Advancing pharmaceutical Intelligence via computationally Prognosticating the in-vitro parameters of fast disintegration tablets using Machine Learning models.

The field of Machine Learning (ML) has garnered significant attention, particularly in healthcare for predicting disease severity. Recently, the pharmaceutical sector has also adopted ML techniques in various stages of drug development. Tablets are the most common pharmaceutical formulations, with their efficacy influenced by the physicochemical properties of active ingredients, in-process parameters, and formulation components. In this study, we developed ML-based prediction models for disintegration time, friability, and water absorption ratio of fast disintegration tablets. The model development process included data visualization, pre-processing, splitting, ML model creation, and evaluation. We evaluated the models using root mean square error (RMSE) and R-squared score (R2). After hyperparameter tuning and cross-validation, the voting regressor model demonstrated the best performance for predicting disintegration time (RMSE: 21.99, R2: 0.76), surpassing previously reported models. The random forest regressor achieved the best results for friability prediction (RMSE: 0.142, R2: 0.7), and the K-nearest neighbor (KNN) regressor excelled in predicting the water absorption ratio (RMSE: 10.07, R2: 0.94). Notably, predicting friability and water absorption ratio using ML models is unprecedented in the literature. The developed models were deployed in a web app for easy access by anyone. These ML models can significantly enhance the tablet development phase by minimizing experimental iterations and material usage, thereby reducing costs and saving time.

Endophyte-based fungal elicitors for enhanced production of valepotriates and sesquiterpenoids in leaf cell suspension cultures of Valeriana jatamansi Jones.

AIMS: The immense therapeutic value of Valeriana jatamansi is attributed to the presence of bioactive secondary metabolites (valepotriates and sesquiterpenoids). Its over-exploitation in wild habitats resulted in extensive depletion, necessitating alternative approaches to produce its therapeutic metabolites. This study sought to assess the ability of endophytes of V. jatamansi to boost the biosynthesis of secondary metabolites in the leaf-cell suspension (LCS) culture of V. jatamansi. METHODS AND RESULTS: A total of 11 fungal endophytes were isolated from the rhizomes of V. jatamansi. Isolated endophytes were found to belong to phylum Ascomycota, Basidiomycota, and Mucoromycota. Supplementation of extracts of endophyte Phaeosphaeriaceae sp. VRzFB, Mucor griseocyanus VRzFD, Penicillium raistrickii VRzFK, and Penicillium sajarovii VRzFL in the LCS culture of V. jatamansi increased the fresh cell biomass by 19.6%-39.1% and dry cell biomass by 23.4%-37.8%. Most of the endophytes' extract could increase the content of valepotriates (26.5%-76.5% valtrate and 40.5%-77.9% acevaltrate) and sesquiterpenoids (19.9%-61.1% hydroxyl valerenic acid) in LCS culture. However, only two endophytes, Irpex lacteus VRzFI and Fusarium oxysporum VRzFF, could increase the sesquiterpenoids acetoxy valerenic acid (36.9%-55.3%). In contrast, some endophytes' extracts caused negative or no significant effect on the cell biomass and targeted metabolites. Increased secondary metabolites were corroborated with increased expression of iridoid biosynthesis genes in LCS culture. Production of H2O2 and lipid peroxidation was also varied with different endophytes indicating the modulation of cellular oxidative stress due to endophyte elicitors. CONCLUSIONS: The results suggest the distinct effect of different fungal endophytes-extract on LCS culture, and endophytes can serve as biotic elicitors for increasing the secondary metabolite production in plant in vitro systems.

Moving population is a challenge for malaria elimination in India: A cross-sectional study to assess malaria parasite infections in walking pilgrims in western Rajasthan, India.

Objectives: India is vigorously pursuing malaria elimination by 2030 and one of the key challenges is how to prevent the malaria risk associated with long-distance migrations of populations from endemic to non-endemic areas. Millions of pilgrims walking to the holy Ramdevra temple stay in temporary shelters along the route in district of Jaisalmer, Rajasthan state in western India. The main pilgrimage period coincides with the post-monsoon period with elevated vector densities. We investigated this situation to assess the potential risk posed by migrant pilgrims along the four highways in the temple district in disseminating malaria infections associated with their annual movements. Methods: A cross-sectional study was conducted for screening malaria in walking pilgrims from neighboring states at selected sites and a follow-up study for screening residents in Rajasthan from 2021 to 2023. The study comprises state entry routes, Ramdevra shrine, and pilgrimage route villages situated in western Rajasthan. Epidemiologic and entomologic surveillance was conducted during the "fair" period (August-September) and in pilgrimage route villages in three different seasons of the year to assess malaria in humans and the vector's infectivity. Results: Of the 5251 individuals tested for malaria, a total of 76 (1.4%) tested positive for malaria, of whom 40.7% were infected with Plasmodium vivax (n = 31), 36.8% with P. falciparum (n = 28), and 22.3% with P. vivax and P. falciparum (n = 17). Anopheles density was highest during the fair season, peaking in August. An. stephensi exhibited a higher human blood index (0.65) than An. culicifacies (0.50). No mosquitoes were found positive for parasites. Conclusions: Up to 1.5% of pilgrims carried malaria parasites, posing a risk of spreading malaria to surrounding communities that otherwise would have low or no malaria burden. Moving populations pose the risk of local malaria transmission and reintroduction to the areas undergoing elimination. Sentinel point surveillance at the border of states will be helpful for states to share information on malaria and subsequently for the prevention of malaria transmission.

Phytochemical screening, molecular docking, antifertility investigations, and ADME potential of various extracts of Pandanus odoratissimus leaves.

OBJECTIVES: The purpose of this study was to explore the molecular docking characteristics and antifertility impacts of petroleum ether extract (PEEPO) and chloroform (CHEPO) derived from Pandanus odoratissimus (PO) leaves. METHODS: TriposSybyl-X 2.1 for molecular docking and Swiss ADME for ADME predictions were used. Antifertility activity was determined by using two in vivo animal models, with a focus on estrogenic/antiestrogenic activity and anti-implantation effects. RESULTS: The findings showed that at different doses (100, 200, and 400 mg/kg), PEEPO had more anti-implantation effect than CHEPO. After taking either extract orally for up to 4,000 mg/kg, no acute toxicity was found. Furthermore, both extracts substantially raised blood oestrogen levels while lowering serum cholesterol and LDL levels, improving their antiimplantation and estrogenic activities, whether given alone or in combination with ethinyl estradiol. Molecular docking scores suggested strong interactions between phytochemicals in the extracts and estrogen receptors. ADME studies highlighted four phytochemicals present in PO leaves, showing high gastrointestinal absorption, blood-brain barrier permeability, and negative Log Kp values, indicating their potential as antifertility agents. CONCLUSIONS: The phytochemicals in both PEEPO and CHEPO demonstrated promising antifertility potential and interactions with estrogen receptors. Isolation of these phytochemicals could lead to the development of effective herbal antifertility formulations.

Realizing visionary goals for the International Year of Millet (IYoM): accelerating interventions through advances in molecular breeding and multiomics resources.

MAIN CONCLUSION: Leveraging advanced breeding and multi-omics resources is vital to position millet as an essential "nutricereal resource," aligning with IYoM goals, alleviating strain on global cereal production, boosting resilience to climate change, and advancing sustainable crop improvement and biodiversity. The global challenges of food security, nutrition, climate change, and agrarian sustainability demand the adoption of climate-resilient, nutrient-rich crops to support a growing population amidst shifting environmental conditions. Millets, also referred to as "Shree Anna," emerge as a promising solution to address these issues by bolstering food production, improving nutrient security, and fostering biodiversity conservation. Their resilience to harsh environments, nutritional density, cultural significance, and potential to enhance dietary quality index made them valuable assets in global agriculture. Recognizing their pivotal role, the United Nations designated 2023 as the "International Year of Millets (IYoM 2023)," emphasizing their contribution to climate-resilient agriculture and nutritional enhancement. Scientific progress has invigorated efforts to enhance millet production through genetic and genomic interventions, yielding a wealth of advanced molecular breeding technologies and multi-omics resources. These advancements offer opportunities to tackle prevailing challenges in millet, such as anti-nutritional factors, sensory acceptability issues, toxin contamination, and ancillary crop improvements. This review provides a comprehensive overview of molecular breeding and multi-omics resources for nine major millet species, focusing on their potential impact within the framework of IYoM. These resources include whole and pan-genome, elucidating adaptive responses to abiotic stressors, organelle-based studies revealing evolutionary resilience, markers linked to desirable traits for efficient breeding, QTL analysis facilitating trait selection, functional gene discovery for biotechnological interventions, regulatory ncRNAs for trait modulation, web-based platforms for stakeholder communication, tissue culture techniques for genetic modification, and integrated omics approaches enabled by precise application of CRISPR/Cas9 technology. Aligning these resources with the seven thematic areas outlined by IYoM catalyzes transformative changes in millet production and utilization, thereby contributing to global food security, sustainable agriculture, and enhanced nutritional consequences.

Temporal effect of flaxseed oil in boar's diet on semen quality, antioxidant status and in-vivo fertility under hot humid sub-tropical condition.

The present study investigates the temporal effects of flaxseed supplementation on boar semen quality, antioxidant status, and in-vivo fertility under high-temperature humidity index (THI) conditions in a sub-tropical climate. Twelve Hampshire crossbreed boars were randomly assigned to control and treatment groups, with the treatment group receiving flaxseed oil supplementation. Semen samples were collected and analyzed for semen quality parameters, sperm kinematics, and antioxidant status. Fertility outcomes were assessed through in-vivo mating trials. Flaxseed supplementation resulted in time dependent significant improvements in semen volume, sperm concentration, total and progressive sperm motility, sperm quality parameters, and antioxidant status. Fertility outcomes, including farrowing rates and litter sizes, were also enhanced in the flaxseed-supplemented group. These findings highlight the potential of flaxseed supplementation to improve boar fertility under high ambient stress conditions, with implications for optimizing reproductive performance in swine production systems.

FEAtl: a comprehensive web-based expression atlas for functional genomics in tropical and subtropical fruit crops.

BACKGROUND: Fruit crops, including tropical and subtropical fruits like Avocado (Persea americana), Fig (Ficus carica), Date Palm (Phoenix dactylifera), Mango (Mangifera indica), Guava (Psidium guajava), Papaya (Carica papaya), Pineapple (Ananas comosus), and Banana (Musa acuminata) are economically vital, contributing significantly to global agricultural output, as classified by the FAO's World Programme for the Census of Agriculture. Advancements in next-generation sequencing, have transformed fruit crop breeding by providing in-depth genomic and transcriptomic data. RNA sequencing enables high-throughput analysis of gene expression, and functional genomics, crucial for addressing horticultural challenges and enhancing fruit production. The genomic and expression data for key tropical and sub-tropical fruit crops is currently lacking a comprehensive expression atlas, revealing a significant gap in resources for horticulturists who require a unified platform with diverse datasets across various conditions and cultivars. RESULTS: The Fruit Expression Atlas (FEAtl), available at http://backlin.cabgrid.res.in/FEAtl/ , is a first-ever extensive and unified expression atlas for tropical and subtropical fruit crops developed using 3-tier architecture. The expressivity of coding and non-coding genes, encompassing 2,060 RNA-Seq samples across 91 tissue types and 177 BioProjects, it provides a comprehensive view of gene expression patterns for different tissues under various conditions. FEAtl features multiple tabs that cater to different aspects of the dataset, namely, Home, About, Analyze, Statistics, and Team and contains seven central functional modules: Transcript Information,Sample Information, Expression Profiles in FPKM and TPM, Functional Analysis, Genes Based on Tau Score, and Search for Specific Gene. The expression of a transcript of interest can be easily queried by searching by tissue ID and transcript type. Expression data can be displayed as a heat map, along with functional descriptions as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. CONCLUSIONS: This atlas represents a groundbreaking compilation of a wide array of information pertaining to eight distinct fruit crops and serves as a fundamental resource for comparative analysis among different fruit species and is a catalyst for functional genomic studies. Database availability: http://backlin.cabgrid.res.in/FEAtl/ .

Rise in rabies cases in Jammu region: A problem that requires urgent attention.

Context: Rabies is a fatal zoonotic disease that is endemic in India. Both forms of rabies, namely, encephalitic and furious, invariably lead to coma and death. Lack of awareness is the most critical barrier in accessing timely post-exposure prophylaxis that can prevent the progression to clinical disease. Aims: To report the case series of fourteen clinically suspected rabies cases. Settings and Design: We followed a retrospective study design. Data were collected from the Anti Rabies Section of Government Medical College, Jammu, which is a tertiary care hospital of Jammu Division. Methods and Material: We collected data of all patients over a period of three years, from 2017 to 2020, who were diagnosed as cases of clinically suspected rabies on the basis of classic signs and symptoms and who finally succumbed to the disease. Statistical Analysis Used: Descriptive statistics was used to describe the results of the study. Results: In the present description, the mean age of the patients was 31 ± 18.6 years. Out of 14 suspected cases, 9 had not received any post-exposure prophylaxis-neither vaccine nor serum-and instead visited spiritual faith healers. The remaining patients had history of either incomplete, unknown, or incorrect vaccination status. Median duration of presentation of symptoms after dog bite was 42 days, with a range of 15-180 days. Mean survival of patients after presentation of symptoms was around 1.8 days. Conclusions: Low level of awareness resulted in non-seeking of health-care services after animal bites.

Current research status and emerging trends in wheat: An integrated scientometric analysis based on ploidy uncovers hidden footprints in the scientific landscape.

Wheat, a highly versatile staple crop cultivated extensively for its grains on a global scale, is poised to experience increased demand to sustain the burgeoning population, owing to its superior nutritional potential. Modern wheat, a hexaploid species, has evolved through the introgression of numerous preceding ploidies, including Einkorn, Emmer, Aegilops, and others, each possessing distinct qualitative and quantitative traits. Scientometric and topical analyses serve as effective tools to quantitatively evaluate scientific research by measuring the knowledge expressed in scientific publications and keywords. Thus, comprehending the research status regarding wheat domestication events within primary, secondary, and tertiary gene pools is paramount for enhancing wheat production. In this study, we analyze data retrieved from PubMed to elucidate the research status and identify bottlenecks across different ploidy of genomic pools of wheat. The publication trends on wheat have experienced exponential growth over the past three decades, with China emerging as a leading center for publications. In contrast to the publication frequency observed in hexaploid common wheat, scholarly output concerning Einkorn and Aegilops is approximately tenfold lesser, with emmer trailing behind at three times fewer publications. This discrepancy underscores the prioritization of expedited research initiatives targeting these species, aimed at elucidating latent biological characteristics and optimizing their breeding capabilities. Keywords such as "stress," "GWAS," and "gene" are prominent, reflecting the challenges posed by climatic factors on wheat production and their mitigation through molecular breeding and gene manipulation. Notably, the keyword "einkorn" highlights its potential as a donor for fine-tuning traits related to wheat adaptation processes and quality, crucial for modern wheat's survivability under adverse climates. Conversely, higher publication rates on emmer are primarily associated with Italy, possibly due to its favorable Mediterranean climate for tetraploid wheat. Keywords like "Pasta" and "Ochratoxin, DON" are prevalent, with the former being derived from durum wheat and the latter being reported in higher amounts in durum compared to other wheat species, rendering it less suitable for consumption. Enriched keywords such as "genome" and "resistance" underscore the critical characteristics of Aegilops. Other significant keywords like "Aceria tosichella" possibly indicate multiple stages of resistance conferred by Aegilops, while the presence of the grain softness protein "puroindoline" enhances its acceptability for donation by Aegilops. Spelt, a close relative of common wheat, exhibits a research trend with thousands of annual publications and enriched keywords such as "stress" and "yield" reflect the current scientific emphasis on wheat research. Furthermore, hierarchical keywords like "bio-control" and "celiac disease" merit consideration for future research on hexaploid wheat.

An Investigation of In Vitro Anti-Cancer Efficacy of Dihydroartemisinin-Loaded Bovine Milk Exosomes Against Triple-Negative Breast Cancer.

Repurposing drugs offers several advantages, including reduced time and cost compared to developing new drugs from scratch. It leverages existing knowledge about drug safety, dosage, and pharmacokinetics, expediting the process of clinical trials and regulatory approval. Dihydroartemisinin (DHA) is a semi-synthetic and active metabolite of all artemisinin molecules and is FDA-approved for the treatment of malaria. Apart from having anti-malarial properties, DHA also possesses anticancer properties. However, its pharmacological actions are limited by toxicity and solubility problems. To overcome these challenges and enhance its anticancer effectiveness, we designed an exosomal formulation of DHA. We isolated exosomes from bovine milk using differential ultracentrifugation and loaded DHA using sonication. Scanning and transition electron microscopy revealed a size of roughly 100 nm, with a spherical shape. Furthermore, in pH 7.4 and 5.5, the exosomes exhibited burst release followed by sustained release. Multiple in vitro cell culture tests demonstrated that Exo-DHA exhibited enhanced anticancer activity, including cytotoxicity, cellular uptake, generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, and inhibition of colony formation. Additional evidence supporting Exo-DHA's anti-migration ability came from transwell migration and scratch assays. Based on these results, it was concluded that the anticancer efficacy of DHA was improved when loaded into bovine milk-derived exosomes. While the in vitro results are encouraging, more in vivo testing in suitable animal models and biochemical marker analysis are warranted.

The struggle to belong: a qualitative exploration of challenges in social spaces faced by children with Duchenne muscular dystrophy attending neuromuscular disorders clinic.

PURPOSE: Duchenne muscular dystrophy (DMD), a genetically linked muscle disease, is one of the most devastating diseases with currently no cure. Developing essential social skills as a child moves into adolescence is particularly problematic in DMD. The present study is an exploration of the social challenges faced by children with DMD. METHODS: A qualitative study was conducted among ten children diagnosed with DMD receiving treatment in a neuromuscular disorder clinic of a tertiary referral care center in Southern India. Participants were recruited purposively and were interviewed face-to-face and through telephone. The recorded interviews were transcribed and analyzed using reflexive thematic analysis. RESULTS: Mean age of the children was 13.9 (range: 13-15) at the time of the interviews, and six children had stopped schooling. The overarching theme generated from the interviews was struggle to belong, a yearning for normalcy in social spaces. Major identified themes were challenges with schooling, disabling society, feeling of being alone, and feeling of being a burden to the family. CONCLUSION: The study highlighted the struggles of children that become a complex social problem for them. Efforts need to be made to be child-centric and encourage inclusion by improving accessibility and social support through sensitization programs.

This is an addition to the existing body of literature from the Indian context and points toward the need for creating awareness about social inclusion in the healthcare professionals, general public and in schools.Strengthening the social support system with referrals to and liaising with other relevant internal and external services and resources, home support services is important.This can prepare the children with Duchenne muscular dystrophy with adequate information about social connections and prepare them emotionally.Mainstreaming of children with the necessary support of various stakeholders in the society will go a long way to ensure quality of life of the children.

Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer.

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8-35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1-43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8-51.4) of patients converted from CD8 <15% pretreatment to ≥15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.

Preclinical evaluation of dalbergin loaded PLGA-galactose-modified nanoparticles against hepatocellular carcinoma via inhibition of the AKT/NF-κB signaling pathway.

Prior research has shown the effectiveness of dalbergin (DL), dalbergin nanoformulation (DLF), and dalbergin-loaded PLGA-galactose-modified nanoparticles (DLMF) in treating hepatocellular carcinoma (HCC) cells. The present investigation constructs upon our previous research and delves into the molecular mechanisms contributing to the anticancer effects of DLF and DLMF. This study examined the anti-cancer effects of DL, DLF, and DLMF by diethyl nitrosamine (DEN)-induced HCC model in albino Wistar rats. In addition, we performed biochemical, antioxidant, lipid profile tests, and histological studies of liver tissue. The anticancer efficacy of DLMF is equivalent to that of 5-fluorouracil, a commercially available therapy for HCC. Immunoblotting studies revealed a reduction in the expression of many apoptotic markers, such as p53, BAX, and Cyt-C, in HCC. Conversely, the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3 was elevated. Nevertheless, the administration of DL, DLF, and DLMF effectively controlled the levels of these apoptotic markers, resulting in a considerable decrease in the expression of Bcl-2, TNF-α, NFκB, p-AKT, and STAT-3. Specifically, the activation of TNF-alpha and STAT-3 triggers the signalling pathways that include the Bcl-2 family of proteins, Cyt-C, caspase 3, and 9. This ultimately leads to apoptosis and the suppression of cell growth. Furthermore, metabolomic analysis using 1H NMR indicated that the metabolites of animals reverted to normal levels after the treatment.

Molecular characterization of DNAH6 and ATPase6 (Mitochondrial DNA) genes in asthenozoospermia patients in the northern region of India.

BACKGROUND: Male infertility due to spermatogenesis defects affects millions of men worldwide. However, the genetic etiology of the vast majority remains unclear. The present study was undertaken to assess the association of DNAH6 and ATPase6 genes in asthenozoospermia patients in the northern region of India. METHODS: A total of 60 semen samples were collected for the study, of which 30 were from the case group and 30 were from the control group. The semen samples for the case group (asthenozoospermia) and control groups were collected from IVF and Reproductive Biology Centre, Maulana Azad Medical College, New Delhi. Sperm count and motility were classified as per World Health Organization (WHO 2021) protocol. A total genomic DNA was extracted as per the stranded TRIZOL method with little modification. RESULTS: In-vitro molecular characterizations of DNAH6 and ATPase6 genes in both groups were checked by Polymerase Chain Reaction (PCR). The 675 bp and 375 bp amplicons were amplified using PCR for ATPase6 and DNAH6 genes. Our study results showed a significant (P ≤ 0.05) null deletion of DNAH6 and ATPase6 genes in asthenozoospermia patients as compared to the control. We found the significant null deletion of DNAH6 in case 45.0%, and the control group was 11.7%. However, in the case of APTase6, it was 26.7% and 10.0%, respectively. CONCLUSIONS: Our study concluded that the presence of DHAH6 and ATPase6 genes had a significant impact on male infertility.

Uncertainty and sensitivity analysis of revised leachate pollution index.

Composite indicators (CIs) are being utilized more frequently to assess and monitor environmental systems. The revised leachate pollution index (r-LPI) is one such composite indicator used to quantify the pollution potential of landfill leachate on a scale of 5-100. The development of CIs involves several steps, and each of these steps has various methodological choices, each of which could lead to different results. Thereby, the reliability of the quantified pollution potential of leachate may be questioned. This study investigated the techniques for developing the r-LPI, examining decisions related to parameter selection, normalization technique, weighting approach, sub-indicator weights, and their aggregation. As the index developer made the decisions, each of these stages was fraught with uncertainty. The uncertainty in the various stages of the development of r-LPI was quantified using the Monte Carlo-based uncertainty analysis and the sensitivity analysis approach. Uncertainty analysis is a helpful but seldom-used step of index development that identifies the model's most dependable sections. Sensitivity analysis was carried out to ascertain the degree of impact the input parameters have on the r-LPI values. The combined use of sensitivity and uncertainty analysis in this study for the formulation of r-LPI affirmed the transparency, credibility, and accuracy of the index.

Efficacy and safety of insomnia treatment with lemborexant in older adults: analyses from three clinical trials.

BACKGROUND: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. METHODS: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2-7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. RESULTS: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. CONCLUSIONS: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. TRIAL REGISTRATION NUMBERS AND DATES OF REGISTRATION: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017.

The prevalence of insomnia increases with age; however, some hypnotics used for treating insomnia do not adequately resolve sleep problems in older adults and may be associated with adverse residual effects. Specifically, some hypnotics pose safety concerns in this population of patients who are generally more vulnerable to treatment-related effects, including increasing the risk of falls, risks of cognitive impairment, automobile accidents, and unresponsiveness to auditory stimuli. Safer and more effective insomnia medications are needed to reduce sleep problems with improved side-effect profiles. This analysis of lemborexant clinical studies conducted in adult subjects at least 65 years old found the drug to be effective without impairing memory, attention or balance the following day compared with placebo. These subjects were normal sleepers (for age) or had insomnia disorder. Furthermore, lemborexant was not associated with impaired ability to drive the next morning or awaken to loud middle-of-the-night sounds. Lemborexant was well tolerated in these older adults, similar to findings for adults aged at least 18 years. These findings indicate that lemborexant may be an appropriate treatment option for insomnia in older adults.

Impact of Irpex lenis and Schizophyllum commune endophytic fungi on Perilla frutescens: enhancing nutritional uptake, phytochemicals, and antioxidant potential.

BACKGROUND: Endophytic fungi (EF) reside within plants without causing harm and provide benefits such as enhancing nutrients and producing bioactive compounds, which improve the medicinal properties of host plants. Selecting plants with established medicinal properties for studying EF is important, as it allows a deeper understanding of their influence. Therefore, the study aimed to investigate the impact of EF after inoculating the medicinal plant Perilla frutescens, specifically focusing on their role in enhancing medicinal properties. RESULTS: In the current study, the impact of two EF i.e., Irpex lenis and Schizophyllum commune isolated from A. bracteosa was observed on plant Perilla frutescens leaves after inoculation. Plants were divided into four groups i.e., group A: the control group, group B: inoculated with I. lenis; group C: inoculated with S. commune and group D: inoculated with both the EF. Inoculation impact of I. lenis showed an increase in the concentration of chlorophyll a (5.32 mg/g), chlorophyll b (4.46 mg/g), total chlorophyll content (9.78 mg/g), protein (68.517 ± 0.77 mg/g), carbohydrates (137.886 ± 13.71 mg/g), and crude fiber (3.333 ± 0.37%). Furthermore, the plants inoculated with I. lenis showed the highest concentrations of P (14605 mg/kg), Mg (4964.320 mg/kg), Ca (27389.400 mg/kg), and Mn (86.883 mg/kg). The results of the phytochemical analysis also indicated an increased content of total flavonoids (2.347 mg/g), phenols (3.086 mg/g), tannins (3.902 mg/g), and alkaloids (1.037 mg/g) in the leaf extract of P. frutescens inoculated with I. lenis. Thus, overall the best results of inoculation were observed in Group B i.e. inoculated with I. lenis. GC-MS analysis of methanol leaf extract showed ten bioactive constituents, including 9-Octadecenoic acid (Z)-, methyl ester, and hexadecanoic acid, methyl ester as major constituents found in all the groups of P. frutescens leaves. The phenol (gallic acid) and flavonoids (rutin, kaempferol, and quercetin) were also observed to increase after inoculation by HPTLC analysis. The enhancement in the phytochemical content was co-related with improved anti-oxidant potential which was analyzed by DPPH (% Inhibition: 83.45 µg/ml) and FRAP (2.980 µM Fe (II) equivalent) assay as compared with the control group. CONCLUSION: Inoculation with I. lenis significantly enhances the uptake of nutritional constituents, phytochemicals, and antioxidant properties in P. frutescens, suggesting its potential to boost the therapeutic properties of host plants.

Highly Efficient Red Emission from Novel Sm3+ Doped Na3La(PO4)2 Nanophosphors for Optoelectronic Applications.

Solution combustion procedure was used to create a succession of Na3LaxSm1 - x(PO4)2 (x = 0.01-0.15 mol) nanocrystals that generate a warm deep reddish light. Both HR-TEM and X-ray diffraction examinations were used to examine the morphology and crystalline phase analysis. Energy-dispersive X-ray analysis (EDAX) approves the elemental examination. The luminescence spectrum exhibits a decent reddish-orange emission at 700 nm wavelength upon near-UV illumination, which aligns with the electronic transition 4G5/2 → 6H11/2. According to Dexter's idea, nearest neighbor interlinkages are responsible for the concentration quenching that occurs after the Sm3+ ion composition reaches 6 mol%. Additionally, a detailed evaluation of the radiative lifespan (0.7519 ms), quantum efficiency (77%), Non radiative rate (307.40), color temperature (3170 K), color purity (99.2%) and color coordinates (0.652, 0.338) was conducted. The optical characteristics that have been observed indicate that Sm3+ doped Na3La(PO4)2 phosphors could be a good option for improving WLED efficiency and color quality.

Formulation and pilot test of tuberculosis patient score card (TB-PSC) in selected public health care facilities of Himachal Pradesh, India.

BACKGROUND: Community engagement is advocated to improve quality of services using community score card. Current study was done with the objective to formulate the TB-PSC and to carry out its feasibility assessment at three selected public healthcare facilities of Himachal Pradesh, India. METHODS: A mixed-method study design was adopted for the study and was carried out from April 2022 to March 2023. A total of 36 IDIs and four FGDs were carried out to conceptualize, and formulate the structure, components, and scoring mechanisms of TB-CSC. To assess the effect of TB-PSC at three primary health centres (PHCs), pre- and post-study design was used for change in level of satisfaction adapting patient satisfaction questionnaire (PSQ-18). RESULTS: Based on gathered information from IDIs and FGDs, TB-PSC was developed. It comprised of a total of 22 questions related to four domains of availability (9), accessibility (4), and quality (5) of services along with perceived stigma and discrimination (4). TB-PSC was implemented for five months in each PHC in interface-meetings. Mean PSQ score was observed to be significantly high (2.5 vs 2.6) after intervention. CONCLUSION: TB-PSC implementation is feasible in interface meetings and makes them more participatory and effective.