Search

Abstract Background To investigate the effects of peptide-based substrate competitive inhibitors of GSK-3β (GSK-3βi) on promoting odontogenic differentiation of human dental pulp stem cells (hDPSCs). Methods The biocompatibility and proliferation of hDPSCs treated with GSK-3βi peptides (pS9, LRP 6a, L803, and L803-mts) were evaluated using the tetrazolium reduction assay and cell counting kit-8 assay, respectively. The differentiation of hDPSCs following peptide treatment was determined using the alkaline phosphatase assay (ALP), calcium mineralization (alizarin red staining), and quantification of mRNA expression of differentiation markers via quantitative real-time polymerase chain reaction. The accumulation of β-catenin in the nucleus of GSK3-βi-treated hDPSCs was determined using immunofluorescence staining. The effect of peptide treatment on hDPSC migration was characterized using the transwell assay. Results All tested concentrations of the peptides were found to be biocompatible with the hDPSCs, with no significant difference compared to the control (p > 0.05). The peptides had no effect on the proliferation of hDPSCs compared to the control (p > 0.05). However, all the tested peptides significantly increased ALP activity and calcium deposition in a dose-dependent manner (p

Abstract We present the first proof-of-concept application to decay processes at higher perturbative orders of loop-tree duality (LTD) causal unitary, a novel methodology that exploits the causal properties of vacuum amplitudes in the LTD and is directly well-defined in the four physical dimensions of the space-time. The generation of loop- and tree-level contributions to the differential decay rates from a kernel multiloop vacuum amplitude is shown in detail, and explicit expressions are presented for selected processes that are suitable for a lightweight understanding of the method. Specifically, we provide a clear physical interpretation of the local cancellation of soft, collinear and threshold singularities, and of the local renormalisation of ultraviolet singularities. The presentation is illustrated with numerical results that showcase the advantages of the method.

In the remote healthcare industry data analytics denotes the computerization of collection, processing, and exploring complicated data to acquire finer perceptions and validate healthcare practitioners to produce familiar decisions. Healthcare basics in the modern age are vital challenges specifically in developing countries owing to the shortfall of difficult hospitals and medical professionals. As fuzzy systems have reformed several areas of work, health has also made the most of it. In this paper, the purpose of the study is to introduce a novel and intelligent remote healthcare system based on modern technologies like the Internet of things (IoT) and Neutrosophic fuzzy systems to ensure precise data analysis with lesser time and energy consumption. In this study, a novel method called, Blinder Oaxaca-based Shapiro Wilk Neutrosophic Fuzzy (BO-SWNF) data analytics for remote healthcare is designed. Data collection is performed with the WESAD dataset. Duplicated data are eliminated by Blinder Oaxaca Linear Regression-based Preprocessing model. With the application of the Blinder Oaxaca function, energy efficiency is enhanced. Finally, the Shapiro Wilk Neutrosophic Fuzzy algorithm is applied for ensuring robust data analysis. The experimental results of the proposed BO-SWNF envisage the data for finer comprehension of attribute distribution. The result is conducted by using PYTHON application to analyze stress detection with the WESAD dataset. The proposed BO-SWNF method achieved an overall accurate data analysis of 12 % with minimum time ensuring 56 % improvement and minimizing energy consumption by 54 %.

Abstract Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity. As seen in luminal BrCa cell lines, this imbalance limits the number of double-capped 19S-20S-19S holocomplexes (30S) formed and promotes free 20S catalytic core accumulation that is widely-believed to confer survival advantage to tumors. By retaining connectivity with key tumor 19S:20S interface nodes, the PSMD9 19S subunit chaperone emerges as a crucial regulator of 26S/30S:20S ratios sustaining tumor cell proteasome function. Disrupting this connectivity by depleting PSMD9 in MCF7 cells introduces structural anomalies in the proteasome, and shifts dependence from 20SHigh to a deregulated 26SHigh state invoking anti-tumor responses which opens up clinically-relevant therapeutic possibilities.

Background: In Nepal, people with disabilities (PWDs) face significant economic challenges, with disparities in income and higher rates of poverty compared to the general population. This study aims to analyze the prevalence of poverty and determinants of income among PWDs, focusing on the impact of government allowances and other socio-economic factors. Methods: Data were collected from 200 PWDs using a purposive sampling method. Information was gathered through face-to-face interviews and structured questionnaires. The analysis utilized the poverty line to assess poverty levels and multiple regression analysis to explore factors influencing income. Results: The study found that 56.5% of PWDs live below the poverty line when government allowances are not considered, compared to 51% with allowances included. Government support was found to decrease the Gini coefficient by 0.10, indicating a reduction in income inequality. Key factors influencing income included education, work hours, experience, and access to assistive devices, while the severity of disability negatively affected income. Conclusion: The findings highlight the critical role of government interventions in reducing poverty among PWDs. Enhanced support for health, education, and employment, as well as targeted policies to improve accessibility and integration, are essential for improving the economic well-being of PWDs in Nepal. The study underscores the need for policies that address the economic and social inclusion of PWDs to mitigate the high rates of poverty within this group.

The proliferation of Wire Arc Additive Manufacturing (WAAM) has significantly enhanced the production capabilities for lightweight and structurally robust components. This study investigates the microstructural characteristics, tensile properties, and preliminary wear performance of AA 5083 aluminum alloy processed via WAAM, focusing on applications for lightweight structures. Using SEM and XRD, microstructural changes during the WAAM process are analyzed, and tensile testing evaluates the mechanical properties, including ultimate tensile strength (UTS) and elongation. The results reveal that the microstructure consists of α-Al and β-(Al5Mg8) phases, with the Al5Mg8 phase distributed along grain boundaries and within grains. Notably, the grain size in the Y-direction (building direction) is larger than in the X-direction (deposition direction) due to temperature variations during processing. Tensile testing shows that horizontal samples (X-direction) have a UTS of 295 ± 5 MPa and elongation of 20.08 ± 0.8 %, while vertical samples (Y-direction) have a UTS of 267 ± 10 MPa and elongation of 16.43 ± 2.1 %. This results in an anisotropy of 9.4 % in tensile strength, reflecting the differences in mechanical properties between the two directions. The WAAM AA 5083 aluminum part exhibits a maximum wear rate of 5.22 × 10⁻³ mm³/m and a coefficient of friction of 0.52 at a load of 3.5 kg and 450 rpm. Under these conditions, deep grooves, layer separation, and load-induced deformation are observed. The primary wear mechanisms include delamination, adhesion, and abrasion. Hardness levels are consistent in the X-direction and show minimal variance in the Y-direction, with an average hardness of 89.4 ± 5.14 HV0.5. The study demonstrates that WAAM-produced AA 5083 aluminum alloy, with an anisotropy below 10 %, is suitable for real-time lightweight structures, offering effective performance in engineering applications such as aerospace and automotive industries. Future research should focus on further quantifying wear behavior and optimizing processing conditions to enhance material performance for specific applications.

The narrative review titled ‘Orbital Blood Flow and Pseudoexfoliation Syndrome’ provides a comprehensive exploration of the intricate interplay between pseudoexfoliation (PEX) syndrome and orbital blood flow, offering insights into its clinical ramifications. Commencing with an overview of the historical context and prevalence of PEX, the review traverses various dimensions, including gender and age considerations, mortality/morbidity rates, and the underlying pathophysiology. It delves into the composition of PEX material and delineates the differential gene expression associated with the syndrome. Central to the discourse is the impact of PEX on orbital vasculature, elucidating its correlation with ocular ischemia and alterations in protein levels within the aqueous humour. Techniques for clinical evaluation, notably colour Doppler imaging, emerge as indispensable tools for assessing blood flow in patients with PEX.The article emphasises the significance of vascular dysfunction in PEX, highlighting the findings of decreased blood flow velocities and elevated resistive indices in affected individuals.The review underscores the imperative of comprehending the vascular implications of PEX to optimise diagnostic and management approaches, with far reaching implications for minimising operative complications and enhancing patient outcomes.

Sesame (Sesamum indicum) is a specialty crop with increasing interest as an alternative, rotational crop for U.S. agricultural systems. This crop is susceptible to several pathogens, including Pseudomonas and Xanthomonas species. Two bacterial isolates were recently cultured from sesame in North Carolina symptomatic of bacterial spot and identified as Pseudomonas amygdali pv. sesami (Pas) and Xanthomonas sp. These isolates were used for hybrid whole-genome sequencing and assembly using Illumina and PacBio to develop robust genomic resources for these disease-causing strains. The results provide the most complete Pas genome available and placed the Xanthomonas sp. isolate into the X. arboricola species designation. Improved genomic resources for pathogens of sesame are needed to accurately detect, characterize, and employ timely management of the disease. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Saprolegniasis is one of the most dangerous fungal diseases of fish, causing significant mortality in fish hatcheries and young ones. The present study aimed to isolate and characterize the causative fungus from fingerlings of Pangasianodon hypophthalmus cultured intensively in freshwater cages in Indian reservoirs and to determine minimum inhibitory concentrations of different antifungal compounds against the fungal hyphae and zoospores. The fungal isolates grown on potato dextrose agar showed an abundance of gemmae, elongated mycelia, non-septate hyphae, primary zoospores, mature zoosporangia with numerous zoospores, cysts with bundles of long hairs and were further identified as Saprolegnia parasitica following PCR amplification and sequencing of internal transcribed spacer region. S. parasitica showed temperature-sensitive optimum growth in a narrow window of 12–24 ℃, which might drive its experimental pathogenesis as well as natural infections in the winter months. In vitro sensitivity testing established negligible inhibitory activity of fluconazole, boric acid, sodium thiosulfate, and potassium permanganate while clotrimazole arrested the spore and hyphal growths at 2 mgL-1 concentration suggesting potential of the imidazole antifungal in treating S. parasitica infection in fish. The present study will serve as the baseline information for developing therapeutic and management strategies for controlling saprolegniasis in the economically significant iridescent catfish.

Abstract Background Despite the increasing integration of competency-based education in medicine, there remains a significant gap in effectively assessing educational outcomes, underscoring the urgent need for designed assessment blueprints that accurately reflect both curriculum content and competency standards in Community Medicine for undergraduate students. This study, conducted across the All-India Institute of Medical Sciences (AIIMS) network, develops a summative assessment blueprint aimed at standardizing evaluations in medical education across diverse geographic locations in India. Methods Twenty-five experts from 10 All India Institutes of Medical Science were invited via email and contributed for summative assessment for a theory paper. Each week, the study lead team sent an online form containing 25 topics. A total of 269 topics were selected to be included in the blueprint development. An Impact and Frequency score was obtained for each topic, with a score between 1 and 3 for both its “Impact (I)” and “Frequency” (F). Results The overall response rate was 71%. “Principle of epidemiology” (14.7%) had the most weight, followed by “Epidemiology of communicable disease” (13.4%) and “National Health Program” (10%). These three chapters constituted more than one-third of the total weight of the summative assessment (theory). 20 out of 24 (83%) chapters have moderate-to-good interrater reliability. Conclusions The blueprint developed in this study is intended to serve as a guideline for setting question papers and aims to enhance objectivity, uniformity, and validity in assessment construction. While it provides a structured approach within the AIIMS network, its broader applicability may be limited, suggesting that its effectiveness in other educational contexts remains to be validated. Continued research is encouraged to explore its utility across diverse educational settings.

Abstract Background Dental anxiety has become a major concern for both dental practitioners and patients and prevents a significant proportion of people from attending dental clinics. The present study aimed to determine dental anxiety and associated factors among adult patients attending a public outpatient dental clinic in a base hospital, in the Eastern Province of Sri Lanka. Methods A descriptive cross-sectional study was conducted among 400 adults aged 18 to 75 years awaiting dental treatment. A validated and pretested interviewer-administered questionnaire was utilised, and it included demographic information, past dental treatment, and the Modified Dental Anxiety Scale (MDAS) which was used to assess dental anxiety. Anxiety scores ranged from 5 to 25, with scores of 5–9 classified as less anxious, 10–18 as moderately anxious, and scores above 18 as extremely anxious. Statistical analysis was done using SPSS version 28. Descriptive analysis, correlation test, chi-square test and multiple logistic regression were applied for statistical analysis. The significance level was set at p

Micropapillary urothelial carcinoma of the renal pelvis is a rare and aggressive variant and poses a diagnostic challenge, especially related to the site and histomorphology of the tumor. A 60-year-old female presented with right pelvic-ureteric junction obstruction and a nonfunctioning right kidney. She underwent a simple right nephrectomy. The microscopy examination revealed a high-grade tumor of the renal pelvis, predominant micropapillary architecture. The tumor infiltrated into the kidney, renal sinus, perinephric fat, adrenal gland, and Gerota’s fascia. Extensive lymphovascular and perineural invasions were also noted. On immunohistochemistry, tumor cells were positive for GATA-binding protein 3, cytokeratin 7, and cytokeratin 20, while negative for paired box gene 8, cluster of differentiation 10, mammaglobin, and alpha-methylacyl-CoA racemase. The p63 was positive in the conventional areas and negative in the micropapillary pattern. We reported an additional case of micropapillary urothelial carcinoma of the renal pelvis, literature review, and discussed the differential diagnosis. Immunonegativity of p63 in the micropapillary component was an additional finding.

Cardiac myxomas are the most common primary cardiac tumors and are usually benign. They vary in size and location, with the left atrium (LA) being the most common site, typically attached to the fossa ovalis. Their manifestations range from asymptomatic to severe obstructive cardiac symptoms, embolic manifestations, or systemic findings, which can often occur without any primary cardiac symptoms. Here is a case of a 48-year-old man who initially presented with ischemic stroke. The myxoma was missed, and he later developed diverse manifestations such as weight loss and anorexia, ultimately presenting with biventricular failure. LA myxoma with biventricular failure is rare. Our patient showed significant improvement in both clinical status and biventricular function following myxoma excision.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive and unique type of T-cell lymphoma. Patients typically present with constitutional B symptoms, generalized lymphadenopathy, hepatosplenomegaly, cytopenias, and rash. We report a 63-year-old male who presented with fever, generalized lymphadenopathy, and features of plasma cell dyscrasia. Our report emphasizes the complexity of the presentation of AITL and aims to sensitize physicians for early diagnosis and an integrated treatment approach.

Mucormycosis is a dreaded condition with high mortality rates noted in immunocompromised hosts. Though iron overload is a known risk factor, children with transfusion-dependent thalassemia have been rarely reported with invasive mucormycosis. We present an 8-year-old girl with transfusion-dependent thalassemia with hypersplenism and iron overload. She had invasive rhino-sino-orbital mucormycosis with a fatal outcome despite aggressive surgical and medical management.

Background and Aims: Adequacy of Anaesthesia (AoA) and CONOX® are combined monitors that assess levels of anaesthesia and analgesia and give a comprehensive score. No studies have measured and compared the total consumption of inhaled anaesthetic agents while using these monitors. We designed a study to compare AoA and CONOX in terms of sevoflurane usage, fentanyl usage and recovery from the effects of anaesthesia. Methods: A randomised trial was conducted in 58 patients. Group A (n = 31) patients were monitored with AoA, and Group C (n = 27) patients were monitored with CONOX. Sevoflurane was titrated to maintain a state entropy value of 40–60 in AoA and a Quantium consciousness index (qCON) value of 40–60 in CONOX. Similarly, fentanyl was titrated with bolus doses of 0.5 μg/kg to maintain a surgical pleth index value of 40–60 in AoA and Quantium noxious index (qNOX) value of 40–60 in CONOX. Intraoperative awareness was assessed postoperatively using a modified Brice questionnaire. The t-test or Chi-square test was used to compare the parameters between the groups. Results: Mean sevoflurane consumption was similar between AoA and CONOX groups [13.2 (standard deviation {SD}: 3.9) (95% confidence interval {CI}:11.8, 14.5) versus 14.4 (SD: 3.7) (95% CI: 13.0, 15.7) ml/h] (P = 0.236). Fentanyl usage was higher in the AoA group compared to the CONOX group [146.2 (SD: 34.28) (95% CI: 134.13, 158.26) versus 128.2 (SD: 26.7) (95% CI: 118.12, 138.27) μg] (P = 0.031). The emergence time and haemodynamic instability events were similar between AoA and CONOX. Conclusion: Both AoA and CONOX measure anaesthetic depth similarly. However, interpreting qNOX values requires caution, as the patient’s consciousness status influences them.

Abstract The current study aims to understand the resistance of Bifidobacterium adolescentis to different anti-tubercular drugs (first-line oral tuberculosis drugs). The bacteria were grown with anti-tubercular drugs such as isoniazid, pyrazinamide, and streptomycin to better understand the resistance phenomena. It was found that even at tenfold higher concentrations, growth rates remained unchanged. In addition, a small number of bacteria were found to aggregate strongly, a property that protects against the toxicity of the drug. Further FE-SEM (Field Emission Scanning Electron Microscopy) analysis revealed that some bacteria became excessively long, elongated, and protruded on the surface. Size scattering analysis confirmed the presence of bifidobacteria in the size range of 1.0–100 μm. After whole genome sequence analysis, certain mutations were found in the relevant gene. In vitro, foam formation and growth in the presence of H2O2 and HPLC (High Performance Liquid Chromatography) studies provide additional evidence for the presence of catalase. According to RAST (Rapid Annotation Using Subsystems Technology) annotation and CARD (Comprehensive Antibiotic Resistance Database analysis), there were not many components in the genome that were resistant to antibiotics. Whole genome sequence (WGS) analysis does not show the presence of bacteriocins and antibiotic resistance genes, but few hypothetical proteins were observed. 3D structure and docking studies suggest their interaction with specific ligands.

Introduction: The degree of conversion of dentin bonding agents contributes to the success of final restorations in adhesive dentistry. It is clinically relevant, as it is directly related to the overall bond strength that maintains these restorations in place and prevents marginal deterioration. However, Matrix metalloproteinases (MMPs) present within the dentin substrate have been known to have a deleterious effect on the bond stability, due to their collagenolytic activity. Inhibition of the effects of MMPs has been studied, and the use of a pre-treatment protocol that includes MMP inhibiting agents before bonding procedures has been explored, and has been found to increase bond strengths. However, the effect that MMP inhibitors have on dental adhesives has not yet been explored, particularly when being used in caries-affected-dentin (CAD). This study aims to report the degree of conversion of an 8th-generation dentin bonding agent in sound dentin (SD) vs caries-affected dentin after pre-treatment using MMP inhibitors. Materials & methods: 60 dentin discs were divided into groups of sound and affected dentin, and pretreated with either Cranberry extract or mulberry extract was applied to half of the discs in each group, followed by the application of an eight-generation bonding agent to the pre-treated discs, which were then light cured. The degree of conversion of the adhesive was calculated using ATR-FTIR spectroscopy. Results: The degree of conversion was found to be the highest in the samples of sound dentin which were pre-treated with Mulberry extract. Conclusion: Pre-treatment of the dentin with MMP inhibitors led to an increase in the degree of conversion in sound dentin but not in CAD.

Abstract Trachinotus blochii is a high-value tropical mariculture species. The present study evaluated the gut microbial impact of therapeutic exposure (80 mg/day/kg biomass for 10 days) to oxytetracycline, the most common aquaculture antibiotic in T. blochii. The cultivable counts, α-diversity measures of taxonomic and functional metagenomics, microbial dysbiosis (MD) index, and microbial taxon abundances showed the resilience of gut microbiota at 16–26 days of treatment. A significant reduction in bacterial abundance, diversity measures, Firmicutes and Actinobacteria and an increase in γ-Proteobacteria was recorded on the 6th and 11th day of treatment. The increased metagenomic stress signatures, decreased beneficial bacterial abundances, decreased abundance of microbial pathways on energy metabolism, and MD index indicated short-term transient stress during the initial days of therapeutic withdrawal, warranting health management measures. Therapeutic exposure reduced the abundance of fish pathogens, including Vibrio spp., kanamycin and ampicillin-resistant bacteria. Strikingly, oxytetracycline treatment did not increase tetracycline-resistant bacterial counts and the predicted abundance of tetracycline resistance encoding genes in the gut, illustrating that therapeutic application would not pose a risk in the context of antimicrobial resistance in short term. Altogether, the present study provides a foundation for oxytetracycline treatment to develop suitable risk minimization tactics in sustainable aquaculture.

Abstract Background Reconstruction of maxillofacial defects is challenging due to the region’s complex anatomy. During the COVID-19 era, many patients lost their maxilla and chewing efficiency as a result of Mucormycosis. In such cases, custom-designed implants offer a graftless solution for seemingly hopeless situations. This case report aims at miraculous dental transformation utilizing the Patient Specific Implant (PSI) approach. Case Presentation A 64-year-old male patient presented to the Prosthodontics Department with the chief complaint of missing teeth. He had been struggling with chewing for two years due to a post-mucormycotic maxillary jaw. A CT scan was obtained to evaluate and investigate the affected site. After a comprehensive diagnosis, the treatment of choice was a patient-specific implant decided using 3D printing technology. Reconstructing maxillofacial defects poses significant challenges due to the region’s intricate anatomy, as well as its aesthetic and functional implications. The use of pre-formed alloplastic implants and autogenous grafts often leads to complications such as resorption, infection, and displacement. However, recent technological advances have made it possible to fabricate customized patient-specific implants (PSIs) through computer modeling, offering new opportunities for reconstructive surgery. Conclusion This case report demonstrates the dental management of post-mucormycotic patients with specially designed implants, customized according to the availability and anatomy of the bone in the entire head region. The absence of complications during follow-up, conducted at 15, 30, 45, and 90 days, and subsequently monthly for two years, highlights the success of this approach. Evaluation parameters included infection, soft tissue recovery, wound separation, masticatory efficiency, stability of the prosthesis, and aesthetic outcomes. The positive outcomes observed at follow-up appointments emphasize the viability and effectiveness of patient-specific implants in addressing maxillary defects caused by post-mucormycosis.

The diagnosis of adult Hirschsprung disease (HD) is rare, furthermore there are only 3 or 4 cases of adult ultrashort segment HD (USHD) reported previously in English literature to our knowledge. Herein, we present a case of a 22-year-old female presented with long standing history of constipation and abdominal distension secondary to USHD. Imaging modalities included plain abdominal X-ray, ultrasound (USG) and computed tomography (CT) scan which collectively aided in establishing the diagnosis. Through this case report, we aim to emphasize that HD should be suspected in every adult population with chronic constipation. Also, it highlights the role of CT scan as how it should be the preferred diagnostic tool for suspected adult HD, as, not only it helps correctly identify the transition zone but rule out other possible causes of chronic obstruction.

Background: Vitamin D deficiency is thought to increase the likelihood of insulin resistance (IR) and diabetes onset. The objective of this study was to examine the association between the triglyceride glucose (TyG) index and vitamin D levels in individuals with prediabetes and type 2 diabetes mellitus (T2DM) in the tribal community of India. Methods: This study included 270 participants, consisting of 90 individuals with prediabetes, 90 individuals with T2DM, and 90 control patients. Anthropometric and biochemical characteristics were evaluated in all participants. 25-hydroxyvitamin D [25(OH)D] levels were measured using a chemiluminescent immunoassay. The TyG index was computed as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Spearman correlation analysis and linear regression analysis were performed to assess the relationship between the TyG index and 25(OH)D levels in people diagnosed with prediabetes and T2DM. The optimum cut-off value of the TyG index for detecting vitamin D deficiency was determined by receiver operating characteristic (ROC) curve analysis. Results: We observed a significant reduction in vitamin D levels in individuals with prediabetes and T2DM compared to those in the control group. However, the TyG index was significantly greater in individuals with prediabetes and T2DM than in controls. Statistical analysis revealed a significant negative correlation between the TyG index and 25(OH)D in both prediabetes and T2DM. Conclusions: The TyG index demonstrated a negative association with vitamin D levels and was identified as an independent predictor of vitamin D deficiency in individuals with prediabetes and T2DM.

Abstract The aim of the experiment was to investigate the pharmacokinetics of oxytetracycline dihydrate after a single oral administration of 80 mg kg−1 day−1 in rainbow trout and assess its biosafety at concentration of 80, 240, 400, and 800 mg kg−1 day−1 over 30 days, focusing on various aspects such as effective feed consumption, physiological responses, drug tolerance, and detection of low drug concentrations in rainbow trout. The pharmacokinetics study spanned a duration of 5 days, while the assessment of biosafety extended for a 30-day safety margin, followed by a subsequent 10-day residual analysis. Pharmacokinetic analysis revealed slow absorption with low-rate constant in tissues. Absorption rates vary among tissues, with the gill showing the highest rate (0.011 h−1) and plasma exhibiting the slowest (0.0002 h−1). According to pharmacokinetic analysis, the highest concentration, Cmax (µg kg−1) was observed in the kidney (9380 µg kg−1) and gill (8710 µg kg−1), and lowest in muscle (2460 µg kg−1). The time (Tmax) to reach peak concentration (Cmax) varied among tissues, ranging from 3 h in the gill to 32 h in the muscle, with 24 h in plasma, 32 h in the kidney, and 16 h in both the liver and skin. The liver and kidney had the highest area under the concentration-time curve (AUC(0−128)), indicating widespread drug distribution. Prolonged elimination occurred at varying rates across tissues, with the gill showing the highest rate. The study found that OTC concentrations exceeded the LOD and LOQ values. Biosafety evaluation showed effective feed consumption, physiological responses, and low drug concentrations in muscle at the recommended dosage of 80 mg kg−1 fish day−1.

Introduction: Aspergillus species cause a broad range of infections, from Allergic Bronchopulmonary Aspergillosis (ABPA) to invasive aspergillosis. Accurate species-level identification is crucial for diagnosis and treatment, especially since some rare Aspergillus species exhibit increased resistance to common antifungal agents. Aim: To identify Aspergillus species at the species complex level and determine the emergence of cryptic Aspergillus species using Multilocus Sequence Analysis (MLSA). Materials and Methods: This descriptive cross-sectional study was conducted over eight months, from January 2023 to August 2023, in three tertiary care centres in Chennai, India. Sixty Aspergillus strains were isolated from various clinical samples. The primary inclusion criteria were patients with suspected aspergillosis, categorised based on the European Organszation for Research and Treatment of Cancer Mycoses Study Group (EORTC-MSG) criteria. Isolates were grown on Oatmeal Agar or Sabouraud Dextrose Agar (SDA) and phenotypically identified using tease mount and slide culture techniques. Genomic fungal Deoxyribonucleic acid (DNA) was extracted and amplified using specific primers for Internal transcribed spacer (ITS), beta-tubulin, hydrophobin, and calmodulin genes, followed by nucleic acid sequencing. Results: Among the 60 Aspergillus isolates, the Aspergillus flavus complex comprised 26 (43.3%), the Aspergillus fumigatus complex 16 (26.7%), the Aspergillus niger complex 12 (20%), and the Aspergillus terreus complex 6 (10%). Initial speciation relied on microscopic and cultural characteristics. Isolates were recovered from various clinical specimens: bronchial wash 6 (10%), Bronchoalveolar lavage (BAL) fluid 10 (16.7%), sputum 3 (5%), ear swab 20 (33.3%), endotracheal aspirate 8 (13.3%), pus and tissue from the nasal cavity and paranasal sinus 11 (18.3%), and tissue from other sites 2 (3.3%). MLSA identified common species such as A. flavus, A. fumigatus, A. terreus, and A. niger, as well as rare species including A. awamori, A. carneus, A. lentulus, A. oryzae, A. tamarii, A. tubingensis, and A. welwitschiae. Sequence identity ranged from 99% to 100%, confirming species diversity. Phylogenetic analysis using ITS, beta-tubulin, hydrophobin, and calmodulin genes supported species identification with robust bootstrap support (1000 replications). Conclusion: Cryptic Aspergillus species are prevalent in clinical samples from the South Indian population, with a notable presence from the section Nigri and the first-time isolation of Aspergillus carneus in clinical samples from India. Molecular identification is essential for determining the invasive potential and guiding appropriate antifungal therapy

Abstract Mutant KRAS promotes the proliferation, metastasis, and aggressiveness of various cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal adenocarcinoma (CRC) respectively. Mutant KRAS therapeutics are limited, while Sotorasib and Adagrasib were the only FDA-approved drugs for the treatment of KRASG12C mutated NSCLC. Chimeric antigen receptor (CAR) T-cell therapy has been emerged as an effective strategy against hematological malignancies and being extended towards solid cancers including PDAC. mesothelin (MSLN) and Carcinoembryonic Antigen (CEA) were reported to be highly overexpressed in KRAS-mutated PDAC. Meanwhile, in clinical trials, several CAR T-cell therapy studies are mainly focused towards these two cancer antigens in PDAC, however, the dual targeting of these two neoantigens is not reported. In the present study, we have designed and developed a novel dual-targeting CAR protein by employing various bioinformatics approaches such as functional analysis (antigenicity, allergenicity, antigen binding sites & signalling cascades), qualitative analysis (physicochemical, prediction, refinement & validation of 2D and 3D structures), molecular docking, and in silico cloning. Our results revealed that the designed CAR protein specifically binds with both MSLN & CEA with significant binding affinities, and was predicted to be stable & non-allergenic. Additionally, the protein–protein interaction network reveals the T-cell mediated antitumor responses of each domain in the designed CAR. Conclusively, we have designed and developed a dual targeting (MSLN & CEA) CAR protein towards KRAS-mutated PDAC using computational approaches. Alongside, we further recommend to engineer this designed CAR in T-cells and evaluating their therapeutic efficiency in in vitro and in vivo studies in the near future.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening multisystem disorder characterized by immune system dysregulation, hypercytokinemia, and hyperinflammation. This excessive inflammatory response is triggered by the uncontrolled activation of macrophages and T-lymphocytes, leading to widespread tissue damage. Systemic Lupus Erythematosus (SLE), a chronic autoimmune disease, involves the immune system’s loss of tolerance to nuclear selfantigens, resulting in the production of damaging autoantibodies that can affect multiple organ systems. In this case report, we describe a rare presentation of HLH in a young female patient with a known history of SLE. She initially presented with acute respiratory distress syndrome (ARDS), an uncommon but serious manifestation of HLH. The patient, who had discontinued her lupus medications two years prior, developed high grade fever, generalized myalgia, and progressive respiratory distress, necessitating mechanical ventilation. Her condition rapidly deteriorated despite aggressive supportive measures, with laboratory investigations revealing pancytopenia, hyperferritinemia, and elevated inflammatory markers, ultimately leading to the diagnosis of HLH. This case highlights the diagnostic challenges and the importance of early recognition of HLH in patients with underlying autoimmune conditions, such as SLE, who present with severe systemic inflammation and respiratory failure. Timely intervention is crucial, as delay in diagnosis and treatment can result in fatal outcomes. The case underscores the need for heightened clinical suspicion of HLH in similar presentations, as well as a multidisciplinary approach to management to improve patient prognosis.

Introduction: The compound 2,4 Dichlorophenoxyacetic acid (2,4-D) is present in most combinations of herbicides and is widely used by farmers in India, especially against weeds in cereal crops. Few self-poisoning cases have been reported worldwide, with guarded prognosis in most cases. Inadequate history regarding deliberate intoxication, indistinct clinical presentation, and unavailability of diagnostic facilities to detect and estimate the agent make it a significant concern in poisoning as it mimics one of the commonest poisoning which is organophosphorus poisoning. The therapy and management of this poisoning as well as prognosis of patients are not well described due to the paucity of cases in published literature.Case report: We present a case of 2,4-D poisoning with a successful clinical outcome and highlight the challenges faced in management. Our patient (A 41-year-old farmer) had a stormy clinical course in the hospital with acute kidney injury developing after a few days; he received supportive therapy along with renal replacement therapy in the form of hemodialysis. He however recovered completely and was well at follow-up. We also review the optimum management of this condition so that emergency medicine physicians and allied health personnel involved in caring for these patients can manage this effectively.Discussion: The toxicity of 2,4 D poisoning mimics the common organophosphorus poisoning in terms of symptoms. Nephrotoxicity has been described mainly due to tubular toxicity though this may manifest later in the course of hospitalization. Early initiation of alkaline diuresis not only augments the elimination of toxins but also prevents nephrotoxicity. The worsening toxin-induced acute kidney injury/acute renal failure should be promptly managed by hemodialysis, as it also helps in the elimination of 2,4-D.Conclusion: 2, 4-D poisoning remains a significant clinical challenge due to its non-specific presentation. This article contributes to the limited available literature on this potentially fatal condition highlighting the successful management of a severe case through a multi-modal approach involving alkaline diuresis, hemodialysis, and potentially corticosteroids. Further research is needed to elucidate the pathophysiology of 2,4-D toxicity and to develop specific antidotes.

The fabrication of dissimilar metal joints, particularly between AA 6061 aluminum alloy (Al) and AZ31B magnesium alloy (Mg), poses significant technical challenges due to their distinct metallurgical characteristics and the inherent difficulties associated with welding such materials. These challenges include the propensity for intermetallic compound formation, thermal cracking, and differences in thermal and mechanical properties between the two alloys. Cold Metal Transfer (CMT) welding, known for its low heat input and controlled metal transfer, offers a potential solution to these issues. However, optimizing the process parameters to ensure strong, defect-free joints requires a systematic approach. This study aims to optimize CMT welding parameters using parametric mathematical modeling (PMM) to produce high-strength Al and Mg dissimilar joints and to study the effects of CMT parameters on tensile strength (TS) and weld metal hardness (WMH), as well as the microstructural features of AA 6061 aluminum alloy/AZ31B magnesium alloy (Al/Mg) dissimilar joints. Al/Mg dissimilar butt joints were produced by the CMT process using ER4043 as filler wire. CMT, a low-heat input welding technique, was used to mitigate issues such as intermetallic compounds (IMCs), wider heat-affected zone (HAZ), and distortion. The CMT parameters, particularly wire feed speed (WFS), welding speed (WS), and arc length correction (ALC), were optimized using response surface methodology (RSM) to maximize the TS and WMH of the Al/Mg dissimilar joints. Polynomial regression was employed to create PMMs that integrated these CMT parameters to forecast the TS and WMH of the joints. An analysis of variance (ANOVA) was applied to assess the feasibility of the PMMs. The results indicated that the Al/Mg dissimilar joints, produced using a WFS of 4700 mm/min, a WS of 280 mm/min, and an ALC of 10%, exhibited higher TS and WMH values of 33 MPa and 95.8 HV, respectively. The PMMs provided precise forecasts for the TS and WMH of the Al/Mg joints with an error rate of less than 1% and a confidence level of 97%.

Abstract Glucokinase (GCK), a key enzyme in glucose metabolism, plays a central role in glucose sensing and insulin secretion in pancreatic β-cells, as well as glycogen synthesis in the liver. Mutations in the GCK gene have been associated with various monogenic diabetes (MD) disorders, including permanent neonatal diabetes mellitus (PNDM) and maturity-onset diabetes of the young (MODY), highlighting its importance in maintaining glucose homeostasis. Additionally, GCK gain-of-function mutations lead to a rare congenital form of hyperinsulinism known as hyperinsulinemic hypoglycemia (HH), characterized by increased enzymatic activity and increased glucose sensitivity in pancreatic β-cells. This review offers a comprehensive exploration of the critical role played by the GCK gene in diabetes development, shedding light on its expression patterns, regulatory mechanisms, and diverse forms of associated monogenic disorders. Structural and mechanistic insights into GCK’s involvement in glucose metabolism are discussed, emphasizing its significance in insulin secretion and glycogen synthesis. Animal models have provided valuable insights into the physiological consequences of GCK mutations, although challenges remain in accurately recapitulating human disease phenotypes. In addition, the potential of human pluripotent stem cell (hPSC) technology in overcoming current model limitations is discussed, offering a promising avenue for studying GCK-related diseases at the molecular level. Ultimately, a deeper understanding of GCK’s multifaceted role in glucose metabolism and its dysregulation in disease states holds implications for developing targeted therapeutic interventions for diabetes and related disorders.

Dendrobium ovatum is a tropical epiphytic orchid endemic to the Western Ghats of India and has been listed as a threatened species in recent research due to its declining populations and changes in flowering and fruit set patterns. This study aims to investigate the mycoflora associated with the roots, stems and leaves of D. ovatum. Both surface‐associated and endophytic fungal associates were isolated and identified using morphological and molecular methods. The study resulted in the isolation of 139 cultures, which were divided into 24 morphotypes, 99% of which belonged to Ascomycota. The most dominant members, Trichoderma harzianum and Colletotrichum gloeosporioides, were consistently observed across all the study sites. Tissue‐specific fungal diversity analysis revealed that each organ was dominated by a distinct fungal group, forming characteristic communities specific to each tissue. The roots of D. ovatum exhibited the highest species richness and diversity, compared to the stem and leaves. This research also represents the first documentation of fungal associates of the threatened orchid D. ovatum.

In Part 1 of this commissioned review, we discussed the basic biology of biofilms, its assembly, biogeography, and physicomechanical properties. In the second part of this review, we critically discuss the literature pertaining to microbiology of endodontic diseases, types of root canal infections, microbial dynamics, and host evasion strategies and highlight the concept of functional redundancy. Then, we review the role of fungi in endodontic diseases and provide an important narrative on the role of biofilms in weakening dentin. Finally, we briefly review the goals of prevention and treatment of apical periodontitis and provide futuristic perspectives to reinforce critical points that will aid future research and discovery.

Background: One potential treatment target for cancer cells is telomerase, an essential enzyme involved in the longevity of cancer cells. Current cancer treatments targeting telomerase often involve synthetic drugs with significant side effects, necessitating alternative approaches such as plant-based therapeutics. This study investigates the anti-telomerase activity of twelve phytochemicals derived from Blumea eriantha for cancer treatment. Methods: We examined the binding relationships between telomerase and the phytochemicals by performing molecular docking using Glide – Schrödinger, CB-Dock2 (Covalent Blind Docking 2), and Achilles Blind Docking. To further assess the interaction and stability of these phytochemicals and predict their behavior in a biological environment when targeting telomerase, we conducted molecular dynamic simulations using Desmond–Schrödinger. A comprehensive pharmacokinetic analysis using SwissADME and pkCSM (Pharmacokinetics and Toxicity by Computational Structure-based Models) supported these results by determining the drug-like qualities of these phytochemicals. The study further went on to identify synergistic treatment combinations using the Handy Recommendation Algorithm for Cancer Synergy (HRACS), where certain pairs of phytochemicals demonstrated enhanced anti-cancer efficacy against telomerase protein in A549 and MCF-7 cancer cell lines, suggesting that combinatorial therapy techniques may have potential. Results: Among the phytochemicals evaluated, Tyrphostin AG494 demonstrated the highest binding affinity to telomerase, as evidenced by its lowest interaction energy, with a Glide – Schrödinger Docking Score of -8.802 kcal/mol and a CB-Dock2 and Achilles Blind Docking Score of -8.5 kcal/mol. The phytochemical also exhibited a robust binding affinity mediated by consistent magnesium metal ion interactions involving key residues such as Asp251, Asp252, Ile252, and Asp343, along with additional hydrogen bonding and water-mediated contacts that enhance its stability and selectivity. Furthermore, all the phytochemicals, except Quassimarin, demonstrated various drug-like ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) parameters and validated Lipinski's rule of five, Veber, and Egan drug-likeness rules. Conclusion: Tyrphostin AG494 is the most effective natural phytochemical for inhibiting telomerase, exhibiting excellent binding affinity and stability, strong ADMET properties, and a safe toxicity profile. Therefore, following experimental validation, Tyrphostin AG494 is the most suitable and prospective candidate for telomerase inhibition and cancer therapy.

Seawater desalination, a promising solution for potable water, faces challenges such as high operational costs, limited durability, and fouling susceptibility that necessitate effective management solutions. This study presents a novel hybrid experimental approach combining magnetic treatment and stacked layer filtration. This study created eight combinations of two-stage treatment using permanent magnets, electromagnets (10 V), and stacked layer filtration to treat artificial seawater (ASW) derived from different salt mixes. The goal was to reduce salinity content rather than relying on brine rejection. It was observed the removal of chloride in all samples, leading to favourable outcomes. Overall, Combinations 2 and 7 consistently perform well across different dilutions, making them the most versatile methods. Combinations 6 and 8 are highly effective in undiluted conditions and moderate dilutions, while pairings 3 and 6 are less reliable, particularly at higher dilutions. Further, it reveals that manual cleaning of fabric filters used in stacked layer filtration removes accumulated salts from evaporation, making them reusable. Furthermore, the conductive graphene sheet showed no signs of swelling. A hybrid combination, such as magnetism and stacked layer filtration, could help address the global water crisis, with continuous testing and development establishing its suitability for various countries and applications.

Background Better affordability of data plans and an increase in “budget” smartphones have resulted in an exponential rise in internet and smartphone users. The ease of access to sexually explicit material (SEM) coupled with adolescents’ impulsivity makes them prone to excessive SEM exposure and may affect the development of sexuality via the perceived realism of such content. This study was done to study the influence between problematic smartphone usage (PSU) and sexuality development among late adolescent boys. Methods One hundred and thirty-four adolescents aged 18-19 years, studying in a medical university, participated in this cross-sectional study. Smartphone Addiction Scale – short version (SAS-SV) to evaluate PSU and a content validated semi-structured proforma to evaluate gender identity, sexual orientation, sources of information on pubertal changes, and exposure to pornographic content was used. We expressed results as proportion and summary measures (Mean±SD), Chi-square test to find influence between PSU and adolescent sexuality development. Results We found a 45.5% prevalence of PSU. Among study participants, 88% were attracted to the opposite sex, 6% were attracted to the same-sex, and 6% were attracted to both sexes. Three per cent of participants liked wearing clothes of the opposite sex, 7.5% wanted to be members of the opposite sex, whereas 10.4% were not comfortable with their genitalia. They obtained information regarding pubertal changes from friends (85) and media (78). Many had exposure to pornographic content (90%), with the youngest being nine years old. Conclusion Nearly half of the late adolescents have PSU. Pornographic contents are accessed through Smartphones.

Introduction Models derived from non-Sri Lankan cohorts are used for cardiovascular (CV) risk stratification of Sri Lankans.Objective To develop a CV risk prediction model using machine learning (ML) based on data from a Sri Lankan cohort followed up for 10 years, and to compare the predictions with WHO risk charts.Design Cohort study.Setting The Ragama Health Study (RHS), an ongoing, prospective, population-based cohort study of patients randomly selected from the Ragama Medical Office of Heath area, Sri Lanka, focusing on the epidemiology of non-communicable diseases, was used to develop the model. The external validation cohort included patients admitted to Colombo North Teaching Hospital (CNTH), a tertiary care hospital in Sri Lanka, from January 2019 through August 2020.Participants All RHS participants, aged 40–64 years in 2007, without cardiovascular disease (CVD) at baseline, who had complete data of 10-year outcome by 2017, were used for model development. Patients aged 40–74 years admitted to CNTH during the study period with incident CV events or a disease other than an acute CV event (CVE) with complete data for CVD risk calculation were used for external validation of the model.Methods Using the follow-up data of the cohort, we developed two ML models for predicting 10-year CV risk using six conventional CV risk variables (age, gender, smoking status, systolic blood pressure, history of diabetes, and total cholesterol level) and all available variables (n=75). The ML models were derived using classification algorithms of the supervised learning technique. We compared the predictive performance of our ML models with WHO risk charts (2019, Southeast Asia) using area under the receiver operating characteristic curves (AUC-ROC) and calibration plots. We validated the 6-variable model in an external hospital-based cohort.Results Of the 2596 participants in the baseline cohort, 179 incident CVEs were observed over 10 years. WHO risk charts predicted only 10 CVEs (AUC-ROC: 0.51, 95% CI 0.42 to 0.60), while the new 6-variable ML model predicted 125 CVEs (AUC-ROC: 0.72, 95% CI 0.66 to 0.78) and the 75-variable ML model predicted 124 CVEs (AUC-ROC: 0.74, 95% CI 0.68 to 0.80). Calibration results (Hosmer-Lemeshow test) for the 6-variable ML model and the WHO risk charts were χ2=12.85 (p=0.12) and χ2=15.58 (p=0.05), respectively. In the external validation cohort, the sensitivity, specificity, positive predictive value, negative predictive value, and calibration of the 6-variable ML model and the WHO risk charts, respectively, were: 70.3%, 94.9%, 87.3%, 86.6%, χ2=8.22, p=0.41 and 23.7%, 79.0%, 35.8%, 67.7%, χ2=81.94, p

Oat or Jai (Avena sativa L.), a vital winter forage crop in India and several other countries, is frequently affected by nitrate toxicity, compromising animal health and fodder quality. This study aimed to identify optimal agronomic management practices that enhance fodder quality and reduce nitrate accumulation in the Trans-Gangetic plains of India. Using a pooled split-plot design, this experiment evaluated the effects of different oat varieties, nutrient management regimes, and seeding rates. The experimental results revealed variability in fodder quality across varieties. Increasing the nitrogen, phosphorus, and potassium (NPK) fertilizer application by 25% above the recommended rate, coupled with 95 kg ha−1 of seed rate, significantly improved fodder yield, nutritional energy status, and reduced fiber fractions (p

AimThe perspectives and practices of healthcare professionals regarding ototoxicity in individuals with head and neck cancers are important for the implementation of ototoxicity monitoring. The current study aims to explore the oncologist's awareness and perspectives of ototoxicity and ototoxicity monitoring for individuals with head and neck cancer in a South-Indian district, using qualitative semi-structured interviews.MethodThe COnsolidated criteria for REporting Qualitative research (COREQ) Checklist was used to guide the method of the current qualitative study. A conceptual framework was developed for the formulation of the interview guides. Three medical oncologists and six radiation oncologists from cancer care centres participated in the study. The interviews were audio recorded and transcribed verbatim. Thematic analysis was carried out using a hybrid inductive-deductive approach to present the findings under the respective overarching themes.ResultsAll oncologists are aware of the ototoxic effects caused by radiation therapy and chemoradiotherapy. It was consistently reported that the severity of the hearing loss was not substantial enough to warrant significant concern. Ototoxicity is not emphasized during the counseling process. All participants reported having awareness and knowledge of ototoxicity monitoring programs and understood their importance. However, none of them reported the implementation of an ototoxicity monitoring program in their facility.DiscussionIt is imperative to enhance the knowledge and understanding of the ototoxic nature of cancer treatment modalities among oncologists. It is crucial to raise awareness regarding the significance of ototoxicity monitoring programs among all physicians involved in the treatment of patients with cancer for maximum impact. The barriers to implementing ototoxicity monitoring programs in high- and low-income countries are similar. The models implemented in high-income countries can be adapted for use in low-middle income countries with suitable restructuring.ConclusionThe current study provides valuable insights into the status of ototoxicity monitoring in the South-Indian context. The findings align with the key components of the health belief model, including perceived susceptibility, perceived barriers, and cues to action. Involving oncologists in the planning phase of the ototoxicity monitoring programs can help tailor future research questions and solutions to improve quality of life, foster collaboration among healthcare professionals, and produce actionable outcomes that may influence policy on ototoxicity monitoring.

Peanut is a vital source of protein, particularly in the tropical regions of Asian and African countries. About three-quarters of peanut production occurs worldwide in arid and semi-arid regions, making drought an important concern in peanut production. In the US about two-thirds of peanuts are grown in non-irrigated lands, where drought accounts for 50 million USD loss each year. The looming threat of climate change exacerbates this situation by increasing erratic rainfall. Drought not only reduces yield but also degrades product quality. Peanuts under drought stress exhibit higher levels of pre-harvest aflatoxin contamination, a toxic fungal metabolite detrimental to both humans and animals. One way to sustain peanut production in drought-prone regions and address pre-harvest aflatoxin contamination is by developing drought-tolerant peanut cultivars, a process that can be accelerated by understanding the underlying physiological and genetic mechanisms for tolerance to drought stress. Different physiological attributes and genetic regions have been identified in drought-tolerant cultivars that help them cope with drought stress. The advent of precise genetic studies, artificial intelligence, high-throughput phenotyping, bioinformatics, and data science have significantly improved drought studies in peanuts. Yet, breeding peanuts for drought tolerance is often a challenge as it is a complex trait significantly affected by environmental conditions. Besides technological advancements, the success of drought-tolerant cultivar development also relies on the identification of suitable germplasm and the conservation of peanut genetic variation.

BackgroundThe effects of physical activity (PA) across different domains and intensities on depressive symptoms remain inconclusive. Incorporating the community-built environment (CBE) into longitudinal analyses of PA’s impact on depressive symptoms is crucial. ObjectiveThis study aims to examine the effects of PA at different intensities—low-intensity PA (eg, walking activities) and moderate-to-vigorous-intensity PA (eg, activities requiring substantial effort and causing faster breathing or shortness of breath)—across leisure-time and occupational domains on depressive symptom trajectories among middle-aged and older adults. Additionally, it investigated how CBEs influence depressive symptoms and PA trajectories. MethodsThis longitudinal study included 6865 middle-aged and older adults from the China Health and Retirement Longitudinal Survey. A CBE variable system was developed using a community questionnaire to assess attributes of the physical built environment. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Latent growth curve modeling was applied to analyze 3 waves of the cohort data (2015, 2018, and 2020) to explore the differential effects of PA on depressive symptoms and the role of the CBE. ResultsIn the 2015 and 2018 waves, higher low-intensity leisure-time physical activity (LTPA) was associated with lower depressive symptoms (β=–.025, P=.01 and β=–.027, P=.005, respectively). Across all waves, moderate-to-vigorous-intensity LTPA showed no significant predictive effects (P=.21 in 2015, P=.57 in 2018, and P=.85 in 2020, respectively). However, higher occupational physical activity (OPA), particularly at moderate-to-vigorous intensities, was consistently associated with higher depressive symptoms. Parallel process latent growth curve modeling revealed that the initial level of total LTPA negatively predicted the initial level of depressive symptoms (β=–.076, P=.01). OPA exhibited dual effects, positively predicting the initial level of depressive symptoms (β=.108, P

The study was carried out during 2020–21 and 2021–22 at ICAR-National Dairy Research Institute, Karnal, Haryana to evaluate biostimulants based nutrient management practices in spring maize (Zea mays L.) under legume based cropping sequence. Experiment was conducted in a randomized block design (RBD) with 9 treatments of biostimulant based nutrient management, viz. T1, Absolute control; T2, 100% RDF (recommended dose of fertilizer); T3, 75% RDF + Azotobacter; T4, 50% RDF + Azotobacter + PGPR (Plant growth promoting rhizobacteria); T5, 75% RDF + Azotobacter + PGPR; T6, 50% RDF + Azotobacter + PGPR + Humic acid (HA); T7, 75% RDF + Azotobacter + PGPR + HA; T8, 50% RDF + Azotobacter + PGPR + HA + Seaweed extract (SWE); and T9, 75% RDF + Azotobacter + PGPR + HA + SWE, replicated thrice. Results showed that the growth parameters, viz. plant height, leaf length, leaf width and number of leaves/plant had no significant response at 30 DAS (days after sowing) during both the studied year. However, at 60 DAS, these parameters were significantly higher in 100% RDF which was statistically on par with 75% RDF + Azotobacter + PGPR + Humic acid (HA) + Seaweed extract (SWE) and 75% RDF + Azotobacter + PGPR + HA. Whereas at harvest, growth attributes were significantly higher in 75% RDF + Azotobacter + PGPR + HA + SWE which was statistically on par with RDF + Azotobacter + PGPR + HA and 100% RDF. Similarly, grain (7.81 and 8.00 t/ha), stover (12.18 and 12.48 t/ha) and biological yield (22.47 and 22.92 t/ha) were significantly higher in 75% RDF + Azotobacter + PGPR + HA + SWE which was statistically on par to RDF + Azotobacter + PGPR + HA and 100% RDF during 2020–21 and 2021–22, respectively. Hence, the treatment 75% RDF + Azotobacter + PGPR + HA + SWE found better and can replace up to 25% RDF as comparable to conventional practice without compromising the crop yield.

BackgroundAquaculture systems that sporadically depend on antibiotics can contribute to the development of adverse effects on the fish, microbial flora and the environment. This study sought to investigate the impacts of extended oxytetracycline supplementation on the freshwater stinging catfish Heteropneustes fossilis through a multi-biomarker approach.MethodsA total of 300 H. fossilis (20 ± 0.5 g) were placed in fibreglass-reinforced plastic tanks. The experimental fish were administered oxytetracycline hydrochloride (OTC) at varying doses, viz., 80 mg/kg fish biomass/day (1x), 240 mg (3x), 400 mg (5x), and 800 mg (10x) for 30 consecutive days. The study also included a control group that did not receive OTC.ResultsOTC was effective against Aeromonas hydrophila, Pseudomonas putida, and Plesiomonas shigelloides, with minimum inhibitory concentrations ranging between 0.5 and 8.0 µg/mL. The OTC supplementation retarded the growth of fish. The respiratory burst activity, myeloperoxidase, and lysozyme increased significantly in the 1x group until day 20. This group showed an increase in serum albumin, whereas other OTC groups exhibited elevated levels of liver functional enzymes, including alanine transaminase, aspartate aminotransferase, and alkaline phosphatase. In addition, OTC groups exhibited increased levels of antioxidant enzymes. The magnitude of the increase was dose- and time-dependent. The liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) study signified a dose-dependent increase in OTC residues in the muscle. After a 10-day discontinuation of OTC, the tissue level retention of residues was minimal in the muscle, specifically in the 1x group compared to other groups. Significant histological alterations were noted in the liver tissues of the 5x and 10x groups, possibly due to oxidative stress and residue accretion.ConclusionThe therapeutic dose of 80 mg/kg biomass/day was safe and tolerated well by H. fossilis, and may be used for sustainable catfish farming practices.

Fructose-1, 6- bisphosphatase deficiency is a rare autosomal recessive inborn error of fructose metabolism which mainly affects gluconeogenesis. It often presents with ketotic hypoglycemia and lactic acidosis, with hyperventilation. The disease has a high mortality rate when undiagnosed.Here we report a case of this rare disorder, referred to our hospital in Western Nepal, diagnosed originally as pneumonia. The patient presented in respiratory distress with severe metabolic acidosis and dehydration. She also demonstrated hypoglycemia, hypernatremia, coagulation dysfunction and albuminuria, all of which gradually improved, though her lactate remained consistently elevated. This led to investigation of urinary ketones which were positive suggesting a defect in the metabolism of carbohydrates. Urine organic acid profile and whole exome sequencing finally confirmed the diagnosis of Fructose-1, 6- bisphosphatase deficiency. To our knowledge this is the first case report of this disease diagnosed in Nepal.

This study employed a simplex lattice mixture design to optimize cabbage chips by blending cabbage powder, maize flour, and rice flour. Fourteen formulations were created using Design-Expert® software, with sensory attributes including crispiness, taste, appearance, aroma, and overall acceptability assessed. The approach revealed that cabbage powder (12 %), maize flour (10 %), and rice flour (27.97 %) effectively produced chips with desirable characteristics. Proximate analysis of the final chips (per 100 g) indicated 409.69 kcal energy, 70.97 g carbohydrates, 7.22 g protein, 10.77 g fat, 5.52 g total sugar, 4.04 % moisture, and 7.00 g ash. Mineral analysis revealed 9.48 mg calcium, 84.26 mg potassium, and 38.46 mg magnesium. This research optimizes cabbage chips, emphasizing their balanced nutrition and potential as a healthier snack.

New solar energy generation is drastically needed as a source of clean electricity as the U.S. and the globe make the transition away from fossil fuels. Yet, even as solar costs have dramatically declined, solar sources still provide less than 5% of global electricity. We examine issues in solar policy leading to this low adoption rate. Examining the variables of cost, baseload power and intermittency, and land use, we evaluate the tradeoffs among policy support for utility-scale, commercial and residential solar systems. We argue that utility-scale solar power makes far more sense if there is adequate grid integration, so that such installations can be placed in locations that minimize land use tradeoffs. By focusing policy support on a few large solar installations, governments can vastly increase the solar contribution to electricity generation.

Ten new non-nucleophilic base (DBU) catalyzed oxazolone-bearing pyrazole derivatives were created to treat infectious diseases caused by bacterial, mycobacterial strains, and cancerous cell lines. Compounds 7b and 7c showed excellent antibacterial and antifungal activity. Compound 7b was highly effective against M. tuberculosis H37Rv, with a MIC of 0.06 μg/mL and significant binding affinities to AcrB of E. coli (−12 Kcal/mol), TriABC of P. aeruginosa (−12.5 Kcal/mol), and MepR of S. aureus (−10.6 Kcal/mol). Based on the findings, compounds 7b, 7c, and 7e exhibit proficient binding affinity with two essential targets, namely Enoyl-[acyl-carrier-protein] reductase and Topoisomerase I, of M. tuberculosis. Compound 7b showed superior cytotoxic activity against all cancer types except leukemia with GI50 values of 1.26–1.83 µM and LC50 values of 5.36–7.88 µM. Compound 7a demonstrated remarkable anticancer activity against colon, melanoma, ovarian, renal, and breast cancer cell lines with GI50 values of 1.60–2.55 µM.

Background: Inpatients are at higher risk of Drug Therapy Related Problems (DTRPs), and early identification and management of these DTRPs is crucial for optimal treatment outcomes and ensuring rational drug therapy. Objective: This study aims to assess DTRPs in a general medicine ward of a tertiary care hospital in eastern Nepal. Methods: A three-month prospective observational study was conducted on inpatients admitted to the general medicine ward of the hospital. Pharmacists routinely performed patient drug therapy reviews, by which suspected DTRPs were identified and recorded as per the Pharmaceutical Care Network Europe Association (PCNE) v.9.1 guidelines. Binary logistic regression analysis was used to determine the influence of predictor variables on the occurrence of DTRPs. Results: A total of 301 inpatients were enrolled, out of which 233 (77.4%) had one or more DTRPs. Altogether, 528 DTRPs with an average of 2.27 ± 0.92 DTRPs per patient were identified. The primary causes of the DTRPs were drug selection (40.47%), treatment duration (16.71%), dispensing (15.75%), and dose selection (13.12%). Antimicrobials were involved in 55.18% of the DTRPs. DTRPs were more prevalent in elderly, comorbid patients, patients with longer hospital stay days, and polypharmacy, which was statistically significant (p

This study investigates the societal benefit of willingness to pay (WTP) green cess on polluting vehicles, to build an ecosystem for promoting zero emissions electric mobility in Western India. A survey method employed enabled data collection from 492 commuters and analysed using an open-ended contingent valuation method (CVM). As per the findings, about 67 % of commuters are in favour to pay green cess to help building an ecosystem for faster adoption of electric vehicles, but at comparatively low price. On positive note, around acknowledged electric mobility adoption needs a supportive ecosystem, while were not so forthcoming. The findings depicted that the average open-ended WTP for green cess evaluates to Rs 370 per month. The study engages commuters as stakeholders, helps analyse their sustainability orientation in terms of WTP and suggests recommendations for utilizing key learnings and monetary tool for inclusive developments towards a cleaner environment.

Many severe aortic stenosis (AS) cases are undetected and/or not considered for potentially life-saving treatment, with a persistent male-bias reported among those undergoing aortic valve replacement (AVR). We evaluated the clinical value of a validated artificial intelligence automated alert system (AI-AAS) that detects severe AS from routine echocardiographic measurements. In a retrospective, clinical cohort of 21,749 adults investigated with transthoracic echocardiography at two tertiary-referral centres, we identified 4057 women (aged 61.6 ± 18.1 years) and 5132 men (60.8 ± 17.5 years) with native aortic valves. We firstly applied the AI-AAS to the cardiologists' reported echo measurements, to detect all AS cases, including guideline-defined severe AS. Two expert clinicians then independently reviewed the original clinical diagnosis/management based on the initial report. Initially, 218/9189 (2.4 %, 95%CI 2.1–2.7 %) severe AS cases were diagnosed. The AI-AAS subsequently increased this number by 158 (52 % women) to 376 cases (4.1 %, 95%CI 3.7–4.5 %) of severe guideline-defined AS. Overall, more women were under-diagnosed (92/169 [54.4 %] versus 80/207 [38.6 %] men – adjusted odds ratio [aOR] 0.21, 95%CI 0.10–0.45). Even when accounting for potential contraindications to valvular intervention, women were persistently less likely to be considered for valvular intervention (aOR 0.54, 95%CI 0.31–0.95) and/or underwent AVR (aOR 0.29, 95%CI 0.09–0.74). Our study suggests an AI-AAS application that is agnostic to gender, haemodynamic bias, symptoms, or clinical factors, provides an objective alert to severe forms of AS (including guideline-defined severe AS) following a routine echocardiogram, and has the potential to increase the number of people (especially women) directed towards more definitive treatment/specialist care.