Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.

Background: Latency reversing agents (LRAs) such as protein kinase C (PKC) modulators can reduce rebound-competent HIV reservoirs in small animal models. Furthermore, administration of natural killer (NK) cells following LRA treatment improves this reservoir reduction. It is currently unknown why the combination of a PKC modulator and NK cells is so potent and whether exposure to PKC modulators may augment NK cell function in some way. Methods: Primary human NK cells were treated with PKC modulators (bryostatin-1, prostratin, or the designed, synthetic bryostatin-1 analog SUW133), and evaluated by examining expression of activation markers by flow cytometry, analyzing transcriptomic profiles by RNA sequencing, measuring cytotoxicity by co-culturing with K562 cells, assessing cytokine production by Luminex assay, and examining the ability of cytokines and secreted factors to independently reverse HIV latency by co-culturing with Jurkat-Latency (J-Lat) cells. Results: PKC modulators increased expression of proteins involved in NK cell activation. Transcriptomic profiles from PKC-treated NK cells displayed signatures of cellular activation and enrichment of genes associated with the NFκB pathway. NK cell cytotoxicity was unaffected by prostratin but significantly decreased by bryostatin-1 and SUW133. Cytokines from PKC-stimulated NK cells did not induce latency reversal in J-Lat cell lines. Conclusions: Although PKC modulators have some significant effects on NK cells, their contribution in "kick and kill" strategies is likely due to upregulating HIV expression in CD4+ T cells, not directly enhancing the effector functions of NK cells. This suggests that PKC modulators are primarily augmenting the "kick" rather than the "kill" arm of this HIV cure approach.

Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

Development of Predictive Models Based on Biochemical Parameters to Triage COVID-19 Patients: A Study Conducted in a Tertiary Care Hospital.

Background The COVID-19 disease continues to cause severe mortality and morbidity. Biochemical parameters are being used to predict the severity of the infection. This study aims to predict disease severity and mortality to help reduce mortality through timely intervention in a cost-effective way. Methods A total of 324 COVID-19 cases admitted at our hospital (All India Institute of Medical Sciences, Patna, BR, India) between June 2020 to December 2020 (phase 1: 190 patients) and April 2021 to May 2021 (phase 2: 134 patients) were recruited for this study. Statistical analysis was done using SPSS Statistics version 23 (IBM Corp., Armonk, NY, USA) and model prediction using Python (The Python Software Foundation, Wilmington, DE, USA). Results There were significant differences in biochemical parameters at the time of admission among COVID-19 patients between phases 1 and 2, ICU and non-ICU admissions, and expired and discharged patients. The receiver operating characteristic (ROC) curves predicted mortality solely based on biochemical parameters. Using multiple logistic regression in Python, a total of four models (two each) were developed to predict ICU admission and mortality. A total of 92 out of 96 patients were placed into the correct management category by our model. This model would have allowed us to preserve 17 of the 21 patients we lost. Conclusions We developed predictive models for admission (ICU or non-ICU) and mortality based on biochemical parameters at the time of admission. A predictive model with a significant predictive capability for IL-6 and procalcitonin values using normal biochemical parameters was proposed. Both can be used as machine learning tools to prognosticate the severity of COVID-19 infections. This study is probably the first of its kind to propose triage for admission in the ICU or non-ICU at the medical emergency department during the first presentation for the necessary optimal treatment of COVID-19 based on a predictive model.

Congenital cardiac anomalies in non-syndromic cleft lip and cleft palate patients: A systematic review and meta-analysis.

The aim was to establish a specific and definite connection between non-syndromic orofacial cleft patients and associated congenital heart disease (CHD). Following PRISMA guidelines, selective databases were searched for data collection. Studies showing a definite association of CHD with orofacial cleft were included, and studies non-specific of the association of orofacial cleft with CHD were excluded. Data extraction criteria were study design, frequency of CHD in overall non-syndromic orofacial cleft and in specific cleft type, and most prevalent congenital cardiac anomaly. DerSimonian Laird random effects model was used to estimate the pooled proportion of CHD, along with corresponding 95% confidence intervals (CIs) for each measure. Publication bias was assessed using Fail-Safe N analysis and the Rosenthel approach. Of a total of 182 articles searched, only 30 studies were assessed. The overall pooled estimate of the proportion of CHD in total cleft lips/palates was 16% (95% CI: 13-19). The odds of developing CHD in cleft palates was 4.08 times more as compared to cleft lips with 95% CIs of 3.86-4.33, and 1.65 more as compared to cleft lips and palates both with 95% CI of 1.52-1.68. We affirm the upsurging prevalence of CHD in non-syndromic cleft children and vehemently propose that it is of utmost importance to inculcate it in practice and policy-making to screen all non-syndromic orofacial cleft children for congenital cardiac anomaly. This study was registered on PROSPERO (ID no. CRD42023391597) on February 24, 2023.

Differential Expression of SRY-Related HMG-Box Transcription Factor 2, Oligodendrocyte Lineage Transcription Factor 2, and Zinc Finger E-Box Binding Homeobox 1 in Serum-Derived Extracellular Vesicles: Implications for Mithramycin Sensitivity and Targeted Therapy in High-Grade Glioma.

Glioblastoma multiforme (GBM) is the most aggressive type of glioma and is often resistant to traditional therapies. Evidence suggests that glioma stem cells (GSCs) contribute to this resistance. Mithramycin (Mit-A) targets GSCs and exhibits antitumor activity in GBM by affecting transcriptional targets such as SRY-related HMG-box transcription factor 2 (SOX2), oligodendrocyte lineage transcription factor 2 (OLIG2), and zinc finger E-box binding homeobox 1 (ZEB1). However, its clinical use has been limited by toxicity. This study explored the diagnostic potential of serum extracellular vesicles (EVs) to identify Mit-A responders. Serum EVs were isolated from 70 glioma patients, and targeted gene expression was analyzed using qRT-PCR. Using chemosensitivity assay, we identified 8 Mit-A responders and 17 nonresponders among 25 glioma patients. The M-score showed a significant correlation (p = 0.045) with isocitrate dehydrogenase 1 mutation but not other clinical variables. The genes SOX2 (p = 0.005), OLIG2 (p = 0.003), and ZEB1 (p = 0.0281) were found to be upregulated in the responder EVs. SOX2 had the highest diagnostic potential (AUC = 0.875), followed by OLIG2 (AUC = 0.772) and ZEB1 (AUC = 0.632).The combined gene panel showed significant diagnostic efficacy (AUC = 0.956) through logistic regression analysis. The gene panel was further validated in the serum EVs of 45 glioma patients. These findings highlight the potential of Mit-A as a targeted therapy for high-grade glioma based on differential gene expression in serum EVs. The gene panel could serve as a diagnostic tool to predict Mit-A sensitivity, offering a promising approach for personalized treatment strategies and emphasizing the role of GSCs in therapeutic resistance.

Novel orexin receptor agonists based on arene- or pyridine-fused 1,3-dihydro-2H-imidazole-2-imines.

A structurally novel class of benzo- or pyrido-fused 1,3-dihydro-2H-imidazole-2-imines was designed and evaluated in an inositol phosphate accumulation assay for Gq signaling to measure agonistic activation of the orexin receptor type 2 (OX2R). These compounds were synthesized in 4-9 steps overall from readily available starting materials. Analogs that contain a stereogenic methyl or cyclopropyl substituent at the benzylic center, and a correctly configured alkyl ether, alkoxyalkyl ether, cyanoalkyl ether, or α-hydroxyacetamido substituted homobenzylic sidechain were identified as the most potent activators of OX2R coupled Gq signaling. Our results also indicate that agonistic activity was stereospecific at both the benzylic and homobenzylic stereogenic centra. We identified methoxyethoxy-substituted pyrido-fused dihydroimidazolimine analog 63c containing a stereogenic benzylic methyl group was the most potent agonist, registering a respectable EC50 of 339 nM and a maximal response (Emax) of 96 % in this assay. In vivo pharmacokinetic analysis indicated good brain exposure for several analogs. Our combined results provide important information towards a structurally novel class of orexin receptor agonists distinct from current chemotypes.

Cadmium toxicity: its' uptake and retaliation by plant defence system and ja signaling.

Cadmium (Cd+2) renders multifarious environmental stresses and highly toxic to nearly all living organisms including plants. Cd causes toxicity by unnecessary augmentation of ROS that targets essential molecules and fundamental processes in plants. In response, plants outfitted a repertory of mechanisms to offset Cd toxicity. The main elements of these are Cd chelation, sequestration into vacuoles, and adjustment of Cd uptake by transporters and escalation of antioxidative mechanism. Signal molecules like phytohormones and reactive oxygen species (ROS) activate the MAPK cascade, the activation of the antioxidant system andsynergistic crosstalk between different signal molecules in order to regulate plant responses to Cd toxicity. Transcription factors like WRKY, MYB, bHLH, bZIP, ERF, NAC etc., located downstream of MAPK, and are key factors in regulating Cd toxicity responses in plants. Apart from this, MAPK and Ca2+signaling also have a salient involvement in rectifying Cd stress in plants. This review highlighted the mechanism of Cd uptake, translocation, detoxification and the key role of defense system, MAPKs, Ca2+ signals and jasmonic acid in retaliating Cd toxicity via synchronous management of various other regulators and signaling components involved under stress condition.

Methyl jasmonate reduces cadmium toxicity by enhancing phenol and flavonoid metabolism and activating the antioxidant defense system in pigeon pea (Cajanus cajan).

Cadmium (Cd) is absorbed by plant roots from soil along with essential nutrients and affects plant growth and productivity. Methyl jasmonate (Me-JA) play important roles to mitigate Cd toxicity in plants. We have investigated the role of Me-JA to ameliorate Cd toxicity in Pigeon pea (Cajanus cajan). Plant root growth, biomass, cellular antioxidant defense system and expression of key regulatory genes in molecular and signaling process have been analyzed. Two Cajanus cajan varieties AL-882 and PAU-881 were grown at 25 °C, 16/8h light/dark conditions in three biological replicates at 5 mM Cd concentration, three concentration of Me-JA (0, 10 nM, 100 nM) and two concentrations in combination of Me-JA + Cd (10 nM Me-JA +5 mM Cd, 100 nM Me-JA +5 mM Cd). The seedlings were exposed to Cd stress consequently plants showed decrease in primary root growth (60.71%, in AL-882 and 8.33%, in PAU-881), shoot and root biomass and antioxidant enzymes activities. Me-JA treatment resulted in increased primary root growth (63.64%, in AL-882) and overall plant biomass. Oxidative stress generated due to Cd stress was counter balanced by Me-JA treatment. Me-JA reduced H2O2 free radicals formation and enhanced antioxidant enzyme activities and phenolic content in stressed seedlings. Me-JA treatment increased expression of CALM, IP3, CDPK2, MPKs (involved in calcium and kinase signaling pathways) and reduced expression of metal transporters (IRT1 and HMA3) genes. This reduction in metal transporters gene expression is a probable reason for low toxicity effect of Cd in root after Me-JA treatment which has potential implications in reducing the risk of Cd in the food chain.

Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors.

Currently, there are no clinically approved drugs that directly thwart mutant KRAS G12D, a major driver of human cancer. Here, we report on the discovery of a small molecule, KRB-456, that binds KRAS G12D and inhibits the growth of pancreatic cancer patient-derived tumors. Protein nuclear magnetic resonance studies revealed that KRB-456 binds the GDP-bound and GCP-bound conformation of KRAS G12D by forming interactions with a dynamic allosteric binding pocket within the switch-I/II region. Isothermal titration calorimetry demonstrated that KRB-456 binds potently to KRAS G12D with 1.5-, 2-, and 6-fold higher affinity than to KRAS G12V, KRAS wild-type, and KRAS G12C, respectively. KRB-456 potently inhibits the binding of KRAS G12D to the RAS-binding domain (RBD) of RAF1 as demonstrated by GST-RBD pulldown and AlphaScreen assays. Treatment of KRAS G12D-harboring human pancreatic cancer cells with KRB-456 suppresses the cellular levels of KRAS bound to GTP and inhibits the binding of KRAS to RAF1. Importantly, KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer whose tumors harbor KRAS G12D and KRAS G12V and who relapsed after chemotherapy and radiotherapy. These results warrant further development of KRB-456 for pancreatic cancer. SIGNIFICANCE: There are no clinically approved drugs directly abrogating mutant KRAS G12D. Here, we discovered a small molecule, KRB-456, that binds a dynamic allosteric binding pocket within the switch-I/II region of KRAS G12D. KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer. This discovery warrants further advanced preclinical and clinical studies in pancreatic cancer.

Acceptance of Annual Booster Doses of COVID-19 Vaccines Among Indian Healthcare Professionals: A Pan-India Cross-Sectional Survey.

Introduction The emergence of coronavirus disease 2019 (COVID-19) posed significant challenges to global health, leading to the declaration of a pandemic by the World Health Organization. Vaccination efforts have effectively reduced severe outcomes and mortality, but breakthrough infections and new variants are of concern. In response, annual booster doses of COVID-19 vaccines are being considered to maintain immunity. Healthcare professionals, as frontline workers, play a pivotal role in vaccination campaigns. This study explores their attitudes toward and willingness to accept annual COVID-19 booster doses in India. Methods A pan-India cross-sectional survey was conducted among healthcare professionals, including faculty, resident doctors, interns, and nursing staff, across Indian medical and nursing colleges. Convenience sampling was used to collect responses via an online questionnaire. The questionnaire assessed demographics, vaccine status, attitudes toward COVID-19 vaccination, and willingness to accept annual booster doses. Multivariate analysis was performed to identify predictors of booster dose acceptance. Results A total of 535 participants responded from 28 states and 8 union territories of India. Most were 34.2 years (± 11.1 SD), and 372 (69.5%) had taken Covishield (Serum Institute of India, Pune, India) as their primary vaccine. While 525 (98.1%) had taken the first dose and 518 (96.8%) of them had taken the second dose, only 333 (62.2%) had received a booster. Around 318 (60%) of healthcare professionals were willing to accept an annual booster dose. The mean attitude score toward annual booster doses was 75.4 (range: 28-111). Healthcare professionals' trust in government recommendations and medical experts significantly influenced their willingness to accept annual booster doses. Conclusion This study provides insights into the attitudes of healthcare professionals in India toward annual COVID-19 booster doses. At the same time, a significant proportion showed a willingness to accept boosters.

Household-level food insecurity and its correlates in rural Bihar: A cross-sectional study.

Introduction: Bihar has experienced high nutritional public health problem among children and women over the years. In this background, this study was planned to find the level of food insecurity and identify contributing factors in rural Bihar. Material and Methods: We conducted community-based cross-sectional study among 255 families residing in villages catered by RHTC, Naubatpur. A pretested semi-structured interview schedule and HFIAS were used. Result: A total of 27.8% of the 255 households were food insecure, of which 73.3% were severely food insecure. Kutcha houses, dispossession of agricultural land, and lower SES were found to be predictors. Conclusion: Around one in three families experienced food insecurity, and it was more among families residing in kutcha houses, without possession of agricultural land and belonging to lower socioeconomic status.

Charge-altering releasable transporters enhance mRNA delivery in vitro and exhibit in vivo tropism.

The introduction of more effective and selective mRNA delivery systems is required for the advancement of many emerging biomedical technologies including the development of prophylactic and therapeutic vaccines, immunotherapies for cancer and strategies for genome editing. While polymers and oligomers have served as promising mRNA delivery systems, their efficacy in hard-to-transfect cells such as primary T lymphocytes is often limited as is their cell and organ tropism. To address these problems, considerable attention has been placed on structural screening of various lipid and cation components of mRNA delivery systems. Here, we disclose a class of charge-altering releasable transporters (CARTs) that differ from previous CARTs based on their beta-amido carbonate backbone (bAC) and side chain spacing. These bAC-CARTs exhibit enhanced mRNA transfection in primary T lymphocytes in vitro and enhanced protein expression in vivo with highly selective spleen tropism, supporting their broader therapeutic use as effective polyanionic delivery systems.

Progress towards universal health coverage in the context of mental disorders in India: evidence from national sample survey data.

BACKGROUND: Universal health coverage (UHC) has emerged as one of the important health policy discourses under the current sustainable development goals in the world. UHC in individual disease conditions is a must for attaining overall UHC. This study measures progress towards UHC in terms of access to health care and financial protection among individuals with mental disorders in India. METHODS: Data from the 75th Round National Sample Survey (NSS), 2017-18, was used, which is the latest round on health in India. Data collected from 555,115 individuals (rural: 325,232; urban: 229,232), from randomly selected 8077 villages and 6181 urban areas, included 283 outpatient and 374 hospitalization cases due to mental disorders in India. Logistic regression models were used for analyses. RESULTS: Self-reporting of mental disorders was considerably lower than the actual disease burden in India. However, self-reporting of ailment was 1.73 times higher (95% CI: 1.18-2.52, p < 0.05) among the richest income group population compared to the poorest in India. The private sector was a major service provider of mental health services with a larger share for outpatient (66.1%) than inpatient care (59.2%). Over 63% of individuals with a mental disorder who reported private sector hospitalization noted unavailability or poor service quality at public facilities. Only 23% of individuals hospitalized had health insurance coverage at All India level. However, health insurance coverage among poorest economic class was a meagre 3.4%. Average out-of-pocket expenditure during hospitalization (public: 123 USD; private: 576 USD) and outpatient care (public: 8 USD; private: 37 USD) was significantly higher in the private sector than in the public sector. Chances of facing catastrophic health expenditure at 10% threshold were 23.33 times (95% CI: 10.85-50.17; p < 0.001) higher under private sector than public sector during hospitalization. Expenditure on medicine, as the share of total medical expenditure, was highest for hospitalization (public: 45%, private:39.5%) and outpatient care (public: 74.1%, private:39.7%). CONCLUSIONS: Social determinants play a vital role in access to healthcare and financial protection among individuals with mental disorders in India. For achieving UHC in mental disorders, India needs to address the gaps in access and financial protection for individuals with mental disorders. TRIAL REGISTRATION: Not applicable.

Tobacco Usage and Its Association With Mental Health Status of School-Going Adolescents Near Patna, Bihar: A Community-Based Cross-Sectional Study in Eastern India.

Background Of all the adolescents in India, 7.3% are suffering from some form of mental disorder. They frequently use tobacco to cope with these problems, but get stuck in a vicious cycle of deteriorating mental health. Our study aimed to determine the effect of tobacco on the mental health status of adolescents studying in the 9th to 12th standards in 10 high schools in urban and rural areas near Patna, Bihar. Methodology An analytical cross-sectional study was conducted among 360 school-going adolescents recruited using stratified random sampling. Selected adolescents were given the Indian Adolescent Health Questionnaire. The mental health status was calculated from the Strengths and Difficulties Questionnaire (SDQ) score. Information on sociodemographic characteristics and tobacco use was also obtained. Independent t-test, analysis of variance, and multiple linear regression analysis were used for predicting the significant factors. Significance was set at p-values <0.05. Results In this study, 40 (11.1%) adolescents had abnormal whereas 55 (15.3%) had borderline overall SDQ scores. The majority of those affected had peer problems (40%) and conduct problems (24.7%). All SDQ components of conduct (F = 2.94, p = 0.013), hyperactivity (F = 2.90, p = 0.014), emotional problems (F = 1.14, p = 0.001), and peer pressure (F = 3.06, p = 0.010), as well as the overall SDQ score (F = 5.74, p < 0.001), were significantly associated with increasing age. The adolescents attending rural schools (13.28 ± 5.22, p = 0.047) had significantly higher SDQ scores than those attending urban schools (12.08 ± 5.60). Hyperactivity scores were significantly higher in those studying in class 10 compared to other classes and in those attending rural rather than urban schools. Emotional problems score was significantly higher in 16-17-year-old students than in 14-15-year-old students, in females than in males, and in class 10 than in class 9 students. Only 24 (6.7%) adolescents had a history of tobacco consumption at least once which was significantly associated with the SDQ score (17.71 ± 5.69; t = 4.95, df = 358, p < 0.001). Around 79.4% of adolescents were exposed to passive smoking from close friends which deteriorated their overall mental health status (14.50 ± 5.99; F = 6.29, df = 2,357, p = 0.002). Those who had smoked for more than 10 days had significantly greater conduct problems and lesser pro-social behavior. Overall, 96.1% agreed that tobacco is harmful to health, and 76.1% had seen anti-smoking messages in the media. Female gender, increasing class and age, and history of smoking or chewing tobacco at least once also led to a significant increase in emotional problems. Age, area of the school, history of tobacco consumption, and exposure to cigarette smoke by either a close friend or male guardian had a significant impact on the conduct, hyperactivity, peer problems, and overall mental health status of school-going adolescents. Conclusions Predicting risk factors such as age, area of the school, and the history of tobacco consumption by self or by close friends is important for decision-making by school administration regarding counseling for mental health and preventing tobacco use.

A comparative surface evaluation of orthodontic mini-implants before and after en masse retraction-A SEM study.

OBJECTIVE: To evaluate the changes in surface morphology of two different types of mini-implants after clinical en masse retraction using scanning electron microscopy. MATERIAL AND METHODS: Fifty mini-implants of Dentos (Korea, Absoanchor, BH-1817-08) and Orlus (Korea, Yesanchor, C-1817) were inserted in patients in a split-mouth design who required en masse anterior retraction and absolute anchorage. Surface characteristics of mini-implants such as pitch (distance between consecutive threads), flank width (distance between root and crest), and taper were studied using scanning electron microscope (FEI nanosem450) before and after clinical use. RESULTS: Statistically significant difference (p value = 0.003) was found in a mean reduction of pitch dimension among the two groups with a mean difference of 25.000 µm. Also, a statistically significant difference was noted (p value = 0.001) in a mean reduction of flank width among Dentos implants as compared to Orlus implants. A statistically significant difference (p = 0.001) was seen in the mean reduction of taper dimension among Dentos group (0.0140 ± 0.02271) as compared to the Orlus group (0.0810 ± 0.05152). CONCLUSION: A marked reduction in surface morphology such as the pitch, flank width, and taper of both mini-implants after retrieval was observed. Dentos group of mini-implants displayed better dimensional stability post-retrieval as compared to the Orlus group of mini-implants. All the mini-screws showed milling defects in form of scratches on observation under scanning electron microscopy despite a smooth appearance to the naked eye.

Effect of educational intervention on knowledge and attitude about the role of vitamins, minerals and nutraceuticals in COVID-19 and other disorders among medical and nursing undergraduates of a tertiary care teaching hospital.

PURPOSE: There must be a perfect balance between Food and Dietary supplements (DS) to ensure optimal well-being. The purpose of this study was to evaluate the impact of a webinar on the change in knowledge and attitude about the role of vitamins, minerals and DS among medical and nursing undergraduates so that they could bring about a positive change in popular practices, as well-informed Health Care Professionals (HCPs). MATERIALS AND METHODS: The study was a cross-sectional analytical study comprising 12 knowledge and 11 attitude questions administered to medical and nursing undergraduates with the help of semi-structured and pre-validated google form both before and after a webinar explaining the role of key nutrients and also the evidence and recommendations surrounding DS. Data were analyzed using STATA.12 to assess the impact of the webinar. RESULTS: There were 415 participants, with 265 medical and 150 nursing students. There was a significant improvement both in the knowledge (4.95 (±1.45), 7.76 (±1.69) and attitude scores (pre-webinar mean score 31.8 (±5.57) post-webinar mean score 27.7 (±4.90))of the participants after the webinar. An overall positive correlation before the webinar changed to a more significant negative correlation, indicating a positive impact of the webinar (0.0054-0.0701). CONCLUSION: The study suggests that continuing education informing various HCPs and undergraduate students about the absolute necessity of a diet rich in nutrients, vitamins, minerals, and probiotics is the need of the hour. Additionally, the efficacy and safety concerns, appropriate indications and dosages of various DS should be adequately stressed so that informed decisions can be made. Such training programs might have a far-reaching impact on the nutrition choices of the population at large.

Cross-sectional study to describe the severity, bio-chemical associations, and final outcomes of COVID-19-associated rhino-orbital-cerebral mucormycosis in a tertiary hospital of East India.

Purpose: The second wave of coronavirus disease 2019 (COVID-19) pandemic triggered a mucormycosis epidemic in India. Diabetes mellitus and dysregulated immune response were contributors, and rhino-orbital-cerebral mucormycosis (ROCM) was the most common presentation. It is however not known whether bio-chemical parameters at presentation correlate with stage of ROCM or final outcome in terms of vision or mortality. Methods: This retrospective, hospital-based study included all in-patients of mucormycosis with ophthalmic manifestations at presentation admitted during June 1, 2021 to August 31, 2021. It aimed to evaluate the association between severity of infection, serum levels of HbA1c, ferritin, interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer levels at presentation and outcome. Results: There were altogether 47 eligible cases having a mean age of 48.8 ± 10.9 years with a male:female ratio of 2.6:1; forty-two (89.4%) had pre-existing diabetes, and five (10.6%) had steroid-induced hyperglycemia. The mean HbA1c among diabetics was 9.7 ± 2.1. HbA1c and serum CRP showed an increase over subsequent stages, which was not statistically significant (P = 0.31). IL-6 values for all stages were similar (P = 0.97). Only serum ferritin levels showed a statistically significant increase over stages (P = 0.04). IL-6 was significantly lower (P = 0.03) in patients who survived, whereas CRP levels were significantly lower in patients who had final visual acuity (VA) better than only perception of light (P = 0.03). Conclusion: Uncontrolled diabetes mellitus is a significant association of ROCM. Serum ferritin levels at presentation best correlate with extent of the disease. CRP levels are best to prognosticate cases that will have sufficient VA to carry on activities of daily living, whereas IL-6 levels are best associated with survival.

Measurement of unmet healthcare needs to assess progress on universal health coverage - exploring a novel approach based on household surveys.

BACKGROUND: Universal Health Coverage (UHC) aims to ensure universal access to quality healthcare according to health needs. The extent to which population health needs are met should be a key measure for progress on UHC. The indicators in use for measuring access mostly relate to physical accessibility or insurance coverage. Or, utilization of services is taken as indirect measure for access but it is assessed against only the perceived healthcare needs. The unperceived needs do not get taken into account. The present study was aimed at demonstrating an approach for measuring the unmet healthcare needs using household survey data as an additional measure of UHC. METHODS: A household survey was conducted in Chhattisgarh state of India, covering a multi-stage sample of 3153 individuals. Healthcare need was measured in terms of perceived needs which would be self-reported and unperceived needs where clinical measurement supplemented the interview response. Estimation of unperceived healthcare needs was limited to three tracer conditions- hypertension, diabetes and depression. Multivariate analysis was conducted to find the determinants of the various measures of the perceived and unperceived needs. RESULTS: Of the surveyed individuals, 10.47% reported perceived healthcare needs for acute ailments in the last 15 days. 10.62% individuals self-reported suffering from chronic conditions. 12.75% of those with acute ailment and 18.40% with chronic ailments received no treatment, while 27.83% and 9.07% respectively received treatment from unqualified providers. On an average, patients with chronic ailments received only half the medication doses required annually. The latent need was very high for chronic ailments. 47.42% of individuals above 30 years age never had blood pressure measured. 95% of those identified with likelihood of depression had not sought any healthcare and they did not know they could be suffering from depression. CONCLUSION: To assess progress on UHC more meaningfully, better methods are needed to measure unmet healthcare needs, taking into account both the perceived and unperceived needs, as well as incomplete care and inappropriate care. Appropriately designed household surveys offer a significant potential to allow its periodic measurement. Their limitations in measuring the 'inappropriate care' may necessitate supplementation with qualitative methods.