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Rana sylvatica (also known as Boreorana sylvatica) is one of the few vertebrates that spend extreme winters showing no physiological signs of life. Up to 70% of the total body water of the wood frog freezes as extracellular ice. Survival in extreme conditions requires regulation at transcriptional and translational levels to activate prosurvival pathways. N6-methyladenosine ([m.sup.6]A) methylation is one of the most common RNA modifications, regulating transcript processing and translation by executing important functions that affect regulatory pathways in stress conditions. In the study, regulation of [m.sup.6]A-related proteins in the liver of R. sylvatica was analyzed during 24 h frozen and 8 h thaw conditions. Decreases in the activity of demethylases of 28.44 [+ or -] 0.4% and 24.1 [+ or -] 0.9% of control values in frozen and thaw tissues, respectively, were observed. Total protein levels of [m.sup.6]A methyltransferase complex components methyltransferase-like 14 and Wilm's tumor associated protein were increased by 1.28-fold and 1.42-fold, respectively, during freezing. Demethylase fat mass and obesity, however, showed a decreasing trend, with a significant decrease in abundance during recovery from frozen conditions. Levels of mRNA degraders YTHDF2 and YTHDC2 also decreased under stress. Overall, increased levels of [m.sup.6]A methylation complex components, and suppressed levels of readers/erasers, provide evidence for the potential role of RNA methylation in freezing survival and its regulation in a hypometabolic state. Key words: epigenetics, freeze tolerance, RNA methylation, metabolic rate depression, Rana sylvatica (Boreorana sylvatica), Introduction The wood frog, Rana sylvatica (Boreorana sylvatica), is one of the freeze-tolerant model organisms that survive sub-zero temperatures for several months. During freezing, the wood frog employs multiple adaptation [...]

Background Objective Design Data Sources Eligibility Criteria Results Conclusion Intravenous lignocaine has been used as an analgesic adjunct in pediatric surgical patients, although its efficacy is still unclear.We aimed to clarify the efficacy of perioperative intravenous lignocaine (bolus followed by an infusion) on pediatric postoperative pain outcomes.A systematic review and meta‐analysis.PubMed, EMBASE, Web of Science, Google Scholar (inception to June 2024).Studies involving pediatric patients (≤18 years) undergoing surgery under general anesthesia with one group receiving perioperative intravenous lignocaine (bolus followed by infusion) and the other group receiving placebo. The primary outcome was 24‐h postoperative opioid consumption. Postoperative pain scores and the need for rescue analgesia were the secondary outcomes.Seven studies (n = 415) were included in the final meta‐analysis. The use of intravenous lignocaine significantly reduced the morphine consumption in the first 24 h after surgery, compared to placebo (SMD ‐1.31, 95% CI ‐2.18 to −0.43, p = 0.003). A meta‐analysis could not be performed for the secondary outcomes.There is low quality evidence to suggest that perioperative intravenous lignocaine bolus followed by an infusion significantly reduced the opioid consumption on the first postoperative day in pediatric surgical patients. The effects of perioperative lignocaine on postoperative pain scores and the need for rescue analgesia are uncertain. [ABSTRACT FROM AUTHOR]

Objective The prevalence of anemia has remained high among Indian adolescent girls over the past decade, despite the ongoing iron and folic acid (IFA) supplementation program. This study was conducted to assess the impact of daily supplementation of a package of IFA with vitamin B.sub.12 on hemoglobin levels among adolescent girls. Methods A community-based cluster-randomized trial was conducted in the rural block of Faridabad District, Haryana, India in the year 2017. A total of 760 adolescent girls in the age group of 12-19 years with mild and moderate anemia were selected from government schools. Daily-supervised administration of iron and folic acid was conducted for 90 days: experimental group--IFA (iron (60 mg), folic acid (500) mcg), and cyanocobalamin (1000 mcg), control group--IFA and placebo. Hemoglobin, serum ferritin, and vitamin B.sub.12 levels were assessed at baseline and endline. Results Two-hundred adolescent girls completed 90 doses of daily supplementation. The mean hemoglobin (experimental group: 1.3 [plus or minus] 1.0 g/dL, control group: 1.6 [plus or minus] 1.2 g/dL, P = 0.004) and ferritin levels (experimental group: 18.6 [plus or minus] 31.5 ng/mL, control group: 18.8 [plus or minus] 35.0 ng/mL, P = 0.188) increased in both the control and experiment groups. Serum vitamin B.sub.12 deficiency significantly reduced to 2.5% in the experimental group and ferritin deficiency alleviated in more than 96% of the girls post intervention. Conclusions Daily supplementation of IFA with/without vitamin B.sub.12 for 90 days eliminated iron, vitamin B.sub.12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B.sub.12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B.sub.12 for prevention and treatment of anemia in this population group., Author(s): Aakriti Gupta [sup.1] , Shashi Kant [sup.2] , Lakshmy Ramakrishnan [sup.3] , Ravindra Mohan Pandey [sup.4] , Ritika Khandelwal [sup.1] , Umesh Kapil [sup.1] , Harshpal Singh Sachdev [sup.5] [...]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics. A comprehensive review of the current literature on post-acute COVID-19, also referred to as long COVID, its pathophysiology and its organ-specific sequelae highlights the need for multidisciplinary follow-up and care of COVID-19 survivors., Author(s): Ani Nalbandian [sup.1] , Kartik Sehgal [sup.2] [sup.3] [sup.4] , Aakriti Gupta [sup.1] [sup.5] [sup.6] , Mahesh V. Madhavan [sup.1] [sup.5] , Claire McGroder [sup.7] , Jacob S. Stevens [...]

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved. Recent clinical observations have prompted clinicians to think of COVID-19 as being more than a respiratory disease., Author(s): Aakriti Gupta [sup.1] [sup.2] [sup.3] , Mahesh V. Madhavan [sup.1] [sup.2] , Kartik Sehgal [sup.4] [sup.5] [sup.6] , Nandini Nair [sup.7] , Shiwani Mahajan [sup.3] [sup.8] , Tejasav S. [...]

Background and Aims Early diagnosis of aortic stenosis (AS) is critical to prevent morbidity and mortality but requires skilled examination with Doppler imaging. This study reports the development and validation of a novel deep learning model that relies on two-dimensional (2D) parasternal long axis videos from transthoracic echocardiography without Doppler imaging to identify severe AS, suitable for point-of-care ultrasonography. Methods and results In a training set of 5257 studies (17 570 videos) from 2016 to 2020 [Yale-New Haven Hospital (YNHH), Connecticut], an ensemble of three-dimensional convolutional neural networks was developed to detect severe AS, leveraging self-supervised contrastive pretraining for label-efficient model development. This deep learning model was validated in a temporally distinct set of 2040 consecutive studies from 2021 from YNHH as well as two geographically distinct cohorts of 4226 and 3072 studies, from California and other hospitals in New England, respectively. The deep learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.978 (95% CI: 0.966, 0.988) for detecting severe AS in the temporally distinct test set, maintaining its diagnostic performance in geographically distinct cohorts [0.952 AUROC (95% CI: 0.941, 0.963) in California and 0.942 AUROC (95% CI: 0.909, 0.966) in New England]. The model was interpretable with saliency maps identifying the aortic valve, mitral annulus, and left atrium as the predictive regions. Among non-severe AS cases, predicted probabilities were associated with worse quantitative metrics of AS suggesting an association with various stages of AS severity. Conclusion This study developed and externally validated an automated approach for severe AS detection using single-view 2D echocardiography, with potential utility for point-of-care screening. [ABSTRACT FROM AUTHOR]