Knowledge of and Self-Expressed Stigma for COVID-19 Vaccination among Pre-University Students in a College in South India: A Cross-Sectional Study.

Background: Coronavirus disease 2019 (COVID-19) is a contagious infection characterized by severe acute respiratory syndrome (SARS-CoV-2). Safe and effective vaccines are game-changers in the global vision of marking an end to the challenges posed by the COVID-19 pandemic. However, vaccine hesitancy due to perceived stigma and misinformation is a grave cause of concern. Objectives: To assess pre-university students' self-expressed stigma regarding COVID-19 vaccination and its association with their knowledge. Materials and Methods: A cross-sectional study was adopted for this research. A structured questionnaire approach was used to gather data from 384 students purposively at the selected pre-university college. The structured questionnaire consisted of three sections that explored the socio-demographic characteristics of the study participants, knowledge of vaccination, and self-expressed stigma, respectively. A total of 384 respondents took part in the study. Results: The study observes a low positive relationship (r = 0.25, P < 0.01) between knowledge and self-expressed stigma toward vaccination. Further, it was observed that participants from rural backgrounds had lower knowledge and self-expressed stigma scores than participants from urban settings. It is pertinent to note that participants with other sources of information had higher knowledge than those who used the internet, friends/peers, or newspapers. Both of the aforementioned findings are statistically significant. Conclusion: The interventions should revive trust in national health authorities, structured awareness campaigns by government agencies, and media coverage about the safety and efficacy of vaccines. In addition, it is also important to support citizens in ensuring that they have access to the right information from authentic sources in times of crisis.

Competencies for Transformational Leadership in Public Health-An International Delphi Consensus Study.

Objectives: This Delphi study intended to develop competencies for transformational leadership in public health, including behavioral descriptions (descriptors) tailored to individuals and their contexts. Methods: The study involved five rounds, including online "e-Delphi" consultations and real-time online workshops with experts from diverse sectors. Relevant competencies were identified through a literature review, and experts rated, ranked, rephrased, and proposed descriptors. The study followed the Guidance on Conducting and REporting DElphi Studies (CREDES) and the COmpeteNcy FramEwoRk Development in Health Professions (CONFERD-HP) reporting guidelines. Results: Our framework comprises ten competencies for transformational public health leadership (each with its descriptors) within four categories, and also describes a four-stage model for developing relevant competencies tailored to different contexts. Conclusion: Educators responsible for curriculum design, particularly those aiming to align curricula with local goals, making leadership education context-specific and -sensitive, may benefit from the proposed framework. Additionally, it can help strengthen links between education and workforce sectors, address competency gaps, and potentially reduce the out-migration of graduates in the health professions.

Spatial Patterns in the Distribution of Hypertension among Men and Women in India and Its Relationship with Health Insurance Coverage.

The present study explores district-level data associated with health insurance coverage (%) and the prevalence of hypertension (mildly, moderately, and severely elevated) observed across men and women as per NFHS 5. Coastal districts in the peninsular region of India and districts in parts of northeastern India have the highest prevalence of elevated blood pressure. Jammu and Kashmir, parts of Gujarat and parts of Rajasthan have a lower prevalence of elevated blood pressure. Intrastate heterogeneity in spatial patterns of elevated blood pressure is mainly seen in central India. The highest burden of elevated blood pressure is in the state of Kerala. Rajasthan is among the states with higher health insurance coverage and a lower prevalence of elevated blood pressure. There is a relatively low positive relationship between health insurance coverage and the prevalence of elevated blood pressure. Health insurance in India generally covers the cost of inpatient care to the exclusion of outpatient care. This might mean that health insurance has limited impact in improving the diagnosis of hypertension. Access to public health centers raises the probability of adults with hypertension receiving treatment with antihypertensives. Access to public health centers has been seen to be especially significant at the poorer end of the economic spectrum. The health and wellness center initiative under Ayushman Bharat will play a crucial role in hypertension control in India.

A Critical Analysis of the World's Largest Publicly Funded Health Insurance Program: India's Ayushman Bharat.

Background: Launched in September 2018, the ABPMJAY is the world's largest publicly funded health insurance (PFHI) program with population coverage of 500 million. A systematic review was conducted. Methods: A comprehensive literature search was conducted in four databases: PubMed, Web of Science, Scopus, and Google Scholar. The literature search was conducted with the search terms: "Ayushman Bharat OR ABPMJAY OR modicare AND RSBY." The search was set to title and abstract. Gray literature and government websites were also searched for relevant documents. A total of 881 documents were identified (PubMed: 53, Web of Science: 46, Scopus: 97, Google Scholar: 681, government websites: two, and gray literature: two). Fifty-two duplicates were identified. After the elimination of the duplicates, 829 unique documents were identified. These 829 unique citations were then subjected to a review of title and abstract independently by 2 reviewers. Six-hundred and ninety-two articles were rejected after review of title and abstract. One-hundred and thirty-seven articles were screened for full text independently by two reviewers. Sixty-six articles were rejected after review of the full text. Disagreements were resolved by discussion. Seventy-one unique articles were included in the final review. To attain the objective of the study, which is to critically analyze and provide an overview of Ayushman Bharat, a narrative synthesis was performed. Results: Seven themes were identified from the review: (1) health and wellness centers (HWCs); (2) out-of-pocket health expenditure (OOPHE); (3) fraud; (4) upcoding and provision of unnecessary medical care; (5) moving focus away from primary care; (6) coverage; and (7) lop-sided access, exclusion at the periphery, and brain drain. There is very little impact evidence of the ABPMJAY available. Conclusions: The government could plan impact evaluation studies in every state that the ABPMJAY is functional in. Any high-quality feedback generated might enable the National Health Authority, the government body leading and coordinating the ABPMJAY, to take necessary steps operationally and advice the government on strategy. Another concern is that the ABPMJAY PFHI might negatively impact the ongoing process of continuous strengthening and development of the government health-care system at all levels-primary, secondary, and tertiary. Continual recalibration and course corrections on the basis of high-quality feedback might enable ABPMJAY reduce catastrophic OOPHE for 500 million Indians. This is more than 6% of humanity: the largest block of people served by a single PFHI in history.

Prevalence of Cyberchondria among Outpatients with Metabolic Syndrome in a Tertiary Care Hospital in Southern India.

Background: In today's world, Internet-based medical information plays a significant role in patient education. There are several accessible health-related websites. It has become common to search Internet before going for a medical consultation. The main objective of this study was to determine the prevalence of cyberchondriasis and its association with demographic variables. Methods: A cross-sectional study was carried out among metabolic syndrome patients attending the cardiology, endocrinology, and neurology outpatient departments of a tertiary care hospital in South India. The prevalence of cyberchondriasis and its constructs were measured using the cyberchondria severity scale (CSS). Inferential statistics revealed no statistically significant difference in the average CSS scores across sociodemographic variables. Spearman correlation was conducted to determine the relationship between the constructs. Results: A total of 379 participants with metabolic syndrome were included in the study. 42.5% of them were severely affected, and 28.0% were moderately affected by cyberchondriasis. Among the constructs studied, compulsion (85.7%), distress (91.8%), excessiveness (96.6%), and reassurance (76.1%) constructs had an impact on a greater number of study participants, compared to mistrust of medical professional construct (33.0%). Cyberchondriasis had a significant relationship with the history of myocardial infarction (p value = 0.03). There was a statistically significant positive linear relationship between mistrust and reassurance (r s = 0.169, p value<0.001). Reassurance had a significant negative linear relationship with distress (r s = -0.147, p value = 0.004). Conclusion: In India, cyberchondriasis is a growing public mental health issue. Awareness among the general population is necessary to minimize the possible outcomes of cyberchondriasis like anxiety and depression. Screening individuals for possible risk factors is recommended.

Eye Donation: Awareness, Knowledge, Willingness, and Barriers among Paramedical and Allied Health Science Students at a Tertiary Care Teaching Hospital in South India.

BACKGROUND: Visual impairments have physical, emotional, social, and economical consequences and are a crucial element influencing one's quality of life. A total of 1.285 million people are estimated to be visually impaired worldwide of which 39 million are categorised as blind. These figures are startling, given that 80 percent of known vision impairments are either treatable or preventable. Corneal transplants appear to be our best hope for resolving this problem; however, a global shortage of available donors continues to dampen efforts addressing this issue. METHODS: This two-year cross-sectional study employed a convenience sampling technique and a standardised questionnaire to survey 150 paramedical and allied health science students at a tertiary care teaching hospital and assessed the awareness, knowledge, willingness and barriers regarding eye donation. RESULTS: The study revealed a 93.3% awareness rate of the donation procedure, of which 46% attributed their awareness to media sources. However, other aspects assessed had much lower awareness rates; when the eyes are donated (53.3%), optimal time period for retrieval of tissue/organ (54%), ideal part transplanted (54%), age limit not restricting donation (67%), donation by donors using spectacles (48%), confidentiality of the donor and recipient (54%), hospital having the facility of an eye bank (63%). 49 percent of the respondents were willing to pledge themselves as eye donors, and a majority of the unwilling respondents reported that familial opposition was the reason for their hesitation. CONCLUSION: Knowledge levels appear to be below expectations, and more effort is required to ensure that knowledge is imparted to our healthcare practitioners, who will then transfer this knowledge to the population, resulting in an increase in donation rates.

An Assessment of the Economic Feasibility of Selected Surgeries in the Obstetrics and Gynaecology Department under Community-Based Health Insurance (CBHI) in a Tertiary Care Hospital in South India.

Community-Based Health Insurance (CBHI) is a form of micro health insurance targeted at low-income groups that permits for grouping of assets to tackle the expenses of future, uncertain, health-related circumstances. According to the International Labour Organisation, more than 80% of India's employed nonagricultural population is in the informal sector, implying that they are possibly excluded from receiving health insurance benefits. This is where CBHI comes into play, wherein groups of people belonging to a community define the demand and benefits and pool their resources to provide financial protection to all their members. This study aims to scrutinize the package prices sanctioned by these schemes and compare them with the cost incurred by the hospital. The expense pattern of three surgeries in the Department of Obstetrics and Gynaecology was analysed under three insurance schemes: Arogya Bhagya Yojana, Arogya Karnataka, and Employees' State Insurance Scheme. Methodology. A retrospective study was conducted in a 2,032-bedded tertiary care hospital in South India. Patients of abdominal hysterectomy, vaginal hysterectomy, and caesarean section surgeries covered by any of the insurance schemes mentioned above were a part of the inclusion criteria. The patient records were examined from the hospital's Medical Records Department (MRD). The patients' bills were assembled from the inpatient billing department to scrutinize all the expenses associated with each surgery. The variable costs include consumables, medicine, electricity and AC, diagnostics, blood bank materials, doctor's fee, package differences, and others. In contrast, fixed costs include bed cost, equipment cost (purchase + annual maintenance cost), manpower cost-OT, manpower cost-nursing, and allocated indirect costs associated with the medical treatment. These were computed and compared with the package price of respective insurance schemes to determine if the schemes are profit-yielding schemes or loss-yielding schemes, using the data from the finance department. Results and Conclusion. It has been observed that the operating loss of the hospital for abdominal hysterectomy, vaginal hysterectomy, and caesarean section under CBHI schemes ranges between 7% and 36%. The highest loss was observed in Arogya Karnataka Scheme for caesarean section surgery (BPL patients). The amount received through these schemes is insufficient to cover the costs acquired by the hospital, let alone make a profit. However, under Arogya Bhagya and ESI Schemes, the hospital has made a profit in covering the variable costs for these surgeries. The study concludes that the hospital is running under loss due to the three Community-Based Health Insurance (CBHI) schemes.

Mechanisms and regulation of IL-22-mediated intestinal epithelial homeostasis and repair.

AIMS: Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic inflammatory disorders of the intestine for which key elements in disease initiation and perpetuation are defects in epithelial barrier integrity. Achieving mucosal healing is essential to ameliorate disease outcome and so new therapies leading to epithelial homeostasis and repair are under investigation. This study was designed to determine the mechanisms by which IL-22 regulates intestinal epithelial cell function. MAIN METHODS: Human intestinal organoids and resections, as well as mice were used to evaluate the effect of IL-22 on stem cell expansion, proliferation and expression of mucus components. IL-22 effect on barrier function was assessed in polarized T-84 cell monolayers. Butyrate co-treatments and organoid co-cultures with immune cells were performed to monitor the impact of microbial-derived metabolites and inflammatory environments on IL-22 responses. KEY FINDINGS: IL-22 led to epithelial stem cell expansion, proliferation, barrier dysfunction and anti-microbial peptide production in human and mouse models evaluated. IL-22 also altered the mucus layer by inducing an increase in membrane mucus but a decrease in secreted mucus and goblet cell content. IL-22 had the same effect on anti-microbial peptides and membrane mucus in both healthy and IBD human samples. In contrast, this IL-22-associated epithelial phenotype was different when treatments were performed in presence of butyrate and organoids co-cultured with immune cells. SIGNIFICANCE: Our data indicate that IL-22 promotes epithelial regeneration, innate defense and membrane mucus production, strongly supporting the potential clinical utility of IL-22 as a mucosal healing therapy in IBD.

Near infrared readouts offer sensitive and rapid assessments of intestinal permeability and disease severity in inflammatory bowel disease models.

Intestinal permeability and neutrophil activity are closely linked to inflammatory bowel disease (IBD) pathophysiology. Here we discuss two techniques for assessing permeability and neutrophil activity in mouse IBD models using near infrared (NIR) detection. To address the limitation of visible light readouts-namely high background-IRDye 800CW was used to enable rapid, non-terminal measurements of intestinal permeability. The increased sensitivity of NIR readouts for colon permeability is shown using dextran sulfate sodium (DSS) and anti-CD40 murine colitis models in response to interleukin-22 immunoglobulin Fc (IL22Fc) fusion protein and anti-p40 monoclonal antibody treatments, respectively. In addition to enhanced permeability, elevated levels of neutrophil elastase (NE) have been reported in inflamed colonic mucosal tissue. Activatable NIR fluorescent probes have been extensively used for disease activity evaluation in oncologic animal models, and we demonstrate their translatability using a NE-activatable reagent to evaluate inflammation in DSS mice. Confocal laser endomicroscopy (CLE) and tissue imaging allow visualization of spatial NE activity throughout diseased colon as well as changes in disease severity from IL22Fc treatment. Our findings with the 800CW dye and the NE probe highlight the ease of their implementation in preclinical IBD research.

Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORγ inverse agonists.

A high-throughput screen against Inventiva's compound library using a Gal4/RORγ-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORγ inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein.

Fc Receptor-mediated Effector Function Contributes to the Therapeutic Response of Anti-TNF Monoclonal Antibodies in a Mouse Model of Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] monoclonal antibodies [infliximab, adalimumab] induce complete mucosal healing in a proportion of patients with Crohn's disease whereas a TNF receptor fusion protein [etanercept] is not effective and the anti-TNF F[ab']2 fragment [certolizumab] shows a very low rate of complete mucosal healing. In contrast, all four TNF-neutralising drugs have demonstrated efficacy in the treatment of rheumatoid arthritis. These observations suggest that factors other than neutralisation of TNF may contribute to clinical outcomes in Crohn's disease. Here we tested the hypothesis that Fc receptor [FcR]-mediated effects may contribute to the therapeutic response of anti-TNF antibodies in inflammatory bowel disease. METHODS: We modified an IgG2c mouse anti-TNF antibody that binds the high-affinity FcRs to generate an IgG1 isotype with strongly diminished binding. We examined the therapeutic effects of both antibodies in the T cell transfer model of inflammatory bowel disease and the collagen-induced arthritis model. RESULTS: The IgG2c anti-TNF antibody prevented colonic inflammation in the T cell transfer model of colitis, whereas the IgG1 anti-TNF did not. Conversely, both the IgG2c and IgG1 anti-TNFs were similarly effective in reducing the severity of articular inflammation in mouse collagen-induced arthritis. CONCLUSION: These data support the concept that the mechanism of action for TNF-neutralising drugs may differ across immune-mediated diseases and, potentially, between therapeutics within a particular disease. Our data suggest a specific role of Fc-mediated immune regulation in the resolution of intestinal inflammation by anti-TNF monoclonal antibodies.

Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1α and IL-1ß.

Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1ß, and IL-1Ra contribute to immune regulation and inflammatory processes by exerting a wide range of cellular responses, including expression of cytokines and chemokines, matrix metalloproteinases, and nitric oxide synthetase. IL-1α and IL-1ß bind to IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar physiological effects. Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA), including cartilage degradation, bone sclerosis, and synovial proliferation. Here, we describe the generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and potently neutralizes IL-1α and IL-1ß. In ABT-981, the IL-1ß variable domain resides in the outer domain of the DVD-Ig, whereas the IL-1α variable domain is located in the inner position. ABT-981 specifically binds to IL-1α and IL-1ß, and is physically capable of binding 2 human IL-1α and 2 human IL-1ß molecules simultaneously. Single-dose intravenous and subcutaneous pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable drug-like-properties including affinity, potency, specificity, half-life, and stability for evaluation in human clinical trials. ABT-981 offers an exciting new approach for the treatment of OA, potentially addressing both disease modification and symptom relief as a disease-modifying OA drug.

Pharmacological modulation of brain activity in a preclinical model of osteoarthritis.

The earliest stages of osteoarthritis are characterized by peripheral pathology; however, during disease progression chronic pain emerges-a major symptom of osteoarthritis linked to neuroplasticity. Recent clinical imaging studies involving chronic pain patients, including osteoarthritis patients, have demonstrated that functional properties of the brain are altered, and these functional changes are correlated with subjective behavioral pain measures. Currently, preclinical osteoarthritis studies have not assessed if functional properties of supraspinal pain circuitry are altered, and if these functional properties can be modulated by pharmacological therapy either by direct or indirect action on brain systems. In the current study, functional connectivity was first assessed in order to characterize the functional neuroplasticity occurring in the rodent medial meniscus tear (MMT) model of osteoarthritis-a surgical model of osteoarthritis possessing peripheral joint trauma and a hypersensitive pain state. In addition to knee joint trauma at week 3 post-MMT surgery, we observed that supraspinal networks have increased functional connectivity relative to sham animals. Importantly, we observed that early and sustained treatment with a novel, peripherally acting broad-spectrum matrix metalloproteinase (MMP) inhibitor (MMPi) significantly attenuates knee joint trauma (cartilage degradation) as well as supraspinal functional connectivity increases in MMT animals. At week 5 post-MMT surgery, the acute pharmacodynamic effects of celecoxib (selective cyclooxygenase-2 inhibitor) on brain function were evaluated using pharmacological magnetic resonance imaging (phMRI) and functional connectivity analysis. Celecoxib was chosen as a comparator, given its clinical efficacy for alleviating pain in osteoarthritis patients and its peripheral and central pharmacological action. Relative to the vehicle condition, acute celecoxib treatment in MMT animals yielded decreased phMRI infusion responses and decreased functional connectivity, the latter observation being similar to what was detected following chronic MMPi treatment. These findings demonstrate that an assessment of brain function may provide an objective means by which to further evaluate the pathology of an osteoarthritis state as well as measure the pharmacodynamic effects of therapies with peripheral or peripheral and central pharmacological action.

Perinucleolar compartment prevalence has an independent prognostic value for breast cancer.

The perinucleolar compartment (PNC) is a multicomponent nuclear structure enriched with RNAs transcribed by RNA pol III and RNA binding proteins. Studies in cultured cells showed an association between PNC and transformed phenotype. To evaluate the relationship between structure and malignancy in vivo, we examined PNC prevalence (the percentage of cells containing at least one PNC) in normal and cancerous paraffin-embedded breast tissues using immunohistochemistry against a PNC-associated protein. Five hundred nuclei in the most active area of each sample were scored for PNC prevalence. The results show that PNC prevalence significantly correlates with the progression of breast cancer (by the criteria of staging). PNC prevalence in primary tumors, lymph nodes, and distant metastases shows a stepwise increase from a median of 23% in primary tumors to approximately 100% in distant metastases. In addition, univariate and multivariate (controlling for tumor size and grade) analyses show that early-stage patients with invasive ductal carcinomas containing a higher PNC prevalence have a significantly poorer prognosis. These findings link PNC prevalence with the progression of breast cancer in vivo and suggest that PNC-containing cells have metastatic advantages. These findings also show the potential of PNC prevalence as a prognostic marker for breast cancer.

Spontaneous and experimental osteoarthritis in dog: similarities and differences in proteoglycan levels.

The unilateral canine model is the most commonly used model of experimental osteoarthritis (OA). In this model, the anterior cruciate ligament (ACL) of one knee is transected and the contralateral joint is usually used as a control. However, dogs, similar to humans, can develop OA spontaneously with old age. Additionally, certain breeds of dogs are genetically predisposed to OA and can develop symptoms at a young age. The goal of this study was to compare the pathological changes of proteoglycans in OA cartilage from dogs that developed OA spontaneously to those that underwent ACL transection. For this reason, biglycan, decorin and fibromodulin levels and degradation patterns were compared by Western blot hybridization, and aggrecan contents were quantified by dimethylmethylene blue assay. The changes in proteoglycan levels in the cartilage of dogs with spontaneous OA, regardless of their age, were very similar to those published for human OA cartilage. However, when OA developed as a result of ACL-surgery, the changes in proteoglycans were different from those of slowly developing spontaneous OA. Therefore, these differences should be taken into consideration when the ACL-transection model is used.