Reappraising the Role of Eplerenone in the Management of Heart Failure

Background: In India, the prevalence of heart failure (HF) is increasing at 1.2/1,000 people according to a study in northern India, and the mortality rate at 1 year (INTERnational Congestive Heart Failure [INTER-CHF]) is 37%. Due to the diverse phenotypes of HF, nonadherence to guideline-directed medical therapy (GDMT), resistance to uptitration of medication and underuse of mineralocorticoid receptor antagonists (MRAs), such as eplerenone, a uniform management approach may not be feasible. This review is aimed at assessing the burden of HF, reasons for underutilization of MRAs in treatment, evaluating the evidence and reappraising the disease-modifying role of eplerenone in HF management. Methods: An electronic database search was performed to identify relevant literature. Results: The review details various studies that demonstrate the role of MRA eplerenone as a disease-modifying agent in patients with mild-to-moderate hypertension and those with acute myocardial infarction (MI) complicated by left ventricular dysfunction and HF. It also outlines different patient profiles for eplerenone use and ways to handle minor side-effects. Conclusions: Eplerenone shows a promising effect in selectively blocking aldosterone receptors to suppress fibrosis and reverse cardiac remodeling

Proper depiction of monsoon depression through IRS-P4 MSMR

In this paper, daily variations of satellite-derived geophysical parameters such as integrated water vapour (IWV), cloud liquid water content (CLW), sea surface temperature (SST) and sea surface wind speed (SSW) have been studied for a case of monsoon depression that formed over the Bay of Bengal during 19th-24th August 2000. For this purpose, IRS P4 MSMR satellite data have been utilized over the domain equator - 25°N and 40°-100°E. An integrated approach of satellite data obtained from IRS-P4, METEOSAT-5 and INSAT was made for getting a signal for the development of monsoon depression over the Indian region. Variations in deep convective activity obtained through visible, infrared and OLR data at 06 UTC was thoroughly analyzed for the complete life cycle of monsoon depression. Geophysical parameters obtained through IRS-P4 satellite data were compared with vorticity, convergence and divergence at 850 and 200 hPa levels generated through cloud motion vectors (CMVs) and water vapour wind vectors (WVWVs) obtained from METEOSAT-5 satellite. This comparison was made for finding proper consistency of geophysical parameters with dynamical aspects of major convective activity of the depression. From the results of this study it is revealed that there was strengthening of sea surface winds to the south of low-pressure area prior to the formation of depression. This indicated the possibility of increase in cyclonic vorticity in the lower troposphere. Hence, wind field at 850 hPa with satellite input of CMVs in objective analysis of wind field using optimum interpolation (OI) scheme was computed. Maximum cyclonic vorticity field at 850 hPa was obtained in the region of depression just one day before its formation. Similarly, with the same procedure maximum anticyclonic vorticity was observed at 200 hPa with WVWVs input. Consistent convergence and divergence at 850 and 200 hPa was noticed with respect to these vorticities. In association with these developments, we could get lowest values of OLR (120W/m 2) associated with major convective activity that was consistent with the maximum values of integrated water vapour (6-8 gm/cm 2) and cloud liquid water content (50-60 mg/cm 2) persisting particularly in the southwest sector of the monsoon depression

Economic evaluation of participatory learning and action with women's groups facilitated by Accredited Social Health Activists to improve birth outcomes in rural eastern India

BACKGROUND: Neonatal mortality remains unacceptably high in many low and middle-income countries, including India. A community mobilisation intervention using participatory learning and action with women’s groups facilitated by Accredited Social Health Activists (ASHAs) was conducted to improve maternal and newborn health. The intervention was evaluated through a cluster-randomised controlled trial conducted in Jharkhand and Odisha, eastern India. This aims to assess the cost-effectiveness this intervention. METHODS: Costs were estimated from the provider’s perspective and calculated separately for the women’s group intervention and for activities to strengthen Village Health Sanitation and Nutrition Committees (VHNSC) conducted in all trial areas. Costs were estimated at 2017 prices and converted to US dollar (USD). The incremental cost-effectiveness ratio (ICER) was calculated with respect to a do-nothing alternative and compared with the WHO thresholds for cost-effective interventions. ICERs were calculated for cases of neonatal mortality and disability-adjusted life years (DALYs) averted. RESULTS: The incremental cost of the intervention was USD 83 per averted DALY (USD 99 inclusive of VHSNC strengthening costs), and the incremental cost per newborn death averted was USD 2545 (USD 3046 inclusive of VHSNC strengthening costs). The intervention was highly cost-effective according to WHO threshold, as the cost per life year saved or DALY averted was less than India’s Gross Domestic Product (GDP) per capita. The robustness of the findings to assumptions was tested using a series of one-way sensitivity analyses. The sensitivity analysis does not change the conclusion that the intervention is highly cost-effective. CONCLUSION: Participatory learning and action with women’s groups facilitated by ASHAs was highly cost-effective to reduce neonatal mortality in rural settings with low literacy levels and high neonatal mortality rates. This approach could effectively complement facility-based care in India and can be scaled up in comparable high mortality settings

The momentum analyticity of two-point correlators from perturbation theory and AdS/CFT

The momentum plane analyticity of two point function of a relativistic thermal field theory at zero chemical potential is explored. A general principle regarding the location of the singularities is extracted. In the case of the N=4 supersymmetric Yang-Mills theory at large $N_c$, a qualitative change in the nature of the singularity (branch points versus simple poles) from the weak coupling regime to the strong coupling regime is observed with the aid of the AdS/CFT correspondence.Comment: 18 pages, 3 figures, typos fixed, 1 figure update

Effectiveness of participatory women’s groups scaled up by the public health system to improve birth outcomes in Jharkhand, eastern India: a pragmatic cluster non-randomised controlled trial

INTRODUCTION: The WHO recommends community mobilisation with women’s groups practising participatory learning and action (PLA) to improve neonatal survival in high-mortality settings. This intervention has not been evaluated at scale with government frontline workers. METHODS: We did a pragmatic cluster non-randomised controlled trial of women’s groups practising PLA scaled up by government front-line workers in Jharkhand, eastern India. Groups prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies and evaluated progress. Intervention coverage and quality were tracked state-wide. Births and deaths to women of reproductive age were monitored in six of Jharkhand’s 24 districts: three purposively allocated to an early intervention start (2017) and three to a delayed start (2019). We monitored vital events prospectively in 100 purposively selected units of 10 000 population each, during baseline (1 March 2017–31 August 2017) and evaluation periods (1 September 2017–31 August 2019). The primary outcome was neonatal mortality. RESULTS: We identified 51 949 deliveries and conducted interviews for 48 589 (93.5%). At baseline, neonatal mortality rates (NMR) were 36.9 per 1000 livebirths in the early arm and 39.2 in the delayed arm. Over 24 months of intervention, the NMR was 29.1 in the early arm and 39.2 in the delayed arm, corresponding to a 24% reduction in neonatal mortality (adjusted OR (AOR) 0.76, 95% CI 0.59 to 0.98), including 26% among the most deprived (AOR 0.74, 95% CI 0.57 to 0.95). Twenty of Jharkhand’s 24 districts achieved adequate meeting coverage and quality. In these 20 districts, the intervention saved an estimated 11 803 newborn lives (min: 1026–max: 20 527) over 42 months, and cost 41 international dollars per life year saved. CONCLUSION: Participatory women’s groups scaled up by the Indian public health system reduced neonatal mortality equitably in a largely rural state and were highly cost-effective, warranting scale-up in other high-mortality rural settings. TRIAL REGISTRATION: ISRCTN99422435

Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice

<p>Abstract</p> <p>Background</p> <p>The current practice of ingesting phytochemicals for supporting the immune system or fighting infections is based on centuries-old tradition. Macrophages are involved at all the stages of an immune response. The present study focuses on the immunostimulant properties of <it>Tinospora cordifolia </it>extract that are exerted on circulating macrophages isolated from CCl₄(0.5 ml/kg body weight) intoxicated male albino mice.</p> <p>Methods</p> <p>Apart from damaging the liver system, carbon tetrachloride also inhibits macrophage functions thus, creating an immunocompromised state, as is evident from the present study. Such cell functions include cell morphology, adhesion property, phagocytosis, enzyme release (myeloperoxidase or MPO), nitric oxide (NO) release, intracellular survival of ingested bacteria and DNA fragmentation in peritoneal macrophages isolated from these immunocompromised mice. <it>T. cordifolia </it>extract was tested for acute toxicity at the given dose (150 mg/kg body weight) by lactate dehydrogenase (LDH) assay.</p> <p>Results</p> <p>The number of morphologically altered macrophages was increased in mice exposed to CCl₄. Administration of CCl₄(i.p.) also reduced the phagocytosis, cell adhesion, MPO release, NO release properties of circulating macrophages of mice. The DNA fragmentation of peritoneal macrophages was observed to be higher in CCl₄intoxicated mice. The bacterial killing capacity of peritoneal macrophages was also adversely affected by CCl_4.However oral administration of aqueous fraction of <it>Tinospora cordifolia </it>stem parts at a dose of 40 mg/kg body weight (<it>in vivo</it>) in CCl₄exposed mice ameliorated the effect of CCl₄, as the percentage of morphologically altered macrophages, phagocytosis activity, cell adhesion, MPO release, NO release, DNA fragmentation and intracellular killing capacity of CCl₄intoxicated peritoneal macrophages came closer to those of the control group. No acute toxicity was identified in oral administration of the aqueous extract of <it>Tinospora cordifolia </it>at a dose of 150 mg/kg body weight.</p> <p>Conclusion</p> <p>From our findings it can be suggested that, polar fractions of <it>Tinospora cordifolia </it>stem parts contain major bioactive compounds, which directly act on peritoneal macrophages and have been found to boost the non-specific host defenses of the immune system. However, the molecular mechanism of this activity of <it>Tinospora cordifolia </it>on immune functions needs to be elucidated.</p

Superconformal Yang-Mills quantum mechanics and Calogero model with OSp(N|2,R) symmetry

In spacetime dimension two, pure Yang-Mills possesses no physical degrees of freedom, and consequently it admits a supersymmetric extension to couple to an arbitrary number, N say, of Majorana-Weyl gauginos. This results in (N,0) super Yang-Mills. Further, its dimensional reduction to mechanics doubles the number of supersymmetries, from N to N+N, to include conformal supercharges, and leads to a superconformal Yang-Mills quantum mechanics with symmetry group OSp(N|2,R). We comment on its connection to AdS_2 \times S^{N-1} and reduction to a supersymmetric Calogero model.Comment: 1+28 pages, no figure; Refs added. To appear in JHE

Comparative genomic analysis of Vibrio parahaemolyticus: serotype conversion and virulence

<p>Abstract</p> <p>Background</p> <p><it>Vibrio parahaemolyticus </it>is a common cause of foodborne disease. Beginning in 1996, a more virulent strain having serotype O3:K6 caused major outbreaks in India and other parts of the world, resulting in the emergence of a pandemic. Other serovariants of this strain emerged during its dissemination and together with the original O3:K6 were termed strains of the pandemic clone. Two genomes, one of this virulent strain and one pre-pandemic strain have been sequenced. We sequenced four additional genomes of <it>V. parahaemolyticus </it>in this study that were isolated from different geographical regions and time points. Comparative genomic analyses of six strains of <it>V. parahaemolyticus </it>isolated from Asia and Peru were performed in order to advance knowledge concerning the evolution of <it>V. parahaemolyticus</it>; specifically, the genetic changes contributing to serotype conversion and virulence. Two pre-pandemic strains and three pandemic strains, isolated from different geographical regions, were serotype O3:K6 and either toxin profiles (<it>tdh+</it>, <it>trh</it>-) or (<it>tdh-</it>, <it>trh</it>+). The sixth pandemic strain sequenced in this study was serotype O4:K68.</p> <p>Results</p> <p>Genomic analyses revealed that the <it>trh</it>+ and <it>tdh</it>+ strains had different types of pathogenicity islands and mobile elements as well as major structural differences between the <it>tdh </it>pathogenicity islands of the pre-pandemic and pandemic strains. In addition, the results of single nucleotide polymorphism (SNP) analysis showed that 94% of the SNPs between O3:K6 and O4:K68 pandemic isolates were within a 141 kb region surrounding the O- and K-antigen-encoding gene clusters. The "core" genes of <it>V. parahaemolyticus </it>were also compared to those of <it>V. cholerae </it>and <it>V. vulnificus</it>, in order to delineate differences between these three pathogenic species. Approximately one-half (49-59%) of each species' core genes were conserved in all three species, and 14-24% of the core genes were species-specific and in different functional categories.</p> <p>Conclusions</p> <p>Our data support the idea that the pandemic strains are closely related and that recent South American outbreaks of foodborne disease caused by <it>V. parahaemolyticus </it>are closely linked to outbreaks in India. Serotype conversion from O3:K6 to O4:K68 was likely due to a recombination event involving a region much larger than the O-antigen- and K-antigen-encoding gene clusters. Major differences between pathogenicity islands and mobile elements are also likely driving the evolution of <it>V. parahaemolyticus</it>. In addition, our analyses categorized genes that may be useful in differentiating pathogenic Vibrios at the species level.</p

Source of Previous Treatment for Re-Treatment TB Cases Registered under the National TB Control Programme, India, 2010

BACKGROUND: In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome. OBJECTIVES: To assess the source of previous treatment for re-treatment TB patients registered under India's Revised National TB control Programme (RNTCP). METHODOLOGY: A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought. RESULTS: Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 'relapse' cases, 105 'failure' cases, 437 'treatment after default (TAD)' cases and 575 're-treatment others' cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%-49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and 'retreatment others' (59%) were likely to be treated outside the National Programme, when compared to the proportion among 'relapse' (22%) or 'failure' (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme. CONCLUSIONS: Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation