Community-based management of severe acute malnutrition in India: new evidence from Bihar.

BACKGROUND: An estimated one-third of the world's children who are wasted live in India. In Bihar state, of children -2 SDs and MUAC >110 mm. These variables changed in July 2010 to admission on the basis of an MUAC <115 mm and discharge at an MUAC ≥120 mm. Uncomplicated SAM cases were treated as outpatients in the community by using a WHO-standard, ready-to-use, therapeutic lipid-based paste produced in India; complicated cases were treated as inpatients by using F75/F100 WHO-standard milk until they could complete treatment in the community. RESULTS: A total of 8274 children were admitted including 5149 girls (62.2%), 6613 children aged 6-23 mo (79.9%), and 87.3% children who belonged to Scheduled Caste, Scheduled Tribe, or Other Backward Caste families or households. Of 3873 children admitted under the old criteria, 41 children (1.1%) died, 2069 children (53.4%) were discharged as cured, and 1485 children (38.3%) defaulted. Of 4401 children admitted under the new criteria, 36 children (0.8%) died, 2526 children (57.4%) were discharged as cured, and 1591 children (36.2%) defaulted. For children discharged as cured, the mean (±SD) weight gain and length of stay were 4.7 ± 3.1 and 5.1 ± 3.7 g · kg(-1) · d(-1) and 8.7 ± 6.1 and 7.3 ± 5.6 wk under the old and new criteria, respectively (P < 0.01). After adjustment, significant risk factors for default were as follows: no community referral for admission, more severe wasting on admission, younger age, and a long commute for treatment. CONCLUSIONS: To our knowledge, this is the first conventional CMAM program in India and has achieved low mortality and high cure rates in nondefaulting children. The new admission criteria lower the threshold for severity with the result that more children are included who are at lower risk of death and have a smaller WHZ deficit to correct than do children identified by the old criteria. This study was registered as a retrospective observational analysis of routine program data at http://www.isrctn.com as ISRCTN13980582

Developing the Next Generation of Entrepreneurs: Giving Students the Opportunity to Gain Experience and Thrive

Higher Education Institutions (HEIs) have increasingly utilized experiential approaches in business education; however, some researchers have suggested that further research is required to investigate the effectiveness and student reaction to such approaches. The aim of this study is to determine the impact of an experiential learning approach on the perceived development of entrepreneurial traits and to measure the level of both student engagement and satisfaction. The approach was designed and tested during a Higher National Diploma (HND) entrepreneurship module in a British HEI. Traditional taught sessions were blended with applied activities that required students to utilize the skills they learned to complete steps of the activities, which increased in length and complexity. Results found both a high level of student satisfaction and engagement and the belief that the module’s experiential approach had, in many instances, helped to develop entrepreneurial traits. Successful practice and modifications are discussed

Transient Reversal of Episome Silencing Precedes VP16-Dependent Transcription during Reactivation of Latent HSV-1 in Neurons

Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected cultures of primary superior cervical ganglion (SCG) sympathetic neurons to profile viral gene expression following a defined reactivation stimulus. Lytic genes are transcribed in two distinct phases, differing in their reliance on protein synthesis, viral DNA replication and the essential initiator protein VP16. The first phase does not require viral proteins and has the appearance of a transient, widespread de-repression of the previously silent lytic genes. This allows synthesis of viral regulatory proteins including VP16, which accumulate in the cytoplasm of the host neuron. During the second phase, VP16 and its cellular cofactor HCF-1, which is also predominantly cytoplasmic, concentrate in the nucleus where they assemble an activator complex on viral promoters. The transactivation function supplied by VP16 promotes increased viral lytic gene transcription leading to the onset of genome amplification and the production of infectious viral particles. Thus regulated localization of de novo synthesized VP16 is likely to be a critical determinant of HSV-1 reactivation in sympathetic neurons

Chronic Diseases in North-West Tanzania and Southern Uganda. Public Perceptions of Terminologies, Aetiologies, Symptoms and Preferred Management

Research outputs produced to support a quantitative population survey, quantitative health facility survey, focus groups and in-depth interviews performed by the projec

Evolution of Sex Chromosome Dosage Compensation in Animals: A Beautiful Theory, Undermined by Facts and Bedeviled by Details

Many animals with genetic sex determination harbor heteromorphic sex chromosomes, where the heterogametic sex has half the gene dose of the homogametic sex. This imbalance, if reflected in the abundance of transcripts or proteins, has the potential to deleteriously disrupt interactions between X-linked and autosomal loci in the heterogametic sex. Classical theory predicts that molecular mechanisms will evolve to provide dosage compensation that recovers expression levels comparable to ancestral expression prior to sex chromosome divergence. Such dosage compensating mechanisms may also, secondarily, result in balanced sex-linked gene expression between males and females. However, numerous recent studies addressing sex chromosome dosage compensation (SCDC) in a diversity of animals have yielded a surprising array of patterns concerning dosage compensation in the heterogametic sex, as well as dosage balance between sexes. These results substantially contradict longstanding theory, catalyzing both novel perspectives and new approaches in dosage compensation research. In this review, we summarize the theory, analytical approaches, and recent results concerning evolutionary patterns of SCDC in animals. We also discuss methodological challenges and discrepancies encountered in this research, which often underlie conflicting results. Finally, we discuss what outstanding questions and opportunities exist for future research on SCDC

Caenorhabditis elegans Semi-Automated Liquid Screen Reveals a Specialized Role for the Chemotaxis Gene cheB2 in Pseudomonas aeruginosa Virulence

Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections in a variety of animal and plant hosts. Caenorhabditis elegans is a simple model with which one can identify bacterial virulence genes. Previous studies with C. elegans have shown that depending on the growth medium, P. aeruginosa provokes different pathologies: slow or fast killing, lethal paralysis and red death. In this study, we developed a high-throughput semi-automated liquid-based assay such that an entire genome can readily be scanned for virulence genes in a short time period. We screened a 2,200-member STM mutant library generated in a cystic fibrosis airway P. aeruginosa isolate, TBCF10839. Twelve mutants were isolated each showing at least 70% attenuation in C. elegans killing. The selected mutants had insertions in regulatory genes, such as a histidine kinase sensor of two-component systems and a member of the AraC family, or in genes involved in adherence or chemotaxis. One mutant had an insertion in a cheB gene homologue, encoding a methylesterase involved in chemotaxis (CheB2). The cheB2 mutant was tested in a murine lung infection model and found to have a highly attenuated virulence. The cheB2 gene is part of the chemotactic gene cluster II, which was shown to be required for an optimal mobility in vitro. In P. aeruginosa, the main player in chemotaxis and mobility is the chemotactic gene cluster I, including cheB1. We show that, in contrast to the cheB2 mutant, a cheB1 mutant is not attenuated for virulence in C. elegans whereas in vitro motility and chemotaxis are severely impaired. We conclude that the virulence defect of the cheB2 mutant is not linked with a global motility defect but that instead the cheB2 gene is involved in a specific chemotactic response, which takes place during infection and is required for P. aeruginosa pathogenicity

Toxin-Based Therapeutic Approaches

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms