1O2 mediated synthesis of carbonyl substituted quinoline-2,4(1H,3H)-diones in visible light: 4CzIPN as a reusable photocatalyst.

A mild and eco-friendly method for the construction of carbonyl-containing quinoline-2,4(1H,3H)-diones has been developed in the presence of O2, photocatalyzed by reusable 4CzIPN in visible light. The method is transition-metal free, cost-effective, sustainable and gives the products in moderate to high yields.

1O2 Mediated Conversion of ß-Enaminonitriles to α-Keto Amides Photosensitized by Recyclable H2TPP in Visible Light.

We report a one-step approach for the conversion of ß-enaminonitriles to synthetically versatile α-keto amides in moderate to high yields under visible light irradiation photosensitized by porphyrins. The method is mild, cost-effective, and sustainable and requires air as the sole reagent/oxidant. The reaction is believed to proceed via an ene-type pathway initiated by 1O2, followed by dehydration, imine hydrolysis, and subsequent nucleophilic substitution of the cyanide group by amine. The method offers a broad substrate scope and has also been extended for synthesis of α-keto esters with aliphatic alcohols as nucleophiles. The porphyrin recovered after the reaction can be reused multiple times.

How Do We Manage Chronic Lymphocytic Leukemia in India.

PURPOSE OF REVIEW: Chronic lymphocytic leukemia was an ignored leukemia in India until a decade back, given its low prevalence and absence of novel drugs to treat it. Healthcare in India is heterogeneous, with variations in population, health systems, and reimbursement options. We have focused on opinions from three hemato-oncologists incorporating an opinion poll from 44 hemato-oncologists across India on the common issues in CLL to give an idea of the practice pan-India. RECENT FINDINGS: More CLL patients are being diagnosed in their early stages. There is an attempt to use prognostic and predictive markers in making shared decisions for managing CLL. There is still a role for chemoimmunotherapy (CIT) in India, given limited health insurance coverage. But with the availability of inexpensive generics, the patient preference for non-CIT options like Bruton's tyrosine kinase (BTK) inhibitors is palpable. The CLL scene in India is changing rapidly. With the wide availability of economical generic small molecule inhibitors, monoclonal antibodies, and coverage by social health insurance schemes, India is poised to cater to most CLL patient needs.

Genomic surveillance reveals early detection and transition of delta to omicron lineages of SARS-CoV-2 variants in wastewater treatment plants of Pune, India.

The COVID-19 pandemic has emphasized the urgency for rapid public health surveillance methods to detect and monitor the transmission of infectious diseases. The wastewater-based epidemiology (WBE) has emerged as a promising tool for proactive analysis and quantification of infectious pathogens within a population before clinical cases emerge. In the present study, we aimed to assess the trend and dynamics of SARS-CoV-2 variants using a longitudinal approach. Our objective included early detection and monitoring of these variants to enhance our understanding of their prevalence and potential impact. To achieve our goals, we conducted real-time quantitative polymerase chain reaction (RT-qPCR) and Illumina sequencing on 442 wastewater (WW) samples collected from 10 sewage treatment plants (STPs) in Pune city, India, spanning from November 2021 to April 2022. Our comprehensive analysis identified 426 distinct lineages representing 17 highly transmissible variants of SARS-CoV-2. Notably, fragments of Omicron variant were detected in WW samples prior to its first clinical detection in Botswana. Furthermore, we observed highly contagious sub-lineages of the Omicron variant, including BA.1 (~28%), BA.1.X (1.0-72%), BA.2 (1.0-18%), BA.2.X (1.0-97.4%) BA.2.12 (0.8-0.25%), BA.2.38 (0.8-1.0%), BA.2.75 (0.01-0.02%), BA.3 (0.09-6.3%), BA.4 (0.24-0.29%), and XBB (0.01-21.83%), with varying prevalence rates. Overall, the present study demonstrated the practicality of WBE in the early detection of SARS-CoV-2 variants, which could help track future outbreaks of SARS-CoV-2. Such approaches could be implicated in monitoring infectious agents before they appear in clinical cases.

Photoredox/Palladium Dual Catalysis for Site-Selective C-H Arylation and Acylation of N-Protected Carbazoles in Visible Light.

An unprecedented C-1 selective mono-arylation/acylation of N-protected carbazoles with aryl diazonium salts/glyoxylic acids has been developed in visible light by dual catalytic system comprising of Eosin Y and palladium acetate. The methodology has good functional group tolerance and high regioselectivity and furnishes the monosubstituted products in moderate to good yields at room temperature.

Selectivity for food in human ventral visual cortex.

Visual cortex contains regions of selectivity for domains of ecological importance. Food is an evolutionarily critical category whose visual heterogeneity may make the identification of selectivity more challenging. We investigate neural responsiveness to food using natural images combined with large-scale human fMRI. Leveraging the improved sensitivity of modern designs and statistical analyses, we identify two food-selective regions in the ventral visual cortex. Our results are robust across 8 subjects from the Natural Scenes Dataset (NSD), multiple independent image sets and multiple analysis methods. We then test our findings of food selectivity in an fMRI "localizer" using grayscale food images. These independent results confirm the existence of food selectivity in ventral visual cortex and help illuminate why earlier studies may have failed to do so. Our identification of food-selective regions stands alongside prior findings of functional selectivity and adds to our understanding of the organization of knowledge within the human visual system.

Efficacy of Arsenicum album 30C in the Prevention of COVID-19 in Individuals Residing in Containment Areas: A Prospective, Multicenter, Cluster-Randomized, Parallel-Arm, Community-Based, Open-Label Study.

OBJECTIVE: During the early part of the COVID-19 pandemic, non-pharmacologic interventions were the strategies for the prevention of severe acute respiratory syndrome coronavirus 2. The Ministry of Ayush, Govt. of India, had advised Arsenicum album 30C as a prophylactic to prevent COVID-19. This study was undertaken to evaluate the protective efficacy and safety of the Arsenicum album 30C. METHODS: We conducted a prospective, multicenter, cluster-randomized, parallel-arm, community-based, open-label study involving apparently healthy individuals residing in containment areas of 7 cities in India. Clusters are defined as the population residing in the containment areas, who are under restriction for movement. Forty-two clusters were randomly assigned at 2:1 to the Arsenicum album 30C group (30 clusters) or to the control group (12 clusters, which received no specific therapy). The medicine was given twice daily for 7 days. The primary outcome was the incidence of COVID-19, as per the case definition notified by the National Centre for Disease Control, Government of India, during 3-week follow-up period. RESULTS: The analysis included 32,186 individuals residing in 42 clusters (containment areas). A total of 22,693 individuals from 30 clusters received Arsenicum album 30C, and 9,493 individuals from 12 clusters were observed in the control group. The overall protective effect of the Arsenicum album 30C was 80.22% (95% confidence interval [CI], 71.16-86.44; 40 cases per 22,693 [6.04 per 10,000 person-weeks] in the Arsenicum album 30C group vs. 84 cases per 9,493 [29.78 per 10,000 person-weeks] in the control group). The protective effect of the Arsenicum album 30C against laboratory-confirmed COVID-19 was 68.22% (95% [CI], 49.64-80; 32 cases per 22,693 [4.83 per 10,000 person-weeks] in the Arsenicum album 30C group vs. 42 cases per 9,493 [14.93 per 10,000 person-weeks] in the control group). Adverse effects observed in both groups were mild and resolved without medication and sequelae. CONCLUSION: Homeopathic medicine Arsenicum album 30C was associated with a decrease in the incidence and provided some protection against COVID-19 as compared to nontreatment. Further randomized, double-blind, placebo-controlled trials may be conducted to validate the results of this study.In der Anfangszeit der COVID-19-Pandemie setzte man auf nicht-medikamentöse Massnahmen zur Prävention von Infektionen mit SARS-CoV-2 (Schweres-Akutes-Respiratorisches-Syndrom-Coronavirus 2). Das Ayush-Ministerium der indischen Regierung empfahl Arsenicum album 30C als Prophylaxe zur COVID-19-Prävention. Das Ziel dieser Studie war die Beurteilung der Schutzwirkung und Sicherheit von Arsenicum album 30C.An unserer prospektiven, multizentrischen, Cluster-randomisierten, unverblindeten Parallelgruppen-Bevölkerungs-Studie nahmen gesund erscheinende Bewohner von Sperrzonen in sieben indischen Städten teil. Die Cluster waren definiert als die Bewohnerpopulation je einer Sperrzone, für welche Mobilitätsbeschränkungen galten. 42 Cluster wurden per Randomisierung im Verhältnis 2:1 dem Arsenicum-album-30C-Arm (30 Cluster) oder dem Kontrollarm (12 Cluster, die keine spezifische Behandlung erhielten) zugeteilt. Das Medikament wurde sieben Tage lang zweimal täglich angewendet. Die primäre Zielgröße war die COVID-19-Inzidenz laut der vom National Centre for Disease Control der indischen Regierung bekannt gegebenen Falldefinition in einem Nachbeobachtungszeitraum von drei Wochen.Die Analyse umfasste 32.186 Personen in 42 Clustern (Sperrzonen). Insgesamt 22.693 Personen in 30 Clustern erhielten Arsenicum album 30C, und 9.493 Personen in 12 Clustern wurden als Kontrollarm beobachtet. Die Ergebnisse für Alter, Geschlecht und Komorbidität waren im Behandlungs- und Kontrollarm vergleichbar. Die Gesamt-Schutzwirkung von Arsenicum album 30C betrug 80,22 % (95-%-Konfidenzintervall [KI]: 71,16­86,44; 40 Fälle unter 22.693 [6,04 pro 10.000 Personen-Wochen] im Arsenicum-album-30C-Arm vs. 84 Fälle unter 9.493 [29,78 pro 10.000 Personen-Wochen] im Kontrollarm). Die Schutzwirkung von Arsenicum album 30C gegen laboranalytisch bestätigte COVID-19-Erkrankung betrug 68,22 % (95-%-KI: 49,64­80; 32 Fälle unter 22.693 [4,83 pro 10.000 Personen-Wochen] im Arsenicum-album-30C-Arm vs. 42 Fälle unter 9.493 [14,93 pro 10.000 Personen-Wochen] im Kontrollarm). Die beobachteten unerwünschten Wirkungen waren in beiden Gruppen von geringer Schwere und klangen ohne Medikation folgenlos ab.Das Homöopathikum Arsenicum album 30C war im Vergleich zur Nichtbehandlung mit einer Verringerung der Inzidenz assoziiert und bot gewissen Schutz vor COVID-19. Weitere randomisierte, doppelblinde, placebokontrollierte Studien könnten durchgeführt werden, um die Ergebnisse dieser Studie zu validieren.

Correlation of perceived stress with monthly cyclical changes in the female body.

Background: Women are liable to stress-related disorders as female sex hormone, estrogen has been indicated to be protective against stress disorders. The hormone level varies with different phases of menstrual cycle. Moreover, postmenopausal women are at risk for stress-related disorders. So this study was done to correlate the different phases of menstrual cycle with the perceived stress in different phases of monthly cycle. Methods: This study was conducted in the Department of Physiology, Shri Guru Ram Rai Institute of Medical and Health Sciences (SGRRIMHS), Dehradun. Four hundred girls in the age group of 18-26 years were selected for the study. The Perceived Stress Scale (PSS) questionnaire was circulated via Google forms after briefing them about the study. Informed consent was also taken. The menstrual history of the subjects was enquired by one-to-one interaction. The participants completed the PSS questionnaire twice in the same cycle. Data collected were statistically analyzed, using Independent t-test and Chi-square test and point biserial correlation test. Result: The analysis showed strong statistical association of PSS with two phases of menstrual cycle. The PSS score was higher in the late luteal and menstrual phase, while it was less in the late follicular phase (P < 0.05). Conclusion: The decreased oestrogen levels in the late luteal & menstrual phase are strongly associated with perceived stress in our study. Hormonal changes in the monthly cycles are related with stress, behavioral shift and many other physical changes in females. This information to the family physicians would be beneficial in counseling the females regarding various changes occurring during the menstrual cycle.

Ru-, Rh- and Ir-Catalyzed Enantioselective sp3 C-H Functionalization.

The development of novel methodologies that enable the construction of complex chiral molecular scaffolds in an atom and step-economic manner has always been an area of immense interest and significant synthetic value. The transition metal-catalyzed enantioselective sp3 C-H activation and functionalization reactions serve as an expeditious means for introducing diverse functionalities in a straightforward manner. However, controlling the chemo- and stereoselectivity of these reactions is a significant challenge owing to their ubiquity and low reactivity. In this review, we present a comprehensive account on the recent advances in inter- and intramolecular asymmetric sp3 C-H bond functionalization utilizing ruthenium, rhodium, and iridium catalysts and get insights into the mechanistic aspects of these transformations.

Clinical Implications of Herbal Supplements in Conventional Medical Practice: A US Perspective.

Herbal supplements are common complementary and alternative medicine (CAM) approaches with an ever-increasing use trend in the last two decades among the US population. Self-medication with herbal supplements which are promoted for general well-being, weight loss, immunity, and memory boost, and mental and physical health claims are very prevalent. There is a misperception that herbal supplements are harmless as they are prepared from natural sources. Unlike conventional drugs, the US Food and Drug Administration (FDA) does not regulate herbal supplements for premarketing purity and potency. Hence, there is a growing concern for health risks due to misbranded toxic ingredients, contaminants, adulterants, and herb-drug interactions (HDI) with co-administered drugs. The spectrum of pharmacological and toxicological effects of herbal supplements includes deranged lab results, allergic reactions, genotoxicity, carcinogenicity, teratogenicity, organ damage, and even fatality contributing to sizable emergency visits and hospitalizations in the US. The use of herbal supplements should be carefully monitored in high-risk groups such as pediatric and geriatric populations, pregnant women, breastfeeding mothers, immunocompromised patients, and surgical candidates. The deleterious health effects of herbal supplements are loosely addressed in conventional medical practice in part due to the limited knowledge of practitioners. This comprehensive narrative review aims to explore the clinical implications of herbal supplements in order to fill the knowledge gaps by summarizing scientific publications. It also highlights the pivotal roles physicians can play in minimizing the health risks of herbal supplements by encouraging patients to disclose usage through a non-judgmental approach, employing HDI screening tools, and reporting adverse reactions to FDA. Formal training of physicians, a standardized pharmacovigilance system, stricter regulation of the herbal industry, and more scientific studies are keys to establishing herbal safety and efficacy in clinical practice.

Photoredox Hydroxy-arylation of the Terminal Double Bond of N-Substituted 3-Methyleneisoindolin-1-ones in Visible Light.

Mild and efficient ruthenium-catalyzed hydroxy-arylation of the terminal double bond of N-substituted 3-methyleneisoindolin-1-ones is described. The reaction takes place with aryl diazonium salt as the arylating reagent and water as the hydroxyl source in visible light at ambient temperature. The strategy entails vicinal difunctionalization of alkene and enables construction of 3-benzyl-3-hydroxyisoindolin-1-one heterocyclic scaffolds in moderate to good yields. C-C and C-O bonds are formed in one pot without any external additive and oxidant through an in situ generation of a carbocation intermediate in green light.

Can Moxidectin Be an Anthelmintic Alternative for Trichuris trichiura and Strongyloides stercoralis: A Systematic Review.

Strongyloides stercoralis and Trichuris trichiura parasitic infections are two of the many neglected tropical diseases. These parasitic infections are of considerable public health relevance, particularly in resource-limited countries. Moxidectin, a well-established drug in veterinary medicine, is now a Food and Drug Administration (FDA) approved medication for human onchocerciasis. For the past five years, this medication has been under clinical trials to evaluate its efficacy and safetiness in other helminthic infections. Moxidectin might complement the already existing treatment and control of soil-transmitted helminthiasis (STH). Therefore, we systematically reviewed existing human interventional studies to evaluate the efficacy and safety of this medication when administered alone or in combination with other antiparasitic medications in order to achieve a cure.

Effect of Intravenous Calcium Gluconate on Prevention of Post Spinal Hypotension during Spinal Anaesthesia for Caesarean Section: A Randomized Double-Blind Controlled Study.

BACKGROUND: Calcium, a physiological ion, causes vasoconstriction and has a positive ionotropic action on heart. Its use to prevent post-spinal hypotension has been suggested but never formally evaluated for patients undergoing caesarean section. This study investigated the hemodynamic effects of calcium administration in parturients with the primary aim of comparing the incidence of post-spinal hypotension. METHODS: Sixty healthy full-term pregnant patients scheduled for caesarean section were randomly allocated to two equal groups to receive either calcium gluconate or normal Saline bolus over 20min by syringe infusion pump under electrocardiography monitoring immediately after the patient was turned supine following spinal anaesthesia. Blood pressure and heart rate were recorded at baseline, and at regular intervals following spinal. Maternal calcium levels were estimated before and after infusion. Neonatal blood gas analysis and calcium level were analyzed. Total mephentermine requirement was recorded in both groups. RESULTS: The heart rate values remained comparable to baseline value in group calcium gluconate while in group normal Saline, it decreased significantly at 8,12 and 16min. Blood pressure decreased significantly as compared to the baseline value from 4min onwards in both the groups. However, it was comparable in the two groups at all time points(0.622). Nineteen patients(63.33%) required mephentermine infusion in group calcium gluconate as compared to 23 patients(76.6%) in group normal Saline for maintenance of systolic blood pressure.(p=0.791) Umbilical venous pH (p=0.038) and partial pressure of carbon dioxide(p=0.038) were significantly better in group calcium gluconate. CONCLUSIONS: Calcium used for prophylaxis of hypotension in healthy parturients undergoing caesarean section reduced the vasopressor requirements and total mephenteramine dose, but the difference did not attain statistical significance.

Nonalcoholic Fatty Liver Disease: An Emerging Modern-Day Risk Factor for Cardiovascular Disease.

Nonalcoholic fatty liver disease (NAFLD), also named metabolic dysfunction-associated fatty liver disease (MAFLD), is a progressive disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. It is a clinically silent disease leading to multiple extra-hepatic complications/comorbidities. It is an independent risk factor for cardiovascular disease (CVD), increasing susceptibility to hypertension, atherosclerosis, arrhythmia, myocardial dysfunction, cardiac valve deformation, and venous thrombosis through putative mechanisms including systemic inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and altered lipid metabolism. Eventually, it increases the CVD prevalence, incident, and fatality, contributing to a huge health care burden. In fact, CVD is becoming the leading cause of mortality among patients with NAFLD. Other cardiometabolic risk factors coexisting with NAFLD may also accelerate the synergistic development of CVD, which warrants assessment targeting hypertension, diabetes mellitus (DM), obesity, and dyslipidemia to be an integral part of NAFLD care. Monitoring metabolic biomarkers (glucose, glycosylated hemoglobin [HbA1c], insulin, lipids, and lipoproteins), cardiovascular (CV) risk scores (American College of Cardiology/American Heart Association [ACC/AHA] or Framingham), and subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness [CIMT], and carotid plaque) are recommended for risk prediction and reduction. There is no universally accepted treatment for NAFLD, and lifestyle changes with weight loss of at least 10% are the mainstay of management. Combination therapy of ezetimibe and statins have a cardioprotective effect and help reduce liver fat. Despite being an emerging risk factor for CVD and its rapidly increasing pattern affecting a quarter of the global population, NAFLD remains overlooked and undetected, unlike the other traditional risk factors. Hence, we conducted a comprehensive narrative review to shed more light on the importance of screening CVD in NAFLD patients. PubMed indexed relevant articles published from 2002 to 2022 (20 years) were searched in April 2022 using medical subject headings (MeSH) as "nonalcoholic fatty liver disease" [Mesh] AND "cardiovascular diseases" [Mesh]. Evidence from 40 observational studies, three clinical trials, one case series, 45 narrative reviews, four systematic reviews and meta-analyses, three systematic reviews, and one meta-analysis were summarized on the epidemiologic data, pathophysiologic mechanisms, clinical features, diagnostic modalities, overlapping management, perceived challenges and health literacy regarding the CVD risk attributed to NAFLD.

Effectiveness of Arsenicum album 30C in Prevention of COVID-19 in Individuals Residing in Containment Zones of Delhi-A Prospective, Community-based, Parallel Cohort Study.

OBJECTIVE: This work was undertaken to evaluate the protective effect of Arsenicum album 30C against COVID-19. DESIGN: The work was designed as a prospective parallel cluster cohort study. INTERVENTION: Participants were enrolled in a homeopathy intervention (HI) cohort (who received Arsenicum album) or in a non-intervention (NI) cohort (who received no systematic intervention) from COVID-19 containment areas of Delhi. Individuals of age 5 years or above were given four medicated pills of Arsenicum album 30C, while those from 1 to 5 years old were given two medicated pills in each dose. RESULTS: The analysis included 10,180 individuals residing in 11 COVID-19 containment areas in Delhi, out of which 6,590 individuals were in the HI cohort and 3,590 individuals were in the NI cohort. The overall protective effect of Arsenicum album 30C was 83.43% (95% confidence interval [CI], 76.77 to 88.17): 45 cases per 6,590 (8.34 per 10,000 person-weeks) in the Arsenicum album 30C group versus 143 cases per 3,590 (45.01 per 10,000 person-weeks) in the NI cohort. The protective effect of Arsenicum album 30C against laboratory confirmed COVID-19 was 74.40% (95% CI, 55.08 to 85.41): 18 cases per 6,590 (3.32 per 10,000 person-weeks) in the Arsenicum album 30C group versus 38 cases per 3,590 (11.85 per 10,000 person-weeks) in the NI cohort. CONCLUSION: The use of Arsenicum album 30C was associated with some protection against probable and laboratory-confirmed COVID-19 in a containment-zone setting. Randomized controlled trials are needed to confirm or refute these results.

Programmed Death-Ligand 1 (PD-L1) Positivity and Factors Associated with Poor Prognosis in Patients with Gastric Cancer: An Umbrella Meta-Analysis.

Gastric cancer (GC) is one of the most common malignancies throughout the world with late diagnosis and poor prognosis. The expression of programmed death-ligand 1 (PD-L1) in GC is attributed to immune evasion and tumor progression. PD-L1 positivity has both predictive and prognostic biomarker potential. Aiming to summarize a large amount of research and to provide a definitive conclusion to the conflicting results on the prognostic significance of PD-L1 expression in GC, we performed an umbrella review based on existing meta-analyses which were published recently (2016-2021) and indexed in the PubMed database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in August 2021 to screen articles, and data extraction with quality assessment was performed on the selected meta-analyses. Review Manager (RevMan) 5.3 software was used to analyze the HR and OR with a 95% confidence interval (CI) among PD-L1 positive GC patients. We also assessed the between-study heterogeneity (I 2). Forest and Funnel plots were obtained, and a P-value of <0.05 was considered statistically significant. A total of 567 articles were screened, and we selected three meta-analyses with a total of 40 studies conducted over a period of 14 years. In our umbrella review, a total of 8,419 GC patients with an average PD-L1 positivity of 39% were analyzed. We found that PD-L1 positivity in GC patients is associated with poor prognosis (pooled HR =1.44, 95% CI: 1.24-1.68, P<0.00001) having higher mortality reducing the chances of overall survival (OS). However, there are no significant differences in PD-L1 expression among different lymph node (LN) metastases (OR=1.31, 95% CI: 0.98-1.74, P=0.07) and tumor, node, and metastasis (TNM) stages (OR=1.13, 95% CI: 0.80-1.58, P=0.50). Early identification of PD-L1 expression may help tailor cost-effective and targeted immunotherapy among GC patients. More research is needed to further understand how PD-L1 affects LN metastasis and tumor invasion.

Vitamin D: The Missing Nutrient Behind the Two Deadly Pandemics, COVID-19 and Cardiovascular Diseases.

The coronavirus (COVID-19) pandemic is claiming millions of lives and creating an additional burden on health care, which is already affected by the rise of non-communicable diseases (NCDs). The scientific community, on the other side, is enormously engaged with studies to best identify the characteristics of the virus and minimize its effect while supporting the fight to contain NCDs, mainly cardiovascular diseases (CVDs), which are contributing hugely to the global death toll. Hence, the roles of vitamin D in COVID-19 immunity and cardiovascular health are gaining traction recently.  This literature review will mainly focus on summarizing pertinent studies and scientific publications which highlight the association of vitamin D levels with the various outcomes of COVID-19 and CVDs. It will also address how low vitamin D correlates with the epidemiology of CVDs and the inflammatory mechanisms attributed to COVID-19 severity. We believe that our review may open up hindsight perspectives and further discussions among the physicians in tapping the potential of vitamin D supplementation to tackle the morbidity, mortality, and health care cost of the two deadly diseases, COVID-19 and CVDs.

Pd and photoredox dual catalysis assisted decarboxylative ortho-benzoylation of N-phenyl-7-azaindoles.

The directing group assisted decarboxylative ortho-benzoylation of N-aryl-7-azaindoles with α-keto acids has been achieved by synergistic visible light promoted photoredox and palladium catalysis. The approach tenders rapid entry to aryl ketone architectures from simple α-keto acid precursors via the in situ generation of a benzoyl radical intermediate. The transformation provides a range of ortho-benzoylated N-aryl-7-azaindoles, with excellent site-selectivity and good functional group compatibility under mild reaction conditions. Biological target predictions indicate that these molecules may serve as potential anti-cancer and anti-viral agents.

Insights of ligand binding in modeled h5-HT1A receptor: homology modeling, docking, MM-GBSA, screening and molecular dynamics.

The pharmacologically characterized receptor subtype of the serotonin family, the 5HT1A receptor is implicated in the pathophysiology and treatment of depression and anxiety-related disorders. Being the most extensively targeted receptor for developing novel antidepressants and anxiolytics, a near-ideal theoretical model can aid in high-throughput screening of promising drug candidates. However, the design of potential drug candidates suffers owing to a lack of complete structural information. In this work, homology models of 5-HT1A receptor are generated using two distinct alignments (CW and PSTA) and model building methods (KB and EB). The developed models are validated for virtual screening using a ligand dataset of agonists and antagonists. The best-suited model was efficient in discriminating agonist/antagonist binding. Correlation plots between pKi and docking (R2agonist≥ 0.6, R2antagonist≥ 0.7) and MM-GBSA dG bind values (R2agonist≥ 0.5, R2antagonist≥ 0.7) revealed optimum corroboration between in vitro and in silico outcomes, which further suggested the usefulness of the developed model for the design of high-affinity probes for the neurological disorders.Communicated by Ramaswamy H. Sarma.

Deep Vein Thrombosis in Intravenous Drug Users: An Invisible Global Health Burden.

The prevalence of intravenous drug use has increased in the past decade and it represents an important risk factor for deep vein thrombosis. Intravenous drug use is a global problem, with the main culprit being heroin. Peer pressure and poverty in high-risk groups such as sex workers, females, and young adults raise the risk of intravenous drug use, which expresses itself in the form of venous thromboembolism eventually. Deep vein thrombosis typically manifests itself eight years after the initial intravenous drug administration, rendering it a silent killer. Aiming to review and summarize existing articles in this context, we performed an exhaustive literature search online on PubMed and Google Scholar indexes using the keywords "Deep Venous Thrombosis (DVT)" and "Intravenous Drug Users (IVDU)." English articles that addressed epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, management, and outcomes of DVT, including those in IVDU, were selected and analyzed. The pathogenesis of DVT development in IVDU is mainly attributed to the interplay of trauma to the vessel by repeated injection and the injected drug itself. The right-sided femoral vein is the most common vein affected. Prevalent clinical presentations include local pain, swelling, and redness with typical systemic symptoms including fever, cough, dyspnea, and chest pain on top of addiction features. There appeared to be a delay in reporting symptoms, which was most likely due to the social stigma attached to IVDU. There are over 50 conditions that present with swollen and painful limbs comparable to DVT in IVDU, making precise diagnosis critical for timely treatment. Venous ultrasound is the method of choice for diagnosing DVT. Extended anticoagulant therapy with low-molecular-weight heparin combined with warfarin is the recommended treatment. Intravenous drug abusers having DVT are affected by multiple complications and poorer outcomes such as slower recovery, recurrent venous thromboembolism (VTE), and a longer hospital stay, which put them at higher risk of morbidity, mortality, reduced productivity, and economic burden.