1*0202, DQB1*0301, and DRB1*0701) were not associated with any of the clinical outcomes related to amebiasis. CONCLUSION: A potential protective association was observed with the HLA class II allele DQB1*0601 and the heterozygous haplotype DQB1*0601/DRB1*1501. This association may explain why amebiasis does not occur in some children who are exposed to the parasite and implicates HLA class II-restricted immune responses in protection against E. histolytica infection.     

Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh

Background: Inorganic arsenic is one of the most common naturally occurring contaminants found in the environment. Arsenic is associated with a number of health outcomes, with epigenetic modification suggested as a potential mechanism of toxicity.Objective: Among a sample of 400 adult participants, we evaluated the association between arsenic exposure, as measured by blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation.Methods: We used linear regression models to examine the associations between arsenic exposure and methylation at each CpG site, adjusted for sex, age, and batch. Differentially methylated loci were subsequently examined in relation to corresponding gene expression for functional evidence of gene regulation.Results: In adjusted analyses, we observed four differentially methylated CpG sites with urinary total arsenic concentration and three differentially methylated CpG sites with blood arsenic concentration, based on the Bonferroni-corrected significance threshold of p < 1 × 10^–7. Methylation of PLA2G2C (probe cg04605617) was the most significantly associated locus in relation to both urinary (p = 3.40 × 10^–11) and blood arsenic concentrations (p = 1.48 × 10^–11). Three additional novel methylation loci—SQSTM1 (cg01225779), SLC4A4 (cg06121226), and IGH (cg13651690)—were also significantly associated with arsenic exposure. Further, there was evidence of methylation-related gene regulation based on gene expression for a subset of differentially methylated loci.Conclusions: We observed significant associations between arsenic exposure and gene-specific differential white blood cell DNA methylation, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. The specific differentially methylated loci identified may inform potential pathways for future interventions.Citation: Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H. 2015. Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh. Environ Health Perspect 123:64–71; http://dx.doi.org/10.1289/ehp.1307884     

Chemokine-induced leishmanicidal activity in murine macrophages via the generation of nitric oxide

This study explored the role of the proinflammatory chemokines macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1 for development of antileishmanial activity. There was substantial inhibition in nitrite generation in Leishmania donovani-infected macrophages. A marked elevation of nitrite generation and induction of inducible nitric oxide (NO) synthase (iNOS) mRNA was found in chemokine-primed parasite-infected macrophages. Tumor necrosis factor-alpha, which is the priming signal for NO production, was also up-regulated under similar experimental conditions. The priming with chemokine inhibited the multiplication of L. donovani amastigotes within the intramacrophageal milieu. The antileishmanial effect of chemokines was almost completely abrogated when the macrophages were preincubated with l-N-monomethyl arginine, the specific inhibitor of iNOS. The results of this investigation suggest that the CC chemokines MIP-1alpha and MCP-1 orchestrate an antileishmanial armamentarium via the induction of an NO-mediated regulatory mechanism to control the intracellular growth and multiplication of the Leishmania protozoan.