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

Septic Abortion Managed in a Tertiary Hospital in West Bengal

Background: Septic abortion is still a challenging problem and a major cause of maternal mortality and morbidity in developing countries.Aim: The present study was conducted to estimate incidence, causes, risk factors, associated microorganisms, and treatment modalities of cases of septic abortion managed in a tertiary health care in West Bengal.Subjects and Methods: It was a cross‑sectional study carried out in Burdwan Medical College and Hospital in West Bengal between July 2011 and June 2012. On admission a thorough history was taken, examination was done, and investigations were carried. Depending on the examination findings the cases were grouped into three grades‑grade I: The infection localized in the uterus; grade II: The infection spread beyond the uterus to the parametrium, tubes, and ovaries or pelvic peritoneum; grade III: Generalized peritonitis and/or endotoxic shock or jaundice or acute renal failure. Statistical analysis was done by using Epi Info™ software (Version 3.5.1, CDC) after proper arrangement of all the data in tabular form and presented as simple percentage.Results: During the period, 1297 cases of abortion were admitted among which 107 were septic abortions, thus giving the incidence of the latter as 8.2% (107/1297). Forty‑three percent cases of septic abortion (46/107) were in grade I, 21.5% (23/107) in grade II, and 35.5% (38/107) in grade III. The modal age group of the patients was 15‑25 years (49.5%). Majority of the subjects were married (77.6%; 83/107) and multiparous (60.7%; 65/107). Similarly, most of them (71%; 76/107) were from low socioeconomic class. Ninety percent of the patients (96/107) had induced abortion. The common clinical features at presentation were pallor (88.8%; 95/107) and fever (86.0%; 92/107). Escherichia coli (62.6%; 67/107) and Klebsiella pneumonia (32.75%; 35/107) were the most common organism isolated. The case fatality from septic abortion in this study was 13.1% and the condition accounted for 15.4% of total maternal mortality within the period reviewed.Conclusion: The incidence of septic abortion in this study is relatively high, and majority of the cases resulted from attempted termination of pregnancy. It is a significant contributor to maternal mortality. Promotion of family planning and legalization of abortion services will go a long way in reducing the incidence of septic abortion and itsassociated complications. Keywords: Asia, management, maternal mortality, outcome, septic abortio

Transcriptional Mutagenesis Induced by 8-Oxoguanine in Mammalian Cells

Most of the somatic cells of adult metazoans, including mammals, do not undergo continuous cycles of replication. Instead, they are quiescent and devote most of their metabolic activity to gene expression. The mutagenic consequences of exposure to DNA–damaging agents are well documented, but less is known about the impact of DNA lesions on transcription. To investigate this impact, we developed a luciferase-based expression system. This system consists of two types of construct composed of a DNA template containing an 8-oxoguanine, paired either with a thymine or a cytosine, placed at defined positions along the transcribed strand of the reporter gene. Analyses of luciferase gene expression from the two types of construct showed that efficient but error-prone transcriptional bypass of 8-oxoguanine occurred in vivo, and that this lesion was not repaired by the transcription-coupled repair machinery in mammalian cells. The analysis of luciferase activity expressed from 8OG:T-containing constructs indicated that the magnitude of erroneous transcription events involving 8-oxoguanine depended on the sequence contexts surrounding the lesion. Additionally, sequencing of the transcript population expressed from these constructs showed that RNA polymerase II mostly inserted an adenine opposite to 8-oxoguanine. Analysis of luciferase expression from 8OG:C-containing constructs showed that the generated aberrant mRNAs led to the production of mutant proteins with the potential to induce a long-term phenotypical change. These findings reveal that erroneous transcription over DNA lesions may induce phenotypical changes with the potential to alter the fate of non-replicating cells

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

MIC_FuzzyNET: fuzzy integral based ensemble for automatic classification of musical instruments from audio signals

Music has been an integral part of the history of humankind with theories suggesting it is more antediluvian than speech itself. Music is an ordered succession of tones and harmonies that produce sounds characterised by melody and rhythm. Our paper proposes an ensemble deep learning musical instrument classification (MIC) framework, named as MIC_FuzzyNET model which aims to classify the dominant instruments present in musical clips. Firstly, the musical data is converted to three different spectrograms: Constant Q-Transform, Semitone Spectrogram and Mel Spectrogram, which is then stacked to form 3 channel 2D data. This stacked spectrogram is fed to transfer learning models namely, EfficientNetV2 and ResNet18 which output the preliminary classification scores. A fuzzy rank ensemble model is finally employed that assigns the classifier ranks, on the testing data in order to achieve final enhanced classification scores which reduces error and biases for the constituent CNN architectures. Our proposed framework has been evaluated on the Persian Classical Music Instrument Recognition (PCMIR) dataset and Instrument Recognition in Musical Audio Signals (IRMAS) dataset. It has achieved considerably high accuracy, making our proposed framework a robust MIC model