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BACKGROUNDRemdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in syrtlptomatic, norillospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving non-hospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.890 were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.690), obesity (55.2%) and hypertension (47.7%). Covid-19--related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P= 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19--related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETKEE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.) [ABSTRACT FROM AUTHOR]

Depression, affecting millions of people worldwide, is a leading cause of disability globally. It affects not only daily functioning but also interpersonal relationships and overall health by increasing the risks of chronic physical and mental illnesses. Creatine, traditionally recognized for boosting physical performance through its role in producing adenosine triphosphate, has recently shown potential as an adjunctive therapy for treating depression. Creatine's ability to enhance brain energy metabolisms and provide neuroprotection suggests that it can alleviate mood disorders by improving mitochondrial function, increasing cellular resilience, and modulating neurotransmitter systems that regulate mood. This narrative review aims to critically evaluate the research on creatine supplementation for depression, focusing on its efficacy, mechanism of action, risks, and benefits as a treatment for mood disorders. It analyzes preclinical and clinical studies to understand creatine's potential as an adjunctive or alternative therapy for major depressive disorder and bipolar depression and underscores any gaps in current research. Both animal models and human trials indicate creatine's efficacy for the treatment of depression. Creatine supplementation reduces depressive symptoms, particularly when combined with selective serotonin reuptake inhibitors, and may improve brain energy metabolism and neuroplasticity. It is generally well tolerated, though caution is warranted due to potential side effects such as manic episodes in bipolar disorder and renal function impairment in patients with kidney dysfunction. Overall, creatine presents a promising addition to current depression treatments, though further research is needed to establish optimal dosing, long-term efficacy, and safety across diverse patient populations., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Juneja et al.)

Background: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter Adaptive COVID-19 Treatment Trial 1, which randomized patients to remdesivir or placebo., Methods: Longitudinal specimens collected during hospitalization from a substudy of 642 patients with COVID-19 were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed., Results: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95% CI, 1.40-2.71) for levels >245 pg/mL vs 1.04 (95% CI, .76-1.42) for levels <245 pg/mL. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive., Conclusions: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy., Clinical Trial Registration: NCT04280705 (ClinicalTrials.gov)., Competing Interests: Potential conflicts of interest . A. L. G. reports contract testing to his institution from Abbott, Cepheid, Novavax, Pfizer, Janssen, and Hologic and research support to his institution from Gilead Sciences, Inc, and Merck outside of the described work. D. P. is an employee and shareholder of Gilead Sciences, Inc. K. J. is a shareholder of and was employed by Gilead Sciences, Inc, at the time of manuscript development. C. A. B. has received grants/contracts to her institution from Gilead Sciences, Inc, and consultant fees from NDA Partners, LLC, related to drug development. C. A. B. served as the president of the CROI Foundation Board of Directors, vice president of the Zimbabwe AIDS Treatment Assistance Project Board of Directors, and secretary/treasurer of the IAS-USA Board of Directors (all nonprofit organizations). C. A. B. recently served as deputy editor for Clinical Infectious Diseases for the Infectious Diseases Society of America. N. J. reports salary support by Sagent Pharmaceuticals to his institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Ketamine, a pharmacological agent that acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, has garnered considerable interest because of its notable and expeditious antidepressant properties observed in individuals diagnosed with major depressive disorder (MDD) who exhibit resistance to conventional therapeutic interventions. A comprehensive and rigorous systematic review was undertaken to evaluate the prevalence of ketamine abuse undergoing ketamine treatment for depressive disorders. A comprehensive search was conducted across the electronic databases to identify pertinent studies published between 2021 and 2023. The present investigation incorporated a comprehensive range of studies encompassing the abuse or misuse of ketamine, including case reports, observational studies, and clinical trials. Data extraction and quality assessment were conducted in accordance with predetermined criteria. The findings of this systematic review demonstrate the importance of monitoring and addressing ketamine abuse in patients receiving ketamine treatment for depressive disorders like MDD. The wide range of reported prevalence rates highlights the need for standardized criteria and measures for defining and assessing ketamine abuse. This study presents a significant contribution to the field by introducing a novel screening questionnaire and assessment algorithm designed to identify and evaluate ketamine misuse among major depressive disorder (MDD) patients undergoing ketamine treatment. This innovative tool holds the potential to enhance clinical practice by providing healthcare professionals with a standardized approach to promptly detect and address ketamine misuse. The integration of this screening tool into routine care protocols can facilitate more effective monitoring and management of ketamine misuse in this population, ultimately leading to improved patient outcomes and safety., (© 2024. The Author(s).)

Background: Ambient air pollution is a major factor that can affect lung growth and reduce lung capacity. This study aims at drawing parallel between respiratory discomfort and lung function between youth of Delhi-National Capital Region (NCR) where air pollution level is poor and hazardous as compared to that of Pauri Garhwal (Uttarakhand) where air pollution level is low via a comparative cross-sectional study., Methods: A community-based cross-sectional study conducted among 354 never-smoker subjects (177 from NCR and 177 from Pauri) between the ages of 15 and 29 years. Pulmonary Function Test coupled with COPD Assessment Test (CAT)-based questionnaire for respiratory problems helped elicit information regarding lung health of subjects., Results: Mean forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1), forced expiratory flow 25-75%, FEV1/FVC ratio, and peak expiratory flow rate were lower by 12.9%, 17%, 5%, 7.8%, and 7.3%, respectively, in NCR participants as compared to that of Pauri. Upon spirometry, restrictive pattern was present in 40 (22.6%), and obstructive pattern was present in 9 (5.1%) of NCR participants. Out of these, nine (5.1%) having obstructive pattern, five (55.6%) had 50% ≤ FEV1<80%, and four (44.4%) had 30% ≤ FEV1<50% of predicted value. Neither restrictive nor obstructive pattern was found evident in subjects from Pauri. The mean CAT score in subjects from NCR was 5.2 ± 4.9 and .46 ± 1.1 in subjects from Pauri., Conclusion: Subjects belonging to NCR performed poorly in spirometry and reported higher respiratory complaints in comparison to participants from Pauri Garhwal., (© 2023 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Objectives: This study aimed to determine self-medication prevalence and its associated factors., Methods: A community-based cross-sectional study was conducted in the urban and rural catchment areas of Uttar Pradesh, India, among 440 adults using a pretested, semistructured questionnaire. The Chi-square test and logistic regression were used to determine the association of self-medication prevalence with various independent variables. The associations were reported as adjusted odds ratios and 95% confidence intervals., Results: The prevalence of medication use was 66.4%. The majority of participants (45%) took medicine for fever, cough (40.1%), and cold (31.8%). Allopathy (83.2%) was the most common medicine system used for self-medication. More than half reported taking medicine such as paracetamol (52%), followed by cough syrup (21%) and antihistaminic (17%). Convenience (46%) and lack of time (35.3%) were commonly cited reasons for self-medication. Also, 64.4% of the respondents practiced self-medication on the pharmacist's recommendation. Urban participants (adjusted odds ratio: 9.85, 95% confidence interval: 5.32-18.23), females (adjusted odds ratio: 2.32, 95% confidence interval: 1.18-4.57), skilled workers (adjusted odds ratio: 5.62, 95% confidence interval: 1.80-17.5), and those who completed primary school (adjusted odds ratio: 2.48, 95% confidence interval: 1.16-5.25) were more likely to self-medicate than rural, male, unemployed, and illiterate participants, respectively. Also, participants whose income was 30,000 Indian rupees (adjusted odds ratio: 3.21, 95% confidence interval: 1.00-10.21) were more likely to self-medicate than those whose income was less than 4000., Conclusions: A high prevalence of self-medication was found, particularly in urban areas. Convenience and lack of time were commonly cited reasons for self-medication. Allopathy was the most widely used medicine system for self-medication. Antipyretics, cough syrups, and antiallergics were most commonly self-medicated. Gender, education, and income were associated with self-medication. The study highlighted the increased usage among females which could be further explored and role of pharmacists' recommendation as a major driver for self-medication., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Context: Hypertension is the leading cause of mortality and disability-adjusted life year (DALY) all over the world. World Health Organization defines quality of life (QOL) as an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns., Aims: The study was aimed to compare the the QOL of adult hypertensive patients with healthy study subjects and to determine the factors associated with poor QOL among the hypertensive subjects., Materials and Methods: A community-based cross-sectional study was conducted from January 2021 to June 2022 in Gautam Budh Nagar District. The study was carried out among 250 hypertensive patients and 50 healthy persons based on World Health Organization-Quality of Life-BREF questionnaire Manual., Statistical Analysis Used: Data collected were entered and statistically analyzed using statistical software (SPSS-22)., Results: Overall QOL and general health scores were significantly lower among hypertensive subjects showing worsening of QOL among diseased persons (P value <0.001). Factors significantly associated with poor overall QOL were low educational status ( P value <0.001), home makers ( P value <0.001), lower socio-economic class ( P value < 0.001), and subjects with co-morbidities ( P value <0.001)., Conclusion: The findings revealed that QOL was poor among the hypertensive subjects as compared to healthy subjects., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Inaccuracy in the All Indian Summer Monsoon Rainfall (AISMR) forecast has major repercussions for India's economy and people's daily lives. Improving the accuracy of AISMR forecasts remains a challenge. An attempt is made here to address this problem by taking advantage of recent advances in machine learning techniques. The data-driven models trained with historical AISMR data, the Niño3.4 index, and categorical Indian Ocean Dipole values outperform the traditional physical models, and the best-performing model predicts that the 2023 AISMR will be roughly 790 mm, which is typical of a normal monsoon year., (© 2024. The Author(s).)

Intravenous remdesivir (RDV) is US Food and Drug Administration-approved for hospitalized and nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS-443902, and other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure and maximize exposure at the site of action. This study evaluated the pharmacokinetics (PK) and safety of inhaled RDV in healthy adults. This phase Ia, randomized, placebo-controlled study evaluated inhaled RDV in healthy participants randomized 4:1 to receive RDV or placebo as single doses (4 cohorts) or multiple once-daily doses (3 cohorts). Doses in cohorts 1-6 were administered as an aerosolized solution for inhalation through a sealed facemask; doses in cohort 7 were administered as an aerosolized solution for inhalation through a mouthpiece. Safety was assessed throughout the study. Seventy-two participants were enrolled (inhaled RDV, n = 58 and placebo, n = 14). Following single RDV doses, RDV, GS-704277, and GS-441524 plasma PK parameters indicated dose-proportional increases in area under the concentration-time curve (AUC) extrapolated to infinite time, AUC from time zero to last quantifiable concentration, and maximum observed concentration. Analyte plasma concentrations after multiple RDV doses were consistent with those for single-dose RDV. Analyte plasma exposures were lower when RDV was administered with a mouthpiece versus a sealed facemask. The most common adverse events included nausea, dizziness, and cough. Single- and multiple-dose inhaled RDV exhibited linear and dose-proportional plasma PK. Administration of RDV via inhalation was generally safe and well-tolerated., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum SARS-CoV-2 viral load and serum anti-SARS-CoV-2 antibodies at baseline as biomarkers for clinical outcomes in patients enrolled in these trials. In adjusted Cox proportional hazard models, serum viral load was a more reliable predictor of clinical outcomes than NP viral load; high serum viral load was associated with higher risk for death and mechanical ventilation/death and lower likelihood of hospital discharge (high vs. negative viral load hazard ratios [95% confidence interval {CI}] were 2.87 [1.57-5.25], 3.86 [2.23-6.68], and 0.23 [0.14-0.36], respectively, in COVACTA and 8.11 [2.95-22.26], 10.29 [4.5-23.55], and 0.21 [0.15-0.29], respectively, in REMDACTA) and high serum viral load correlated with levels of inflammatory cytokines and lung damage biomarkers. High anti-SARS-CoV-2 spike protein antibody (ACOV2S) levels were associated with higher likelihood of hospital discharge (high vs. below the limit of quantification hazard ratios [95% CI] were 2.55 [1.59-4.08] for COVACTA and 1.54 [1.13-2.09] for REMDACTA). These results support the role of baseline SARS-CoV-2 serum viral load and ACOV2S antibody titers in predicting clinical outcomes for patients hospitalized with COVID-19., (© 2023 F. Hoffmann-La Roche Ltd and The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: In the PINETREE study, early remdesivir treatment reduced risk of coronavirus disease 2019 (COVID-19)-related hospitalizations or all-cause death versus placebo by 87% by day 28 in high-risk, non-hospitalized patients. Here we report results of assessment of heterogeneity of treatment effect (HTE) of early outpatient remdesivir, focusing on time from symptom onset and number of baseline risk factors (RFs)., Methods: PINETREE was a double-blind, placebo-controlled trial of non-hospitalized patients with COVID-19 who were randomized within 7 days of symptom onset and had ≥ 1 RF for disease progression (age ≥ 60 years, obesity [body mass index ≥ 30], or certain coexisting medical conditions). Patients received remdesivir intravenously (200 mg on day 1 and 100 mg on days 2 and 3) or placebo., Results: In this subgroup analysis, HTE of remdesivir by time from symptom onset at treatment initiation and number of baseline RFs was not detected. Treatment with remdesivir reduced COVID-19-related hospitalizations independent of stratification by time from symptom onset to randomization. Of patients enrolled ≤ 5 days from symptom onset, 1/201 (0.5%) receiving remdesivir and 9/194 (4.6%) receiving placebo were hospitalized (hazard ratio [HR] 0.10; 95% confidence interval [CI] 0.01-0.82). Of those enrolled at > 5 days from symptom onset, 1/78 (1.3%) receiving remdesivir and 6/89 (6.7%) receiving placebo were hospitalized (HR 0.19; 95% CI 0.02-1.61). Remdesivir was also effective in reducing COVID-19-related hospitalizations when stratified by number of baseline RFs for severe disease. Of patients with ≤ 2 RFs, 0/159 (0.0%) receiving remdesivir and 4/164 (2.4%) receiving placebo were hospitalized; of those with ≥ 3 RFs, 2/120 (1.7%) receiving remdesivir and 11/119 (9.2%) receiving placebo were hospitalized (HR 0.16; 95% CI 0.04-0.73)., Conclusions: In the outpatient setting, benefit of remdesivir initiated within 7 days of symptoms appeared to be consistent across patients with RFs. Therefore, it may be reasonable to broadly treat patients with remdesivir regardless of comorbidities., Trial Registration: ClinicalTrials.gov number NCT04501952., (© 2023. The Author(s).)

Background: Remdesivir (RDV) is an intravenous antiviral with activity against SARS-CoV-2 for treatment of hospitalized COVID-19 patients with moderate-to-severe disease. Biomarkers associated with clinical outcomes have been identified for COVID-19, but few evaluated in context of antiviral treatment. Here, we assessed baseline (day 1, prior to first RDV dose) biomarkers and the impact of RDV treatment on longitudinal biomarker readouts., Methods: Recently, RDV was evaluated in high-risk, non-hospitalized patients with confirmed SARS-CoV-2 infection and was highly effective at preventing disease progression. The randomized, double-blind, placebo-controlled Phase 3 study included 562 participants who received at least 1 dose of study drug, of which 312 consented for longitudinal biomarker assessments at baseline, day 3, and day 14. We assessed sixteen baseline biomarkers and the impact of RDV treatment on longitudinal biomarker readouts., Results: Six well-known, inflammation-associated biomarkers are elevated at baseline in participants meeting the primary endpoint of hospitalization or death by day 28. Moreover, in comparison to placebo, biomarkers in RDV-treated participants show accelerated improvement, including reduction of soluble angiopoietin-2, D-dimer, and neutrophil-to-lymphocyte ratio, as well as an increase in lymphocyte counts., Conclusions: Overall, the findings in this study suggest that RDV treatment may accelerate the improvement of multiple biomarkers of COVID-19 severity, which are associated with better clinical outcomes during infection. These findings have implications for better understanding the activity of antiviral treatments in COVID-19., (© 2023. The Author(s).)

Ruta chalepensis, a medicinal plant, produces biologically active coumarins (CRs) and furanocoumarins (FCRs). However, their yield is quite low in cultivated plants. In this work, the influence of light-emitting diodes (LEDs) was investigated on the accumulation of CRs and FCRs in the callus cultures and field-grown plants of R. chalepensis. Among the various tested wavelengths of LED lights, maximum accumulation of CR and FCRs was recorded under blue LED treatment in both the callus cultures as well as field-grown plants when compared with respective controls treated with white LED. Metabolite analyses of LED-treated field-grown plants showed that highest concentrations of CR (umbelliferone, 2.8-fold), and FCRs (psoralen, 2.3-fold; xanthotoxin, 3.8-fold and bergapten, 1.16-fold) were accumulated upon blue LED-treatment for 6 days. CR and FCRs contents were also analyzed in the blue LED- and red LED-treated in vitro callus tissue. Upon blue LED-treatment, callus accumulated significantly high levels of umbelliferone (48.6 ± 1.2 µg g -1 DW), psoralen (370.12 ± 10.6 µg g -1 DW) and xanthotoxin (10.16 ± 0.48 µg g -1 DW). These findings imply that blue LED-treatment is a viable option as a noninvasive and low-cost elicitation technology for the enhanced production of biologically active CR and FCRs in field-grown plants and callus cultures of R. chalepensis., (© 2022 American Society for Photobiology.)

Background & Objectives: In the current health system, cash incentives are given to accredited social health activists for referring women to public health facilities for specific maternal and child health services, however many reproductive health problems are not included in these services. The objective of this study was to assess the impact of involvement of self-help groups (SHGs) in improving reproductive health seeking behaviour and service utilization by tribal women., Methods: An experimental study was conducted in two tribal blocks of Nasik district (Kalvan and Surgana) in Maharashtra, India, over a period of 18 months. Interventions included training of SHG women and providing incentives to them for conducting health education sessions for reproductive age group women in the community and referring those with the requisite problems, to the health facilities. Pre- and post-intervention focus group discussions and in-depth interviews among SHG women were conducted. Training of service providers on diagnosis and treatment of reproductive morbidities was done, and health service utilization was assessed., Results: Sixty five per cent of the referred women with reproductive morbidities availed services at the public health facilities. A review of records of women seeking services for reproductive health problems showed that there was a significant improvement in the intent for seeking services in the study block as compared to the control block (χ [2] -9.06, P<0.002)., Interpretation & Conclusions: This study demonstrates the feasibility of utilizing the potential of SHGs for improving reproductive health seeking behaviour of the tribal women. The results suggest that this model could be scaled up to address the neglected reproductive health needs of women without burdening the existing human resources.

The urgent response to the COVID-19 pandemic required accelerated evaluation of many approved drugs as potential antiviral agents against the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Using cell-based, biochemical, and modeling approaches, we studied the approved HIV-1 nucleoside/tide reverse transcriptase inhibitors (NRTIs) tenofovir (TFV) and emtricitabine (FTC), as well as prodrugs tenofovir alafenamide (TAF) and tenofovir disoproxilfumarate (TDF) for their antiviral effect against SARS-CoV-2. A comprehensive set of in vitro data indicates that TFV, TAF, TDF, and FTC are inactive against SARS-CoV-2. None of the NRTIs showed antiviral activity in SARS-CoV-2 infected A549-hACE2 cells or in primary normal human lung bronchial epithelial (NHBE) cells at concentrations up to 50 µM TAF, TDF, FTC, or 500 µM TFV. These results are corroborated by the low incorporation efficiency of respective NTP analogs by the SARS-CoV-2 RNA-dependent-RNA polymerase (RdRp), and lack of the RdRp inhibition. Structural modeling further demonstrated poor fitting of these NRTI active metabolites at the SARS-CoV-2 RdRp active site. Our data indicate that the HIV-1 NRTIs are unlikely direct-antivirals against SARS-CoV-2, and clinicians and researchers should exercise caution when exploring ideas of using these and other NRTIs to treat or prevent COVID-19.

Background: Uncontrolled truncal hemorrhage remains the most common cause of potentially preventable death after injury. The notion of earlier hemorrhage control and blood product resuscitation is therefore attractive. Some systems have successfully implemented prehospital advanced resuscitative care (ARC) teams. Early identification of patients is key and is reliant on rapid decision making and communication. The purpose of this simulation study was to explore the feasibility of early identification of patients who might benefit from ARC in a typical US setting., Methods: We conducted a prospective observational/simulation study at a level I trauma center and two associated emergency medical service (EMS) agencies over a 9-month period. The participating EMS agencies were asked to identify actual patients who might benefit from the activation of a hypothetical trauma center-based ARC team. This decision was then communicated in real time to the study team., Results: Sixty-three patients were determined to require activation. The number of activations per month ranged from 2 to 15. The highest incidence of calls occurred between 4 pm to midnight. Of the 63 patients, 33 were transported to the trauma center. The most common presentation was with penetrating trauma. The median age was 27 years (interquartile range, 24-45 years), 75% were male, and the median Injury Severity Score was 11 (interquartile range, 7-20). Based on injury patterns, treatment received, and outcomes, it was determined that 6 (18%) of 33 patients might have benefited from ARC. Three of the patients died en-route to or soon after arrival at the trauma center., Conclusion: The prehospital identification of patients who might benefit from ARC is possible but faces challenges. Identifying strategies to adapt existing processes may allow better utilization of the existing infrastructure and should be a focus of future efforts., Level of Evidence: Prognostic/Epidemiologic, level III., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Piper betle leaves possess several ethnomedicinal properties and are immensely used in traditional medicinal practices in regions of Asian and African subcontinents. However, their effects in treating skeletal complications are least known. In this study, we evaluated cellular and molecular effects of betel leaf extract (BLE) and its major phytoconstituent, hydroxychavicol (HCV) in promoting osteogenesis in vitro and alleviating glucocorticoid induced osteoporosis (GIO) in vivo. Both BLE and HCV markedly stimulated osteoblast differentiation of C3H10T1/2 cells with increased expression of RUNX2 and osteopontin through the GSK-3β/β-catenin-signaling pathway. Also, oral administration of BLE and HCV in GIO rats resulted in restoration of bone mass and tissue microarchitecture. Thus, with our findings we conclude that BLE and HCV promote osteogenesis of C3H10T1/2 cells via the GSK-3β/β-catenin pathway and alleviate GIO in rats.

Abstract: Trauma remains a leading cause of death, and hemorrhage is the leading cause of preventable trauma deaths. Resuscitation strategies in trauma have changed dramatically over the last 20 years. In the pre damage control resuscitation (DCR) era, we used large volume crystalloid resuscitation and packed red blood cells as the primary resuscitative fluids. Now, a 1:1:1 ratio of packed red blood cells, fresh plasma, and platelets with minimal crystalloids is the preferred resuscitative strategy (DCR era). As we have changed how we resuscitate patients, the detrimental effects associated with large volume resuscitation have also changed. In this article, we review the effects of large volume blood product resuscitation, and where possible present a contrast between the pre-DCR era and the DCR era resuscitation strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Paratesticular leiomyosarcomas are uncommon malignant tumours that originate from smooth muscle and show aggressive tumour behaviour due to a high incidence of local recurrence and distant metastasis. Orbital metastasis is also rare and associated with a poor prognosis. Clinical suspicion plays an essential role in the diagnosis of orbital leiomyosarcoma because of its uncommon presentation. Comprehensive neuroimaging and histopathological work-up are warranted for definitive diagnosis and management. To date, surgical resection remains the best curative treatment. However, leiomyosarcomas are usually friable and unencapsulated, which makes surgery challenging. Also, whether adjunctive chemotherapy will alter the long-term prognosis remains to be determined. Herein, we report the case of a middle-aged man who presented with proptosis and decreased vision, who was subsequently diagnosed with metastatic orbital leiomyosarcoma from a primary paratesticular tumour. We performed orbital enucleation with negative margins. The patient is currently under systemic pazopanib chemotherapy., Learning Points: Orbital metastasis from paratesticular leiomyosarcoma is rarely encountered and shows aggressive behaviour.Clinical suspicion plays an essential role in diagnosing orbital leiomyosarcoma as this is an uncommon and atypical cause of proptosis and can be easily misdiagnosed by physicians.Curative surgical treatment should be considered due to the high recurrence rate., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2021.)

Boerhavia diffusa is a perennial herb belonging to the Nyctaginaceae family. This plant has been widely used in Indian traditional medicinal system to cure several human ailments. However, traditional use of this plant in the treatment and management of wounds has not been validated by any comprehensive scientific study. The present study was aimed to explore the in vitro and in vivo wound healing potential of methanol extract (ME) and chloroform extract (CE) from B. diffusa leaf and subsequent identification of the bioactive metabolites, which might be responsible for enhancement of wound healing property of the extracts. The study included in vitro cell viability and wound scratch assays as well as in vivo excision wound assays in rat models. Both ME and CE were analysed for their antioxidant properties and phenolics content. The gas chromatography-mass spectrometry analyses were performed for identification of bioactive metabolites present in the ME and CE. ME of B. diffusa leaf significantly enhanced viability and migration of human keratinocyte cells (HaCaT) as compared to the untreated and CE-treated groups. The topical application of ME of B. diffusa leaf in excision wound model significantly decreased the wound area by the 14th day (91%) as compared to control (22%) ( p  < 0.05). The GC-MS analysis revealed the presence of caffeic acid, ferulic acid and D-pinitol as the major bioactive metabolites in ME. These results suggest that ME of B. diffusa possesses significant wound healing potential, where D-pinitol and caffeic acid served as the lead constituent metabolites responsible for the healing., (© 2019 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Objective: Type 1 diabetes (T1DM) is associated with other autoimmune diseases (AIDs), which may have serious health consequences. The epidemiology of AIDs in T1DM is not well defined in adults with T1DM. In this cross-sectional cohort study, we sought to characterize the incident ages and prevalence of AIDs in adults with T1DM across a wide age spectrum., Research Design and Methods: A total of 1,212 adults seen at the Washington University Diabetes Center from 2011 to 2018 provided informed consent for the collection of their age, sex, race, and disease onset data. We performed paired association analyses based on age at onset of T1DM. Multivariate logistic regression was used to evaluate the independent effects of sex, race, T1DM age of onset, and T1DM duration on the prevalence of an additional AID., Results: Mean ± SD age of T1DM onset was 21.2 ± 14.4 years. AID incidence and prevalence increased with age. Female sex strongly predicted AID risk. The most prevalent T1DM-associated AIDs were thyroid disease, collagen vascular diseases, and pernicious anemia. T1DM age of onset and T1DM duration predicted AID risk. Patients with late-onset T1DM after 30 years of age had higher risks of developing additional AIDs compared with patients with younger T1DM onset., Conclusions: The prevalence of AIDs in patients with T1DM increases with age and female sex. Later onset of T1DM is an independent and significant risk factor for developing additional AIDs. Individuals who are diagnosed with T1DM at older ages, particularly women, should be monitored for other autoimmune conditions., (© 2018 by the American Diabetes Association.)