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A cluster randomized control trial study was conducted in Ballabgarh block of Faridabad District, Haryana, India. Baseline data of a total of 198 non-anemic and 202 anemic adolescent girls (12–19 years) was analyzed for hemoglobin and serum level of hepcidin, ferritin, folate acid, soluble transferrin receptor, vitamin B12 and CRP. Deficiency of iron (p < 0.001), folate (p < 0.01) and their mixed deficiency (p < 0.001) significantly increased with increasing severity of anaemia and contributed to 48.7% mild anaemia and 66.9% moderate anaemia. Anaemia of inflammation contributed to 16.2% of mild anaemia and 11.7% of moderate anaemia. More than one third of mild anaemia is caused by other causes. Current iron and folic acid program can alleviate around more than 2/3rd moderate anaemia and around half of mild anaemia among adolescent girls. Unknown causes of anaemia need further investigation. [ABSTRACT FROM AUTHOR]

Lipids are complex organic molecules that fulfill energy demands and sometimes act as signaling molecules. They are mostly found in membranes, thus playing an important role in membrane trafficking and protecting the cell from external dangers. Based on the composition of the lipids, their fluidity and charge, their interaction with embedded proteins vary greatly. Bacteria can hijack host lipids to satisfy their energy needs or to conceal themselves from host cells. Intracellular bacteria continuously exploit host, from their entry into host cells utilizing host lipid machinery to exiting through the cells. This acquisition of lipids from host cells helps in their disguise mechanism. The current review explores various mechanisms employed by the intracellular bacteria to manipulate and acquire host lipids. It discusses their role in manipulating host membranes and the subsequence impact on the host cells. Modulating these lipids in macrophages not only serve the purpose of the pathogen but also modulates the macrophage energy metabolism and functional state. Additionally, we have explored the intricate pathogenic relationship and the potential prospects of using this knowledge in lipid-based therapeutics to disrupt pathogen dominance. [ABSTRACT FROM AUTHOR]

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]

Purpose of Review: The purpose of this review is threefold: (i) to give an overview of well-established invasive methods for assessing patients with ischemia with no obstructive coronary arteries (INOCA) in the cardiac catheterization laboratory; (ii) to describe the prognostic and treatment implications based on these findings, and (iii) to discuss current knowledge gaps and future perspectives. Recent Findings: Recent studies have demonstrated that invasive coronary function testing not only allows for risk stratification of patients with INOCA but also guides medical therapy with improvement in symptoms and quality of life. Based on these findings, invasive coronary function assessment is now a class 2a recommendation in the 2021 ACC/AHA chest pain guideline to improve the diagnosis of coronary microvascular dysfunction and to enhance risk stratification. Summary: Invasive functional testing for patients with INOCA is well established and easily performed in the catheterization laboratory. Comprehensive invasive assessment is a key to differentiating INOCA endotypes and optimizing both medical therapy and preventive strategies including lifestyle modification. [ABSTRACT FROM AUTHOR]

The management and follow-up of moderate aortic stenosis (AS) lacks consensus as the progression patterns are not well understood. This study aimed to identify the hemodynamic progression of AS, and associated risk factors and outcomes. We included patients with moderate AS with at least three transthoracic echocardiography (TTE) studies performed between 2010 and 2021. Latent class trajectory modeling was used to classify AS groups with distinctive hemodynamic trajectories, which were determined by serial systolic mean pressure gradient (MPG) measurements. Outcomes were defined as all-cause mortality and aortic valve replacement (AVR). A total of 686 patients with 3093 TTE studies were included in the analysis. Latent class model identified two distinct AS trajectory groups based on their MPG: a slow progression group (44.6%) and a rapid progression group (55.4%). Initial MPG was significantly higher in the rapid progression group (28.2 ± 5.6 mmHg vs. 22.9 ± 2.8 mmHg, P < 0.001). The prevalence of atrial fibrillation was higher in the slow progression group; there was no significant between-group difference in the prevalence of other comorbidities. The rapid progression group had a significantly higher AVR rate (HR 3.4 [2.4–4.8], P < 0.001); there was no between-group difference in mortality (HR 0.7 [0.5–1.0]; P = 0.079). Leveraging longitudinal echocardiographic data, we identified two distinct groups of patients with moderate AS: slow and rapid progression. A higher initial MPG (≥ 24 mmHg) was associated with more rapid progression of AS and higher rates of AVR, thus indicating the predictive value of MPG in management of the disease. [ABSTRACT FROM AUTHOR]

Background: A patient with chronic kidney disease and recurrent catheter-related thrombosis. Case presentation: The patient had femoral vein thrombosis and was scheduled for laparoscopically assisted continuous ambulatory peritoneal dialysis catheter insertion. The chief concerns during the perioperative period were the risk of pulmonary thromboembolism, limited venous access, and risk of bleeding as the patient was on anticoagulation therapy. Meticulous attention was paid to history, clinical examination, and to the ongoing treatment with regard to risk of systemic thrombosis. Conclusions: Management was tailored according to risk of thrombosis and bleeding during perioperative period along with identification adverse events associated with anticoagulation and preparedness for management of pulmonary embolism. [ABSTRACT FROM AUTHOR]

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 (m6A) 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 m6A-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 ± 0.4% and 24.1 ± 0.9% of control values in frozen and thaw tissues, respectively, were observed. Total protein levels of m6A 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 m6A 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. [ABSTRACT FROM AUTHOR]

Objective: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India. Design: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation. Setting: Three schools in Ballabgarh block of Faridabad District, Haryana, India. Participants: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12–19 years). Results: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %). Conclusions: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research. [ABSTRACT FROM AUTHOR]

Background: Checkpoint inhibitor (CPI) therapy has significantly improved overall survival in several cancers including metastatic melanoma (MM) and in the adjuvant setting. Cutaneous immune‐related adverse events (irAEs) secondary to CPIs are commonly observed; however, autoimmune blistering disorders such as bullous pemphigoid (BP) are rare. Objectives: To review the prevalence, incidence risk, clinicopathological features and management of toxicity in bullous cutaneous irAEs associated with CPI therapy. Methods: A multicentre, retrospective, observational study of CPI‐associated bullous irAEs in adults with all cancers across four UK specialist centres between 2006 and 2019. Results: In total, 7391 patients were identified. CPI‐associated bullous irAEs including BP (n = 16) occurred in 0·3% (n = 22). The median age of onset was 76 years, and there was a male predominance. Most patients had cutaneous melanoma (73%, n = 16), of which 81% (13 of 16) were BRAF wildtype. Grade 1, 2, 3 and 4 skin toxicity occurred in 9%, 45%, 41% and 5%, respectively. The mucosae were involved in 27%, and 25% of confirmed cases of BP did not present with bullae. The median time to onset of bullous irAEs was 12 months, with a median total symptom duration of 6 months. Single PD‐1/PD‐L1 agents had a longer time to onset of symptoms than combination therapy (median 12 vs. 7 months, respectively). Overall, 91%, 64% and 9% of patients required one, two or three lines of treatment, respectively. Two cases occurred after completion of CPIs (1 and 3 months). Of the 20 cases that presented while on CPIs this was permanently discontinued in 55% (11 of 20) and temporarily held in 20% (four of 20). In the four held cases of CPI, bullous eruption reflared in 50%. Conclusions: CPI‐associated bullous skin toxicity is a rare cutaneous irAE occurring in approximately 0·3% of cases over 13 years of treated patients in this series. Not all cases are diagnostic of BP, but management remains the same. There is a prolonged latency of onset compared with other cutaneous irAEs, with a median time of 12 months, and they can occur after cessation of therapy. Discontinuation of CPIs may be required. Recognizing bullous irAEs promptly and referral to dermatology are essential to optimize management and improve patient outcomes and tumour responses. What is already known about this topic?Checkpoint inhibitor (CPI)‐associated bullous pemphigoid is a rare dermatological immune‐related adverse event (irAE) that has been reported in small case series and reports. What does this study add?This is the largest multicentre, observational study conducted in the UK over the longest period of 13 years, which demonstrates an overall incidence of bullous cutaneous irAEs secondary to CPIs of 0·3%.Clinical presentation is variable, with one‐quarter of patients with bullous pemphigoid presenting without bullae, and mucosal involvement was noted in 27%. Prolonged pruritus is frequently a prodromal symptom.The median time to diagnosis is 12 months and irAEs rarely present after cessation of treatment. Time to onset of symptoms is longer with a single CPI, but with a shorter duration of symptoms compared with combination CPI therapy.Most patients had cutaneous melanoma, of which 81% were BRAF wildtype. [ABSTRACT FROM AUTHOR]

The ability of an animal to survive prolonged periods of oxygen deprivation is a critical area of study, both in terms of its importance to better understanding the physiology of these incredible animals and to its potential applicability to medical fields. The freshwater crayfish, Faxonius virilis, is one such animal capable of resisting anoxia, but it remains understudied and much of the metabolic mechanisms underlying this anoxia tolerance remain largely unprofiled. This study examines the activity and regulation of apoptosis and autophagy in F. virilis in response to 20-h anoxia. Apoptosis signaling was assessed through pro- and anti-apoptosis targets, whereas autophagy was assessed via expression response of multiple autophagy proteins. An anoxia-triggered, tissue-specific result arose, potentially based on the importance of individual organ integrity through hypometabolism. Tail muscle, which showed increased expression profiles of all three target groups, contrasted with hepatopancreas, which appeared to not be susceptible to either apoptotic or autophagic signaling during anoxia. This is likely due to the importance of the hepatopancreas, given that apoptosis or autophagy of this organ at any significant level could be fatal to the organism. The data provides a comprehensive overview of the responses and integration of multiple stress-responsive signaling pathways in F. virilis that provide a novel contribution to our understanding of pro-survival mechanisms supporting invertebrate anoxia resistance. [ABSTRACT FROM AUTHOR]

Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19. [ABSTRACT FROM AUTHOR]

Background: Data on health status outcomes after spontaneous coronary artery dissection (SCAD) are limited. Methods and findings: Using the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients (VIRGO) study we compared patients with SCAD and other acute myocardial infarction (AMI) at presentation (baseline), 1-month, and-12 months using standardized health status instruments. Among 3572 AMI patients ≤ 55 years, 67 had SCAD. SCAD patients were younger (median age (IQR) 45 (40.5–51) years vs. 48 (44–52) in other AMI, p = 0.003), more often female (92.5% vs. 66.6%), have college education (73.1% vs. 51.7%) and household income >$100,000 (43.3% vs. 17.7% (All p<0.001). SCAD patients at baseline had higher mean ± SD Short Form-12 [SF-12] physical component scores [PCS] (48.7±10.2 vs. 43.8±12.1, p<0.001) and mental component scores [MCS] (49.6±12.4 vs. 45.4±12.5, p = 0.008), and at 12-months [PCS (50.1±9.0 vs. 44.3±12.3, p<0.001) and MCS (53±10.1 vs 50.2±11.0, p = 0.045)]. The Euro-Quality of Life Scale [EQ-5D] VAS and EQ-5D index scores were similar at baseline, but higher at 12-months for SCAD (EQ-5D VAS: 82.2±10.2 vs. 72.3±21.0, p<0.001; EQ-5D index scores; 90.2±15.3 vs. 83.7±19.8, p = 0.012). SCAD patients had better baseline Seattle Angina Questionnaire [SAQ] physical limitation (88.8±20.1 vs. 81.2±25.4, p = 0.017). At 12-months SCAD patients had better physical limitation (98.0±8.5 vs. 91.4±18.8, p = 0.007), angina frequency (96.4±8.8 vs. 91.3±16.8, p = 0.018) and quality of life scores (80.7±14.7 vs 72.2±23.2, p = 0.005). Magnitude of change in health status from baseline to 12-months was not statistically different between the groups. After adjustment for time and comorbidities there remained no difference in most health status outcomes. Conclusions: SCAD patients fare marginally better than other AMI patients on most health status instruments and have similar 12-month health status recovery. Better pre-event health status suggests a need to modify exercise prescriptions and cardiac rehabilitation protocols to better assist this physically active population to recover. [ABSTRACT FROM AUTHOR]

Background: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. Objective: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. Methods: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. Results: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). Conclusion: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is associated with increased risk of morbidity and mortality amongst elderly population. Lack of scientific evidence exists on the status of malnutrition amongst elderly population residing at high altitude regions of Uttarakhand, India. Materials and methods: A community based cross-sectional study was conducted in high altitude regions of District Nainital. A total of 980 elderly subjects were selected from 30 clusters identified using population proportionate to size sampling method. Nutritional status of the elderly population was assessed using Mini Nutritional Assessment (MNA) tool. Data was entered in MS Excel 2007 and analyzed using SPSS version 20.0. Results: The results of MNA revealed that 14.3% of the elderly subjects were malnourished. High prevalence of malnutrition was found among subjects who were illiterate (74.5%), financially dependent (75.2%), belonged to low monthly income (43.3%) had poor appetite (71.6%) and chewing problems (63.1%); (p<0.0001). Conclusions: High prevalence of malnutrition was present amongst the elderly population in India. There is a need for timely assessment of malnutrition for maintenance of nutritional status and prevention of chronic diseases. [ABSTRACT FROM AUTHOR]

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P < 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed (P = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids. [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 B12 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 B12 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 ± 1.0 g/dL, control group: 1.6 ± 1.2 g/dL, P = 0.004) and ferritin levels (experimental group: 18.6 ± 31.5 ng/mL, control group: 18.8 ± 35.0 ng/mL, P = 0.188) increased in both the control and experiment groups. Serum vitamin B12 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 B12 for 90 days eliminated iron, vitamin B12 deficiency and reduced the overall proportion of anemia by 53.5%. However, addition of vitamin B12 to IFA supplementation had no impact on improving the hemoglobin levels among adolescent girls. The present study does not recommend provision of vitamin B12 for prevention and treatment of anemia in this population group. [ABSTRACT FROM AUTHOR]

Background: Amitraz is an insecticidal agent and its poisoning cases are rare. We report the successful treatment of amitraz poisoning using yohimbine as an antidote. There is only a single other case report in literature of usage of yohimbine as antidote to amitraz poisoning in a 3-year-old child. Case presentation: A 27-year-old woman presented to the hospital with features of severe amitraz intoxication-respiratory depression and loss of consciousness. Along with supportive management in the intensive care unit, she was administered parenteral yohimbine, which resulted in quick recovery and discharge from hospital. Conclusions: Yohimbine may serve as a useful antidote in severe amitraz intoxication. However, the conclusive benefit of yohimbine in human cases of amitraz poisoning is yet to be established and is a potential area of research. [ABSTRACT FROM AUTHOR]

As there are few reports of fasting by caregivers,1,2 we conducted an audit to determine the prevalence and reasons of fasting among the caregivers of children scheduled for elective surgery. The parental fasting did not differ with father's ( I p i = .575) or mother's education ( I p i = .813), family income ( I p i = .188), and the source of fasting instructions ( I p i = .311). Preoperative fasting guidelines aim to allow sufficient time for gastric emptying with minimum patient discomfort. [Extracted from the article]

The limitations that hypoxia imparts on mitochondrial oxygen supply are circumvented by the activation of anaerobic metabolism and prosurvival mechanisms in hypoxia-tolerant animals. To deal with the hypoxia that jumbo squid (Dosidicus gigas) experience in the ocean’s depth, they depress their metabolic rate by up to 52% relative to normoxic conditions. This is coupled with molecular reorganization to facilitate their daily descents into the ocean’s oxygen minimum zone, where they face not only low oxygen levels but also higher pressures and colder frigid waters. Our current study explores the tissue-specific hypoxia responses of three central processes: (1) antioxidant enzymes responsible for defending against oxidative stress, (2) early apoptotic machinery that signals the activation of cell death, and (3) mitogen-activated protein kinases (MAPKs) that act as central regulators of numerouscellular processes. LuminexxMAP technology was used to assess protein levels and phosphorylation states under normoxic and hypoxic conditions in brains, branchial hearts, and mantle muscles. Hypoxic brains were found to activate apoptosis via up-regulation of phospho-p38, phospho-p53, activated caspase 8, and activated caspase 9, whereas branchial hearts were the only tissue to show an increase in antioxidant enzyme levels. Hypoxic muscles seemed the least affected by hypoxia. Our results suggest that hypoxic squid do not undergo large dynamic changes in the phosphorylation states of key apoptotic and central MAPK factors, except for brains, suggesting that these mechanisms are involved in squid hypometabolic responses. [ABSTRACT FROM AUTHOR]

Anesthetics such as isoflurane are known to cause apoptosis in the developing mammalian brain. However, isoflurane may have protective effects on the heart via relieving ischemia and downregulating genes related to apoptosis. Ischemic preconditioning, e.g. through the use of low levels of carbon monoxide (CO), has promise in preventing ischemia-reperfusion injury and cell death. However, it is still unclear how it either triggers the stress response in neonatal hearts. For this reason, thirty-three microRNAs (miRNAs) known to be differentially expressed following anesthesia and/or ischemic or hypoxic heart damage were investigated in the hearts from neonatal mice exposed to isoflurane or low level of CO, using an air-exposed control group. Only miR-93-5p increased with isoflurane exposure, which may be associated with the suppression of cell death, autophagy, and inflammation. By contrast, twelve miRNAs were differentially expressed in the heart following CO treatment. Many miRNAs previously shown to be responsible for suppressing cell death, autophagy, and myocardial hypertrophy were upregulated (e.g., 125b-3p, 19-3p, and 21a-5p). Finally, some miRNAs (miR-103-3p, miR-1a-3p, miR-199a-1-5p) which have been implicated in regulating energy balance and cardiac contraction were also differentially expressed. Overall, this study demonstrated that CO-mediated miRNA regulation may promote ischemic preconditioning and cardioprotection based on the putative protective roles of the differentially expressed miRNAs explored herein and the consistency of these results with those that have shown positive effects of CO on heart viability following anesthesia and ischemia-reperfusion stress. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1st through May 12th, 2020 with study period ending on June 11th, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36–0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality. Statins, which have anti-inflammatory and antithrombotic properties, could have effects in COVID-19 patients. Here, the authors find in a retrospective analysis of patients hospitalized with COVID-19 that antecedent statin use is associated with lower inpatient mortality. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vi tamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our c urrent understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immuni ty and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 diseas e deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data asso ciating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypoth etical. [ABSTRACT FROM AUTHOR]

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.Exposures: Ticagrelor vs clopidogrel.Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting. [ABSTRACT FROM AUTHOR]

Introduction: The present study was conducted to assess the association of tobacco and alcohol consumption with cardiovascular risk factors among elderly population living at high altitude regions of India. Materials and Methods: A cross-sectional study was conducted among 1003 elderly people living in district Nainital, Uttarakhand state, India. Thirty subjects were identified from 30 villages using population proportionate to size sampling methodology. The data on the consumption of tobacco and alcohol, mini nutritional assessment, Barthel activities of daily living scale, height, weight, blood pressure, fasting blood sugar, triglycerides, and total cholesterol was collected. Results: We found that smoking tobacco was associated with high cholesterol, lower body mass index, and low nutritional status (all, P < 0.05). Elderly subjects who consumed alcohol had 1.56 times higher risk of having high fasting blood glucose. Conclusions: Consumption of tobacco and alcohol increased the risk of cardiovascular diseases among elderly subjects. There is a need to improve these modifiable health behaviors through targeted educational and rehabilitation programs. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of the study was to enumerate the sedative drugs used, assess the efficacy of sedative drugs, and determine the incidence of adverse events. Material and Methods: A prospective audit of children sedated for computerized tomography (CT) by anesthesiology team was conducted for a period of 4 months. The data included patient demographic variables, fasting period, medications administered, adequacy of sedation, imaging characteristics, adverse events, and requirement for escalated care. Results: A total of 331 children were enrolled for sedation by the anesthesia team. The drugs used for sedation were propofol, ketamine, and midazolam. Twenty-two percent children received one sedative drug, 60% children were administered two drugs, and 5% children required a combination of all three drugs for successful sedation. Sedation was effective for successful conduct of CT scan in 95.8% patients without the requirement of a repeat scan. Twelve (5%) children experienced adverse events during the study period. However, none of the adverse events necessitated prolonged postprocedural hospitalization or resulted in permanent neurologic injury or death. Conclusions: The current practice of sedation with propofol, ketamine, and midazolam, either single or in combination was efficacious in a high percentage of patients. The incidence of adverse events during the study period was low. [ABSTRACT FROM AUTHOR]

Introduction: Anemia is a major public health problem amongst elderly population in India. Anemia in old age further worsens the age-related decline in functional ability, mobility, fatigue, bone density, and skeletal muscle mass. There is lack of evidence on the prevalence and risk factors of anemia among elderly population. Hence, this study was undertaken. Methodology: A community-based cross-sectional study was conducted during the year 2015–2016 in District Nainital, Uttarakhand state, India. A total of 958 subjects were selected from 30 clusters (villages) identified using population proportional to size methodology. Information on sociodemographic profile, nutritional status, body mass index, and dietary intake was obtained. Blood sample was collected from each subject on the filter paper for estimation of hemoglobin (Hb) level using cyanmethemoglobin method. Results: We found that 92.1% of the elderly subjects were anemic. Moderate and severe anemia was found to be significantly higher among female subjects, unemployed, illiterates, subjects using smoke-producing fuel, subjects belonging to lower socioeconomic status, malnourished and underweight subjects, subjects with self-reported hyperacidity, and subjects who had not utilized health facility and had lower iron and vitamin C intake when compared with subjects with mild anemia and normal hemoglobin levels. Conclusion: High prevalence of anemia exists amongst elderly subjects living at high-altitude region of rural Uttarakhand State, India. There is a need to educate the elderly population about the importance of adequate intake of foods rich in iron and vitamin C to reduce the prevalence of anemia among them. [ABSTRACT FROM AUTHOR]

Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India - CORRIGENDUM In the published article, the authors overlooked mentioning that 0.5g/dl was added to the original hemoglobin values to correct for the difference using direct and indirect cyanmethaemoglobin method. Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India. [Extracted from the article]

Anemia is a major public health problem in India with prevalence of more than 50% amongst children and adolescents. The decline in the burden of anemia has been insignificant over the past 5 decades. The present review assesses the National Guidelines for Prevention and Control of Anemia in India, the current status of the program implementation and possible reasons for the continued high prevalence of anemia in the country. [ABSTRACT FROM AUTHOR]

Background and Aims: Parenteral analgesics and epidural analgesia are two standard options to treat postoperative pain after total abdominal hysterectomy (TAH). Fascial plane blocks such as transversus abdominis plane (TAP) block have gained popularity recently. However, effect of these analgesic regimens on quality of postoperative recovery (QoR) has not been studied. Hence we aimed to assess and compare the QoR with three different postoperative analgesic regimens---parenteral analgesia, epidural analgesia, and TAP block in patients undergoing TAH under general anesthesia. Material and Methods: Sixty female patients undergoing TAH were randomized into three groups of 20 each for postoperative analgesia. Epidural group received boluses of 0.125% bupivacaine for 24 h, parenteral group received injection diclofenac and injection tramadol alternately every 6 h for 24 h, and TAP group received bilateral TAP block with 0.25% bupivacaine at end of operation. QoR was assessed postoperatively by 40-item questionnaire-QOR-40 and pain was assessed by numerical rating scale (NRS). Results: QOR-40 score was comparable across the three groups at 24, 48, and 72 h postoperatively. TAP block prolonged the time to first rescue analgesic (P = 0.02) and reduced the total 24-h postoperative morphine consumption by 2.4 (95% CI: 1.0, 3.8) mg (P = 0.002) and 7.8 (95% CI: 6.4, 9.1) mg (P < 0.001) when compared with epidural and parenteral groups, respectively. Conclusion: The QoR after abdominal hysterectomy is similar with either intravenous analgesics or epidural analgesia or TAP block when used with rescue analgesia to manage postoperative pain. TAP block provides superior analgesia and reduces 24-h morphine consumption when compared with parenteral and epidural analgesia. [ABSTRACT FROM AUTHOR]

Background: Poor dental health status has been suggested to negatively impact the food selection, ultimately leading to malnutrition. Objective: This study was undertaken to assess the association of dental health and nutritional status among elderly subjects in India. Methodology: A community-based cross-sectional study was conducted during 2015–2016 in district Nainital, Uttarakhand state, India. A total of 1003 elderly population were enrolled from 30 clusters (villages) identified using population proportionate to size sampling methodology. Information on sociodemographic profile and anthropometric measurements was collected. Body mass index (BMI) and Mini Nutritional Assessment scale (MNA) were calculated for assessment of nutritional status. A trained professional assessed the dental health status through physical examination. Dietary intake data was collected using 24-h dietary recall methodology. Results: We found that the prevalence of complete edentulism was 11%. Use of dentures was reported among only 9.6% subjects who were completely edentulous. Prevalence of underweight as defined by BMI and malnutrition as defined by MNA was higher among subjects with complete loss of teeth complete loss of teeth and chewing problems chewing problems and who did not wear dentures when compared with others. Subjects who wore dentures had significantly lower prevalence of malnutrition when compared with subjects who did not wear dentures. Conclusion: Dental health status was significantly associated with poor nutritional status among elderly subjects in India. There is a need for providing restorative dental healthcare services to elderly population to improve their nutritional status. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HTN) and diabetes mellitus (DM) both are rapidly emerging as public health problems among geriatric population in developing countries. HTN can lead to stroke, myocardial infarction, congestive heart failure, and chronic kidney diseases among geriatric population. DM increases the risk of coronary heart disease, cerebrovascular disease, peripheral vascular disease, retinopathy, nephropathy, and neuropathy among geriatric population. Methodology: A community‑based, cross‑sectional study was conducted during 2015–2016 in District Nainital, Uttarakhand. A list of all villages with their population in the district was developed. From this list, 30 villages were identified using population proportionate to size sampling method. From each village, 30 geriatric subjects were selected. A total of 1003 geriatric subjects age 60 years and above were included in the study. Data were collected on sociodemographic profile, blood pressure, fasting blood glucose, anthropometry, and lipid profile from all the enrolled subjects. The prevalence of HTN and DM was assessed. Univariate and multivariate analyses were done to identify risk factors associated with HTN and DM. Results: The prevalence of HTN and DM was found to be 54.5% and 14.6%, respectively. For HTN, advancing age, high educational level and body mass index (BMI) (≥25 kg/m2) and for DM higher education level and BMI (≥25 kg/m2) were found to be significant risk factors. Conclusion: A high prevalence of HTN and DM was found in geriatric population residing in rural area of Uttarakhand. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy is a significant problem in the elderly. The veteran population is unique in terms of better access to health-care services and higher educational qualifications. However, the studies to assess the burden and effects of polypharmacy in this cohort are rare. Hence, the research was done to find the prevalence of polypharmacy in the veteran population. Methods: In this cross-sectional observational study, we included veterans with more than 35 years visiting the medical outpatient department. All participants were interviewed about polypharmacy after taking informed consent. Results: Out of 394 patients included in the study, 110 were prescribed five or more medicines for their illnesses (27.91%: 95% confidence interval [CI] 21.1%-30%). More than 95% (377/394) of the study participants were unaware of the concept of polypharmacy. There was high compliance to treatment in veterans (97.46%, 95% CI 95.1%-98.6%). Conclusion: This study shows that the prevalence of polypharmacy is significant in veterans, including patients in their fourth and fifth decades of life, despite fewer morbidities. [ABSTRACT FROM AUTHOR]

Paediatric airway tumours can prove to be quite challenging for anaesthesiologists. We attempted to secure airway in a toddler with a large tongue haemangioma using total intravenous anaesthesia (TIVA) with dexmedetomidine and propofol while preserving spontaneous ventilation. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and risk factors of underweight, overweight and obesity among a geriatric population living in a high-altitude region of India.Design: Community-based cross-sectional study. Data were collected on sociodemographic profile and anthropometric parameters. Weight and height measurements were utilized for calculation of BMI. Nutrient intake data were collected using 24 h dietary recall.Setting: High-altitude region of Nainital District, Uttarakhand State, North India.Subjects: Community-dwelling geriatric subjects (n 981) aged 60 years or above.Results: We found that 26·6 % of the elderly subjects were underweight (BMI<18·5 kg/m2). Overweight (BMI 25·0-29·9 kg/m2) and obesity (BMI≥30·0 kg/m2) was seen among 18·0 % and 4·6 %, respectively. After controlling for potential cofounders, risk factors such as low level of education and income, chewing problems and lower number of daily meals were found to be associated with underweight. On the other hand, risk factors for overweight/obesity were lower age, high income and unskilled work.Conclusions: There is a need to develop and implement intervention strategies to prevent underweight, overweight and obesity among the geriatric population of India. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic syndrome (MetS) is responsible for 2.5-fold increase in cardiovascular mortality and a 5-fold higher risk of developing diabetes. Materials and Methods: A community-based cross-sectional study was conducted during 2015–2016 in District Nainital. A list of all villages was developed. From this list, thirty villages were identified using population proportionate to size sampling method. From each village, thirty geriatric subjects (GSs) were selected. The study population included 979 GSs aged 60 years and above. The data were collected on anthropometry, blood pressure, blood glucose, and lipid profile from all the enrolled subjects. The prevalence of MetS was estimated using International Diabetes Federation criteria. Univariate and multivariate analysis was done to identify factors associated with MetS. Results: The prevalence of MetS was found to be 28.6%. Step-wise multivariate logistic regression analysis found that female gender, higher income, and body mass index ≥25 were significant and independent risk factors of MetS amongst GP. Conclusion: There is a need for screening of GP living in high altitude region so that efforts can be initiated to prevent complications of MetS. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a major contributing determinant in the development of ischemic heart diseases, stroke, and other vascular diseases. It increases the risk of mortality amongst the geriatric population. Aims & Objectives: To assess the prevalence of dyslipidemia in geriatric rural population residing in a hilly district of Uttarakhand state, India. Material & Methods: A community based cross-sectional study was conducted during 2015 - 2016 in District Nainital, Uttarakhand. A list of all villages with their population in the district was developed. From this list, thirty villages were identified using population proportionate to size sampling method. From each village 30 geriatric subjects were selected. A total of 1003 geriatric subjects aged 60 years and above were included in the study. The data was collected on socio demographic profile and lipid profile from all the enrolled subjects. The prevalence of dyslipidemia was assessed using National Cholesterol Education Programme (NCEP) criteria. Result: The overall prevalence of dyslipidemia was 50.6%. A total of 26.3% participants had hypercholesterolemia, 34.2% had hypertriglyceridemia and 23.5% had high LDL levels. The prevalence of dyslipidemia was higher in women compared to men. Conclusion: High prevalence of dyslipidemia was found amongst geriatric rural population. [ABSTRACT FROM AUTHOR]

Introduction: Recently, an increasing trend in the prevalence of pediatric metabolic syndrome (PMS) among school-age children has been documented in different parts of India. There is lack of data on the prevalence of PMS and its associated risk factors among school-age children living in district Shimla, Himachal Pradesh. Hence, to fill in the gap in the existing knowledge, the present study was conducted. Methodology: A cross-sectional study was conducted during 2015-2016. Thirty clusters (schools) were identified from a list of all schools using population proportionate to size sampling methodology. From each school, 70 children in the age group of 10-16 years were selected. Data was collected on the sociodemographic characteristics, anthropometry, waist circumference, blood pressure, and physical activity. Fasting venous blood samples were collected for estimation of blood glucose, triglycerides, and high-density lipoprotein levels. Results: The prevalence of PMS using International Diabetes Federation classification was 3.3% and using modified-adult treatment panel classification criteria was 3.5%. Risk factors identified to be associated with PMS among school-age children were (i) male gender, (ii) high family monthly income, (iii) sedentary lifestyle, (iv) consumption of evening snack, (v) television/computer viewing, and (vi) motorized transportation for commuting to school. Conclusion: The PMS prevalence was 3.3% in school-age children residing in District Shimla. There is a need to formulate interventions to prevent and correct metabolic syndrome among them for reducing early onset of cardiovascular disease during adulthood. [ABSTRACT FROM AUTHOR]