Anti-Hyperglycemic And Anti-Hyperlipidemic Potential Of A Polyherbal Preparation “Diabegon” In Metabolic Syndrome Subject With Type 2 Diabetes

Background: In the present study, “Diabegon” a poly-herbal preparation, with hypoglycemic activity, was evaluated for its preventive effect inmetabolic syndrome subjects with type 2 diabetes and also to reveal its side effects, on liver and kidney.Materials and Methods: Type 2 diabetic subjects with metabolic syndrome (N=58) were categorized on the basis of age and fasting blood glucose.The grouping was as follows: Group I (35-50 yrs), Group II (51-65 yrs), Group III >65 yrs, Group IV FBS<145.9, Group V FBS>145. Each group wasadministered 4 gm of diabegon daily. Blood glucose levels, lipid profile, liver and kidney function of the subjects were regularly monitored within 3months of interval to 18 months.Results: The reduction in fasting blood glucose level ranged from 12.3% (P<0.05) to 42% (P<0.001) after 18 month of therapy whereas in postprandial blood glucose, the decrease ranged from 28% (P<0.05) to 32% (P<0.05) after 18 month of therapy. Overall reductions in the individual parameters of the metabolic syndrome subjects were significantly higher in Group I. Cholesterol level decreased from 11% to 27.2% (P<0.001), triglyceride levels decreased from 24% to 55%, VLDL and LDL levels reduced by 60% & 54% respectively after 18 months of therapy. The HDL-C level increased in all groups. Moreover, diabegon administration for 1.5 years exhibited no alteration in liver and kidney function tests, which indicate its non-toxicity.Conclusion: Our study suggests that diabegon could be included as a preventive treatment in metabolic syndrome subjects with type 2 diabetesespecially for long term treatment as it efficiently shows anti-hyperglycemic and anti-lipidemic effects with no adverse impacts on the liver and kidney.Key words: Metabolic syndrome, Type 2 diabetes, Diabegon, Polyherbal preparation

Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Study.

BACKGROUND: Nonobstructive coronary plaques manifesting high-risk morphology (HRM) associate with an increased risk of adverse clinical cardiovascular events. We sought to test the hypothesis that statins have a greater anti-inflammatory effect within coronary plaques containing HRM. METHODS AND RESULTS: In this prospective multicenter study, 55 subjects with or at high risk for atherosclerosis underwent 18F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and after 12 weeks of treatment with atorvastatin. Coronary arterial inflammation (18F-fluorodeoxyglucose uptake, expressed as target-to-background ratio) was assessed in the left main coronary artery (LMCA). While blinded to the PET findings, contrast-enhanced computed tomographic angiography was performed to characterize the presence of HRM (defined as noncalcified or partially calcified plaques) in the LMCA. Arterial inflammation (target-to-background ratio) was higher in LMCA segments with HRM than those without HRM (mean+/-SEM: 1.95+/-0.43 versus 1.67+/-0.32 for LMCA with versus without HRM, respectively; P=0.04). Moreover, atorvastatin treatment for 12 weeks reduced target-to-background ratio more in LMCA segments with HRM than those without HRM (12 week-baseline Deltatarget-to-background ratio [95% confidence interval]: -0.18 [-0.35 to -0.004] versus 0.09 [-0.06 to 0.26]; P=0.02). Furthermore, this relationship between coronary plaque morphology and change in LMCA inflammatory activity remained significant after adjusting for baseline low-density lipoprotein and statin dose (beta=-0.27; P=0.038). CONCLUSIONS: In this first study to evaluate the impact of statins on coronary inflammation, we observed that the anti-inflammatory impact of statins is substantially greater within coronary plaques that contain HRM features. These findings suggest an additional mechanism by which statins disproportionately benefit individuals with more advanced atherosclerotic disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00703261

Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems

Prokaryotes use type IV secretion systems (T4SSs) to translocate substrates (e.g., nucleoprotein, DNA, and protein) and/or elaborate surface structures (i.e., pili or adhesins). Bacterial genomes may encode multiple T4SSs, e.g., there are three functionally divergent T4SSs in some Bartonella species (vir, vbh, and trw). In a unique case, most rickettsial species encode a T4SS (rvh) enriched with gene duplication. Within single genomes, the evolutionary and functional implications of cross-system interchangeability of analogous T4SS protein components remains poorly understood. To lend insight into cross-system interchangeability, we analyzed the VirB8 family of T4SS channel proteins. Crystal structures of three VirB8 and two TrwG Bartonella proteins revealed highly conserved C-terminal periplasmic domain folds and dimerization interfaces, despite tremendous sequence divergence. This implies remarkable structural constraints for VirB8 components in the assembly of a functional T4SS. VirB8/TrwG heterodimers, determined via bacterial two-hybrid assays and molecular modeling, indicate that differential expression of trw and vir systems is the likely barrier to VirB8-TrwG interchangeability. We also determined the crystal structure of Rickettsia typhi RvhB8-II and modeled its coexpressed divergent paralog RvhB8-I. Remarkably, while RvhB8-I dimerizes and is structurally similar to other VirB8 proteins, the RvhB8-II dimer interface deviates substantially from other VirB8 structures, potentially preventing RvhB8-I/RvhB8-II heterodimerization. For the rvh T4SS, the evolution of divergent VirB8 paralogs implies a functional diversification that is unknown in other T4SSs. Collectively, our data identify two different constraints (spatiotemporal for Bartonella trw and vir T4SSs and structural for rvh T4SSs) that mediate the functionality of multiple divergent T4SSs within a single bacterium. IMPORTANCE:&nbsp; Assembly of multiprotein complexes at the right time and at the right cellular location is a fundamentally important task for any organism. In this respect, bacteria that express multiple analogous type IV secretion systems (T4SSs), each composed of around 12 different components, face an overwhelming complexity. Our work here presents the first structural investigation on factors regulating the maintenance of multiple T4SSs within a single bacterium. The structural data imply that the T4SS-expressing bacteria rely on two strategies to prevent cross-system interchangeability: (i) tight temporal regulation of expression or (ii) rapid diversification of the T4SS components. T4SSs are ideal drug targets provided that no analogous counterparts are known from eukaryotes. Drugs targeting the barriers to cross-system interchangeability (i.e., regulators) could dysregulate the structural and functional independence of discrete systems, potentially creating interference that prevents their efficient coordination throughout bacterial infection.</p

Immunohistochemical Detection of MYC-driven Diffuse Large B-Cell Lymphomas

Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease. A small subset of DLBCLs has translocations involving the MYC locus and an additional group has a molecular signature resembling Burkitt lymphoma (mBL). Presently, identification of such cases by morphology is unreliable and relies on cytogenetic or complex molecular methods such as gene transcriptional profiling. Herein, we describe an immunohistochemical (IHC) method for identifying DLBCLs with increased MYC protein expression. We tested 77 cases of DLBCL and identified 15 cases with high MYC protein expression (nuclear staining in >50% of tumor cells). All MYC translocation positive cases had increased MYC protein expression by this IHC assay. In addition, gene set enrichment analysis (GSEA) of the DLBCL transcriptional profiles revealed that tumors with increased MYC protein expression (regardless of underlying MYC translocation status) had coordinate upregulation of MYC target genes, providing molecular confirmation of the IHC results. We then generated a molecular classifier derived from the MYC IHC results in our cases and employed it to successfully classify mBLs from two previously reported independent case series, providing additional confirmation that the MYC IHC results identify clinically important subsets of DLBCLs. Lastly, we found that DLBCLs with high MYC protein expression had inferior overall survival when treated with R-CHOP. In conclusion, the IHC method described herein can be used to readily identify the biologically and clinically distinct cases of MYC-driven DLBCL, which represent a clinically significant subset of DLBCL cases due to their inferior overall survival

Social gradients in self-reported health and well-being among adults aged 50 and over in Pune District, India

Background: India&#146;s older population is projected to increase up to 96 million by 2011 with older people accounting for 18% of its population by 2051. The Study on Global Ageing and Adult Health aims to improve empirical understanding of health and well-being of older adults in developing countries. Objectives: To examine age and socio-economic changes on a range of key domains in self-reported health and well-being amongst older adults. Design: A cross-sectional survey of 5,430 adults aged 50 and over using a shortened version of the SAGE questionnaire to assess self-reported assessments (scales of 1&#x2013;5) of performance, function, disability, quality of life and well-being. Self-reported responses were calibrated using anchoring vignettes in eight key domains of mobility, self-care, pain, cognition, interpersonal relationships, sleep/energy, affect, and vision. WHO Disability Assessment Schedule Index and WHO health scores were calculated to examine for associations with socio-demographic variables. Results: Disability in all domains increased with increasing age and decreasing levels of education. Females and the oldest old without a living spouse reported poorer health status and greater disability across all domains. Performance and functionality self-reports were similar across all SES quintiles. Self-reports on quality of life were not significantly influenced by socio-demographic variables. Discussion: The study provides standardised and comparable self-rated health data using anchoring vignettes in an older population. Though expectations of good health, function and performance decrease with age, self-reports of disability severity significantly increased with age, more so if female, if uneducated and living without a spouse. However, the presence or absence of spouse did not significantly alter quality of life self-reports, suggesting a possible protective effect provided by traditional joint family structures in India, where older people are social if not financial assets for their children

GO Explorer: A gene-ontology tool to aid in the interpretation of shotgun proteomics data

<p>Abstract</p> <p>Background</p> <p>Spectral counting is a shotgun proteomics approach comprising the identification and relative quantitation of thousands of proteins in complex mixtures. However, this strategy generates bewildering amounts of data whose biological interpretation is a challenge.</p> <p>Results</p> <p>Here we present a new algorithm, termed GO Explorer (GOEx), that leverages the gene ontology (GO) to aid in the interpretation of proteomic data. GOEx stands out because it combines data from protein fold changes with GO over-representation statistics to help draw conclusions. Moreover, it is tightly integrated within the PatternLab for Proteomics project and, thus, lies within a complete computational environment that provides parsers and pattern recognition tools designed for spectral counting. GOEx offers three independent methods to query data: an interactive directed acyclic graph, a specialist mode where key words can be searched, and an automatic search. Its usefulness is demonstrated by applying it to help interpret the effects of perillyl alcohol, a natural chemotherapeutic agent, on glioblastoma multiform cell lines (A172). We used a new multi-surfactant shotgun proteomic strategy and identified more than 2600 proteins; GOEx pinpointed key sets of differentially expressed proteins related to cell cycle, alcohol catabolism, the Ras pathway, apoptosis, and stress response, to name a few.</p> <p>Conclusion</p> <p>GOEx facilitates organism-specific studies by leveraging GO and providing a rich graphical user interface. It is a simple to use tool, specialized for biologists who wish to analyze spectral counting data from shotgun proteomics. GOEx is available at <url>http://pcarvalho.com/patternlab</url>.</p

Paniya Voices: A Participatory Poverty and Health Assessment among a marginalized South Indian tribal population

<p>Abstract</p> <p>Background</p> <p>In India, indigenous populations, known as <it>Adivasi </it>or Scheduled Tribes (STs), are among the poorest and most marginalized groups. 'Deprived' ST groups tend to display high levels of resignation and to lack the capacity to aspire; consequently their health perceptions often do not adequately correspond to their real health needs. Moreover, similar to indigenous populations elsewhere, STs often have little opportunity to voice perspectives framed within their own cultural worldviews. We undertook a study to gather policy-relevant data on the views, experiences, and priorities of a marginalized and previously enslaved tribal group in South India, the Paniyas, who have little 'voice' or power over their own situation.</p> <p>Methods/design</p> <p>We implemented a Participatory Poverty and Health Assessment (PPHA). We adopted guiding principles and an ethical code that promote respect for Paniya culture and values. The PPHA, informed by a vulnerability framework, addressed five key themes (health and illness, well-being, institutions, education, gender) using participatory approaches and qualitative methods. We implemented the PPHA in five Paniya colonies (clusters of houses in a small geographical area) in a <it>gram panchayat </it>(lowest level decentralized territorial unit) to generate data that can be quickly disseminated to decision-makers through interactive workshops and public forums.</p> <p>Preliminary findings</p> <p>Findings indicated that the Paniyas are caught in multiple 'vulnerability traps', that is, they view their situation as vicious cycles from which it is difficult to break free.</p> <p>Conclusion</p> <p>The PPHA is a potentially useful approach for global health researchers working with marginalized communities to implement research initiatives that will address those communities' health needs in an ethical and culturally appropriate manner.</p

Patterning in Birthweight in India: Analysis of Maternal Recall and Health Card Data

National data on birthweight from birth certificates or medical records are not available in India. The third Indian National Family Health Survey included data on birthweight of children obtained from health cards and maternal recall. This study aims to describe the population that these data represent and compares the birthweight obtained from health cards with maternal recall data in terms of its socioeconomic patterning and as a risk factor for childhood growth failure.The analytic sample consisted of children aged 0 to 59 months with birthweight data obtained from health cards (n = 3227) and maternal recall (n = 16,787). The difference between the card sample and the maternal recall sample in the distribution across household wealth, parental education, caste, religion, gender, and urban residence was compared using multilevel models. We also assessed the ability of birthweight to predict growth failure in infancy and childhood in the two groups. The survey contains birthweight data from a majority of household wealth categories (>5% in every category for recall), both genders, all age groups, all caste groups, all religion groups, and urban and rural dwellers. However, children from the lowest quintile of household wealth were under-represented (4.73% in card and 8.62% in recall samples). Comparison of data across health cards and maternal recall revealed similar social patterning of low birthweight and ability of birthweight to predict growth failure later in life. Children were less likely to be born with low birthweight if they had mothers with over 12 years of education compared to 1-5 years of education with relative risk (RR) of 0.79 (95% confidence interval [CI]: 0.52, 1.2) in the card sample and 0.70 (95% CI: 0.59, 0.84) in the recall sample. A 100 gram difference in a child's birthweight was associated with a decreased likelihood of underweight in both the card (RR: 0.95; 95% CI: 0.94, 0.96) and recall (RR: 0.96; 95% CI: 0.96, 0.97) samples.Our results suggest that in the absence of other sources, the data on birthweight in the third Indian National Family Health Survey is valuable for epidemiologic research

Stat3 and c-Myc Genome-Wide Promoter Occupancy in Embryonic Stem Cells

Embryonic stem (ES) cell pluripotency is regulated in part by transcription factor (TF) pathways that maintain self-renewal and inhibit differentiation. Stat3 and c-Myc TFs are essential for maintaining mouse ES cell self-renewal. c-Myc, together with Oct4, Sox2, and Klf4, is a reprogramming factor. While previous studies have investigated core transcriptional circuitry in ES cells, other TF pathways that promote ES cell pluripotency have yet to be investigated. Therefore, to further understand ES cell transcriptional networks, we used genome-wide chromatin immunoprecipitation and microarray analysis (ChIP-chip) to map Stat3 and c-Myc binding targets in ES cells. Our results show that Stat3 and c-Myc occupy a significant number of genes whose expression is highly enriched in ES cells. By comparing Stat3 and c-Myc target genes with gene expression data from undifferentiated ES cells and embryoid bodies (EBs), we found that Stat3 binds active and inactive genes in ES cells, while c-Myc binds predominantly active genes. Moreover, the transcriptional states of Stat3 and c-Myc targets are correlated with co-occupancy of pluripotency-related TFs, polycomb group proteins, and active and repressive histone modifications. We also provide evidence that Stat3 targets are differentially expressed in ES cells following removal of LIF, where culture of ES cells in the absence of LIF resulted in downregulation of Stat3 target genes enriched in ES cells, and upregulation of lineage specific Stat3 target genes. Altogether, we reveal transcriptional targets of two key pluripotency-related genes in ES cells – Stat3 and c-Myc, thus providing further insight into the ES cell transcriptional network