Polarizing the T helper 17 response in Citrobacter rodentium infection via expression of resistin-like molecule α

Citrobacter rodentium infection is a murine model of pathogenic Escherichia coli infection that allows investigation of the cellular and molecular mechanisms involved in host-protective immunity and bacterial-induced intestinal inflammation. We recently demonstrated that following C. rodentium infection, the absence of Resistin-Like Molecule (RELM) α resulted in attenuated Th17 cell responses and reduced intestinal inflammation with minimal effects on bacterial clearance. In this addendum, we investigated the cytokine modulatory effects of RELMα and RELMα expression in the intestinal mucosa following C. rodentium infection. We show that in addition to promoting Th17 cytokine responses, RELMα inhibits Th2 cytokine expression and Th2-cytokine effector macrophage responses in the C. rodentium-infected colons. Second, utilizing reporter C. rodentium, we examined RELMα expression and macrophage recruitment at the host pathogen interface. We observed infection-induced macrophage infiltration and RELMα expression by intestinal epithelial cells. The influence of infection-induced RELMα on macrophage recruitment in the intestine is discussed.     

L-Ascorbic Acid and α-Tocopherol Reduces Hepatotoxicity Associated with Arsenic Trioxide Chemotherapy by Modulating Nrf2 and Bcl2 Transcription Factors in Chang liver Cells

Arsenic trioxide (As₂O₃) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind As₂O₃ toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and α-TOC against As₂O₃ toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 µM) and α-TOC (50 µM) recovered As₂O₃ (10 µM) cytotoxicity. Furthermore, As₂O₃ treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with As₂O₃ resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression.     

Setting priorities for a research agenda to combat drug-resistant tuberculosis in children

Setting: Numerous knowledge gaps hamper the prevention and treatment of childhood drug-resistant tuberculosis (TB). Identifying research priorities is vital to inform and develop strategies to address this neglected problem.Objective: To systematically identify and rank research priorities in childhood drug-resistant TB.Design: Adapting the Child Health and Nutrition Research Initiative (CHNRI) methodology, we compiled 53 research questions in four research areas, then classified the questions into three research types. We invited experts in childhood drug-resistant TB to score these questions through an online survey.Results: A total of 81 respondents participated in the survey. The top-ranked research question was to identify the best combination of existing diagnostic tools for early diagnosis. Highly ranked treatment-related questions centred on the reasons for and interventions to improve treatment outcomes, adverse effects of drugs and optimal treatment duration. The prevalence of drug-resistant TB was the highest-ranked question in the epidemiology area. The development type questions that ranked highest focused on interventions for optimal diagnosis, treatment and modalities for treatment delivery.Conclusion: This is the first effort to identify and rank research priorities for childhood drug-resistant TB. The result is a resource to guide research to improve prevention and treatment of drug-resistant TB in children.     

Synthesis of a 35S‐labeled dinucleoside phosphorothioate prodrug,an orally bioavailable anti‐HBV agent

The ³⁵S‐labeled, dinucleoside phosphorothioate 1, an orally available agent against hepatitis B virus, was prepared in eight steps with high specific activity and radiochemical purity. Radiolabeled 3H‐benzodithiole‐3‐one‐1,1‐dioxide was synthesized in four steps from ³⁵S₈ and was used as the sulfurizing reagent. Copyright © 2012 John Wiley & Sons, Ltd.     

Does postural stability affect grasping?

We examined whether challenging upright stance influences the execution of a grasping task. Participants reached to grasp a small sphere while standing either on a stable surface or on foam. Before reaching for the sphere, participants exhibited more body sway and greater fluctuations in the centre of pressure when standing on foam. While reaching for the sphere, the overall body posture changed less when standing on foam than when standing on the stable surface. The digits’ and wrist's movements towards the sphere were no different when standing on foam than when standing on the stable surface. Presumably, the redundancy in the way movements can be performed is exploited to choose the most suitable changes in joint angles to achieve the desired movements of the digits under the prevailing conditions.     

Operational research leading to rapid national policy change: tuberculosis-diabetes collaboration in India

In 2011, bi-directional screening for tuberculosis (TB) and diabetes mellitus (DM) was recommended by the World Health Organization (WHO), although how best to implement the activity was not clear. In India, with early engagement of national programme managers and all important stakeholders, a countrywide, multicentre operational research (OR) project was designed in October 2011 and completed in 2012. The results led to a rapid national policy decision to routinely screen all TB patients for DM in September 2012. The process, experience and enablers of implementing this unique and successful collaborative model of operational research are presented.