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Abstract Breast Cancer (BC) is the most common cause of cancer-associated deaths in females worldwide. Despite advancements in BC treatment driven by extensive characterization of its molecular hallmarks, challenges such as drug resistance, tumor relapse, and metastasis persist. Therefore, there is an urgent need for alternative treatment approaches with multi-modal efficacy to overcome these hurdles. In this context, natural bioactives are increasingly recognized for their pivotal role as anti-cancer compounds. This study focuses on predicting molecular targets for key herbal phytoconstituents—gallic acid, piperine, quercetin, resveratrol, and beta-sitosterol—present in the polyherbal formulation, Krishnadi Churna. Using an in-silico network pharmacology model, key genes were identified and docked against these marker compounds and controls. Mammary carcinoma emerged as the most significant phenotype of the putative targets. Analysis of an online database revealed that out of 135 predicted targets, 134 were mutated in breast cancer patients. Notably, ESR1, CYP19A1, and EGFR were identified as key genes which are known to regulate the BC progression. Docking studies demonstrated that the herbal phytoconstituents had similar or better docking scores than positive controls for these key genes, with convincing protein-ligand interactions confirmed by molecular dynamics simulations, MM/GBSA and free energy landscape (FEL) analysis. Overall, this study highlights the predictive potential of herbal phytoconstituents in targeting BC genes, suggesting their promise as a basis for developing new therapeutic formulations for BC.

Abstract Late blight is a serious disease of potato worldwide. Our study aimed to unveil genes involved in late blight resistance in potato by RNA-seq analysis after artificial inoculation under controlled conditions. In this study, two potato somatic hybrids (P7 and Crd6) and three varieties such as Kufri Girdhari, Kufri Jyoti and Kufri Bahar (control) were used. Transcriptiome analysis revealed statistically significant (p

Introduction: Focal Segmental Glomerulosclerosis (FSGS) is a nephrotic syndrome with a variety of clinicopathological presentations and varied responses to treatment. Hence, this study attempts to classify FSGS based on clinical presentation and pathological findings on kidney biopsy, which is essential for appropriate treatment and avoidance of inappropriate use of immunosuppressants. Aim: To analyse clinicopathological findings and responses to immunosuppressants in FSGS. Materials and Methods: A retrospective cohort study was conducted at Department of Nephrology, Vydehi Institute of Medical Sciences and Research Centre Bengaluru, Karnataka, India, to analyse clinicopathological parameters such as urine analysis, 24-hour urine protein, serum creatinine, serum albumin, lipid profile, renal biopsy details, and response to treatment in 97 patients. The study was planned, analysed, and executed between January 2023 and February 2023. All variables were expressed as mean±standard deviation or percentage. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 16.0. Results: Among a total of 97 patients, 64% were males. Sudden onset oedema was observed in 90% of the cases, while nephrotic proteinuria was seen in 71%. The Not Otherwise Specified (NOS) variant was noted in 60% of the cases. Complete remission was observed in 61%, suggesting a possible primary FSGS. Persistent nephrotic proteinuria with a poor response to therapy was noted in 32%, indicating a possible secondary/genetic FSGS, despite adequate immunosuppressive therapy. Therefore, differentiating between primary and secondary forms of FSGS has therapeutic and prognostic implications. Accurate diagnosis of each form of FSGS is vital to avoid unnecessary immunosuppressive-based therapy and establish appropriate treatment. Conclusion: Resistance to steroid therapy was observed in one-third of FSGS patients. It is likely that unrecognised genetic FSGS or secondary FSGS were included among the study group of primary FSGS, leading to misinterpretation of treatment responses in primary FSGS. Hence, a clinicopathological approach for correctly differentiating between primary FSGS, secondary (maladaptive, viral, or toxic) FSGS, and genetic FSGS helps in making correct treatment decisions.

Abstract Background SARS-CoV-2 infections caused mild-to-moderate illness. However, a sizable portion of infected people experience a rapid progression of hyper-inflammatory and hypoxic respiratory illness that necessitates an effective and safer remedy to combat COVID-19. Methods A total of 150 COVID-19-positive patients with no to mild symptoms, between the age groups 19–65 years were enrolled in this randomized, open-labeled three-armed clinical trial. Among them, 136 patients completed the study with RT-PCR negative reports. The patients received herbal drugs orally (Group A (Adhatoda vasica; AV; 500 mg; n = 50); Group B (Tinospora cordifolia; TC; 500 mg; n = 43), and Group C (AV + TC; 250 mg each; n = 43)) for 14 days. Clinical symptoms, vital parameters, and viral clearance were taken as primary outcomes, and biochemical, hematological parameters, cytokines, and biomarkers were evaluated at three time points as secondary outcomes. Results We found that the mean viral clearance time was 13.92 days (95% confidence interval [CI] 12.85–14.99) in Group A, 13.44 days (95% confidence interval [CI] 12.14–14.74) in Group B, and 11.86 days (95% confidence interval [CI] 10.62–13.11) days in Group C. Over a period of 14 days, the mean temperature in Groups A, and B significantly decreased linearly. In Group A, during the trial period, eosinophils, and PT/INR increased significantly, while monocytes, SGOT, globulin, serum ferritin, and HIF-1α, a marker of hypoxia reduced significantly. On the other hand, in Group B hsCRP decreased at mid-treatment. Eosinophil levels increased in Group C during the treatment, while MCP-3 levels were significantly reduced. Conclusions All the patients of the three-armed interventions recovered from COVID-19 and none of them reported any adverse effects from the drugs. Group C patients (AV + TC) resulted in a quicker viral clearance as compared to the other two groups. We provide the first clinical report of AV herbal extract acting as a modifier of HIF-1α in COVID-19 patients along with a reduction in levels of ferritin, VEGF, and PT/INR as the markers of hypoxia, inflammation, and thrombosis highlighting the potential use in progression stages, whereas the TC group showed immunomodulatory effects. Trial registration Clinical Trials Database -India (ICMR-NIMS), CTRI/2020/09/028043. Registered 24th September 2020, https://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=47443&EncHid=&modid=&compid=%27,%2747443det%27 Graphical Abstract

Immunological dysregulation and inflammation may play a role in the nature of menstruation. Coronavirus disease 2019 (COVID-19) can produce a systemic inflammatory reaction that involves extrapulmonary organs and can also affect the immune system. This study aimed to analyze changes in the menstrual cycle in coronavirus (COVID)-positive women of reproductive age. Methods: The data of 35 women of reproductive age were collected telephonically from said patients admitted to the COVID Health Centre (CHC) ward of All India Institute of Ayurveda, New Delhi, during June 20, 2020, to October 31, 2020. Purposive sampling was used for data collection. Wyatt menstrual pictogram and Visual Analogue Scale (VAS) were used to assess the bleeding pattern and pain during menstruation, respectively. Results: Clinically, changes were noted in post-COVID menstruation such as irregularity, polymenorrhea, oligomenorrhea, clots, and menstrual flow in days. However, all results were statistically non-significant. But significant (P = 0.003) menstrual pain was reported. Conclusion: Menstrual changes were observed in COVID-19-positive women belonging to the reproductive age group.

Abstract Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Pyomyositis or tropical pyomyositis is an uncommon infection of skeletal muscle that may be primary or secondary. Primary type has bacterial aetiology, and Staphylococcus aureus is associated in most cases. The diagnosis requires high index of suspicion and careful assessment of radiological investigations. Diagnosis often requires magnetic resonance imaging (MRI) for better delineation of the disease process, associated site involvement and exclusion of related conditions. Evacuation of pus coupled with appropriate antibiotic therapy is the mainstay and curative in most cases. Caution, however, is required due to increased morbidity, protracted course of recovery and mortality in few cases. The association with comorbidities including immunocompromised status compounds the problem. We describe our experience with this condition in a series of five cases (four male and one female) with diverse involvement of scapular muscle. All cases had primary pyomyositis except one case secondary to shoulder joint tuberculosis. Right side was involved in three and left in two cases. Infraspinatus was commonly involved, and one case had extensive involvement around scapula. All cases were managed by one or multiple aspiration, except one managed with open surgical drainage. The outcome was good in all cases with no recurrence or complication noted in their respective follow-up. Primary care centres may play important role in the early diagnosis of this condition with clinical evaluation and judicious use of imaging. Cases with severe involvement or those requiring advanced procedures may be referred to higher centres as per the requirement. Most of the times, timely diagnosis, antibiotic therapy and drainage of the pus is required and may also be performed in the primary care level through a standard protocol.

Abstract Human mobility has played a critical role in the spread of COVID-19. The understanding of mobility helps in getting information on the acceleration or control of the spread of disease. The COVID-19 virus has been spreading among several locations despite all the best efforts related to its isolation. To comprehend this, a multi-patch mathematical model of COVID-19 is proposed and analysed in this work, where-in limited medical resources, quarantining, and inhibitory behaviour of healthy individuals are incorporated into the model. Furthermore, as an example, the impact of mobility in a three-patch model is studied considering the three worst-hit states of India, i.e. Kerala, Maharashtra and Tamil Nadu, as three patches. Key parameters and the basic reproduction number are estimated from the available data. Through results and analyses, it is seen that Kerala has a higher effective contact rate and has the highest prevalence. Moreover, if Kerala is isolated from Maharashtra or Tamil Nadu, the number of active cases will increase in Kerala but reduce in the other two states. Our findings indicate that the number of active cases will decrease in the high prevalence state and increase in the lower prevalence states if the emigration rate is higher than the immigration rate in the high prevalence state. Overall, proper travel restrictions are to be implemented to reduce or control the spread of disease from the high-prevalence state to other states with lower prevalence rates.

The laboratory-scale (in-vitro) microbial fermentation based on screening of process parameters (factors) and statistical validation of parameters (responses) using regression analysis. The recent trends have shifted from full factorial design towards more complex response surface methodology designs such as Box-Behnken design, Central Composite design. Apart from the optimisation methodologies, the listed designs are not flexible enough in deducing properties of parameters in terms of class variables. Machine learning algorithms have unique visualisations for the dataset presented with appropriate learning algorithms. The classification algorithms cannot be applied on all datasets and selection of classifier is essential in this regard. To resolve this issue, factor-response relationship needs to be evaluated as dataset and subsequent preprocessing could lead to appropriate results. The aim of the current study was to investigate the data-mining accuracy on the dataset developed using in-vitro pyruvate production using organic sources for the first time. The attributes were subjected to comparative classification on various classifiers and based on accuracy, multilayer perceptron (neural network algorithm) was selected as classifier. As per the results, the model showed significant results for prediction of classes and a good fit. The learning curve developed also showed the datasets converging and were linearly separable.

Objective: India has a tribal population of 8.6%. Health concerns of the high-altitude tribal population in India play a vital role in overall socio-economic development and health transformation of the country. Therefore, the aim of this study was to determine the current health problems among the tribal population of Lahaul and Spiti district of Himachal Pradesh. Material and Methods: The study area encompasses one regional hospital (RH) in Keylong (the district headquarters), three community health centers (CHCs), and 16 primary health care centers (PHCs). In addition, the district has 37 sub-centers (SCs) and 21 Ayurveda dispensaries to serve the district. The data for this study were gathered over a 4-year period from records of daily out-patient department registration from the various health centers (RH, CHCs, and PHCs) from 2017 to 2020. Results: In terms of communicable diseases, the population in the concerned region was more likely to have acute respiratory infection, enteric fever, tuberculosis, and typhoid. Hypertension, asthma, bronchitis, and diabetes mellitus type II were determined to be the most common non-communicable diseases. Conclusion: Acute respiratory disease, hypertension, diarrhea, accidental injuries, and eye problems were shown to be prevalent in the study area. The population’s position in relation to these five diseases indicates the community’s sensitivity to a variety of common conditions. There is a need to review the needs and priorities of the concerned population and create goals and targets to meet those needs using validated public health measures.

Introduction Women-controlled HIV prevention technologies that overcome adherence challenges of available daily oral pre-exposure prophylaxis and give women a choice of options are urgently needed. Broadly neutralising monoclonal antibodies (bnAbs) administered passively may offer a valuable non-antiretroviral biological intervention for HIV prevention. Animal and human studies have demonstrated that bnAbs which neutralise HIV can prevent infection. The optimal plasma antibody concentrations to confer protection against HIV infection in humans is under intense study. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 012C trial will evaluate extended safety and pharmacokinetics of CAP256V2LS and VRC07-523LS among young HIV-negative South African and Zambian women. The study design also allows for an evaluation of a signal of HIV prevention efficacy.Methods and analysis CAPRISA 012 is a series of trials with three distinct protocols. The completed CAPRISA 012A and 012B phase 1 trials provided critical data for the CAPRISA 012C trial, which is divided into parts A and B. In part A, 90 participants were randomised to receive both CAP256V2LS and VRC07-523LS at 20 mg/kg or placebo, subcutaneously every 16 or 24 weeks. Part B will enrol 900 participants in South Africa and Zambia who will be randomised in a 1:1 ratio and receive an initial loading dose of 1.2 g of CAP256V2LS and VRC07-523LS or placebo followed by 600 mg of CAP256V2LS and 1.2 g of VRC07-523LS or placebo subcutaneously every 6 months. Safety will be assessed by frequency and severity of reactogenicity and other related adverse events. Pharmacokinetics of both antibodies will be measured in systemic and mucosal compartments over time, while participants will be monitored for breakthrough HIV infections.Ethics and dissemination of study findings The University of KwaZulu-Natal Biomedical Research Ethics Committee and South African Health Products Regulatory Authority have approved the trial (BREC/00002492/2021, SAHPRA20210317). Results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number PACTR202112683307570.

Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults and remains an important public health issue worldwide. Here we demonstrate that the expression of stimulator of interferon genes (STING) is increased in patients with DR and animal models of diabetic eye disease. STING has been previously shown to regulate cell senescence and inflammation, key contributors to the development and progression of DR. To investigate the mechanism whereby STING contributes to the pathogenesis of DR, diabetes was induced in STING-KO mice and STINGGT (loss-of-function mutation) mice, and molecular alterations and pathological changes in the retina were characterized. We report that retinal endothelial cell senescence, inflammation, and capillary degeneration were all inhibited in STING-KO diabetic mice; these observations were independently corroborated in STINGGT mice. These protective effects resulted from the reduction in TBK1, IRF3, and NF-κB phosphorylation in the absence of STING. Collectively, our results suggest that targeting STING may be an effective therapy for the early prevention and treatment of DR.

Introduction: Hepatic encephalopathy (HE) is a decline in brain function as a result of severe liver disease and its inadequacy to remove toxins from the body. It is characterized by personality changes, intellectual impairment, and loss of consciousness. This study was conducted to determine the precipitating factors and endoscopic features of hepatic encephalopathy in patients with liver cirrhosis and evaluate the associated clinical features admitted in a tertiary hospital in Central India. Materials and Methods: This hospital-based descriptive cross-sectional study was conducted from November 2016 to October 2018 on 102 patients with hepatic encephalopathy type C, aged above 18. All patients were carefully examined, relevant investigations performed, and data collected through pre-designed proforma. They were sent for statistical analysis where categorical outcomes were compared between study groups using the Chi-square test /Fisher's Exact test. Results: The prevalence of HE was 19.6% in our study. In this study, we observed that constipation (26.5%), electrolyte imbalance (21.6%), renal failure (18.6%), and upper GI bleeding (18.6%) be among the leading precipitants for HE. Besides liver failure, the associated abnormalities in various factors like coagulation abnormalities, renal derangement, and changes in serum sodium levels can lead to the progression of HE to higher grades. Conclusion: It is essential to identify the different factors like constipation, electrolyte imbalance, renal failure, and upper GI bleeding early in the course of cirrhosis to help prevent the development of HE.

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (−) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of −0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Justification : In recent years, there has been increasing recognition of children with heart disease in our country. These children belong to different age groups and have untreated, partially treated, or completely treated heart disease. The role of physical activity for optimal physical, emotional, and psychosocial well-being for children is well understood. There is a challenge for the parents and the medical professionals to take a decision regarding the type of physical activity safe for the child as heart disease may affect the hemodynamic demands. Most of the existing international guidelines focus on competitive sports in operated heart disease children. This may be of limited use when we have a mixed population of children with heart disease, different types of sports in our country and where a larger subset is looking for recommendations to leisure time activities. Process : The Pediatric Cardiac Society of India decided to formulate recommendations for physical activity in children with heart diseases. A committee of experts, who were well-versed with the subject of physical activity in children with heart disease, volunteered to take up the task of writing the guidelines. The recommendations emerged following deliberations of the committee members, on the virtual platform as well as mails. The final version of manuscript was approved by all committee members and all members are co-authors of this manuscript. The different types of physical activities were defined including leisure sports and competitive sports. The exercise was classified based on the mechanical action of muscles involved into dynamic and static components. Each type of exercise was then classified based on the intensity into low, medium, and high. Recommendations for the type of physical activity for individual heart lesions were decided based on the rationale available. Objectives : The recommendations here are made with an intention to provide general guidelines for physical activity in children with operated and unoperated heart diseases, not excluding a need for individualizing a plan, serial assessment, and comprehensive checkup in special situations. Recommendations : We hope the recommendations mentioned below would provide basic clarity in planning physical activity in children with heart disease. This is with the hope to encourage physically active life, at the same time ensuring a safety net.

Abstract Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (γδT) cells and NKT cells. Tear fluid collected using Schirmer’s strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and γδT cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1β, IL-6, LIF, IL-17A, TNFα, IFNα/β/γ, EPO, TGFβ1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1α and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.

Abstract Picrorhiza kurrooa is an endangered medicinal herb which is distributed across the Himalayan region at an altitude between 3000–5000 m above mean sea level. The medicinal properties of P. kurrooa are attributed to monoterpenoid picrosides present in leaf, rhizome and root of the plant. However, no genomic information is currently available for P. kurrooa, which limits our understanding about its molecular systems and associated responses. The present study brings the first assembled draft genome of P. kurrooa by using 227 Gb of raw data generated by Illumina and PacBio RS II sequencing platforms. The assembled genome has a size of n = ~ 1.7 Gb with 12,924 scaffolds. Four pronged assembly quality validations studies, including experimentally reported ESTs mapping and directed sequencing of the assembled contigs, confirmed high reliability of the assembly. About 76% of the genome is covered by complex repeats alone. Annotation revealed 24,798 protein coding and 9789 non-coding genes. Using the assembled genome, a total of 710 miRNAs were discovered, many of which were found responsible for molecular response against temperature changes. The miRNAs and targets were validated experimentally. The availability of draft genome sequence will aid in genetic improvement and conservation of P. kurrooa. Also, this study provided an efficient approach for assembling complex genomes while dealing with repeats when regular assemblers failed to progress due to repeats.

Introduction: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are risk factors for COVID-19 infection. Patients with kidney disease also have other co-morbidities like hypertension, diabetes mellitus, cardiovascular disease that are risk factors for poor outcome in COVID-19 infections. Severe COVID-19 has multiorgan involvement including AKI. Compared to normal population, renal failure patients with COVID-19 have extensive lung involvement, need more ventilator support, and have higher mortality. Aim: To assess outcome (mortality, recovery) and association between factors (age, gender, co-morbidities), biochemical parameters with mortality in COVID-19 patients requiring haemodialysis. Materials and Methods: It was a retrospective observational study wherein, data was collected, entered and analysed with Statistical Package for the Social Sciences (SPSS) version 19.0 using medical records of all COVID-19 patients who had renal failure (AKI or CKD) requiring haemodialysis. The study period was from June-September 2020 at Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India. Results: Out of total 68 COVID-19 positive patients, mean age of presentation was 55.08 years and with 75% of the study population were males. Most patients presented with severe COVID-19 illness with tachypnoea and hypoxia. The AKI occurrence and mortality was noted in 44.1% and 47%, respectively. It was noted that medication usage was higher for corticosteroids, oseltamivir, vitamin C, zinc therapy. Conclusion: In the present single centre study involving COVID19 patients requiring haemodialysis, it was noticed that severe COVID-19 illness, presence of AKI, chronic respiratory illness and high inflammatory markers were associated with higher mortality

A disequilibrium between immunosuppressive Tregs and inflammatory IL-17–producing Th17 cells is a hallmark of autoimmune diseases, including multiple sclerosis (MS). However, the molecular mechanisms underlying the Treg and Th17 imbalance in CNS autoimmunity remain largely unclear. Identifying the factors that drive this imbalance is of high clinical interest. Here, we report a major disease-promoting role for microRNA-92a (miR-92a) in CNS autoimmunity. miR-92a was elevated in experimental autoimmune encephalomyelitis (EAE), and its loss attenuated EAE. Mechanistically, miR-92a mediated EAE susceptibility in a T cell–intrinsic manner by restricting Treg induction and suppressive capacity, while supporting Th17 responses, by directly repressing the transcription factor Foxo1. Although miR-92a did not directly alter Th1 differentiation, it appeared to indirectly promote Th1 cells by inhibiting Treg responses. Correspondingly, miR-92a inhibitor therapy ameliorated EAE by concomitantly boosting Treg responses and dampening inflammatory T cell responses. Analogous to our findings in mice, miR-92a was elevated in CD4+ T cells from patients with MS, and miR-92a silencing in patients’ T cells promoted Treg development but limited Th17 differentiation. Together, our results demonstrate that miR-92a drives CNS autoimmunity by sustaining the Treg/Th17 imbalance and implicate miR-92a as a potential therapeutic target for MS.

Autoimmune diseases/mixed connective tissue disorders are chronic and complex group of disorders with multi-systemic involvement. Untreated cases have significant morbidity and poor quality of life. There is a T helper cell paradigm from T helper1 to T helper 2 in pregnancy and autoimmune diseases may flare or improve in pregnancy depending on the type of autoimmune disease and pre-conception disease activity. There is enough evidence to support that individuals affected with autoimmune diseases are susceptible to tuberculosis (TB) infection and conversely auto-antibodies like antinuclear antibody, and rheumatoid factor are detected in sera of patients with active tuberculosis. If this association applies in pregnancy and if immunosuppressive state of pregnancy would further augment this association is not reported. We report a rare case of a 40 year old multigravida with mixed connective tissue disorder (MCTD) with features of systemic lupus erythematosus, deforming rheumatoid arthritis with gangrenous changes and auto-amputation of toes. She had reactivation of TB in the index pregnancy. She was also a chronic hypertensive, hypothyroid and had recurrent pregnancy losses. Index pregnancy was following invitro fertilisation (IVF) conception with donor oocyte and was managed by a multidisciplinary team in obstetric high dependency unit and delivered a healthy baby; both mother and baby were discharged in stable condition. We report this case as there are no reports of MCTD with active TB in pregnancy and to review if pregnancy affects the course of MCTD, TB or association between these two, and management options in such high risk cases.

Diabetes is one among the various lifestyle disorders and was reported to be 7th leading cause of death by the WHO in 2016. To manage blood glucose levels and combat associated medical conditions, polypharmacy is becoming the choice of treatment by diabetics. Due to the unawareness of diabetics regarding the polypharmacy, it was thought to gather the scientific published literature at a place which will guide both the physicians as well as patients to choose a right herb along with conventional medicine. The scientific online portals were reviewed, and data reporting synergistic or antagonistic effects were searched for their clinical as well as preclinical evidence. There are several herbs mentioned in classical texts, which have antidiabetic potential and other beneficial effects on one's body. These drugs do exhibit synergistic as well as antagonistic effects when used along with conventional medicines. One should opt for polypharmacy cautiously and judiciously under medical supervision only.

The Major Histocompatibility Complex (MHC) makes the largest genetic contribution to multiple sclerosis (MS) susceptibility, with 32 independent effects across the region explaining 20% of the heritability in European populations. Variation is high across populations with allele frequency differences and population-specific risk alleles identified. We sought to identify MHC-specific MS susceptibility variants and assess the effect of ancestral risk modification within 2652 Latinx and Hispanic individuals as well as 2435 Black and African American individuals. We have identified several novel susceptibility alleles which are rare in European populations including HLA-B*53:01, and we have utilized the differing linkage disequilibrium patterns inherent to these populations to identify an independent role for HLA-DRB1*15:01 and HLA-DQB1*06:02 on MS risk. We found a decrease in Native American ancestry in MS cases vs controls across the MHC, peaking near the previously identified MICB locus with a decrease of ~5.5% in Hispanics and ~0.4% in African Americans. We have identified several susceptibility variants, including within the MICB gene region, which show global ancestry risk modification and indicate ancestral differences which may be due in part to correlated environmental factors. We have also identified several susceptibility variants for which MS risk is modified by local ancestry and indicate true ancestral genetic differences; including HLA-DQB1*06:02 for which MS risk for European allele carriers is almost two times the risk for African allele carriers. These results validate the importance of investigating MS susceptibility at an ancestral level and offer insight into the epidemiology of MS phenotypic diversity.

BackgroundMolecular tests in solid tumours for targeted therapies call for the need to ensure precision testing. To accomplish this participation in the External Quality Assessment Program (EQAS) is required. This evaluates the consistency of diagnostic testing procedures and offers guidance for improving quality. Outbreak of COVID-19 pandemic led to worldwide lockdown and disruption of healthcare services including participation in EQAS.The present study describes the extended scope of EQAS offered byMPQAP (Molecular Pathology Quality Assurance Program), the first proficiency test provider for solid tumor diagnostics in India. The study surveys the preparedness of molecular testing laboratories in routine diagnostics and participation for quality assessment scheme.MethodsA documented guideline for measures and precautions to be carried by testing laboratories in performing routine diagnostic tests during the lockdown period were charted and distributed to all MPQAP participant centres. A survey was conducted for MPQAP participants to check whether laboratories were involved in COVID-19 testing and to evaluate the impact of lockdown on the operations of diagnostics procedures. From the acquired response of the survey, 2 cycles out of initially proposed 11 cycles were executed with transformed approach using digital tools and image interpretation modules.FindingsOut of 25 solid tumour testing laboratories registered as participants, 15 consented to participate in survey. The summary of survey conveyed the impact of COVID-19onroutine operations of diagnostics tests such as shortcomings in inventory and human resource management. Thirteen participants showed active willingness and consented to participate in EQAS test scheme.InterpretationsThe survey findings and assessment of EQAS cycles endorsed the quality testing procedures carried by participating laboratories throughout the lockdown. It highlighted the utility of EQAS participation during pandemic along with emphasis on safety measures for continual improvement in quality of diagnostic services.

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

Mitochondrial activity determines aging rate and the onset of chronic diseases. The mitochondrial permeability transition pore (mPTP) is a pathological pore in the inner mitochondrial membrane thought to be composed of the F-ATP synthase (complex V). OSCP, a subunit of F-ATP synthase, helps protect against mPTP formation. How the destabilization of OSCP may contribute to aging, however, is unclear. We have found that loss OSCP in the nematode Caenorhabditis elegans initiates the mPTP and shortens lifespan specifically during adulthood, in part via initiation of the mitochondrial unfolded protein response (UPRmt). Pharmacological or genetic inhibition of the mPTP inhibits the UPRmt and restores normal lifespan. Loss of the putative pore-forming component of F-ATP synthase extends adult lifespan, suggesting that the mPTP normally promotes aging. Our findings reveal how an mPTP/UPRmt nexus may contribute to aging and age-related diseases and how inhibition of the UPRmt may be protective under certain conditions.

Introduction: Cholera is an acute diarrhoeal disease caused by Vibrio cholerae (V.cholerae). Based on antigenic differences of O antigen, O1 serogroup can be divided into three serotypes. In addition, by performing various biochemical reactions, O1 Serogroup can be differentiated into two biotypes. Outbreaks of Cholera occur seasonally. It is associated with monsoon season, warm temperature, heavy rainfall and increased plankton population. Aim: The aim was to determine the trends in resistance pattern and phenotypic Pattern of Vibrio cholerae. Materials and Methods: A retrospective study was conducted during the period from June 2019-December 2019. Culture of Stool specimens were done on different agar media. Biotyping was done by conventional methods. Serotyping and phage typing was also done along with the Antibiotic susceptibility testing. Descriptive analysis was used and presented in terms of percentage. Results: V.cholerae was isolated in 72 patients and they belonged to serogroup O1 and biotype El Tor. The most common serotype was Ogawa. The predominant phage type were T2 by old scheme and T27 by new scheme of phage typing. The maximum number of V. cholerae isolates was seen in the month of November, 2019 followed by October, 2019. Conclusion: The phenotypic pattern and fluctuating seasonal trend of V. cholerae and antimicrobial resistance encourage the continued epidemiological and microbiological surveillance of the disease.

The long-standing pain in fingers is not only agonising and disabling to the patient but also affects the quality of life. Pointed fingertip pain is also inappropriately managed for years leading to further morbidity. Pinpoint tenderness, paroxysmal pain, and cold hypersensitivity at finger pulp space may be features of glomus tumor. Judicious use of investigations and surgical excision ensure an optimal outcome. We report a case of glomus tumor at an unusual location at the pulp space of distal phalanx of the little finger that was managed by en bloc removal and confirmed on biopsy. History of 6 years of clinical symptoms and multiple treatments underlines the importance of the knowledge of this lesion for early diagnosis.

In a non-obstetric patient, uterine inversion is a rare complication of intrauterine tumors. Till date, only 200 cases have been reported worldwide. The typical presentation is with features of haemorrhagic shock. Delay in diagnosis and management deteriorates the general health and future reproductive potential of the patient. We present a 30 year old multiparous lady, a diagnosed case of submucosal fibroid who had acute uterine inversion and was managed by performing a laparotomy with Haultains procedure. The case is bring presented as it is a rare gynaecological emergency, which requires immediate resuscitative and definitive procedures. Uterine conservation is a feasible option in selected cases of uterine inversion; chronic and neglected cases are a challenge for both conservative surgery and hysterectomy. High index of suspicion for malignancy should be a consideration irrespective of age, parity, previous benign conditions to optimize outcome.

Background: Hemophilia is underdiagnosed in India, and there is lack of state specific data on the extent and morbidity. This article provides the real world demographic and clinical data of patients with hemophilia (PwH) in a resource-constrained setting in Punjab, India. Patients and Methods: This is a retrospective analysis of PwH in the institutional hemophilia registry over 9 years. Eligible patients who had a confirmed diagnosis at our institute were included in the analysis. Demographic, clinical, and treatment data used in the current analysis were extracted from medical records using a standardized data collection form. Results: A total of 211 patients were from Punjab, comprising 175 PwH A (91.3%) and 36 with PwH B for uniformity. The mild, moderate, and severe hemophilia in the cohort were 32 (15.1%), 45 (21.3%), and 132 (62.5%), respectively. No patient was on continuous prophylaxis. Inhibitors were positive in 7.9% of patients. Joint deformity was found in 83.5% of severe PwH. Transfusion-transmitted infections were found in 24 (18.3%). There were no statistically significant differences between hemophilia A and B groups with regard to demographic or clinical characteristics. The current median age of the group was 22 years against a national average of 27.6 years. Only 7.4% of the estimated cases of PwH are diagnosed in Punjab. Conclusion: There are significant underdiagnoses, increased incidence of transfusion-transmissible infection, and joint deformity among PwH in Punjab. Therefore, it warrants an immediate need to develop a registry, increase awareness about hemophilia, and provide comprehensive care.

Introduction New HIV prevention strategies are urgently required. The discovery of broadly neutralising antibodies (bNAbs) has provided the opportunity to evaluate passive immunisation as a potential prevention strategy and facilitate vaccine development. Since 2014, several bNAbs have been isolated from a clade C-infected South African donor, CAPRISA 256. One particular bNAb, CAP256-VRC26.25, was found to be extremely potent, with good coverage against clade C viruses, the dominant HIV clade in sub-Saharan Africa. Challenge studies in non-human primates demonstrated that this antibody was fully protective even at extremely low doses. This bNAb was subsequently structurally engineered and the clinical variant is now referred to as CAP256V2LS.Methods and analysis CAPRISA 012B is the second of three trials in the CAPRISA 012 bNAb trial programme. It is a first-in-human, phase I study to assess the safety and pharmacokinetics of CAP256V2LS. The study is divided into four groups. Group 1 is a dose escalation of CAP256V2LS administered intravenously to HIV-negative and HIV-positive women. Group 2 is a dose escalation of CAP256V2LS administered subcutaneously (SC), with and without the dispersing agent recombinant human hyaluronidase (rHuPH20) as single or repeat doses in HIV-negative women. Groups 3 and 4 are randomised placebo controlled to assess two (CAP256V2LS+VRC07-523LS; CAP256V2LS+PGT121) and three (CAP256V2LS+VRC07-523LS+PGT121) bNAb combinations administered SC to HIV-negative women. Safety will be assessed by the frequency of reactogenicity and adverse events related to the study product. Pharmacokinetic disposition of CAP256V2LS alone and in combination with VRC07-523LS and PGT121 will be assessed via dose subgroups and route of administration.Ethics and dissemination The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and the South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval (trial reference numbers: BREC00000857/2019 and SAHPRA 20200123). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry.Trial registration number PACTR202003767867253; Pre-results.

Nitrogen is an important nutrient for plant growth and tuber quality of potato. Since potato crop requires high dose of N, improving nitrogen use efficiency (NUE) of plant is an inevitable approach to minimize N fertilization. The aim of this study was to identify and characterize microRNAs (miRNAs) by small RNA sequencing in potato plants grown in aeroponic under two contrasting N (high and low) regimes. A total of 119 conserved miRNAs belonging to 41 miRNAs families, and 1002 putative novel miRNAs were identified. From total, 52 and 54 conserved miRNAs, and 404 and 628 putative novel miRNAs were differentially expressed in roots and shoots, respectively under low N stress. Of total 34,135 predicted targets, the gene ontology (GO) analysis indicated that maximum targets belong to biological process followed by molecular function and cellular component. Eexpression levels of the selected miRNAs and targets were validated by real time-quantitative polymerase chain reaction (RT-qPCR) analysis. Two predicted targets of potential miRNAs (miR397 and miR398) were validated by 5' RLM-RACE (RNA ligase mediated rapid amplification of cDNA ends). In general, predicted targets are associated with stress-related, kinase, transporters and transcription factors such as universal stress protein, heat shock protein, salt-tolerance protein, calmodulin binding protein, serine-threonine protein kinsae, Cdk10/11- cyclin dependent kinase, amino acid transporter, nitrate transporter, sugar transporter, transcription factor, F-box family protein, and zinc finger protein etc. Our study highlights that miR397 and miR398 play crucial role in potato during low N stress management. Moreover, study provides insights to modulate miRNAs and their predicted targets to develop N-use efficient potato using transgenic/genome-editing tools in future.

Background: Hemophilia center, treatment center (TC), hemophilia TC (HTC), and Hemophilia Comprehensive Care Center (CCC) are terminologies used to describe centers caring for persons with hemophilia (PWH). These are based on their capability to provide multidisciplinary care and laboratory services. Widely described are the European HTCs (EHTCs) and the European Hemophilia CCCs (EHCCCs). However, most centers in developing countries providing care for PWH have variable clinical expertise and laboratory facilities, which do not qualify for the existing models. Materials and Methods: This cross-sectional study was done to evaluate the laboratory and clinical care facilities available in HTCs in India. The survey questionnaire was sent to 62 HTCs in India. Laboratory and clinical care facilities were categorized based on a predefined stratification model. Level IV being the minimum and Level I the maximum were used to define clinical and laboratory facilities. Results: Fifty-two (85%) centers responded representing 17 states in India. Only 28 HTCs had attached laboratory services. Although all the centers cared for acute bleeds, only half managed chronic joint disease (Level III) while one-sixth could perform surgeries (Level II). Only one-third of the laboratories had instituted quality control measures and performed factor assays. Only four centers qualified for EHTC criteria and two for the EHCCC criteria. Conclusion: This HTC stratification model provides assessment and differentiation of the clinical and laboratory services. It allows an individual HTC to identify the standard of care and provides a framework for objectively planning, implementing, and evaluating its services.

Background: Fetal echocardiography is being increasingly used for prenatal diagnosis of congenital cardiac malformations, but its impact on the neonatal outcomes in low- and middle-income countries is still unknown. Aims: The objective of this study is to determine the impact of fetal echocardiography on immediate postnatal and short.term outcome in a tertiary pediatric cardiac center. Study Design: This is a prospective study. Materials and Methods: One hundred consecutive patients with critical congenital heart defects (CHD) requiring active medical or surgical interventions in the 1st month of life were included in the study. The detailed history, postnatal examination findings, and fetal echocardiogram report were recorded. They were divided into two groups as antenatally diagnosed and postnatally diagnosed. Pre- and post-procedural variables were compared between the two groups. Results: Twenty-nine neonates were diagnosed antenatally while 71 were diagnosed postnatally. Totally, 10 babies (34.5%) among the antenatally diagnosed group were delivered in a tertiary health-care setup. The mean age at presentation was 0. day in the antenatally diagnosed group while 10 days. (0–30 days) in the postnatally diagnosed group. (P = 0.01). A total of 17 (58.6%) patients in the antenatal group had duct dependent CHD, and 15 (88.2%) of these patients were transported on prostaglandin E1. In comparison, 19/34 (55.9%) patients in the postnatal group were transported on prostaglandin. The pH on admission in the antenatal group was 7.32 ± 0.05 as compared to 7.28 ± 0.05 in the postnatal group. (P = 0.0004). There were 4 (5.6%) deaths in the postnatal group during transfer. There was no significant difference in the postoperative variables in both groups. Conclusions: Fetal echocardiography identifies patients with complex CHD resulting in better parental counseling, thus facilitating delivery at a tertiary care center and preoperative stabilization. This results in improved preoperative mortality and better stabilization.

Postmenopausal bleeding may be a presenting complaint for genital tract malignancy. Benign uterine causes predominate while endometrial cancer contributes 10% of symptomatic cases. Extra-uterine causes are rare and include carcinoma cervix or hormone secreting tumours of the ovary. We report a case of 50-year-old postmenopausal lady that presented with postmenopausal bleeding. On evaluation, she was found to have a complex adnexal mass, normal ovarian tumour markers and endometrial histology was normal on biopsy. She underwent exploratory laparotomy and total abdominal hysterectomy with bilateral salpingooophorectomy. The postoperative diagnosis was cystadenofibroma of ovary. We reported this case because of its rare incidence and varied symptomatology and presentation on imaging. One should consider diagnosis of a cystadenofibroma of ovary when a postmenopausal lady presents with a triad of an adnexal mass, postmenopausal bleeding with normal endometrial evaluation.

Background: Nonalcoholic fatty liver disease (NAFLD) also called as hepatic steatosis is a manifestation of excessive triglyceride accumulation in the liver. NAFLD has been described by histological features ranging from simple fatty liver, nonalcoholic steatohepatitis, progressive fibrosis, and liver failure. Objective: The objective was to evaluate the effect of herbomineral drugs and pathya0 (Ayurvedic dietary regime and physical exercise) in the management of NAFLD. Materials and Methods: It is a randomized, retrospective, open-ended study. A total of 32 patients presenting with raised alanine transaminase (>1.5 times normal levels) combined with sonological evidence of fatty liver in the absence of any other detectable cause of liver disease were included in the study. The recruited patients were randomly divided into two groups - The patients in Group-A (n = 21) were given a combination of herbomineral drugs Ārogyavardhinī vaṭi and Triphalā Guggulu along with prescription of pathya (Ayurvedic dietary regime and physical exercise); the patients in Group-B ( n = 11) were advised only pathya. Results: Group-A (combined therapy group) showed statistically significant improvement in clinical symptoms, biochemical parameters-liver function test, lipid profile, fasting blood sugar, and body mass index (P < 0.001) in comparison to Group-B (pathya group). Conclusion: Combination of herbomineral drugs along with pathya has shown promising results toward the effective management of this metabolic disorder.

Background: During Middle Ear Surgeries (MES) done under Local Anesthesia (LA), patients may feel discomfort due to noise of suction, manipulation of instruments, positioning of head-neck and sometimes due to pain. A bloodless microscopic field is also essential to facilitate surgical exposure in MES. Various combinations of analgesics and sedatives have been tried to alleviate apprehension of the patients and improve microscopic field which may result into reduction in surgical time. In the present study, we have compared Dexmedetomedine (Dex) with Midazolam-Fentanyl (MF) and PentazocinePromethazine (PP) combinations for their sedoanalgesia, anxiolysis and other pharmacological effects when administered during MES, not lasting for more than 60 min. Material and Methods: Ninety American Society of American Society of Anesthesiologists (ASA) group I /II patients admitted in either of the three hospitals during May 2014 to January 2015 for MES under LA were randomly divided into three groups by an independent observer. Group D received intravenous bolus of Injection Dexmedetomidine 1 µg/ kg over 10 min. Group MF received Injection Midazolam 0.06 mg/ kg + Inj. Fentanyl 1 µg/ kg and Group PP received Injection Pentazocine 0.3 mg/kg + Injection Promethazine 0.5mg/kg given intravenously followed by LA before taking incision for the surgery. Need of a rescue sedoanalgesic dose of (Midazolam 0.01 mg/kg + Fentanyl 0.5 µg/kg) during the surgery was noted. All the patients received 500 ml of normal saline infusion till the end of the surgery. All surgeries were finished within 60 min. Vital parameters and Ramsay Sedation Score (RSS) of the patients were noted from the time of administration of sedative till the end of the surgery. Patient and surgeon satisfaction scores were recorded immediately after the surgery. Drug combinations of three groups were compared for their effectiveness, adverse effects and satisfaction scores in given doses. Children, mentally unstable patients, uncooperative patients, patients requesting general anesthesia, patients with known sensitivity to local anesthetic drug Lignocaine, and allergy to study drugs, pregnant and lactating females were excluded from the study. Results: RSS were satisfactory in Group D and Group MF but not in Group PP. Percentage of patients requiring rescue sedoanalgesic dose of (Midazolam 0.01 mg/kg + Fentanyl 0.5 µg/kg) was the highest (20%) in Group PP. It was the least in Group D. Intraoperative heart rate and mean arterial pressure in Group D were significantly lower than the baseline values and the corresponding values in Group MF and Group PP. Incidence of postoperative nausea was higher in Group PP. One patient in Group D had significant bradycardia with hypotension while one patient in Group MF got desaturated needing Oxygen therapy. Statistically significant number of patients from Group D had bloodless microscopic field compared to Group MF and Group PP. Surgeon satisfaction scores which showed statistically significant correlation with type of microscopic field were better in Group D. Patient satisfaction scores were better in Group D than Group MF and Group PP. Conclusion: Out of the sedoanalgesics tested, Dexmedetomidine was found to be the best drug for MES patients performed under local anaesthesia. It produced near bloodless microscopic surgical field with better surgeon and patient satisfaction.

A good dressing is mandatory to an uncomplicated wound healing, especially when foreign particles contaminate the wound. Various forms of dressing preparations are available for use and differ in chemical composition and efficacy. Silver has been a known agent with good antimicrobial and healing properties and recent times has seen an upsurge in various silver-based dressing supplements. We describe our report of use and efficacy of a silver nanoparticle- based gel dressing in the healing of multiple superficial firearm pellet wounds.

OBJECTIVE:To explore the value of machine learning methods for predicting multiple sclerosis disease course. METHODS:1693 CLIMB study patients were classified as increased EDSS≥1.5 (worsening) or not (non-worsening) at up to five years after baseline visit. Support vector machines (SVM) were used to build the classifier, and compared to logistic regression (LR) using demographic, clinical and MRI data obtained at years one and two to predict EDSS at five years follow-up. RESULTS:Baseline data alone provided little predictive value. Clinical observation for one year improved overall SVM sensitivity to 62% and specificity to 65% in predicting worsening cases. The addition of one year MRI data improved sensitivity to 71% and specificity to 68%. Use of non-uniform misclassification costs in the SVM model, weighting towards increased sensitivity, improved predictions (up to 86%). Sensitivity, specificity, and overall accuracy improved minimally with additional follow-up data. Predictions improved within specific groups defined by baseline EDSS. LR performed more poorly than SVM in most cases. Race, family history of MS, and brain parenchymal fraction, ranked highly as predictors of the non-worsening group. Brain T2 lesion volume ranked highly as predictive of the worsening group. INTERPRETATION:SVM incorporating short-term clinical and brain MRI data, class imbalance corrective measures, and classification costs may be a promising means to predict MS disease course, and for selection of patients suitable for more aggressive treatment regimens.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is characterized by a persistent pattern of inattention and/or hyperactivity-impulsivity. In view of the adverse effects associated with psycho-stimulants used for the treatment of this disorder, efficacy of Brāhmīghṛtam was evaluated in this condition. Materials and Methods: After following due ethical considerations, children of either sex between the age group of 6 and 12 years diagnosed to be suffering from mixed variety of ADHD as per The Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria irrespective of other co-morbid psychiatric illnesses were recruited in the study. Initially a pilot study (n = 10) was carried out to confirm the efficacy of the identified dose of Brāhmīghṛtam. Using this dose, further therapeutic confirmatory study (n = 27) was carried out, wherein Brāhmīghṛtam was compared with methylphenidate. Effect on ADHD symptoms was assessed using the Dupaul ADHD rating scale and this was the main efficacy parameter. Results: In the pilot exploratory study, Brāhmīghṛtam showed 66% decrease in total ADHD score. In the therapeutic confirmatory study, only 16% improvement was seen with Brāhmīghṛtam, which was similar to methylphenidate, standard treatment for ADHD that was used as a comparator in the present study. No side-effects were reported in both studies. Conclusion: Our study thus has adequately demonstrated efficacy and safety of Brāhmīghṛtam in ADHD.

Introduction: Preeclampsia may lead to heart failure in late pregnancy and early puerperium. Diastolic dysfunction may be the cause of heart failure in these patients. There is paucity of data on diastolic dysfunction in patients with preeclampsia. Aim: To assess cardiac diastolic dysfunction in women with preeclampsia by Doppler echocardiography and to correlate severity of dysfunction with severity of preeclampsia. Materials and Methods: One hundred and fifty nulliparous women in age group of 20-35 years were recruited for the study. Among these, 120 women with preeclampsia were taken as cases and 30 normotensive women as controls. Doppler echocardiography was carried out between 28-36 weeks of gestation in both groups to assess and grade severity of diastolic dysfunction. Results: Of 120 women with preeclampsia, 61 had mild preeclampsia and 59 had severe preeclampsia. Diastolic dysfunction was seen in 25(20.8%) cases. Among these, grade I diastolic dysfunction was seen in 40% and the rest 60% had grade II diastolic dysfunction. In the mild preeclampsia group, only 2(3.3%) patients had diastolic dysfunction. Both had grade I dysfunction. Of severe preeclampsia patients, 8(13.6%) had grade I and 15(25.4%) had grade II diastolic dysfunction (p=0.001). None of these progressed to heart failure or pulmonary oedema. Systolic function assessed by left ventricular ejection fraction was normal in all cases. All controls had normal systolic and diastolic functions. Conclusion: Cardiac diastolic dysfunction occurred in one-fifth of women with preeclampsia. Grade of diastolic dysfunction correlated with the severity of preeclampsia.

Introduction: Body image is an essential aspect of young girls’ self-definition and individual identity which is influenced by various biological, psychological and social factors. Excessive concern about body image, body image misconception are leading to dissatisfaction, disturbed eating patterns, affecting the nutritional status and also leading to depression and anxiety disorders. This concept of body image has been less explored in Indian context, especially among young girls. Aims: The objectives of the study were to assess the body image perception among young college going girls, using a visual analog scale and to compare body image perception and satisfaction with their BMI levels and weight changing methods adopted. Materials and Methods: An exploratory cross-sectional study was conducted among 63 female students studying BBM course at a private commerce institution in Vijayapur city. Data was collected using a self administered questionnaire containing details of basic socio-demographic information and a validated visual analogue scale. Height was measured by Seca Stadiometer, weight was measured using Digital weighing machine and Body Mass Index levels were calculated. Percentages were calculated for descriptive variables. Chisquare test was applied for analysing categorical variables. Spearman Rank correlation test was applied for analysing ordinal data. Results: A 39.7% of participants were underweight and 15.9% were overweight/obese. Majority of underweight and overweight girls (72% and 89%, respectively) perceived themselves as normal weight. Body image satisfaction of participants was found to be significantly associated with their body image perception, mothers’ educational status and also with relatives’ and peer group’s opinions about their body weight. Unhealthy weight changing patterns like skipping meals (13%), increasing quantity and frequency of meals (17%) were reported among study participants. Conclusion: This exploratory study highlights the gap between young girls’ body image perception and their BMI levels, indicating body image misconception. Lower literacy level of mothers and opinions of relatives and friends significantly influenced body image satisfaction among study participants. Higher percentage of underweight (39.7%) coupled with unhealthy weight changing patterns reportedly adopted by participants (30%) indicates need for further research on this issue, to help inform public health nutrition programmes.

Calcinosis cutis is an uncommon disorder resulting in the deposition of calcium salts underneath the skin and subcutaneous tissues. Asymptomatic, giant lesion is a rare finding and rarer if present bilaterally over iliac bones. Frictional ulceration may at times be presenting feature of a chronic lesion that requires excisional biopsy.

Background: Enteric opportunistic parasitic infections are the major source of diarrheal disease in developing countries mainly in Human Immunodeficiency virus (HIV) infected patients. Objective: The study was to detect enteric parasites causing diarrhea and their association with immune status in HIV-seropositive patients. Methods: The present study was conducted in tertiary care teaching Hospital, Baroda between January 2006 to January 2007 involving 100 Human Immunodeficiency virus (HIV) seropositive patients.From all patients stool samples collected and stool was examined for enteric parasites by microscopy with special staining methods. Results: A total of 100 HIV sero-positive patients with and without diarrhea were included in the study. Of the 100 patients, the protozoan parasitic infection was found in 28% (28/100). Out of 100 patients, 50 had diarrhea in which parasitic infection was 24 (48%) and 4 (4/50) protozoal parasites positive cases did not have diarrhea. A significant difference (p

Background and Aim: Sedation plays a pivotal role in the care of the critically ill patient. It is equally important to assess depth of sedation. The present study had been designed to compare dexmedetomidine and propofol for sedation in mechanically ventilated intensive care patients. It also intended to verify the clinical validity, reliability and applicability of objective assessment tool bispectral index (BIS) for monitoring sedation and observe for correlation with the commonly used subjective scale, Ramsay sedation score (RSS). Materials and Methods: This prospective randomized study was carried out in 60 haemodynamically stable patients, aged between 18 to 80 years, requiring sedation and mechanical ventilation. These were divided equally into two groups. Group A received dexmedetomidine loading dose (1μg/kg) over 10 min followed by maintenance infusion of 0.5μg/kg/hr (0.2-0.7 μg/kg/hr). Group B received propofol loading dose (1mg/kg) over 5 min followed by infusion of 2mg/kg/hr (1-3mg/kg/hr). All patients received fentanyl 1 μg/kg prior to the study drugs. Vital parameters and sedation levels (using RSS and BIS) were monitored for the study period of 12 hours with level 4 or 5 of RSS as target for sedation. Ramsay score was compared with the average of BIS values. Statistical analysis was done using SPSS VERSION 17 software. Results: The study revealed statistically significant lower heart rates during sedation in dexmedetomidine group whereas fall in mean arterial pressure (MAP) following loading dose in propofol group. Patients sedated with dexmedetomidine were easily arousable. Need for rescue drug for achieving the desired RSS as well as incidence of bradycardia was more in dexmedetomidine group than other. Good correlation exists between Ramsay score and BIS values. Conclusion: Dexmedetomidine reduces heart rate while propofol transiently affects MAP. However, adequate sedation is achieved with both the drugs. The data obtained from the study validate BIS monitoring for ICU sedation.

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.