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IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or Long COVID) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIHs REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Patterns in a semiarid ecosystem are important because they directly and indirectly affect ecological processes, biodiversity, and ecosystem resilience. Understanding the causes and effects of these patterns is critical for long-term land surface management and conservation efforts in semiarid regions, which are especially sensitive to climate change and human-caused disturbances. In addition, developing mathematical models is challenging because of the involvement of several interacting components within an ecosystem. It is known that there is a regular connection between the vegetation and the living species in a habitat since some animals evolved to live in a semiarid ecosystem and rely on plants for food. In this work, we have constructed a coupled mathematical model to connect the water resource, vegetation, and living organisms and have investigated how the soil surface affects the resulting patterns in the long term. This study contributes to a better understanding of ecological patterns and processes in semiarid environments by shedding light on the complex interaction mechanisms that depend on the structure of semiarid ecosystems. For example, the impact of intensive rainfall on ecosystem dynamics can be profound, triggering critical transitions and leading to significant yield loss. The energy lost as it moves from one trophic level to the next, the potential for diversity to exacerbate species extinction rates, and the role of water flow in driving the system towards more robust stripe pattern formations are all significant factors. Despite these complexities, the findings offer critical insights into the influence of efforts to enhance ecosystem resilience and adapt to the challenges of climate change and human activities.

Advancement of AI has opened new possibility for accurate diagnosis and prognosis using digital histopathology slides which not only saves hours of expert effort but also makes the estimation more standardized and accurate. However, preserving the AI model performance on the external sites is an extremely challenging problem in the histopathology domain which is primarily due to the difference in data acquisition and/or sampling bias. Although, AI models can also learn spurious correlation, they provide unequal performance across validation population. While it is crucial to detect and remove the bias from the AI model before the clinical application, the cause of the bias is often unknown. We proposed a Causal Survival model that can reduce the effect of unknown bias by leveraging the causal reasoning framework. We use the model to predict recurrence-free survival for the colorectal cancer patients using quantitative histopathology features from seven geographically distributed sites and achieve equalized performance compared to the baseline traditional Cox Proportional Hazards and DeepSurvival model. Through ablation study, we demonstrated benefit of novel addition of latent probability adjustment and auxiliary losses. Although detection of cause of unknown bias is unsolved, we proposed a causal debiasing solution to reduce the bias and improve the AI model generalizibility on the histopathology domain across sites. Open-source codebase for the model training can be accessed from https://github.com/ramon349/fair_survival.git.

One key goal of basic aging research is the development of reliable assays of both current and future health. These assays could dramatically accelerate progress toward developing health-extending interventions by obviating the need for full lifespan studies, especially if they were informative relatively early in life. One potential approach is the assessment of physiological resilience, defined as the ability to recover from an adverse event. Here, using CB6F1 mice, we evaluated four potential resilience assays, each quantifying recovery from a physiological challenge with clear relevance to humans. The challenges were: (1) anesthesia recovery, (2) restoration of hemoglobin levels after a blood draw, (3) speed of wound healing, and (4) survival after pathogen exposure. We evaluated how each changed with age and with interventions known to extend health in males only (17α-estradiol) or both sexes (calorie restriction). We found that three of the four (recovery from anesthesia, blood draw, and pathogen exposure) showed significant and expected age effects, but wound healing did not. None of the three age-sensitive assays responded to the health-extending interventions in the way we expected, and for some assays, including anesthesia response, interventions actually worsened outcomes. Possible explanations are: (1) our interventions were too brief, (2) the ages we evaluated were too young, (3) our assays did not capture important features of organismal resilience, or (4) organismal resilience is not as clearly related to current or future health as hypothesized. Future studies are needed to determine which of these interpretations is valid and to determine whether other resilience metrics may be more informative about current and future health.

Considerable effort is required to build mathematical models of large protein regulatory networks. Utilizing computational algorithms that guide model development can significantly streamline the process and enhance the reliability of the resulting models. In this article, we present a perturbation approach for developing data-centric Boolean models of cell cycle regulation. To evaluate networks, we assign a score based on their steady states and the dynamical trajectories corresponding to the initial conditions. Then, perturbation analysis is used to find new networks with lower scores, in which dynamical trajectories traverse through the correct cell cycle path with high frequency. We apply this method to refine Boolean models of cell cycle regulation in budding yeast and mammalian cells.

To analyse the effect of nutrient management on the growth, physiology, energy utilization, production and quality of black gram, a field trial on black gram was conducted at eastern Indian Gangetic alluvium during the autumn of 2020 and 2021. Treatments were two soil applications of cobalt (Co) and foliar spray of potassium (K) and boron (B) in five combinations. All treatments were arranged in a split-plot design and repeated three times. Two soil applications of cobalt (Co) were assigned in the main plots and foliar spray of potassium (K) and boron (B) in five combinations were assigned in sub-plots. Applications of Co in soil and foliar K+B facilitated significantly higher (p≤0.05) values for aerial dry matter (ADM), leaf area index (LAI), nodules per plant, total chlorophyll, net photosynthetic rate and nitrate reductase content in both 2020 and 2021, with a greater realization of photosynthetically active radiation interception, and use efficiency (IPAR and PARUE respectively), seed yield, seed nutrients and protein contents. Differences in LAI exhibited positive and linear correlation with IPAR explaining more than 60% variations in different growth stages. The innovative combination of soil Co (beneficial nutrient) application at 4 kg ha-1 combined with foliar 1.25% K (macronutrient) + 0.2% B (micronutrient) spray is a potential agronomic management schedule for the farmers to sustain optimum production of autumn black gram through substantial upgradation of growth, physiology, energy utilization, production and quality in Indian subtropics.

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.

In Kenya, approximately one in five girls aged 15-19 years old are pregnant or already a mother. Adolescent girls and young women experience significant mental health vulnerabilities during the pregnancy and postpartum periods, leading to poor antenatal and postnatal care attendance and inferior infant and maternal health outcomes. Pregnant adolescents often experience stigma and disenfranchisement due to their pregnancy status and at the same time lack access to mental health support within health settings, schools, religious institutions, and communities. This paper presents the results of qualitative interviews embedded within the human-centered design (HCD) process used to adapt the Helping Adolescents Thrive (HAT) program for Kenyan peripartum adolescents including young fathers. This qualitative study used two phases. First, a HAT advisory group participated in a series of four workshops to help identify and articulate mental health promotion needs and deepened the team's understanding of youth-centered thinking. Second, qualitative interviews were conducted with 39 pregnant and parenting adolescents to understand their perspectives on mental health prevention and promotion. Pregnant and parenting adolescents articulated different needs including poor support, stigma, and psychological disturbances. Parenting adolescents reported disturbed relationships, managing motherhood, poor health, and social empowerment. Participants highlighted sources of stress including economic challenges, fear of delivery, strained relationships, rejection, and stigma. Participants described psychological disturbances such as feeling stressed, worthless, withdrawn, and suicidal. Coping mechanisms reported by participants included engaging in domestic activities, hobbies, and social networking. Peers, family and spirituality were identified as important sources of support, as well as school integration, livelihoods, support groups and mentorships. Findings from this study can be used to strengthen and adapt HAT program, policy and practice for mental health prevention and promotion for pregnant and parenting adolescents.

RationaleThere is little doubt that aerosols play a major role in the transmission of SARS-CoV-2. The significance of the presence and infectivity of this virus on environmental surfaces, especially in a hospital setting, remains less clear.ObjectivesWe aimed to analyze surface swabs for SARS-CoV-2 RNA and infectivity, and to determine their suitability for sequence analysis.MethodsSamples were collected during two waves of COVID-19 at the University of California, Davis Medical Center, in COVID-19 patient serving and staff congregation areas. qRT-PCR positive samples were investigated in Vero cell cultures for cytopathic effects and phylogenetically assessed by whole genome sequencing.Measurements and main resultsImproved cleaning and patient management practices between April and August 2020 were associated with a substantial reduction of SARS-CoV-2 qRT-PCR positivity (from 11% to 2%) in hospital surface samples. Even though we recovered near-complete genome sequences in some, none of the positive samples (11 of 224 total) caused cytopathic effects in cultured cells suggesting this nucleic acid was either not associated with intact virions, or they were present in insufficient numbers for infectivity. Phylogenetic analysis suggested that the SARS-CoV-2 genomes of the positive samples were derived from hospitalized patients. Genomic sequences isolated from qRT-PCR negative samples indicate a superior sensitivity of viral detection by sequencing.ConclusionsThis study confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces contains infectious virus, disputing the importance of fomites in COVID-19 transmission. Ours is the first report on recovering near-complete SARS-CoV-2 genome sequences directly from environmental surface swabs.

Introduction Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. Methods and analysis This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as “standard of care” in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6–10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. Ethics and dissemination The protocol was reviewed by South Central—Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. Trial registration number ISRCTN10665760.

In the post genomic era, high throughput data augment stoichiometric flux balance models to compute accurate metabolic flux states, growth and energy phenotypes. Investigating altered metabolism in the context of evolved resistant genotypes potentially provide simple strategies to overcome drug resistance and induce susceptibility to existing antibiotics. A genome-scale metabolic model (GSMM) for Chromobacterium violaceum, an opportunistic human pathogen, was reconstructed using legacy data. Experimental constraints were used to represent antibiotic susceptible and resistant populations. Model predictions were validated using growth and respiration data successfully. Differential flux distribution and metabolic reprogramming were identified as a response to antibiotics, chloramphenicol and streptomycin. Streptomycin resistant populations (StrpR) redirected tricarboxylic acid (TCA) cycle flux through the glyoxylate shunt. Chloramphenicol resistant populations (ChlR) resorted to overflow metabolism producing acetate and formate. This switch to fermentative metabolism is potentially through excess reducing equivalents and increased NADH/NAD ratios. Reduced proton gradients and changed Proton Motive Force (PMF) induced by antibiotics were also predicted and verified experimentally using flow cytometry based membrane potential measurements. Pareto analysis of NADH and ATP maintenance showed the decoupling of electron transfer and ATP synthesis in StrpR. Redox homeostasis and NAD+ cycling through rewiring metabolic flux was implicated in re-sensitizing antibiotic resistant C. violaceum. These approaches can be used to probe metabolic vulnerabilities of resistant pathogens. On the verge of a post-antibiotic era, we foresee a critical need for systems level understanding of pathogens and host interaction to extend shelf life of antibiotics and strategize novel therapies.

BackgroundThe adoption of maternity services and postpartum modern contraception are the two most crucial components that help in reducing maternal and infant mortality; still, India is consistently struggling with it. This paper, therefore, aimed to examine the linkages between use of maternity services and postpartum modern contraceptive adoption.Data and methodsThe required reproductive calendar data were extracted from the 2015-16 and 2019-21 National Family Health Survey (NFHS) datasets. The assessment was made based on a sample of currently married women aged 15-24 years who had given most recent childbirth in five years preceding the survey. For the analysis, a time-to-event approach was applied using the Kaplan-Meier survival statistic, Log-Rank Chi-square test and Cox-Proportional Hazard (Cox-PH) models.ResultsThe results revealed that the proportion of postpartum modern contraceptive uptake among young users increased by 9%, from 33% in 2015-16 to 42% in 2019-21. The Cox-PH models revealed that, in both NFHS waves, the associations between various components of maternity services and postpartum modern contraceptive uptake were strongly significant, even after controlling for selected socio-economic and demographic correlates.ConclusionsThe findings of this study reinforced urgent need for implementing integrated maternal-child health and family planning programmes and for boosting effective family planning counselling by health professionals to promote and motivate young women with a desire to early adoption of modern contraception in subsequent months after a recent childbirth.

BackgroundPatients with kidney failure suffer high mortality, and we currently lack markers for risk stratification for these patients. We carried out a quality control study of a modified aptamer assay (SomaScan v.4.0) that measures ~ 5000 proteins, in preparation for a larger study using this platform in cohorts with kidney failure.MethodsForty participants from the Cardiac, Endothelial Function and Arterial Stiffness in End-Stage Renal Disease (CERES study) were selected to analyze technical and short-term biological variability, orthogonal correlations and differential protein expression in plasma from patients who died during 2.5 year follow-up. Long-term (one year) variability was studied in 421 participants in the Chronic Renal Insufficiency Cohort. We evaluated 4849 aptamers (4607 unique proteins) using data formats including raw data and data formatted using Adaptive Normalization by Maximum Likelihood (ANML), an algorithm developed for SomaScan data in individuals with normal kidney function.ResultsIn ANML format, median[IQR] intra-assay coefficient of variation (CV) was 2.38%[1.76, 3.40] and inter-assay CV was 7.38%[4.61, 13.12]. Short-term within-subject CV was 5.76% [3.35, 9.72]; long-term CV was 8.71%[5.91, 13.37]. Spearman correlations between aptamer and traditional assays for PTH, NT-proBNP, FGF-23 and CRP were all > 0.7. Fold-change (FC) in protein levels among non-survivors, significant after Bonferroni correction, included SVEP1 (FC[95% CI] 2.14 [1.62, 2.82]), keratocan (1.74 [1.40, 2.15]) and LanC-like protein 1 (0.56 [0.45, 0.70]). Compared to raw aptamer data, technical and short-term biological variability in paired samples was lower in ANML-formatted data. ANML formatting had minimal impact on orthogonal correlations with traditional assays or the associations of proteins with the phenotype of mortality.ConclusionsSomaScan had excellent technical variability and low within-subject short-term variability. ANML formatting could facilitate comparison of biomarker results with other studies that utilize this format. We expect SomaScan to provide novel and reproducible information in patients with kidney failure on dialysis.

In late 2019, the emergence of COVID-19 in Wuhan, China, led to the implementation of stringent measures forming the zero-COVID policy aimed at eliminating transmission. Zero-COVID policy basically aimed at completely eliminating the transmission of COVID-19. However, the relaxation of this policy in late 2022 reportedly resulted in a rapid surge of COVID-19 cases. The aim of this work is to investigate the factors contributing to this outbreak using a new SEIR-type epidemic model with time-dependent level of immunity. Our model incorporates a time-dependent level of immunity considering vaccine doses administered and time-post-vaccination dependent vaccine efficacy. We find that vaccine efficacy plays a significant role in determining the outbreak size and maximum number of daily infected. Additionally, our model considers under-reporting in daily cases and deaths, revealing their combined effects on the outbreak magnitude. We also introduce a novel Physics Informed Neural Networks (PINNs) approach which is extremely useful in estimating critical parameters and helps in evaluating the predictive capability of our model.

The current study investigated the association between psychological factors and financial behaviour during the COVID-19 pandemic in older people. Older people were chosen compared to other age groups because of the relatively greater impact in this age group of suboptimal financial decisions on future financial wellbeing. We hypothesised that the psychological factors facilitating general wellbeing during the COVID-I9 pandemic, i.e., positive mental wellbeing, hope, and positive coping, will have positive effects on financial behaviour. Based on telephone interviews, 1501 older Australians (Men = 750 and Women = 751; 55-64y = 630; > 65y = 871) completed an omnibus questionnaire examining coping, hope, mental wellbeing, and financial behaviour. Data was analysed using logistic regression and an ordinary and two-stage least square frameworks. Analyses revealed that the psychological factors identified as facilitating general wellbeing during the COVID-I9 pandemic also facilitated positive financial behaviour with hope and mental wellbeing emerging as significant determinants. Based on weightings from principal component analysis, one item each from the hope and mental wellbeing scale with eigenvalues > 1 were found to be robust predictors of positive financial behaviours. In conclusion, the findings support the assumption that the psychological factors associated with general wellbeing during the COVID-19 pandemic are also associated with positive financial behaviour. They further raise the possibility that single hope and positive mental well-being items can also be used to monitor psychological health and predict financial behaviour in older people and, in particular, at times of crisis. The latter may be useful measures for government to monitor psychological and financial wellbeing and inform policy for supporting older people at times of crisis.

Background and aimLong Covid is a significant public health concern with potentially negative implications for health inequalities. We know that those who are already socially disadvantaged in society are more exposed to COVID-19, experience the worst health outcomes and are more likely to suffer economically. We also know that these groups are more likely to experience stigma and have negative healthcare experiences even before the pandemic. However, little is known about disadvantaged groups' experiences of Long Covid, and preliminary evidence suggests they may be under-represented in those who access formal care. We will conduct a pilot study in a defined geographical area in London, United Kingdom to test the feasibility of a community-based approach of identifying Long Covid cases that have not been clinically diagnosed and have not been referred to Long Covid specialist services. We will explore the barriers to accessing recognition, care, and support, as well as experiences of stigma and perceived discrimination.MethodsThis protocol and study materials were co-produced with a Community Advisory Board (CAB) made up primarily of people living with Long Covid. Working with voluntary organisations, a study leaflet will be distributed in the local community to highlight Long Covid symptoms and invite those experiencing them to participate in the study if they are not formally diagnosed. Potential participants will be assessed according to the study's inclusion criteria and offered the opportunity to participate if they fit them. Awareness of Long Covid and associated symptoms, experiences of trying to access care, as well as stigma and discrimination will be explored through qualitative interviews with participants. Upon completion of the interviews, participants will be offered a referral to the local social prescribing team to receive support that is personalised to them potentially including, but not restricted to, liaising with their primary care provider and the regional Long Covid clinic.

BackgroundThe need to improve support following a diagnosis of dementia is widely recognised, but it is unclear how this can best be achieved within UK health and social care systems. A task-shared and task-shifted approach has been recommended, but there is limited guidance on how to achieve this in practice. As part of a programme of research, we developed an intervention to enhance the role of primary care in post-diagnostic care and support for people living with dementia and carers.MethodsWe used the Theory of Change to develop a complex intervention informed by initial literature reviews and qualitative work. The intervention was developed through an iterative series of workshops, meetings and task groups with a range of stakeholders, including the multidisciplinary project team, people living with dementia and carers, service managers, frontline practitioners, and commissioners.Results142 participants contributed to intervention development through face-to-face or virtual meetings. The intervention comprises three complementary strands of work focusing on: developing systems, delivering tailored care and support, and building capacity and capability. Clinical dementia leads, based in primary care networks, will facilitate the intervention providing tailored expertise and support.ConclusionThe Theory of Change proved useful in providing structure and engaging stakeholders. The process was challenging, took longer and was less participative than intended due to restrictions caused by the COVID-19 pandemic. We will next conduct a feasibility and implementation study to explore whether the intervention can be successfully delivered within primary care. If successful, the intervention offers practical strategies for delivering a task-shared and task-shifted approach to post-diagnostic support that could be adapted for similar health and social care contexts internationally.

We have recently been witnessing that our society is starting to heal from the impacts of COVID-19. The economic, social and cultural impacts of a pandemic cannot be ignored and we should be properly equipped to deal with similar situations in future. Recently, Monkeypox has been concerning the international health community with its lethal impacts for a probable pandemic. In such situations, having appropriate protocols and methodologies to deal with the outbreak efficiently is of paramount interest to the world. Early diagnosis and treatment stand as the only viable option to tackle such problems. To this end, in this paper, we propose an ensemble learning-based framework to detect the presence of the Monkeypox virus from skin lesion images. We first consider three pre-trained base learners, namely Inception V3, Xception and DenseNet169 to fine-tune on a target Monkeypox dataset. Further, we extract probabilities from these deep models to feed into the ensemble framework. To combine the outcomes, we propose a Beta function-based normalization scheme of probabilities to learn an efficient aggregation of complementary information obtained from the base learners followed by the sum rule-based ensemble. The framework is extensively evaluated on a publicly available Monkeypox skin lesion dataset using a five-fold cross-validation setup to evaluate its effectiveness. The model achieves an average of 93.39%, 88.91%, 96.78% and 92.35% accuracy, precision, recall and F1 scores, respectively. The supporting source codes are presented in https://github.com/BihanBanerjee/MonkeyPox.

JC Polyomavirus (JCV) is a human polyomavirus encoding T-antigen protein, which is implicated in carcinogenesis. JCV is prevalent in the upper and lower gastrointestinal track. Several studies have reported JCV associations with the risk of developing colorectal cancer (CRC), however, these findings remain controversial. Since JCV DNA may be present in healthy tissues as well as transformed tissues, JCV T-antigen expression could be a more useful measure of JCV's association with cancer development. The aim of this study is to conduct a meta-analysis of case-control studies to investigate if there is a significant association between JCV T-antigen protein expression and risk of CRC. A systematic review was performed to identify studies reporting JCV DNA prevalence in CRC and JCV T-antigen expression. The strength of the association was estimated by odds ratios (ORs). Five (of 66) studies satisfied analysis inclusion criteria, and spanned years 1999 to 2022. Random effects meta-analysis of CRC cases versus controls showed an 11-fold increased risk of CRC development in JCV DNA positive samples with JCV T-antigen expression versus normal tissues (OR 10.95; 95% CI: 2.48-48.24; P = 0.0016). The results of this meta-analysis of JCV infection followed by JCV T-antigen protein expression for the risk of CRC support the argument that JCV infection significantly increases the risk of colorectal cancer in tissues where the JCV T-antigen protein is expressed. Further research with JCV T-antigen expression in relation to CRC development is needed.

Antibiotics are frequently prescribed for children in the outpatient setting. Although sometimes necessary, antibiotic use is associated with important downstream effects including the development of antimicrobial resistance among human and environmental microorganisms. Current outpatient stewardship efforts focus on guiding appropriate antibiotic prescribing practices among providers, but little is known about parents' understanding of antibiotics and appropriate disposal of leftover antibiotics. To help bridge this gap, we conducted a qualitative study to assess parental understanding of their children's antibiotics, their adherence to antibiotic instructions, and their disposal practices. We conducted a semi-structured interview with parents of 13 children diagnosed with acute respiratory illnesses and prescribed antibiotics in an urban outpatient clinic. We found that parents had limited understanding of how antibiotics work. Although they received instructions about antibiotic use during the healthcare visit, adherence to the prescription and appropriate disposal of antibiotics was suboptimal. Limited baseline understanding of antibiotics, their prior experiences with antibiotics, perceptions about their social networks' antibiotic use, and information provided to them by healthcare providers may influence these behaviors. Our findings can inform educational efforts of outpatient stewardship programs to help optimize parental understanding of how to use and dispose of their children's antibiotics.

BackgroundBuilding on a distinguished history of community medicine training, public health programs have been expanding in India in recent years. The COVID-19 pandemic has brought additional attention to the importance of public health programs and the need for a strong workforce. This paper aims to assess the current capacity for public health education and training in India and provide recommendations for improved approaches to meet current and future public health needs.MethodsWe conducted a desk review of public health training programs via extensive internet searches, literature reviews, and expert faculty consultations. Among those programs, we purposively selected faculty members to participate in in-depth interviews. We developed summary statistics based on the desk review. For qualitative analysis, we utilized a combination of deductive and inductive coding to identify key themes and systematically reviewed the strengths and weaknesses of each theme.ResultsThe desk review captured 59 institutions offering public health training across India. The majority of training programs were graduate level degrees including Master of Public Health and Master of Science degrees. Key factors impacting these programs included collaborations, mentorship, curriculum standardization, tuition and funding, and student demand for public health education and careers. Collaborations and mentorship were highly valued but varied in quality across institutions. Curricula lacked standardization but also contained substantial flexibility and innovation as a result. Public sector programs were perceived to be affordable though fees and stipends varied across institutions. Further development of career opportunities in public health is needed.ConclusionPublic health education and training in India have a strong foothold. There are numerous opportunities for continued expansion and strengthening of this field, to support a robust multi-disciplinary public health workforce that will contribute towards achieving the sustainable development goals.

BackgroundDespite the progress in achieving gender equality to a certain extent, women are found to be more susceptible to health disadvantages compared to men in the older ages. However, research in the Indian context has mainly remained restricted to subjective health that heavily depends on the individual's perception, which may affect the validity of results. This study addresses this gap by complementing the investigation of the gender differentials in self-reported health outcomes (mobility and functional limitations) with that of objectively measured health status (hand-grip strength and static balance) among the older population of India. Besides, there is a dearth of literature that considers financial empowerment in explaining the gender differentials in health. Women's ability to participate in household decision-making, especially for important matters like major purchases, including property, indicates their empowerment status. Furthermore, the ability to extend financial support can be considered an important 'non-altruistic' driver for kins to care for older adults, indirectly affecting their health and well-being. Thus, the present paper explores the influence of financial empowerment on gender differentials in poor health outcomes.MethodsUsing the Longitudinal Aging Study in India, Wave-1 (2017-18), six logistic regression models have been specified to capture the adjusted association between gender and poor health outcomes. The first three models successively control for the demographic and social support factors; socioeconomic factors and pre-existing health conditions; and financial empowerment indicators. The last three models investigate the interactions between gender and marital status, living arrangement and involvement in financial decisions, respectively.ResultsThe findings reveal that women tend to be more perceptive about their physical discomfort than men and reported a higher prevalence of poor subjective health. In terms of objectively measured health status, older men had a higher prevalence of low hand-grip strength but a lower prevalence of poor balance. Gender demonstrated a strong, adjusted association with poor health outcomes among older adults. However, the magnitude of gender difference either shrunk considerably or became statistically insignificant for all the poor health outcomes after controlling the effect of indicators of financial empowerment. Further, the interaction between gender and involvement in financial matters demonstrated a stronger effect for men in reversing poor subjective health.ConclusionThe study reinforced the positive effect of financial empowerment in mitigating gender disparity in health among older adults.

BACKGROUND: Risk prediction is crucial in many areas of medical practice, such as cardiac transplantation, but existing clinical risk-scoring methods have suboptimal performance. We develop a novel risk prediction algorithm and test its performance on the database of all patients who were registered for cardiac transplantation in the United States during 1985-2015. METHODS AND FINDINGS: We develop a new, interpretable, methodology (ToPs: Trees of Predictors) built on the principle that specific predictive (survival) models should be used for specific clusters within the patient population. ToPs discovers these specific clusters and the specific predictive model that performs best for each cluster. In comparison with existing clinical risk scoring methods and state-of-the-art machine learning methods, our method provides significant improvements in survival predictions, both post- and pre-cardiac transplantation. For instance: in terms of 3-month survival post-transplantation, our method achieves AUC of 0.660; the best clinical risk scoring method (RSS) achieves 0.587. In terms of 3-year survival/mortality predictions post-transplantation (in comparison to RSS), holding specificity at 80.0%, our algorithm correctly predicts survival for 2,442 (14.0%) more patients (of 17,441 who actually survived); holding sensitivity at 80.0%, our algorithm correctly predicts mortality for 694 (13.0%) more patients (of 5,339 who did not survive). ToPs achieves similar improvements for other time horizons and for predictions pre-transplantation. ToPs discovers the most relevant features (covariates), uses available features to best advantage, and can adapt to changes in clinical practice. CONCLUSIONS: We show that, in comparison with existing clinical risk-scoring methods and other machine learning methods, ToPs significantly improves survival predictions both post- and pre-cardiac transplantation. ToPs provides a more accurate, personalized approach to survival prediction that can benefit patients, clinicians, and policymakers in making clinical decisions and setting clinical policy. Because survival prediction is widely used in clinical decision-making across diseases and clinical specialties, the implications of our methods are far-reaching.

Genetic switches frequently include DNA loops secured by proteins. Recent studies of the lambda bacteriophage repressor (CI), showed that this arrangement in which the protein links two sets of three operators separated by approximately 2.3 kbp, optimizes both the stability and dynamics of DNA loops, compared to an arrangement with just two sets of two operators. Because adjacent dimers interact pairwise, we hypothesized that the odd number of operators in each set of the lambda regulatory system might have evolved to allow for semi-specific, pair-wise interactions that add stability to the loop while maintaining it dynamic. More generally, additional CI dimers may bind non-specifically to flanking DNA sequences making the genetic switch more sensitive to CI concentration. Here, we tested this hypothesis using spectroscopic and imaging approaches to study the binding of the lambda repressor (CI) dimer protein to DNA fragments. For fragments with only one operator and a short flanking sequence, fluorescence correlation spectroscopy measurements clearly indicated the presence of two distinct DNA-CI complexes; one is thought to have a non-specifically bound CI dimer on the flanking sequence. Scanning force micrographs of CI bound to DNA with all six operators revealed wild-type or mutant proteins bound at operator positions. The number of bound, wild-type proteins increased with CI concentration and was larger than expected for strictly specific binding to operators. In contrast, a mutant that fails to oligomerize beyond a dimer, D197G, only bound to operators. These data are evidence that CI cooperativity promotes oligomerization that extends from operator sites to influence the thermodynamics and kinetics of CI-mediated looping.

Pure tense (T) and relaxed (R) quaternary state polymerized human hemoglobins (PolyhHbs) were synthesized and their biophysical properties characterized, along with mixtures of T- and R-state PolyhHbs. It was observed that the oxygen affinity of PolyhHb mixtures varied linearly with T-state mole fraction. Computational analysis of PolyhHb facilitated oxygenation of a single fiber in a hepatic hollow fiber (HF) bioreactor was performed to evaluate the oxygenation potential of T- and R-state PolyhHb mixtures. PolyhHb mixtures with T-state mole fractions greater than 50% resulted in hypoxic and hyperoxic zones occupying less than 5% of the total extra capillary space (ECS). Under these conditions, the ratio of the pericentral volume to the perivenous volume in the ECS doubled as the T-state mole fraction increased from 50 to 100%. These results show the effect of varying the T/R-state PolyhHb mole fraction on oxygenation of tissue-engineered constructs and their potential to oxygenate tissues.

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.

IntroductionAs mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs.Methods and analysisThis study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID.Ethics and disseminationEthical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID.RegistrationResearchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

Introduction The continuum of care (CoC) throughout pregnancy, delivery and post-delivery has recently been highlighted as an integrated intervention programme for maternal, new-born, and child health. Existing literature suggests the importance of continuum of care (CoC) for improved maternal and child health outcomes. However due to unavailability of data at the lowest administrative levels, literature on spatial pattern of uptake of full CoC is lacking. The present study attempts to focus on the spatial analysis of CoC in maternal health care in India. Data and methods The study is based on the fourth round of National Family Health Survey data conducted in 2015–16 in India. The outcome variable used is maternal health continuum of care which includes- at least 4 ANC visits, delivery through skilled birth attendant and postnatal check-up within 48 hours of delivery. Univariate and bivariate Local Indicator of Spatial Association (LISA) maps have been generated to show the spatial pattern of CoC across 640 districts in India. We also employed spatial regression techniques to explore the determinants of CoC. Findings Percentage of women who followed full CoC was observed to be least for East Kameng (0.0%) district of Arunachal Pradesh and highest in North Goa district (90.4%). Majority of districts where uptake of full CoC was more than 80 percent were found concentrated in southern region on India. Equivalently, findings indicated a strong spatial clustering of full CoC with high-high clusters mostly concentrated in southern districts. Low-low district clusters are concentrated in the states of Uttar Pradesh, Bihar and Madhya Pradesh. For complete CoC the global Moran’s I is 0.73 indicating the spatial dependence. The spatial regression analysis suggested that modern contraceptive use, meeting with health worker, urbanization and secondary or above education for women have positive impact on the utilisation of CoC. Conclusion The spatial pattern indicates district level clustering in uptake of CoC among women. The study suggests policymakers and stakeholders to implement comprehensive interventions at sub-regional levels for ensuring the completion of CoC for women which acts as a preventive measure for adverse outcomes such as-maternal and child mortality.

BackgroundThe COVID-19 pandemic has threatened continued access to public health services worldwide, including HIV prevention and care. This study aimed to evaluate the impact of the COVID-19 pandemic on HIV service access and delivery in the Asia region.MethodsA descriptive, cross-sectional, online study, conducted between October-November 2020, assessed the impact of COVID-19 on HIV prevention and care among people living with HIV (PLHIV), key populations (KPs), and healthcare providers (HCPs). The study populations were recruited across ten Asian countries/territories, covering Hong Kong, India, Japan, Malaysia, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam.ResultsAcross the region, 702 PLHIV, 551 KPs, and 145 HCPs were recruited. Both PLHIV and KPs reported decreased or had yet to visit hospitals/clinics (PLHIV: 35.9%; KPs: 57.5%), reduced HIV RNA viral load testing (21.9%; 47.3%), and interruptions in antiretroviral therapy (ART) (22.3%) or decreased/complete stop of HIV prevention medication consumption (40.9%). Travel constraints (40.6%), financial issues (28.9%), and not receiving prescription refills (26.9%) were common reasons for interrupted ART access, whereas reduced engagements in behaviours that could increase the risks of HIV acquisition and transmission (57.7%), travel constraints (41.8%), and less hospital/clinic visits (36.7%) underlie the disruptions in HIV preventive medications. Decreased visits from PLHIV/KPs and rescheduled appointments due to clinic closure were respectively reported by 50.7%-52.1% and 15.6%-17.0% of HCPs; 43.6%-61.9% observed decreased ART/preventive medication refills. Although 85.0% of HCPs adopted telemedicine to deliver HIV care services, 56.4%-64.1% of PLHIV/KPs were not using telehealth services.ConclusionsThe COVID-19 pandemic substantially disrupted HIV prevention to care continuum in Asia at the time of the study. The findings highlighted differences in HIV prevention to care continuum via telehealth services utilisation by PLHIV, KPs, and HCPs. Efforts are needed to optimise infrastructure and adapt systems for continued HIV care with minimal disruptions during health emergency crises.

Infection prevention and control (IPC) program is obligatory for delivering quality services in any healthcare setup. Lack of administrative support and resource-constraints (under-staffing, inadequate funds) were primary barriers to successful implementation of IPC practices in majority of the hospitals in the developing countries. The Coronavirus Disease 2019 (COVID-19) brought a unique opportunity to improve the IPC program in these hospitals. A PDSA (Plan-Do-Study- Act) model was adopted for this study in a tertiary care hospital which was converted into a dedicated COVID-19 treatment facility in Varanasi, India. The initial focus was to identify the deficiencies in existing IPC practices and perceive the opportunities for improvement. Repeated IPC training (induction and reinforce) was conducted for the healthcare personnel (HCP) and practices were monitored by direct observation and closed-circuit television. Cleaning audits were performed by visual inspection, review of the checklists and qualitative assessment of the viewpoints of the HCP was carried out by the feedbacks received at the end of the training sessions. A total of 2552 HCP and 548 medical students were trained in IPC through multiple offline/onsite sessions over a period of 15 months during the ongoing pandemic. Although the overall compliance to surface disinfection and cleaning increased from 50% to >80% with repeated training, compliance decreased whenever newly recruited HCP were posted. Fear psychosis in the pandemic was the greatest facilitator for adopting the IPC practices. Continuous wearing of personal protective equipment for long duration, dissatisfaction with the duty rosters as well as continuous posting in high-risk areas were the major obstacles to the implementation of IPC norms. Recognising the role of an infection control team, repeated training, monitoring and improvisation of the existing resources are keys for successful implementation of IPC practices in hospitals during the COVID-19 pandemic.

The uncontrolled spread of (mis)information, news and propaganda related to COVID 19 created an ‘infodemic’ leading to panic and unscientific practices among the mass. With the largest number of internet users in the world, India has witnessed a steep rise in the number of people seeking information on social media related to COVID-19, which reached a staggering 22.3 million by March, 2020. This study aimed to evaluate the trend of COVID-19 associated food and nutrition news search by Indian internet users between 27th January 2020 to 30th June 2021 (time period between the first detected COVID-19 case and the end of the second wave in India) and its impact on their perceptions and practices. The association between the change in Relative Search Volume (RSV) on Google Trends (GT) of 34 popularly searched keywords classified by the researchers under 5 different categories—“Immunity”, “Eating behavior”, “Food safety”, “Food scares and concerns” and “Covid scare” showed a steep rise in search for immunity boosters, vitamin supplement brands “ayush kadha (ayurvedic decoction) during the first wave (April- August 2020). With a brief period of decline in the search trend, it again hiked correspondingly with the growing number of positive cases during the second wave in India. An online survey conducted on adult Indian internet users (n = 572) reported high (71.9%) consumption of Vitamin C rich fruits as well as Vitamin C (68.2%) and Zinc (61.4%) supplements to boost immunity. Traditional Indian spices like ginger and garlic were used by 62.9% and 50.9% respondents respectively. Most respondents reported to rely on social media for gathering COVID-19 associated tips for boosting immunity, however those with history of COVID-19 infection reported to rely more on doctors and health professionals for information. This study highlights the need of media and health literacy to advocate for the use of health information cautiously.

IntroductionCOVID-19 has placed unprecedented pressure on dementia health and social care systems worldwide. This has resulted in reduced services and support for people with dementia and their family carers. There are gaps in the evidence on the impact of the pandemic on Quality of Life (QoL). We carried out a study on the impact of the pandemic on the QoL of a group of people with dementia and their family carers who were part of a larger existing cohort study.MethodsWe quantitatively measured QoL, on two occasions during the two national lockdowns in 2020 and compared these data with those obtained when they entered the study (before the pandemic). Measures used included: DEMQOL-Proxy, Clinical Dementia Rating Scale and C-DEMQOL. To understand how QoL changed over time, a repeated measures ANOVA was run for each dependent variable with the following variables entered as co-variates: duration in study, baseline dementia severity, gender of the family carer, gender of the person with dementia, family carer relationship, dementia type, living status, age of the person with dementia, and age of the family carer.Results248 participants took part in the study. QoL scores did not significantly decline between either time period for the person with dementia or their family carer. There was variation in subgroups; with co-resident status, carer relationship, gender of the person with dementia, age of the person with dementia, and baseline cognitive status influencing QoL outcomes in family carers.DiscussionIt is striking that people with dementia and their carers did not report a decline in QoL during the pandemic or in the months following restrictions suggesting the possibility of resilience. Variation in subgroups suggests that specific groups of family carers were more vulnerable to lower QoL; indicating the need for more tailored, nuanced support during this period.

Intraguild predation (IGP) is common in the freshwater insect communities, involving a top predator, intraguild prey (IG prey) and a shared prey. Influence of the habitat complexity on the prey-predator interactions is well established through several studies. In the present instance, the IGP involving the heteropteran predators and the dipteran prey were assessed in the background of the habitat complexity. The three predators Diplonychus rusticus, Ranatra filiformis, and Laccotrephes griseus, one intraguild prey Anisops bouvieri and two dipteran prey Culex quinquefasciatus and Chironomus sp. were used in different relative density against the complex habitat conditions to deduce the impact on the mortality on the prey. In comparison to the open conditions, the presence of the macrophytes and pebbles reduced the mortality of the shared prey under intraguild system as well as single predator system. The mortality of the shared prey was however dependent on the density of the predator and prey. Considering the shared prey mortality, predation on mosquito larvae was always higher in single predator system than chironomid larvae irrespective of identity and density of predators. However, for both the shared prey, complexity of habitat reduced the prey vulnerability in comparison to the simple habitat condition. Higher observed prey consumption depicts the higher risk to predation of shared prey, though the values varied with habitat conditions. Mortality of IG prey (A. bouvieri) in IGP system followed the opposite trend of the shared prey. The lower mortality in simple habitat and higher mortality in complex habitat conditions was observed for the IG prey, irrespective of shared prey and predator density. In IGP system, the shared prey mortality was influenced by the habitat conditions, with more complex habitat reducing the vulnerability of the shared prey and increased mortality of the IG prey. This implies that the regulation of the mosquitoes, in the IGP system will be impeded by the habitat conditions, with the heteropteran predators as the top predator.

Introduction Diarrhoeal diseases are common among children and older adults. Yet, majority of the scientific studies deal with children, neglecting the other vulnerable and growing proportion of the population–the older adults. Therefore, the present study aims to find rural-urban differentials in the prevalence of diarrhoea among older adults in India and its states. Additionally, the study aims to find the correlates of diarrhoea among older adults in India. The study hypothesizes that there are no differences in the prevalence of diarrhoea in rural and urban areas. Methods Data for this study was utilized from the recent Longitudinal Ageing Study in India (2017–18). The present study included eligible respondents aged 60 years and above (N = 31,464). Descriptive statistics along with bivariate analysis was presented to reveal the preliminary results. In addition, binary logistic regression analysis was used to fulfil the study objectives. Results About 15% of older adults reported that they suffered from diarrhoea in the last two years. The prevalence of diarrhoea among older adults was found to be highest in Mizoram (33.5 per cent), followed by Chhattisgarh (30.7 per cent) and Bihar (30.2 per cent). There were significant rural-urban differences in the prevalence of diarrhoea among older adults in India (difference: 7.7 per cent). The highest rural-urban differences in the prevalence of diarrhoea were observed among older adults who were 80+ years old (difference: 13.6 per cent), used unimproved toilet facilities (difference: 12.7 per cent), lived in the kutcha house (difference: 10.2 per cent), and those who used unclean source of cooking fuel (difference: 9 per cent). Multivariate results show that the likelihood of diarrhoea was 17 per cent more among older adults who were 80+ years compared to those who belonged to 60–69 years’ age group [AOR: 1.17; CI: 1.04–1.32]. Similarly, the older female had higher odds of diarrhoea than their male counterparts [AOR: 1.19; CI: 1.09–1.30]. The risk of diarrhoea had declined with the increase in the educational level of older adults. The likelihood of diarrhoea was significantly 32 per cent more among older adults who used unimproved toilet facilities than those who used improved toilet facilities [AOR: 1.32; CI: 1.21–1.45]. Similarly, older adults who used unimproved drinking water sources had higher odds of diarrhoea than their counterparts [AOR: 1.45; CI: 1.25–1.69]. Moreover, older adults who belonged to urban areas were 22 per cent less likely to suffer from diarrhoea compared to those who belonged to rural areas [AOR: 0.88; CI: 0.80–0.96]. Conclusion The findings of this study reveal that diarrhoea is a major health problem among older adults in India. There is an immediate need to address this public health concern by raising awareness about poor sanitation and unhygienic practices. With the support of the findings of the present study, policy makers can design interventions for reducing the massive burden of diarrhoea among older adults in rural India.

IntroductionIndividuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor. In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients' experiences of stigma and discrimination.Methods and analysisA mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received.Ethics and disseminationEthical approval was obtained from South Central-Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.

Particle encapsulated hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have clear advantages over their acellular counterparts because of their larger molecular diameter and lack of vasoactivity upon transfusion. Poly(ethylene glycol) surface conjugated liposome encapsulated Hb (PEG-LEH) nanoparticles are considered a promising class of HBOC for use as a red blood cell (RBC) substitute. However, their widespread usage is limited by manufacturing processes which prevent material scale up. In this study, PEG-LEH nanoparticles were produced via a scalable and robust process using a high-pressure cell disruptor, and their biophysical properties were thoroughly characterized. Hb encapsulation, methemoglobin (metHb) level, O2-PEG-LEH equilibria, PEG-LEH gaseous (oxygen, carbon monoxide, nitric oxide) ligand binding/release kinetics, lipocrit, and long-term storage stability allowed us to examine their potential suitability and efficacy as an RBC replacement. Our results demonstrate that PEG-LEH nanoparticle suspensions manufactured via a high-pressure cell disruptor have Hb concentrations comparable to whole blood (~12 g/dL) and possess other desirable characteristics, which may permit their use as potential lifesaving O2 therapeutics.

Endophytes are silent microbial partners of green plants that ensure hosts' survival in odd conditions. They are known as the factories of multipotent metabolites with diverse bioactivities beneficial to modern pharmaceuticals industry. Endophytic fungi have been screened from a variety of plants and it is the first-time endophytes of club moss is being studied for production of antibacterial and antioxidative compounds. The present study reveals that Lycopodium clavatum L. harbors a potent niche of bioactive endophytic fungi and Colletotrichum alatae LCS1 was the prime producer of antibacterial and antioxidative compounds among them. The minimum inhibitory and bactericidal concentrations of ethyl- acetate culture extract ranged from 15.62 to 250 μg/mL against four Gram negative and three Gram positive microorganisms including methicillin resistant Staphylococcus aureus (ATCC-33591). Bio-autogram based screening followed by Gas chromatographic analysis confirmed the occurrence of 17 bioactive compounds and α-bisabolol is known to be the prime one. Alfa bisabolol is a unique and versatile bioactive essential oil and facilitates variety of functions. Killing kinetics data along with leakage of macromolecules into extracellular environment supports the cidal activity of the antibacterial principles at MBC values. Isolate C. alatae LCS1 was optimized by one variable at a time system coupled with response surface methodology for broad spectrum antibacterial production. The organism yielded maximum response (22.66±0.894 mm of zone of inhibition against MRSA) in 250 mL Erlenmeyer flask containing 50 mL potato dextrose broth supplemented with (g/L) glucose, 7.53; yeast extract concentration, 0.47; NaCl, 0.10 with medium pH 6.46; after 134 hours of incubation at 26°C. Optimized fermentation parameters enhanced antibacterial activity up-to more than 50% than the pre-optimized one (10.33±0.57 mm). Endophytic LCS1 was also efficient in free radical scavenging tested by DPPH, ABTS, H2O2 and FRAP assay with an IC50 values of 23.38±5.32 to 82.873±6.479 μg/mL.

BackgroundWith the increase in elderly population, the risk of cardiovascular diseases (CVD) among Indian older adults is also increasing. The present paper tries to assess how different anthropometric measures of obesity and physical activity affects cardiovascular disease risk among older adults in India.MethodsThe data from Longitudinal Ageing Study in India (LASI) has been used. The total sample size for the present study is 31,464 older adults aged 60 years and above. Chi-square test and binary logistic regression has been used to measure the association of obesity measures and CVD prevalence.ResultsAbout 35.2% (n = 11,058) of the older adults suffered from CVD. Moreover, 22.2% (n = 6,217) of the older adults were obese/overweight, 23.7% (n = 6,651) had high risk waist circumference and 77.0% (n = 21,593) had high risk waist-Hip ratio. The likelihood of CVD was 60%, 50%, and 34% significantly higher among older adults who were obese/overweight [Adjusted odds ratio (AOR): 1.60; CI: 1.48-1.72], had high risk waist circumference [AOR: 1.50; CI: 1.39-1.62] and high risk waist-Hip ratio [AOR: 1.34; CI: 1.25-1.44], respectively compared to older adults with normal BMI and those who do not have a high risk waist circumference and high risk waist hip ratio. Moreover, older adults who never did physical activity had 22 per cent higher risk of CVD than those who did frequent [AOR: 1.22; CI: 1.13-1.32] physical activity.ConclusionThe burden of overweight and obesity along with physical inactivity increases the risk of CVD in older adults. These findings highlight the urgent need for framing direct and indirect strategies to control obesity in order to reduce the burden of CVD among older adults in India.

Exogenous application of an electric field can direct cell migration and improve wound healing; however clinical application of the therapy remains elusive due to lack of a suitable device and hence, limitations in understanding the molecular mechanisms. Here we report on a novel FDA approved redox-active Ag/Zn bioelectric dressing (BED) which generates electric fields. To develop a mechanistic understanding of how the BED may potentially influence wound re-epithelialization, we direct emphasis on understanding the influence of BED on human keratinocyte cell migration. Mapping of the electrical field generated by BED led to the observation that BED increases keratinocyte migration by three mechanisms: (i) generating hydrogen peroxide, known to be a potent driver of redox signaling, (ii) phosphorylation of redox-sensitive IGF1R directly implicated in cell migration, and (iii) reduction of protein thiols and increase in integrinαv expression, both of which are known to be drivers of cell migration. BED also increased keratinocyte mitochondrial membrane potential consistent with its ability to fuel an energy demanding migration process. Electric fields generated by a Ag/Zn BED can cross-talk with keratinocytes via redox-dependent processes improving keratinocyte migration, a critical event in wound re-epithelialization.

BackgroundThere has been a shift in focus of international dementia policies from improving diagnostic rates to enhancing the post-diagnostic support provided to people with dementia and their carers. There is, however, little agreement over what constitutes good post-diagnostic support. This study aimed to identify the components of post-diagnostic dementia support.MethodsWe adopted a qualitative design using interviews, focus groups and observation to explore the perspectives of key stakeholders on the content of post-diagnostic dementia support. Purposive sampling was used to identify sites in England and Wales recognised as delivering good practice. Participants included 17 people with dementia, 31 carers, 68 service managers or funders, and 78 frontline staff. Interviews and focus groups were audio recorded and transcribed for analysis. Forty-eight sessions of observation were completed and recorded in fieldnotes. Components were identified through an inductive, thematic approach and cross-checked against national guidelines and existing frameworks; they were subsequently critically reviewed by a range of experts and our mixed stakeholder panel.ResultsTwenty distinct components of post-diagnostic support were identified, related to five themes: timely identification and management of needs; understanding and managing dementia; emotional and psychological wellbeing; practical support; and integrating support. The first and last of these were cross-cutting themes facilitating the delivery of a unique constellation of components of post-diagnostic support to each individual living with dementia or dyad at a particular time.ConclusionsOur work offers an empirically based framework to inform the development and delivery of holistic, integrated and continuous dementia care from diagnosis to end of life. It highlights the relevance of many components to both people living with dementia and their carers. Since the framework was developed in England and Wales, further research is needed to explore the relevance of our components to other sectors, countries and care systems.

The restrictive measures implemented in response to the COVID-19 pandemic have triggered sudden massive changes to travel behaviors of people all around the world. This study examines the individual mobility patterns for all transport modes (walk, bicycle, motorcycle, car driven alone, car driven in company, bus, subway, tram, train, airplane) before and during the restrictions adopted in ten countries on six continents: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. This cross-country study also aims at understanding the predictors of protective behaviors related to the transport sector and COVID-19. Findings hinge upon an online survey conducted in May 2020 (N = 9,394). The empirical results quantify tremendous disruptions for both commuting and non-commuting travels, highlighting substantial reductions in the frequency of all types of trips and use of all modes. In terms of potential virus spread, airplanes and buses are perceived to be the riskiest transport modes, while avoidance of public transport is consistently found across the countries. According to the Protection Motivation Theory, the study sheds new light on the fact that two indicators, namely income inequality, expressed as Gini index, and the reported number of deaths due to COVID-19 per 100,000 inhabitants, aggravate respondents' perceptions. This research indicates that socio-economic inequality and morbidity are not only related to actual health risks, as well documented in the relevant literature, but also to the perceived risks. These findings document the global impact of the COVID-19 crisis as well as provide guidance for transportation practitioners in developing future strategies.

After an epidemic outbreak, the infection persists in a community long enough to engulf the entire susceptible population. Local extinction of the disease could be possible if the susceptible population gets depleted. In large communities, the tendency of eventual damp down of recurrent epidemics is balanced by random variability. But, in small communities, the infection would die out when the number of susceptible falls below a certain threshold. Critical community size (CCS) is considered to be the mentioned threshold, at which the infection is as likely as not to die out after a major epidemic for small communities unless reintroduced from outside. The determination of CCS could aid in devising systematic control strategies to eradicate the infectious disease from small communities. In this article, we have come up with a simplified computation based approach to deduce the CCS of HIV disease dynamics. We consider a deterministic HIV model proposed by Silva and Torres, and following Nåsell, introduce stochasticity in the model through time-varying population sizes of different compartments. Besides, Metcalf's group observed that the relative risk of extinction of some infections on islands is almost double that in the mainlands i.e. infections cease to exist at a significantly higher rate in islands compared to the mainlands. They attributed this phenomenon to the greater recolonization in the mainlands. Interestingly, the application of our method on demographic facts and figures of countries in the AIDS belt of Africa led us to expect that existing control measures and isolated locations would assist in temporary eradication of HIV infection much faster. For example, our method suggests that through systematic control strategies, after 7.36 years HIV epidemics will temporarily be eradicated from different communes of island nation Madagascar, where the population size falls below its CCS value, unless the disease is reintroduced from outside.

BackgroundThe remarkable progress seen in maternal and child health (MCH) in India over the past two decades has been impacted by the COVID-19 pandemic. We aimed to undertake a rapid assessment to identify key priorities for public health research in MCH in India within the context and aftermath of the COVID-19 pandemic.MethodsA web-based survey was developed to identify top research priorities in MCH. It consisted of 26 questions on six broad domains: vaccine preventable diseases, outbreak preparedness, primary healthcare integration, maternal health, neonatal health, and infectious diseases. Key stakeholders were invited to participate between September and November 2020. Participants assigned importance on a 5-point Likert scale, and assigned overall ranks to each sub-domain research priority. Descriptive statistics were used to examine Likert scale responses, and a ranking analysis was done to obtain an "average ranking score" and identify the top research priority under each domain.ResultsAmongst the 84 respondents from across 15 Indian states, 37% were public-health researchers, 25% healthcare providers, 20% academic faculty and 13% were policy makers. Most respondents considered conducting systems strengthening research as extremely important. The highest ranked research priorities were strengthening the public sector workforce (vaccine preventable diseases), enhancing public-health surveillance networks (outbreak preparedness), nutrition support through community workers (primary care integration), encouraging at least 4-8 antenatal visits (maternal health), neonatal resuscitation to reduce birth asphyxia (neonatal health) and screening and treatment of tuberculosis (infectious diseases). Common themes identified through open-ended questions primarily included systems strengthening priorities across domains.ConclusionsThe overall focus for research priorities in MCH in India during the COVID-19 pandemic is on strengthening existing services and service delivery, rather than novel research. Our results highlight pivotal steps within the roadmap for advancing and sustaining maternal and child health gains during the ongoing COVID-19 pandemic and beyond.