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We developed a bio-cheminformatics method, exploring disease inhibition mechanisms using machine learning-enhanced quantitative structure-activity relationship (ML-QSAR) models and knowledge-driven neural networks. ML-QSAR models were developed using molecular fingerprint descriptors and the Random Forest algorithm to explore the chemical spaces of Chalcones inhibitors against diverse disease properties, including antifungal, anti-inflammatory, anticancer, antimicrobial, and antiviral effects. We generated and validated robust machine learning-based bioactivity prediction models (https://github.com/RatulChemoinformatics/QSAR) for the top genes. These models underwent ROC and applicability domain analysis, followed by molecular docking studies to elucidate the molecular mechanisms of the molecules. Through comprehensive neural network analysis, crucial genes such as AKT1, HSP90AA1, SRC, and STAT3 were identified. The PubChem fingerprint-based model revealed key descriptors: PubchemFP521 for AKT1, PubchemFP180 for SRC, PubchemFP633 for HSP90AA1, and PubchemFP145 and PubchemFP338 for STAT3, consistently contributing to bioactivity across targets. Notably, chalcone derivatives demonstrated significant bioactivity against target genes, with compound RA1 displaying a predictive pIC50 value of 5.76 against HSP90AA1 and strong binding affinities across other targets. Compounds RA5 to RA7 also exhibited high binding affinity scores comparable to or exceeding existing drugs. These findings emphasize the importance of knowledge-based neural network-based research for developing effective drugs against diverse disease properties. These interactions warrant further in vitro and in vivo investigations to elucidate their potential in rational drug design. The presented models provide valuable insights for inhibitor design and hold promise for drug development. Future research will prioritize investigating these molecules for mycobacterium tuberculosis, enhancing the comprehension of effectiveness in addressing infectious diseases.

Background and Aim: There is no consensus on the appropriate use of mixtures of local anaesthetic drugs in various combinations for nerve blocks. We intended to compare short-acting lignocaine and long-acting ropivacaine as a mixture versus undiluted sequential injections on block characteristics of ultrasound-guided (USG) supraclavicular brachial plexus block for upper limb surgeries. Methods: A double-blinded randomised study was conducted on 64 adult patients scheduled for upper limb surgery who received 15 mL each of 2% lignocaine with adrenaline and 0.75% ropivacaine as a 1:1 mixture in the mixed group (Group M) or sequential injections in the sequential group (Group S) by using a USG technique. The primary outcome was the percentage of participants with complete four nerve sensory blocks at 10 minutes post block injection. Secondary outcomes were sensory and motor block characteristics till 30 minutes, total duration of analgesia, sensory and motor block, and complications. Results: Demographic characteristics and time taken for the procedure were similar. The percentage of participants with a complete four-nerve sensory block at 10 minutes was higher in Group S (69%) versus Group M (41%) (P = 0.04). Complete sensory and motor block rates were similar at 30 minutes. The block procedure time, total duration of analgesia, and sensory and motor block were similar in both groups. There were no major complications. Conclusion: Sequential lignocaine-ropivacaine, compared to the mixed injection technique, has a higher initial rate of sensory and motor block onset with a similar total block duration.

IntroductionThe current financing of public-sector district hospitals in India relies on historical budget allocations rather than actual utilization or healthcare needs. We utilized empirical data on healthcare delivery costs to develop the financing framework for these hospitals using a blended payment approach.MethodsThe primary data on cost of delivering services in 27 district hospitals across nine states of India was analysed along with indicators influencing the demand and supply of health services. Payment for outpatient, inpatient, and indirect services was assessed using the risk adjusted global budget, case-based bundled payment, and per-bed-global budget, respectively. Risk adjustment weights were computed by regressing the cost of outpatient care with demand and supply side factors which are likely to influence the utilization or the prices. Budget impact analysis was conducted to assess the fiscal implications of this payment approach, accounting for current care standards and two scenarios: upgrading district hospitals to Indian Public Health Standards (IPHS) or medical colleges.ResultsThe average annual budget for a district hospital in India is estimated at ₹326 million (US$3.35 million), ranging from ₹66 million to ₹2.57 billion (US$0.8–31.13 million). Inpatient care comprises the largest portion (78%) of the budget. Upgrading to IPHS-compliant secondary hospitals or medical colleges would increase average budgets by 131 and 91.5%, respectively.ConclusionImplementing a blended payment approach would align funding with healthcare needs, enhance provider performance, and support ongoing financing reforms aimed at strategic purchasing and universal health coverage.

Abstract Background In spite of the increased prevalence of Polycystic Ovary Syndrome in bilateral ovaries (PCOS) in females globally (~ 20%), the rate of decisive treatment is limited due to late and invasive diagnostics and the unavailability of stand-alone drugs against phenotypic symptoms associated with PCOS. This study aims at unravelling molecular mechanisms allied with this disorder and identifying genes and pathways that are altered causing PCOS as a pre-requisite need. Furthermore, this study intends at assessing the therapeutic potentials of Gymnema sylvestre phytocompounds mainly triterpene saponins against targeted proteins and helps in seeking exemplar drug candidates. The study is designed in 2 major parts—firstly identifying key proteins involved in pathophysiology by tracing back the deregulated genes in mRNA expression profiles of PCOS Patients obtained from GEO datasets database further compared and analysed by GEO2R Analyzer and significantly deregulated genes were subjected to PPI network, KEGG and GO analysis using STRING and ShinyGO tools. The second half of the study involved molecular docking its visualisation and in silico pharmacological analysis of imminent phytocompounds revealing plausible drug candidates. Results In the study, most implied deregulated genes were MRP gene family, ICT1, NDUFA12, VDAC3, APOO, TOMM5, COX6C, COX7B, EDN1 and EDN3 genes whose functional enrichment suggests flawed metabolism of proteins and damaged mitochondrial translation. With high binding affinity, less toxicity at higher dose level Lupeol, Beta-Amyrin, Beta-Elemene, Stigmasterol, Gymnestrogenin and Dammarane proves to be efficient drug candidates. Conclusion The findings of this study imply better understanding of the molecular mechanism of the disorder and encourage further clinical studies pertaining to medicinal natural phytocompounds of Gymnema sylvestre.

Background Due to the risk of viral transmission during in-person training, a shift toward online platforms is imperative in the current pandemic. Therefore, we compared the effectiveness of an in-person interactive course with a structurally similar online course designed to improve cognitive skills among clinical health professionals in arterial blood gas analysis, management of electrolyte imbalances, and approaches to mechanical ventilation in critically ill patients. Methods In an observational, outcome assessor-blinded, cohort trial, group A included participants enrolled prospectively in an online course, while group B included those who took part in an in-person course (retrospective arm). The primary objective was comparison of cognitive skills through a pre and post-test questionnaire. Statistical analysis was performed using Student t-test. Results In total, 435 participants were analyzed in group A, while 99 participants were evaluated in group B. The mean pre-test score was 9.48±2.75 and 10.76±2.42, while the mean post-test score was 11.94±1.90 (passing rate, 64.6%) and 12.53±1.63 (passing rate, 73.3%) in groups A and B, respectively. Group B scored significantly higher in both pre-test (P=0.001) and post-test evaluations (P=0.004). The improvement in post-test score was significantly greater (P=0.001) in group A (2.46±2.22) compared to group B (1.77±1.76). The medical specialties fared better in group B, while surgical specialties scored higher in group A. The pre-test vs. post-test scores exhibited a moderate correlation in both groups (P3.5 for most points in both groups. Conclusions The online teaching module exhibited a significant benefit in terms of participant sensitization and knowledge sharing.

BACKGROUND: Video-based teaching has become rapidly popular during the coronavirus disease 2019 (COVID-19) pandemic. The current study aimed to assess the efficacy of a hybrid video-based teaching module of oxygen therapy and critical care troubleshooting in nursing professionals managing COVID-19 patients in our institute. MATERIALS AND METHODS: A retrospective analytical study (pretest and posttest design) was conducted in our medical education department in March 2022 using the data from a workshop conducted on oxygen therapy and critical care area troubleshooting during COVID-19 patient management for 296 nursing professionals. A hybrid video-based teaching module was used. Pretest and posttest data were compared along with subgroup analysis. P value

ObjectivesThe National Mental Health Survey (NMHS) of India was undertaken with the objectives of (1) estimating the prevalence and patterns of various mental disorders in representative Indian population and (2) identifying the treatment gap, healthcare utilisation, disabilities and impact of mental disorders. This paper highlights findings pertaining to depressive disorders (DD) from the NMHS.DesignMultisite population-based cross-sectional study. Subjects were selected by multistage stratified random cluster sampling technique with random selection based on probability proportionate to size at each stage.SettingConducted across 12 states in India (representing varied cultural and geographical diversity), employing uniform, standardised and robust methodology.ParticipantsA total of 34 802 adults (>18 years) were interviewed.Main outcome measurePrevalence of depressive disorders (ICD-10 DCR) diagnosed using Mini International Neuropsychiatric Interview V.6.0.ResultsThe weighted prevalence of lifetime and current DD was 5.25% (95% CI: 5.21% to 5.29%, n=34 802) and 2.68% (95% CI: 2.65% to 2.71%, n=34 802), respectively. Prevalence was highest in the 40–59 age groups (3.6%, n=10 302), among females (3.0%, n=18 217) and those residing in cities with population >1 million (5.2%, n=4244). Age, gender, place of residence, education and household income were found to be significantly associated with current DD. Nearly two-thirds of individuals with DD reported disability of varying severity, and the treatment gap for depression in the study population was 79.1%. On an average, households spent INR1500/month (~US$ 23.0/month) towards care of persons affected with DD.ConclusionAround 23 million adults would need care for DD in India at any given time. Since productive population is affected most, DD entails considerable socioeconomic impact at individual and family levels. This is a clarion call for all the concerned stakeholders to scale up services under National Mental Health Programme in India along with integrating care for DD with other ongoing national health programmes.

Chronic inflammation and long-standing oxidative stress are potential predisposing factors for developing malignancies, including ovarian cancer (OVCA). Information on the association of ovarian chronic abnormal conditions, including polycystic ovarian syndrome (PCOS), with the development of OVCA is unknown. The goal of this study was to examine if polycystic ovarian conditions are associated with OVCA development. In the exploratory study, 3–4-year-old laying hens were randomly selected and examined for the presence of polycystic ovaries with cancer (PCOC). In the prospective study, hens were monitored by ultrasound scanning to detect the incidence of a polycystic ovaries and subsequent development of OVCA. Tissues from normal ovaries and PCOC were examined for macrophage infiltration, expression of interleukin-16, and superoxide dismutase 2. The exploratory study detected spontaneous PCOC at early and late stages in hens. PCOC in hens were accompanied with influx of macrophages (17.33 ± 2.26 in PCOC at the early stage and 24.24 ± 2.5 in PCOC at the late stage in 20 mm2 areas of tissue as compared with 6.77 ± 1.58 in normal hens). Expression of interleukin-16 was more than 2.5-fold higher and superoxide dismutase 2 was approximately 3-fold higher in PCOC hens than normal hens. The prospective study showed the development of OVCA in some hens with polycystic ovarian condition (PCO). PCOC development in hens was associated with chronic inflammation in the ovary. Laying hens may represent a potential model for the study of spontaneous PCOS and its long-term risk of PCOC development.

Development of a commercially successful animal vaccine is not only influenced by various immunological factors, such as type of antigen but also by formulation and delivery aspects. The latter includes the need for a vector or specific delivery system, the choice of route of administration and the nature of the target animal population and their habitat. This review describes the formulation and delivery aspects of various types of antigens such as killed microorganisms, proteins and nucleic acids for the development of efficacious and safe animal vaccines. It also focuses on the challenges associated with the different approaches that might be required for formulating and delivering species specific vaccines, particularly if their intended use is for improved animal management with respect to disease and/or reproductive control.