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Diastolic dysfunction and delayed ventricular repolarization are typically observed in the elderly, but whether these defects are intimately associated with the progressive manifestation of the aging myopathy remains to be determined. In this regard, aging in experimental animals is coupled with increased late Na+ current (INa,L) in cardiomyocytes, raising the possibility that INa,L conditions the modality of electrical recovery and myocardial relaxation of the aged heart. For this purpose, aging male and female wild-type (WT) C57Bl/6 mice were studied together with genetically engineered mice with phosphomimetic (gain of function, GoF) or ablated (loss of function, LoF) mutations of the sodium channel Nav1.5 at Ser571 associated with, respectively, increased and stabilized INa,L. At ∼18 mo of age, WT mice developed prolonged duration of the QT interval of the electrocardiogram and impaired diastolic left ventricular (LV) filling, defects that were reversed by INa,L inhibition. Prolonged repolarization and impaired LV filling occurred prematurely in adult (∼5 mo) GoF mutant mice, whereas these alterations were largely attenuated in aging LoF mutant animals. Ca2+ transient decay and kinetics of myocyte shortening/relengthening were delayed in aged (∼24 mo) WT myocytes, with respect to adult cells. In contrast, delayed Ca2+ transients and contractile dynamics occurred at adult stage in GoF myocytes and further deteriorated in old age. Conversely, myocyte mechanics were minimally affected in aging LoF cells. Collectively, these results document that Nav1.5 phosphorylation at Ser571 and the late Na+ current modulate the modality of myocyte relaxation, constituting the mechanism linking delayed ventricular repolarization and diastolic dysfunction. NEW & NOTEWORTHY: We have investigated the impact of the late Na current (INa,L) on cardiac and myocyte function with aging by using genetically engineered animals with enhanced or stabilized INa,L, due to phosphomimetic or phosphoablated mutations of Nav1.5. Our findings support the notion that phosphorylation of Nav1.5 at Ser571 prolongs myocardial repolarization and impairs diastolic function, contributing to the manifestations of the aging myopathy. [ABSTRACT FROM AUTHOR]

Introduction: Globally, Coronavirus Disease-2019 (COVID-19) pandemic era is on the decline, and now, after three years, much lower rates of mortality and morbidity are witnessed. The emergence of new variants and subvariants like Omicron is leading into a transition phase where one would only see sporadic surges. After the 3rd wave, Punjab also experienced such surges, prompting this retrospective study to observe the trend of COVID-19 and emerging variants in the Northwest region of Punjab, India. Aim: To assess the prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection during the past year and to analyse demographic variables like age and gender distribution of positive cases of SARS-CoV-2. Materials and Methods: The present study was a retrospective study, with study period of one year from 1st July 2022 to 30th June 2023, all samples (n=3,04,273) from suspected SARS-CoV-2 patients received at the Virology Research and Diagnostic Laboratory at Government Medical College, Amritsar, Punjab, India, were included in the study. The results of Real-Time Polymerase Chain Reaction (RT-PCR) were analysed to determine the prevalence in that region, and basic demographic variables of SARS-CoV-2 cases were compared. Additionally, 100 random positive samples were sent for whole-genome sequencing to study the prevalent variants and subvariants in this region. The results were analysed to study the prevalence of COVID-19 cases in the region. Demographic parameters like age group distribution and sex distribution were calculated. To study the dynamics of transmission during the one-year study period, an epidemiological curve was plotted over the period of 12 months. Results: Out of the total 3,04,273 samples, 2,102 samples (0.69%) tested positive for the COVID-19 virus by RT-PCR. The study showed more prevalence of infection among young adults, with 853 (40.6%) cases in the age group of 21-40 years, followed by 614 (29.2%) cases in the 41-60 years age group. Of the total positive cases, 1153 (54.85%) were males, compared to 949 (45.15%) were females. The maximum number of positive cases was reported during the months of July 2022 to September 2022, totaling 1,273 cases. Whole-genome sequencing results showed predominance of the Omicron variant, with 44 (49.44%) strains belonging to the XBB lineage of Omicron. Conclusion: There was a definite reduction in the prevalence of SARS-CoV-2 cases during the study period and that Omicron and its subvariants, like XBB lineages, are prevalent in this part of India as well. Despite the decrease in the number and severity of COVID-19 cases, maintaining vigilance and monitoring sporadic cases using tools like Whole Genome Sequencing (WGS) can help in tracking major pandemics in the future. [ABSTRACT FROM AUTHOR]

Introduction: Severe Acute Respiratory Illness (SARI) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) and influenza viruses represent a significant global public health concern. The disease spectrum ranges from mild to life-threatening conditions. Surveillance of hospitalised SARI patients is an essential public health tool used to identify cause of the disease, track changes in circulating viruses and serve as an alert mechanism for potential pandemic viruses. Aim: To determine the rate of SARS-CoV-2 and influenza virus positivity among SARI cases and to investigate the epidemiological and clinical characteristics of the patients. Materials and Methods: A cross-sectional study was conducted on 400 SARI patients admitted to Guru Nanak Dev Hospital, Amritsar, Punjab, India between February 2021 and June 2022. The clinical, demographic, and epidemiological data, as well as co-morbidities of all patients were recorded. Oropharyngeal and nasopharyngeal samples were collected and tested for SARSCoV-2, Influenza A, Influenza A (H3N2), Influenza A (H1N1) pdm09-pandemic 2009, and Influenza B using real-time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) version 23.0 for Windows. Results: Out of the 400 SARI patients, 117 (29.25%) tested positive for SARS-CoV-2, 14 (3.5%) for Influenza A, 7 (1.75%) for Influenza A (H1N1) pdm09, and 4 (1%) for Influenza A (H3N2). The majority of cases in both SARS-CoV-2 and influenza were in the 41-60 years age group (47.86% and 57.14%, respectively). Males were predominantly infected in SARS-CoV-2 positive patients (62/117, 52.99%), while females were more infected in influenza positive cases (9/14, 64.28%). The most common presenting symptoms were fever, cough, dyspnoea, and sore throat in both cases. Hypertension, diabetes mellitus, Chronic Obstructive Pulmonary Disease (COPD), and coronary artery disease were the most common co-morbidities observed. Conclusion: Evaluation of clinical and epidemiological profiles of SARI patients can aid in better understanding and management of outbreaks. Close monitoring and quarantine measures will be necessary to prevent extensive transmission within the community. [ABSTRACT FROM AUTHOR]

This paper proposes the improvements in deviation settlement mechanism of Indian electricity grid system through demand response management (DRM) with the objective to minimize real-time under-injection/over-drawl or maximize real-time over-injection/under-drawl with respect to scheduled injection/drawl such that the deviation settlement charge (DSC) is minimum, subject to the network power flow equations, transmission line capability constraints, DRM constraints and bounds on variables. The mechanism to settle the unscheduled transactions, commonly named as deviation settlement mechanism (DSM), has been implemented to achieve grid frequency stability by imposing penalties and paying incentives, also known as DSC, for over- and under-drawls from the scheduled transactions. In this paper, the improvements in DSM have been solved as an optimization problem to minimize the DSC for a time period of 96 time-blocks (each of 15 min duration). The proposed improvement in DSM has been tested on modified IEEE 9-Bus system. It has been assumed that the generators installed at bus numbers 1, 2 and 3 are the central generating stations, which are monitored and controlled by the regional load dispatch center (RLDC). The simulation results are obtained (with varying percentages of shifting and different participating patterns of prosumers) for which the remarkable benefits of the proposed improvement in DSM (in terms of DSC minimization and improvement in the voltage profile and power flow) have been presented. [ABSTRACT FROM AUTHOR]