Epidemiology of rare bacterial, parasitic, and fungal pathogens in India.

Rare human pathogens are infrequently observed clinically but can lead to undiagnosed infections, delays in treatment, severe complications, including death. Traditional diagnostic tools cannot routinely detect rare infections in public health settings. This study focuses on the incidence and outcomes of rare pathogenic microorganisms over 13 years (2010-2022) using PubMed database to obtain epidemiological data on rare bacterial, parasitic, and fungal infections in hospitals throughout India. A total of 974 articles were screened using case studies, datasets, comments, classical articles, letters, editorials, observational studies, and meta-analyses. Our analysis identified 28 rare bacteria, six parasites, and five fungal species infections in India. Fatal cases were associated with rare bacterial and fungal infections, including two from pan-drug-resistant bacteria (both from the Myroides genus). A total of 10 bacterial species displayed multi-drug resistance; one was extensively drug-resistant, and eight remained unclassified. Of the 83 patients with these rare infections, the mortality was ∼8.4% (seven of 83). Considering drug resistance and high mortality, prompt diagnosis of rare pathogens is crucial to controlling their spread. An increased awareness within the Indian health care system focusing on diagnostics, record keeping, and data sharing will be necessary to enhance surveillance.

Avocado-derived extracellular vesicles loaded with ginkgetin and berberine prevent inflammation and macrophage foam cell formation.

Atherosclerosis, a chronic inflammatory disease of aorta, remains the major cause of morbidity and mortality among cardiovascular disease patients. Macrophage foam cell formation and inflammation are critically involved in early stages of atherosclerosis, hence chemopreventive targeting of foam cell formation by nutraceuticals may be a promising approach to curbing the progression of atherosclerosis. However, many nutraceuticals including berberine and ginkgetin have low stability, tissue/cell penetration and bioavailability resulting in inadequate chemotherapeutic effects of these nutraceuticals. We have used avocado-derived extracellular vesicles (EV) isolated from avocado (EVAvo ) as a novel carrier of nutraceuticals, in a strategy to alleviate the build-up of macrophage foam cells and expression of inflammatory genes. Our key findings are: (i) Avocado is a natural source of plant-derived EVs as shown by the results from transmission electron microscopy, dynamic light scattering and NanoBrook Omni analysis and atomic force microscopy; (ii) EVAvo are taken up by macrophages, a critical cell type in atherosclerosis; (iii) EVAvo can be loaded with high amounts of ginkgetin and berberine; (iv) ginkgetin plus berberine-loaded EVAvo (EVAvo(B+G) ) suppress activation of NFκB and NLRP3, and inhibit expression of pro-inflammatory and atherogenic genes, specifically Cd36, Tnfα, Il1ß and Il6; (v) EVAvo(B+G) attenuate oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation and (vi) EVAvo(B+G) inhibit oxLDL uptake but not its cell surface binding during foam cell formation. Overall, our results suggest that using EVAvo as a natural carrier of nutraceuticals may improve strategies to curb the progression of atherosclerosis by limiting inflammation and pro-atherogenic responses.

Role of riboflavin deficiency in malaria pathophysiology.

The emergence of resistance against antimalarials and insecticides poses a significant threat to malaria elimination strategies. It is crucial to explore potential risk factors for malaria to identify new targets and alternative therapies. Malnutrition is a well-established risk factor for malaria. Deficiencies of micronutrients such as vitamin A, zinc, iron, folic acid, and phenotypic measures of malnutrition, such as stunting and wasting, have been studied extensively in the context of malaria. Vitamin B2, also known as riboflavin, is a micronutrient involved in maintaining cellular homeostasis. Riboflavin deficiency has been shown to have an inverse correlation with malarial parasitaemia. This article reviews the role of riboflavin in maintaining redox homeostasis and probes how riboflavin deficiency could alter malaria pathogenesis by disrupting the balance between oxidants and antioxidants. Though riboflavin analogues have been explored as antimalarials, new in vivo and patient-based research is required to target riboflavin-associated pathways for antimalarial therapy.

Rate of response to initial antiretroviral therapy according to level of pre-existing HIV-1 drug resistance detected by next-generation sequencing in the strategic timing of antiretroviral treatment (START) study.

OBJECTIVES: The main objective of this analysis was to evaluate the impact of pre-existing drug resistance by next-generation sequencing (NGS) on the risk of treatment failure (TF) of first-line regimens in participants enrolled in the START study. METHODS: Stored plasma from participants with entry HIV RNA >1000 copies/mL were analysed using NGS (llumina MiSeq). Pre-existing drug resistance was defined using the mutations considered by the Stanford HIV Drug Resistance Database (HIVDB v8.6) to calculate the genotypic susceptibility score (GSS, estimating the number of active drugs) for the first-line regimen at the detection threshold windows of >20%, >5%, and >2% of the viral population. Survival analysis was conducted to evaluate the association between the GSS and risk of TF (viral load >200 copies/mL plus treatment change). RESULTS: Baseline NGS data were available for 1380 antiretroviral therapy (ART)-naïve participants enrolled over 2009-2013. First-line ART included a non-nucleoside reverse transcriptase inhibitor (NNRTI) in 976 (71%), a boosted protease inhibitor in 297 (22%), or an integrase strand transfer inhibitor in 107 (8%). The proportions of participants with GSS <3 were 7% for >20%, 10% for >5%, and 17% for the >2% thresholds, respectively. The adjusted hazard ratio of TF associated with a GSS of 0-2.75 versus 3 in the subset of participants with mutations detected at the >2% threshold was 1.66 (95% confidence interval 1.01-2.74; p = 0.05) and 2.32 (95% confidence interval 1.32-4.09; p = 0.003) after restricting the analysis to participants who started an NNRTI-based regimen. CONCLUSIONS: Up to 17% of participants initiated ART with a GSS <3 on the basis of NGS data. Minority variants were predictive of TF, especially for participants starting NNRTI-based regimens.

Drug Repurposing: Insights into Current Advances and Future Applications.

Drug development is a complex and expensive process that involves extensive research and testing before a new drug can be approved for use. This has led to a limited availability of potential therapeutics for many diseases. Despite significant advances in biomedical science, the process of drug development remains a bottleneck, as all hypotheses must be tested through experiments and observations, which can be time-- consuming and costly. To address this challenge, drug repurposing has emerged as an innovative strategy for finding new uses for existing medications that go beyond their original intended use. This approach has the potential to speed up the drug development process and reduce costs, making it an attractive option for pharmaceutical companies and researchers alike. It involves the identification of existing drugs or compounds that have the potential to be used for the treatment of a different disease or condition. This can be done through a variety of approaches, including screening existing drugs against new disease targets, investigating the biological mechanisms of existing drugs, and analyzing data from clinical trials and electronic health records. Additionally, repurposing drugs can lead to the identification of new therapeutic targets and mechanisms of action, which can enhance our understanding of disease biology and lead to the development of more effective treatments. Overall, drug repurposing is an exciting and promising area of research that has the potential to revolutionize the drug development process and improve the lives of millions of people around the world. The present review provides insights on types of interaction, approaches, availability of databases, applications and limitations of drug repurposing.

Exploration of the Potential Application of Banana Peel for Its Effective Valorization: A Review.

The production of banana peel by the food-processing industry is substantial and the disposal of this waste material has become a matter of concern. However, recent studies have demonstrated that banana peel is a rich source of biologically active compounds that can be transformed into valuable products. This review aims to explore the potential of converting banana peel into valuable products and provides a comprehensive analysis of the physical and chemical composition of banana peel. Additionally, the utilization of banana peel as a substrate to produce animal feed, bio fertilizer, dietary fibers, renewable energy, industrial enzymes, and nanomaterials has been extensively studied. According to the researches that has been done so far, it is clear that banana peel has a broad range of applications and its effective utilization through biorefinery strategies can maximize its economic benefits. Based on previous studies, A plan for feasibility of a banana peel biorefinery has been put up which suggest its potential as a valuable source of renewable energy and high-value products. The utilization of banana peel through biorefinery strategies can provide a sustainable solution for waste management and contribute to the development of a circular economy.

Recent Trends of Vibrational Spectroscopy in Examination of Sequence of Strokes: Application in Forensic Documents Examination.

Chronological sequencing of ink strokes has been a challenge for the Forensic Document Examiners (FDE). Document forgery is a common practice and the ability to determine the order in which the primary and the subsequent strokes have been made is crucial for establishing the authenticity of a document. Lately, the prime thrust of establishing the sequence of intersection of ink lines has shifted from an optical to an analytical approach. Several studies have been reported to explore the use of spectroscopic techniques in determining the sequence of ink strokes made using gel pen inks, ball pen inks, fountain inks, printed ink, stamp inks, etc. The present study aims to study the existing trends in examining the sequence of ink strokes or crossing of lines using vibrational spectroscopic techniques viz. Infrared and Raman Spectroscopy. Several interesting inferences have been drawn, such as factors like paper type and time gap between the application of two intersecting strokes does not influence the determination of the sequence of inter-crossing strokes. A trend of using two analytical techniques viz. VSC, AFM, HPTLC, TOF-SIMS, and SEM/EDX with vibrational spectroscopic techniques have been found to provide reliable results. The study also suggests future research directions in the field, aiming to address challenges faced by the FDEs and provide accurate and reliable solutions for document examination.

HuR and Its Interactions with Noncoding RNAs in Gut Epithelium Homeostasis and Diseases.

The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and its homeostasis is tightly controlled by numerous factors at multiple levels. The RNA-binding protein HuR (human antigen R) is intimately involved in many aspects of gut mucosal pathobiology and plays an important role in maintaining integrity of the intestinal epithelium by regulating stability and translation of target mRNAs. Nonetheless, deregulation of HuR expression and altered binding affinity of HuR for target transcripts occur commonly in various gut mucosal disorders. In this review, we highlight the essential role of HuR in the intestinal epithelium homeostasis and discuss recent results that interactions between HuR and noncoding RNAs (ncRNAs), including circular RNAs, long ncRNAs, small vault RNAs, and microRNAs, influence gut mucosal regeneration and regulate barrier function in various pathophysiological conditions. These exciting discoveries advance our knowledge of HuR biological function in the gut mucosa and also create a fundamental basis for developing novel therapies to protect intestinal epithelial integrity in critically ill patients.

Relationship Between Body Mass Index and Body Fat Percentage in a Group of Indian Participants: A Cross-Sectional Study From a Tertiary Care Hospital.

Background Body mass index (BMI) is an important indicator of overweight and obesity. Unlike BMI, body fat percentage (BF%) can be utilized to estimate body composition regardless of weight and height. The association between BMI and BF%, as well as the impact of age and gender, may help estimate the prevalence of obesity more clearly. This study aimed to assess the relationship between BMI and BF%, examine the effect of age and gender on this relationship, and establish the linearity/curvilinearity of this relationship. Methodology The body composition analysis of 1,150 participants in various institutional events (institution foundation day) during 2019 and 2023 was performed using the Accuniq bio-electrical impedance analyzer (BIA) (Accuniq, Netherlands). The participants included undergraduate, postgraduate medical, and PhD students, as well as employees of All India Institute of Medical Sciences, New Delhi. Age groups were categorized as under 17 years, young adults (18-25 years), adults (26-44 years), middle-aged adults (45-59 years), and older adults (≥60 years). Pearson's correlation coefficient (r) was used for analyzing the relationship between BMI and BF%. To assess the effect of age and gender on this relationship, multiple regression analysis was applied, and polynomial regression was applied to test its linearity. The data were analyzed using SPSS version 25 (IBM Corp., Armonk, NY, USA). Results Males made up a larger proportion of the participants (56.3%; 647). The mean age of the participants was 36.5 ± 13.6 years. The mean BMI and BF% were 24.7 ± 4.0 kg/m2 and 29.1 ± 8.7%, respectively. A significant and moderate positive correlation (r = 0.630, p < 0.01) was observed between BMI and BF%. The mean ± SD of BMI and BF% had a directly proportional relationship with age. Among both genders, females showed a greater correlation (r = 0.852). Both age and gender had a significant effect on this relationship, with gender impacting more than age (ß = 0.488, p < 0.000). The curvilinear nature of the relationship between BMI and BF% was demonstrated with the female model showing a more precise fit (R2 = 0.72, standard error of the estimate = 3.3%). Conclusions The relationship between BMI and BF% was significant and positive in this group of Indians. This relationship was significantly impacted by age and gender and was curvilinear in nature. Females had a higher association than males between BMI and BF%. The study suggests that BMI, BF%, and the effects of age and gender should be taken into consideration when predicting obesity.

Exploring the effect of surfactants on the interactions of manganese dioxide nanoparticles with biomolecules.

Interactions of manganese dioxide nanoparticles (MnO2 NPs) with vital biomolecules namely deoxyribonucleic acid (DNA) and serum albumin (BSA) have been studied in association with different surfactants by using fluorescence (steady state, synchronous and 3D), UV-visible, resonance light scattering (RLS), dynamic light scattering (DLS), and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The esterase activity of serum albumin was tested in associations with MnO2 NPs and surfactants. The antioxidant potential of prepared NPs was also evaluated (DPPH method). Gel electrophoresis was carried out to analyze the effect of MnO2 NPs and surfactants on DNA. Presence of CTAB, Tween 20, DTAB and Tween 80 enhanced nanoparticle-protein binding. Tween 20 based nanoparticle systems showed long-term stability and biocompatibility. The quenching of BSA fluorescence emission in presence of MnO2 NPs alone and along with Tween 20 revealed stronger association of nanoparticles with proteins. Enhancement in the esterase activity (BSA) was observed in the presence of Tween 20. Furthermore, radical scavenging activity showed highest antioxidant potential in presence of Tween 20. The enthalpy and entropy assessment for protein-NPs association showed the predominance of Vander Waals interactions and hydrogen bonding. The synchronous fluorescence analysis highlighted the involvement of tryptophan (Trp) in the MnO2 NPs-protein interactions. The study evaluates the influence of surfactant on the associations of MnO2 NPs with the essential biomolecules. The findings can be crucially utilized in designing biocompatible MnO2 formulations for long term applications.Communicated by Ramaswamy H. Sarma.

Topical Anti-ulcerogenic Effect of the Beta-adrenergic Blockers on Diabetic Foot Ulcers: Recent Advances and Future Prospectives.

BACKGROUND: Patients with diabetes suffer from major complications like Diabetic Retinopathy, Diabetic Coronary Artery Disease, and Diabetic Foot ulcers (DFUs). Diabetes complications are a group of ailments whose recovery time is especially delayed, irrespective of the underlying reason. The longer duration of wound healing enhances the probability of problems like sepsis and amputation. The delayed healing makes it more critical for research focus. By understanding the molecular pathogenesis of diabetic wounds, it is quite easy to target the molecules involved in the healing of wounds. Recent research on beta-adrenergic blocking drugs has revealed that these classes of drugs possess therapeutic potential in the healing of DFUs. However, because the order of events in defective healing is adequately defined, it is possible to recognize moieties that are currently in the market that are recognized to aim at one or several identified molecular processes. OBJECTIVE: The aim of this study was to explore some molecules with different therapeutic categories that have demonstrated favorable effects in improving diabetic wound healing, also called the repurposing of drugs. METHOD: Various databases like PubMed/Medline, Google Scholar and Web of Science (WoS) of all English language articles were searched, and relevant information was collected regarding the role of beta-adrenergic blockers in diabetic wounds or diabetic foot ulcers (DFUs) using the relevant keywords for the literature review. RESULT: The potential beta-blocking agents and their mechanism of action in diabetic foot ulcers were studied, and it was found that these drugs have a profound effect on diabetic foot ulcer healing as per reported literatures. CONCLUSION: There is a need to move forward from preclinical studies to clinical studies to analyze clinical findings to determine the effectiveness and safety of some beta-antagonists in diabetic foot ulcer treatment.

A Recent Advance on Phytochemicals, Nutraceutical and Pharmacological Activities of Buckwheat.

Buckwheat, a member of the Fagopyrum genus in the Polygonaceae family, is an ancient pseudocereal with noteworthy nutraceutical properties that have been relatively less explored. This crop holds great promise for the future due to its gluten-free protein, wellbalanced amino acid profile, and the presence of bioactive flavonoids that promote good health. With its gluten-free nature and a combination of beneficial nutritional components, buckwheat shows significant potential for a variety of health benefits. The objective of the present review aims to explore various nutritional and pharmacological properties of buckwheat. With the help of various search engines Pubmed, Google and Semantic Scholar, research and review papers. Data were analyzed and summarized in a comprehensive review. A fascinating spectrum of nutritional and pharmacological activities of common buckwheat and Tartary buckwheat were explored such as antidiabetic, anti-inflammatory, neurological disorders, antiobesity, anticancer, cardiovascular agents and many more. This review provides a concise overview of the current understanding of the chemical composition of both common buckwheat and Tartary buckwheat and the captivating spectrum of pharmacological activity and also underscoring their immense potential for future advancements.

Acute Cerebellar Ataxia: A Rare Association of Hepatitis a Infection.

Acute cerebellar ataxia (ACA) is a self-limited syndrome that is frequently post-infectious, most commonly following Varicella infection having an autoimmune mechanism. ACA is the commonest cause of childhood ataxia. We report a 14-year-old male who presented with acute onset wide-based gait and slurring of speech with dysdiadochokinesia, incoordination of voluntary movements, pendular knee jerk, and intentional tremors. He had worsening transaminitis and rising bilirubin during his hospital course and was subsequently found to be hepatitis A virus (HAV) immunoglobulin-M antibody positive. Thus, we report a case of ACA with HAV infection who developed jaundice after three weeks of onset of ataxia, a rarity that has not been reported so far in medical literature.

High-Performance Thermomagnetic Gd-Si-Ge Alloys.

Exploring low-grade waste heat energy harvesting is crucial to address increasing environmental concerns. Thermomagnetic materials are magnetic phase change materials that enable energy harvesting from low-temperature gradients. To achieve a high thermomagnetic conversion efficiency, there are three main material requirements: (i) magnetic phase transition near room temperature, (ii) substantial change in magnetization with temperature, and (iii) high thermal conductivity. Here, we demonstrate a high-performance Gd5Si2.4Ge1.6 thermomagnetic alloy that meets these three requirements. The magnetic phase transition temperature was successfully shifted to 306 K by introducing Ge doping in Gd5Si4, and a sharper and more symmetric magnetization behavior with saturation magnetization of Mmax = 70 emu/g at a 2 T magnetic field was achieved in the ferromagnetic state. The addition of SeS2, as a low-temperature sintering aid, to the Gd-Si-Ge alloy improved the material's density and thermal conductivity by ∼45 and ∼275%, respectively. Our results confirm that the (Gd5Si2.4Ge1.6)0.9(SeS2)0.1 alloy is a suitable composite material for low-grade waste heat recovery in thermomagnetic applications.

Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies.

Aging accompanied by several age-related complications, is a multifaceted inevitable biological progression involving various genetic, environmental, and lifestyle factors. The major factor in this process is oxidative stress, caused by an abundance of reactive oxygen species (ROS) generated in the mitochondria and endoplasmic reticulum (ER). ROS and RNS pose a threat by disrupting signaling mechanisms and causing oxidative damage to cellular components. This oxidative stress affects both the ER and mitochondria, causing proteopathies (abnormal protein aggregation), initiation of unfolded protein response, mitochondrial dysfunction, abnormal cellular senescence, ultimately leading to inflammaging (chronic inflammation associated with aging) and, in rare cases, metastasis. RONS during oxidative stress dysregulate multiple metabolic pathways like NF-κB, MAPK, Nrf-2/Keap-1/ARE and PI3K/Akt which may lead to inappropriate cell death through apoptosis and necrosis. Inflammaging contributes to the development of inflammatory and degenerative diseases such as neurodegenerative diseases, diabetes, cardiovascular disease, chronic kidney disease, and retinopathy. The body's antioxidant systems, sirtuins, autophagy, apoptosis, and biogenesis play a role in maintaining homeostasis, but they have limitations and cannot achieve an ideal state of balance. Certain interventions, such as calorie restriction, intermittent fasting, dietary habits, and regular exercise, have shown beneficial effects in counteracting the aging process. In addition, interventions like senotherapy (targeting senescent cells) and sirtuin-activating compounds (STACs) enhance autophagy and apoptosis for efficient removal of damaged oxidative products and organelles. Further, STACs enhance biogenesis for the regeneration of required organelles to maintain homeostasis. This review article explores the various aspects of oxidative damage, the associated complications, and potential strategies to mitigate these effects.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

An Overview of Security Materials in Banknotes and Analytical Techniques in Detecting Counterfeits.

Counterfeiting or forged imitation of banknotes is a perpetual practice engulfing global economies. This not only poses challenges for the material scientists to come forth with advanced security materials but also demands veracious forensic examination to detect counterfeits. The present article pursues novel efforts in summarizing a study that lays focus on the recent optical and analytical examinations being used for the characterization and detection of chemical profiles of authentic and counterfeited banknotes. The article briefs the trends in banknote materials, security paper manufacturing process, security inks used for printing, and types of the security printing process in banknote practices. Reported literature shows the introduction of new anti-counterfeiting materials viz. magnetically-responsive photonic anti-counterfeiting watermarks, and fluorescent nanoparticles that can be used as anti-counterfeiting inks, anti-stokes inks, metameric inks, etc. Analytical techniques such as IR spectroscopy, Raman spectroscopy, Mossbauer spectroscopy, X-ray diffraction, X-ray fluorescence, LIBS, XRF, ELDI-MS, EASI/DESI-MS, HPLC, VSC, AFM, etc. in conjunction with different chemometrics approaches have been critically discussed. The study also presents the future scope in banknote examination like the use of hyper spectral imaging and sensor-based counterfeit detection systems.

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Study on Effects of Sublingual Immunotherapy in Allergic Rhinitis Patients.

Allergic Rhinitis is one of the most common allergic disease and characterized by sneezing, rhinorrhea, nasal congestion and nasopharyngeal itching. The initial management includes pharmacological treatment and the patients who are refractory to pharmacological treatment are then reffered for immunotherapy. SLIT has been widely used for treatment of allergic rhinitis and has proven its clinical efficacy. The objective of the present study was to assess the clinical effects, safety and tolerability of sublingual immunotherapy (SLIT) among the patients suffering from allergic rhinitis. The study was conducted from Aug 2018 to April 2021 and 40 patients with convincing history, positive skin prick test to one or more allergen extracts were recruited. SLIT was conducted with antigens (mix), namely dust mites, tree pollens, grass pollens and weed pollens in patients of allergic rhinitis for 1 year. There was significant improvement in quality of life and symptoms severity(Nasal and Non-Nasal) from base line to end of 1 year. SLIT lowers the total IgE, absolute eosinophilic count and medication requirement. Sublingual Immunotherapy for specific allergens decreases clinical symptoms in patients with allergic rhinitis and sensitivity to multiple allergen.

Strategic Approaches to Improvise Peptide Drugs as Next Generation Therapeutics.

In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers' attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird's-eye view to researchers aiming to develop peptides with therapeutic applications.