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One Anastomosis Gastric Bypass (OAGB) vs Roux en Y Gastric Bypass (RYGB) for Remission of T2DM in Patients with Morbid Obesity: a Randomized Controlled Trial.
Singh, B, Saikaustubh, Y, Singla, V, Kumar, A, Ahuja, V, Gupta, Y, Kashyap, L, Aggarwal, S
Obesity surgery. 2023;(4):1218-1227
Abstract
INTRODUCTION Majority of the studies comparing Roux en Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are non-randomized. Moreover, few randomized studies have focussed on weight loss as the primary outcome rather than the impact on type 2 diabetes mellitus (T2DM). This randomized trial compared OABG over RYGB with the hypothesis that OAGB is not inferior to RYGB in terms of remission of T2DM. METHODS This was an open-labelled, randomized trial in which patients having a BMI greater than 30 kg/m2 with T2DM were included. The primary outcome was the remission of T2DM. RESULTS In the study, 25 and 24 patients were recruited in OAGB and RYGB groups respectively. The remission rates of T2DM were similar at all timelines. The highest rate was achieved at 1 year (86.36% vs 85.71%) for both the groups and a 4-year remission rate of (72.22% vs 71.43%), for OAGB vs RYGB respectively. The % EWL was also comparable with the highest rate achieved again at 1 year (69.23% vs 66.67%) and a 4-year rate of (58.33% vs 53.33%), for OAGB vs RYGB respectively. Remission of other co-morbidities, major and minor complication rate, re-admission rate, and nutritional issues were similar in both groups. CONCLUSION OAGB is non-inferior to RYGB in terms of remission of type 2 diabetes mellitus, weight loss, and early and late complications with a shorter operating time.
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The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.
Gupta, Y, Kapoor, D, Lakshmi, JK, Praveen, D, Santos, JA, Billot, L, Naheed, A, de Silva, HA, Gupta, I, Farzana, N, et al
Diabetes research and clinical practice. 2023;:110893
Abstract
AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).
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Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.
Barry, A, McNulty, MT, Jia, X, Gupta, Y, Debiec, H, Luo, Y, Nagano, C, Horinouchi, T, Jung, S, Colucci, M, et al
Nature communications. 2023;(1):2481
Abstract
Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
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Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.
Tandon, N, Gupta, Y, Kapoor, D, Lakshmi, JK, Praveen, D, Bhattacharya, A, Billot, L, Naheed, A, de Silva, A, Gupta, I, et al
JAMA network open. 2022;(3):e220773
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Abstract
IMPORTANCE Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. OBJECTIVE To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. DESIGN, SETTING, AND PARTICIPANTS This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. INTERVENTIONS A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. MAIN OUTCOMES AND MEASURES The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. RESULTS A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. CONCLUSIONS AND RELEVANCE This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. TRIAL REGISTRATION Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.
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Repurposing Lansoprazole and Posaconazole to treat leishmaniasis: Integration of in vitro testing, pharmacological corroboration, and mechanisms of action.
Gupta, Y, Goicoechea, S, Romero, JG, Mathur, R, Caulfield, TR, Becker, DP, Durvasula, R, Kempaiah, P
Journal of food and drug analysis. 2022;(1):128-149
Abstract
Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing of compounds against Leishmania amastigotes and selected the most promising active compounds, Lansoprazole and Posaconazole. We identified possible Leishmania drug targets of Lansoprazole and Posaconazole using several available servers. Our in-silico screen identified likely Lansoprazole targets as the closely related calcium-transporting ATPases (LdBPK_352080.1, LdBPK_040010.1, and LdBPK_170660.1), and the Posaconazole target as lanosterol 14-alpha-demethylase (LdBPK_111100.1). Further validation showed LdBPK_352080.1 to be the most plausible target based on induced-fit docking followed by long (100ns) MD simulations to confirm the stability of the docked complexes. We present a likely ion channel-based mechanism of action of Lansoprazole against Leishmania calcium-transporting ATPases, which are essential for parasite metabolism and infectivity. The LdBPK_111100.1 interaction with Posaconazole is very similar to the known fungal orthologue. Herein, we present two novel anti-leishmanial agents, Posaconazole and Lansoprazole, already approved by the FDA for different indications and propose plausible mechanisms of action for their antileishmanial activity.
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Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit.
Gupta, Y, Maciorowski, D, Medernach, B, Becker, DP, Durvasula, R, Libertin, CR, Kempaiah, P
Journal of cellular biochemistry. 2022;(3):601-619
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After more than a year of the COVID-19 pandemic, SARS-CoV-2 infection rates with newer variants continue to devastate much of the world. Global healthcare systems are overwhelmed with high positive patient numbers. Silent hypoxia accompanied by rapid deterioration and some cases with septic shock is responsible for COVID-19 mortality in many hospitalized patients. There is an urgent need to further understand the relationships and interplay with human host components during pathogenesis and immune evasion strategies. Currently, acquired immunity through vaccination or prior infection usually provides sufficient protection against the emerging variants of SARS-CoV-2 except Omicron variant requiring recent booster. New strains have shown higher viral loads and greater transmissibility with more severe disease presentations. Notably, COVID-19 has a peculiar prognosis in severe patients with iron dysregulation and hypoxia which is still poorly understood. Studies have shown abnormally low serum iron levels in severe infection but a high iron overload in lung fibrotic tissue. Data from our in-silico structural analysis of the spike protein sequence along with host proteolysis processing suggests that the viral spike protein fragment mimics Hepcidin and is resistant to the major human proteases. This functional spike-derived peptide dubbed "Covidin" thus may be intricately involved with host ferroportin binding and internalization leading to dysregulated host iron metabolism. Here, we propose the possible role of this potentially allogenic mimetic hormone corresponding to severe COVID-19 immunopathology and illustrate that this molecular mimicry is responsible for a major pathway associated with severe disease status. Furthermore, through 3D molecular modeling and docking followed by MD simulation validation, we have unraveled the likely role of Covidin in iron dysregulation in COVID-19 patients. Our meta-analysis suggests the Hepcidin mimetic mechanism is highly conserved among its host range as well as among all new variants to date including Omicron. Extensive analysis of current mutations revealed that new variants are becoming alarmingly more resistant to selective human proteases associated with host defense.
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Ocular sequelae in severe COVID-19 recovered patients of second wave.
Dipu, T, Goel, R, Arora, R, Thakar, M, Gautam, A, Shah, S, Gupta, Y, Chhabra, M, Kumar, S, Singh, K, et al
Indian journal of ophthalmology. 2022;(5):1780-1786
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Abstract
PURPOSE To evaluate the retinal microvascular changes in patients, recovered from severe COVID-19 during the second wave of the pandemic in North India. METHODS In this observational cross-sectional study, 70 eyes of 35 patients who recovered from severe COVID-19 during the second wave underwent detailed ophthalmic evaluation 4-6 weeks after discharge. Twelve controls were also enrolled, and the difference in the findings between the case and control groups on optical coherence tomography (OCTA) were studied. RESULT The ages of study participants ranged from 27 to 60 years with the male:female ratio being 1.05:1. The fundus changes suggestive of ischemia in the form of cotton wool spots and vascular tortuosity were seen in 25 eyes (35.71%). Increased venous tortuosity was the most common finding seen in 23 eyes (32.85%), of which 10 eyes (28.57%) had concurrent hypertensive retinopathy (HTR) changes. There was a significant reduction in the mean vascular density (VD) and perfusion density (PD) for both the superficial capillary plexus (SCP) and deep capillary plexus (DCP) at inner, outer ring, and whole (P < 0.05). Foveal avascular zone was significantly enlarged in both the SCP (P = 0.01) and the DCP (P = 0.03). The mean ganglion cell-inner plexiform layer (GC-IPL) was significantly reduced in comparison to controls (P < 0.001). CONCLUSION Severe COVID-19 can result in microvascular changes at the macula in the form of reduction in vascular and perfusion density, which can be evaluated using OCTA. As structural changes precede functional changes, a close watch is recommended in patients showing compromise in retinal microvasculature.
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Emergence of nutrigenomics and dietary components as a complementary therapy in cancer prevention.
Srivastava, S, Dubey, AK, Madaan, R, Bala, R, Gupta, Y, Dhiman, BS, Kumar, S
Environmental science and pollution research international. 2022;(60):89853-89873
Abstract
Cancer is an illness characterized by abnormal cell development and the capability to infiltrate or spread to rest of the body. A tumor is the term for this abnormal growth that develops in solid tissues like an organ, muscle, or bone and can spread to other parts of the body through the blood and lymphatic systems. Nutrition is a critical and immortal environmental component in the development of all living organisms encoding the relationship between a person's nutrition and their genes. Nutrients have the ability to modify gene expression and persuade alterations in DNA and protein molecules which is researched scientifically in nutrigenomics. These interactions have a significant impact on the pharmacokinetic properties of bioactive dietary components as well as their site of action/molecular targets. Nutrigenomics encompasses nutrigenetics, epigenetics, and transcriptomics as well as other "omic" disciplines like proteomics and metabolomics to explain the vast disparities in cancer risk among people with roughly similar life style. Clinical trials and researches have evidenced that alternation of dietary habits is potentially one of the key approaches for reducing cancer risk in an individual. In this article, we will target how nutrigenomics and functional food work as preventive therapy in reducing the risk of cancer.
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Vitamin D Deficiency and Interleukin Levels in Allergic Rhinitis: A Case-Control Study.
Kajal, S, Shrestha, P, Gupta, Y, Deepak, R, Verma, H
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2022;(Suppl 2):1720-1724
Abstract
Various studies have shown a positive co-relation between Vitamin D deficiency and severity of Allergic Rhinitis (AR) based on subjective symptoms. AR is also associated with serum eosinophilia and raised levels of various interleukins (IL)-particularly IL-4, IL-5 and IL-13. To compare serum Vitamin D levels, IL-4, IL-5, and IL-13 levels, and eosinophilia in AR patients with healthy controls and co-relate disease severity using Sino-nasal Outcome Test-22 (SNOT-22) score in patients with Vitamin D deficiency. 30 patients and 30 healthy controls were recruited. 10 ml blood sample was drawn from each patient and healthy control. It was then processed to evaluate absolute eosinophil count, serum levels of Vitamin D, and IL-4, IL-5, and IL-13. 93.33% of patients with AR and 70% of healthy controls had decreased Vitamin D levels (below 25 ng/ml). The mean Vitamin D levels was 10.50 ± 2.34 ng/ml and 17.54 ± 2.84 ng/ml in the patient and control group, respectively (p = 0.001). But there was no significant co-relation between SNOT-22 score and Vitamin D level, and between interleukin levels in patient and control group. Vitamin D deficiency is associated with Allergic Rhinitis and therefore, checking Vitamin D levels in patients with AR can be considered as routine practice in outpatient clinics. However, co-relation between severity of Allergic Rhinitis and Vitamin D levels and the proven therapeutic role of Vitamin D in Allergic Rhinitis is still debatable and thus, requires large sample size randomised controlled trials.
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Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.
Priya, G, Bajaj, S, Kalra, B, Coetzee, A, Kalra, S, Dutta, D, Lim, V, Diwakar, H, Deshmukh, V, Mehta, R, et al
Journal of family medicine and primary care. 2021;(12):4350-4363
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The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.