Metabolic adaptation to the changing nutrient levels in the cellular microenvironment plays a decisive role in the maintenance of homeostasis. Eukaryotic cells are equipped with nutrient sensors, which sense the fluctuating nutrients levels and accordingly program the cellular machinery to mount an appropriate response. Nutrients including amino acids play a vital role in maintaining cellular homeostasis. Therefore, over the evolution, different species have developed diverse mechanisms to detect amino acids abundance or scarcity. Immune responses have been known to be closely associated with the cellular metabolism especially amino acid sensing pathway, which influences innate as well as adaptive immune-effector functions. Thus, exploring the cross-talk between amino acid sensing mechanisms and immune responses in disease as well as in normal physiological conditions might open up avenues to explore how this association can be exploited to tailor immunological functions toward the design of better therapeutics for controlling metabolic diseases. In this review, we discuss the advances in the knowledge of various amino acid sensing pathways including general control nonderepressible-2 kinase in the control of inflammation and metabolic diseases.

More than 7 million cases of COVID have been detected in India by the middle of October 2020 and more than 100 thousand deaths have occurred. In this communication, we present an estimate the years of life lost (YLL) due to COVID-19 so far and the projection for the full year so that the health damage by this new disease can be compared with some other ailments. The YLL by one premature death is the expectation of life at that age. To calculate YLL, age-wise distribution of COVID cases and deaths was obtained from the official sources of the government of India. Similar calculations were done for the general population from all causes for comparison. A total of more than 2 million years of life have already lost due to COVID-19 and the pattern indicates that we may end up with nearly 4 million YLL due to this disease in India. This is nearly 20 years lost per COVID death, 303 years lost per 1000 cases of COVID, and about 3 years lost per 1000 population in the full year. The age-group 50-59 years has been particularly affected. Other important findings are summarized as key messages. The years of life lost so far and anticipated in full year are enormous but may still be lower compared with some other causes such as road injuries.

Almost all bio-statisticians and medical researchers believe that a large sample is always helpful in providing more reliable results. Whereas this is true for some specific cases, a large sample may not be helpful in more situations than we contemplate because of the higher possibility of errors and reduced validity. Many medical breakthroughs have occurred with self-experimentation and single experiments. Studies, particularly analytical studies, may provide more truthful results with a small sample because intensive efforts can be made to control all the confounders, wherever they operate, and sophisticated equipment can be used to obtain more accurate data. A large sample may be required only for the studies with highly variable outcomes, where an estimate of the effect size with high precision is required, or when the effect size to be detected is small. This communication underscores the importance of small samples in reaching a valid conclusion in certain situations and describes the situations where a large sample is not only unnecessary but may even compromise the validity by not being able to exercise full care in the assessments. What sample size is small depends on the context.

Background COVID‐19 disease‐related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID‐19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. Methods We did a systematic review and meta‐analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID‐19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo‐controlled trials were included. Analyses of data were conducted using the Mantel–Haenszel random‐effects model (DerSimonian–Laird analysis). The study is registered with PROSPERO (CRD42021265948). Results We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID‐19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 –0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 –0%]. Conclusion Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk–benefit ratio must be considered while using either of them.

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Aim: To design a health system model for scaling-up Kangaroo mother care (KMC) and assess its impact on the population-level coverage and quality of KMC in Uttar Pradesh, India. Methods:We co-developed the model with mothers and health system stakeholders using human-centred design over multiple cycles of implementation, learning and data-driven refinement. Infants with birthweight <2000 g in the study district were prospectively followed to assess the 'effective coverage' of KMC. Effective coverage referred to the proportion of eligible infants receiving ≥8 h of daily skin-to-skin contact and exclusive breastfeeding.Results: High delivery load facilities were equipped with a KMC Lounge to ensure comfort, respectful care of mothers and high-quality KMC over prolonged periods.Systems to ensure weighing at birth, referral of infants with birthweight <2000 g to KMC facilities, initiation of KMC for all stable low birthweight infants, improving quality of care within KMC facilities and supporting families to continue KMC at home post discharge, were integrated into existing services. KMC was initiated in 93.3% of eligible infants with effective coverage of 52.7% and 64.8% at discharge and 7 days post discharge, respectively. Conclusion:The model addressed critical barriers to KMC implementation and adoption, contributing to its scale-up across the state.