A Prospective Randomised Comparative Four-arm Intervention Study of Efficacy and Safety of Saroglitazar and Vitamin E in Patients With Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH)-SVIN TRIAL.

Background and aim: Vitamin E is widely prescribed for non-alcoholic steatohepatitis (NASH). Saroglitazar, a novel dual peroxisome proliferator-activator receptor ɑ/γ agonist, is approved in India for non-alcoholic fatty liver disease (NAFLD). No head-to-head comparative study for vitamin E and saroglitazar is available. We studied the efficacy and safety of saroglitazar and vitamin E in NAFLD/NASH. Materials and methods: We prospectively randomised 175 NAFLD patients into four arms as Saroglitazar 4 mg daily alone (n = 44), vitamin E 800IU daily alone (n = 41), vitamin E and saroglitazar combination (n = 47), and control arm (n = 43). All the baseline variables including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were recorded. Reassessment was done after 24 weeks of treatment. Results: The mean age and body mass index was 45 ± 11 years and 26 ± 3.6 kg/m2, respectively. Compared to control, the decrease in alanine amino transferase levels with saroglitazar, vitamin E, and combination therapy was significant (95% confidence interval [CI]: 6.27-28.25, P = 0.002, 95% CI: -3.39 to 18.88, P = 0.047 and 95% CI: 8.10-29.54, P = 0.001, respectively). The reduction in CAP was significant with saroglitazar and combination therapy (95% CI: -31.94 to 11.99, P = 0.015 and 95% CI: -10.48 to 30.51, P = 0.026, respectively). Only combination therapy shows significant reduction in LSM (95% CI: 0.41-1.68, P = 0.001). Among glycaemic parameters, both saroglitazar alone and combination therapy significantly improved glycosylated haemoglobin levels (P = 0.001 and P = 0.015, respectively), and only combination therapy significantly improved homoeostasis model assessment-estimated insulin resistance (P = 0.047). Saroglitazar alone showed significant reduction in triglyceride and low-density lipoprotein levels (P = 0.038 and P = 0.018, respectively), and combination therapy showed significant increase in high-density lipoprotein levels (P = 0.024). Conclusions: Combination of Saroglitazar and vitamin E showed statistically significant reduction of LSM and CAP along with biochemical, glycaemic, and lipid parameters. Clinical trial registry India no: CTRI/2022/01/039538.

Acute kidney injury in acute liver failure: A narrative review.

Acute kidney injury (AKI) is a frequent complication of acute liver failure (ALF) and it worsens the already worse prognoses of ALF. ALF is an uncommon disease, with varying etiologies and varying definitions in different parts of the world. There is limited literature on the impact of AKI on the outcome of ALF with or without transplantation. The multifaceted etiology of AKI in ALF encompasses factors such as hemodynamic instability, systemic inflammation, sepsis and direct nephrotoxicity. Indications of renal replacement therapy (RRT) for AKI in ALF patients extend beyond the conventional criteria for dialysis and continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridge to liver transplantation (LT). LT is a life-saving option for ALF, so despite somewhat lower survival rates of LT in ALF patients with AKI, LT is not usually deferred. In this review, we will discuss the guidelines' recommended definition and classification of AKI in ALF, the impact of AKI in ALF, the pathophysiology of AKI and the role of CRRT and LT in ALF patients with AKI.

Hepatitis B in Trans-Himalayan Tribal Population: High Prevalence, High Pediatric Burden, Virologic Patterns, and Implications for Public Health Interventions.

Background/Aims: The prevalence of hepatitis B is higher in tribal populations, compared to non-tribal populations in India. Therefore, this study aimed to investigate the risk factors, virological and biochemical profile of patients with hepatitis B in a tribal population. Methods: This study analyzed data collected from a community-based project conducted in Spiti, Himachal Pradesh, from July 2015 to 2017. The study included adults and children inhabiting 40 cluster villages out of 82 villages in the subdivision. The blood samples were collected for liver panel, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), Anti-HBe antibody (anti-HBe Ab) and Hepatitis B virus DNA (HBV-DNA). Results: HBsAg was positive in 23.08% of the population (968/4201), with a prevalence of 13.51% in children under 5 years of age. HBeAg positivity was seen in 22.4% of the participants, while anti-HBe Ab positivity was seen in 59.03% of the participants. HBeAg positive infection, HBeAg positive hepatitis, HBeAg negative hepatitis and HBeAg negative infection were seen in 18.06%, 1.98%, 6.17% and 74.01% of the participants, respectively. HBeAg positivity was highest in 2nd decade (40.83% vs 22% overall). Patients with HBeAg positivity exhibited higher levels of HBV DNA [1960 (IQR: 0-108) IU/ml vs 97.2 (IQR: 0-2090) IU/ml, P < 0.001] and alanine transaminase (ALT) [22.5 (IQR: 16-33) U/L vs 19 (IQR: 14-26) U/L, P = 0.003] levels compared to HBeAg negative patients. Conclusion: This study shows a high prevalence of hepatitis B in tribal population, particularly among children under 5 years of age.

Commercial suitability and characterization of newly developed Erucastrum canariense (Can) sterile cytoplasm based cytoplasmic male sterile (CMS) lines in Indian cauliflower.

The study presents the first to characterize novel Erucastrum canarianse Webb and Berthel (or Can) sterile cytoplasm-based CMS lines in Indian cauliflower (Brassica oleracea var. botrytis L.) and investigating their commercial suitability. Eleven Can-based CMS lines were examined for 12 agro-morphological and yield traits,18 floral traits, four seed yield traits together with three each of the Ogura (source: wild Japanese Radish) and Tour (Source: Brassica tournefortii) cytoplasms. All of the recorded floral and seed traits showed significant (P > 0.05) differences between the CMS lines of each group. Agro-morphological and yield traits in CMS lines and their maintainers, however, were non-significantly different. All the Can- and Ogura-based CMS lines showed flowering and appropriate seed formation by natural cross-pollination. Only two Tour cytoplasm-based CMS lines, Tour (DC-41-5) and Tour (DC-67), produced the smallest malformed flowers and stigma. The highest seed yield per plant in CMS lines was in Ogu (DC-98-4) and the lowest in Tour (DC-67). P14 and P15, two polymorphic mtDNA markers, were discovered for the Can CMS system for early detection. Five primers (ITS5a-ITS4, atpF-atpH, P16, rbeL and trnL), along with their maintainers, were sequenced and aligned to detect nucleotide changes including as additions and or deletions at different positions. The newly introduced E. canariense sterile cytoplasm-based CMS system in cauliflower is the subject of the first comprehensive report, which emphasises their potential as a further stable and reliable genetic mechanism for hybrid breeding.

Intentional Ingestion of a Foreign Body - Why We Need Psychiatrists.

Foreign body ingestions are common medical emergencies. In adults, foreign body ingestions occur in patients with psychiatric disorders and prison inmates. A majority (80-90%) of foreign bodies pass spontaneously. Endoscopic and surgical interventions are required in only 10-20% and 1%, respectively. A plain radiograph may be the only diagnostic test required. A computed tomography scan may be needed when a perforation is suspected. Food boluses are the most commonly ingested foreign bodies. Snare and rat tooth forceps are frequently used accessories for the retrieval of foreign bodies. The focus of the emergency team is on the management of an acute case of foreign body ingestion, and the psychiatric aspect of the disease gets often ignored.

Occurrence, Source and Dietary Exposure of Toxic and Essential Elements in the Indian Food Basket.

In this study, representative urban and peri-urban Indian food baskets have been studied for the presence of toxic and essential elements. The concentration of target toxic and essential elements was used to estimate dietary intakes (EDIs) and health risks. Across all food matrices, toxic elements like Cd and Pb were dominant. The highest concentrations of the target elements were found in vegetables, with Cd, Pb, and Ni being beyond permissible limits of the Food and Agriculture Organization of the United Nations and the World Health organization (0.05 mg/kg, 0.1 mg/kg, and 1.5 mg/kg, respectively) in okra, spinach, and cauliflower. The sum of concentrations of the toxic elements (As, Ni, Hg, Cr, Cd, Pb) in vegetables had a range of 0.54-12.08 mg/kg, the highest sum was found in spinach (median 12.08 mg/kg), followed by okra (median 1.68 mg/kg). The EDI was observed for vegetables with a contribution as high as 92% for Cd. Dairy products were found with the highest loading for Ni with a dietary intake of 3.1 mg/kg/day for adults and twice as much for children. Carcinogenic risk for Ni was the highest and found above the threshold for all food categories, as was the case with As. Cumulative carcinogenic and non-carcinogenic risks were mostly contributed by milk and vegetables, in particular, spinach.

Etomidate-ketamine versus dexmedetomidine-ketamine for entropy-guided procedural sedation during endoscopic retrograde cholangiopancreatography procedures: A randomized single blind study.

BACKGROUND AND AIMS: The major challenge for the anesthetist in endoscopic retrograde cholangiopancreatography (ERCP) procedures is to provide moderate to deep levels of sedation in prone position with preservation of spontaneous respiratory efforts in shared airway scenario with an endoscopist. These patients have other comorbidities, making them vulnerable to complications during the routinely used sedation with propofol. We compared the entropy-guided efficacy of combination of etomidate-ketamine to dexmedetomidine-ketamine in patients undergoing ERCP. METHODS: This prospective single blind randomized entropy-guided trial was conducted on 60 patients with etomidate-ketamine in group I (n = 30) and dexmedetomidine-ketamine in group II (n = 30). The purpose was to compare etomidate-ketamine versus dexmedetomidine-ketamine for ERCP in terms of intraprocedural hemodynamics with desaturation, onset of sedation, recovery time and endoscopist's satisfaction. RESULTS: Hypotension was observed only in six (20%) patients of group II (p < 0.009). Two patients of group I and three in group II desaturated (Spo2 < 90) briefly during the procedure, but none of the patient required intubation (p > 0.05). The mean time in minutes of onset of sedation was 1.15 in group I and 5.6 in group II (p < 0.001). Endoscopists' satisfaction was better in group I (p ≤ 0.001) and length of recovery room stay was shorter in group I as compared to that in group II (p ≤ 0.007). CONCLUSION: We conclude that entropy-guided intravenous procedural sedation with etomidate-ketamine combination provides faster onset of sedation, stable periprocedural hemodynamics, rapid recovery and fair to excellent endoscopist satisfaction compared to dexmedetomidine-ketamine combination for ERCP.

Decoding allelic diversity, transcript variants and transcriptional complexity of CENH3 gene in Brassica oleracea var. botrytis.

Histone proteins play a critical role in the primary organization of nucleosomes, which is the fundamental unit of chromatin. Among the five types of the histones, histone H3 has multiple variants, and the number differs among the species. Amongst histone H3 variants, centromeric histone H3 (CENH3) is crucial for centromere identification and proper chromosomal segregation during cell division. In the present study, we have identified 17 putative histone H3 genes of Brassica oleracea. Furthermore, we have done a detailed characterization of the CENH3 gene of B. oleracea. We showed that a single CENH3 gene exhibits allelic diversity with at least two alleles and alternative splicing pattern. Also, we have identified a CENH3 gene-specific co-dominant cleaved amplified polymorphic sequence marker SNP34(A/C) to distinguish CENH3 alleles and follow their expression in leaf and flower tissues. The gene structure analysis of the CENH3 gene revealed the conserved 5'-CAGCAG-3' sequence at the intron 3-exon 4 junction in B. oleracea, which serves as an alternative splicing site with one-codon (alanine) addition/deletion. However, this one-codon alternative splicing feature is not conserved in the CENH3 genes of wild allied Brassica species. Our finding suggests that transcriptional complexity and alternative splicing might play a key role in the transcriptional regulation and function of the CENH3 gene in B. oleracea. Altogether, data generated from the present study can serve as a primary information resource and can be used to engineer CENH3 gene towards developing haploid inducer lines in B. oleracea.

Unlocking India's Potential in Managing Endocrine-Disrupting Chemicals (EDCs): Importance, Challenges, and Opportunities.

Endocrine-disrupting chemicals (EDCs) are a prime concern for the environment and health globally. Research shows that in developing countries such as India both the environment and human populations are severely exposed to EDCs and consequently experience rising incidents of adverse health effects such as diabetes and cancers. In this paper, we discuss the current EDC management approach in India, critically assess its limitations, and describe opportunities for potential improvements. Foremost, current EDC management actions and interventions in India are fragmented and outdated, and far behind the modern and comprehensive approaches adopted in the European Union and other developed countries. Strong and well-planned actions are required on various fronts of science, policy, commerce, and public engagement. These actions include the adoption of a dedicated and modern regulatory framework for managing EDCs, enhancing capacity and infrastructure for EDC monitoring in the environment and human population, employing public-private partnership programs for not only managing EDCs but also in the sectors that indirectly contribute toward the mismanagement of EDCs in the country, and raising awareness on EDCs and promoting health-preserving consumption habits among the public. As India hosts a large proportion of the global human population and biodiversity, the success or failure of its actions will substantially affect the direction of global efforts to manage EDCs and set an example for other developing countries.

Dyspepsia with alarm symptoms in patients aged less than 60 years: Is upper gastrointestinal endoscopy justified in Indian scenario?

BACKGROUND: Newer American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guidelines do not suggest endoscopy to investigate alarm features for dyspepsia patients under the age of 60 to exclude upper gastrointestinal (GI) neoplasia. The validity of this recommendation has not been evaluated in our population. So, this study was conducted to assess the utility of upper GI endoscopy to investigate alarm features in dyspepsia patients less than 60 years of age to exclude upper GI neoplasia. METHODS: This prospective observational study evaluated consecutive patients of dyspepsia between 18 and 60 years of age, with at least one or more of the alarm symptoms (unintentional weight loss; loss of appetite; GI bleeding; anemia; recurrent or persistent vomiting; dysphagia with predominant epigastric pain; and family history of upper GI cancer) with upper GI endoscopy to exclude any organic lesion and malignancy. RESULTS: Of total 294 patients evaluated with endoscopy, 34.7% (n=102) had normal endoscopy (functional dyspepsia [FD]) while 65.3% (n=192) had abnormal endoscopic findings (organic dyspepsia [OD]). Of 192 patients with OD, 146 patients (49.6% of the total study population) had benign abnormality (benign OD) while 46 patients (15.6% of the total study population) had malignancy of the upper GI tract (malignant OD). CONCLUSION: The investigation of alarm features in dyspepsia patients less than 60 years of age with upper GI endoscopy leads to detection of organic lesion (65.3%) including malignancy (15.6%) in a significant percentage of patients.

Unraveling Origin, History, Genetics, and Strategies for Accelerated Domestication and Diversification of Food Legumes.

Domestication is a dynamic and ongoing process of transforming wild species into cultivated species by selecting desirable agricultural plant features to meet human needs such as taste, yield, storage, and cultivation practices. Human plant domestication began in the Fertile Crescent around 12,000 years ago and spread throughout the world, including China, Mesoamerica, the Andes and Near Oceania, Sub-Saharan Africa, and eastern North America. Indus valley civilizations have played a great role in the domestication of grain legumes. Crops, such as pigeon pea, black gram, green gram, lablab bean, moth bean, and horse gram, originated in the Indian subcontinent, and Neolithic archaeological records indicate that these crops were first domesticated by early civilizations in the region. The domestication and evolution of wild ancestors into today's elite cultivars are important contributors to global food supply and agricultural crop improvement. In addition, food legumes contribute to food security by protecting human health and minimize climate change impacts. During the domestication process, legume crop species have undergone a severe genetic diversity loss, and only a very narrow range of variability is retained in the cultivars. Further reduction in genetic diversity occurred during seed dispersal and movement across the continents. In general, only a few traits, such as shattering resistance, seed dormancy loss, stem growth behavior, flowering-maturity period, and yield traits, have prominence in the domestication process across the species. Thus, identification and knowledge of domestication responsive loci were often useful in accelerating new species' domestication. The genes and metabolic pathways responsible for the significant alterations that occurred as an outcome of domestication might aid in the quick domestication of novel crops. Further, recent advances in "omics" sciences, gene-editing technologies, and functional analysis will accelerate the domestication and crop improvement of new crop species without losing much genetic diversity. In this review, we have discussed about the origin, center of diversity, and seed movement of major food legumes, which will be useful in the exploration and utilization of genetic diversity in crop improvement. Further, we have discussed about the major genes/QTLs associated with the domestication syndrome in pulse crops and the future strategies to improve the food legume crops.

Application of a pharmacokinetic model in characterizing sources of polychlorinated biphenyl exposure and determining threshold daily intakes for adverse health effects in infants and toddlers.

Characterization of PCB exposure sources for vulnerable population groups is essential to minimize the health effects of PCB exposure. At the same time, it is important to consolidate the knowledge on threshold intakes of PCBs for infants and toddlers to prevent health effects. We estimated total PCB concentrations from birth to 2 years of age in children from Slovak and Czech populations, which continue to have high PCB concentrations in breast milk. Using a pharmacokinetic (PK) model, we characterized dominant PCB exposure sources and estimated new threshold estimated daily intakes (TEDI) (above which adverse effects cannot be excluded) for postnatal PCB exposure in infants and toddlers. In the PK model, concentrations of seven indicator PCBs in breast milk and cord blood samples from 291 mother-child pairs from the Slovak birth cohort, and 396 breast milk samples from Czech mothers we used, together with their physiological characteristics and PCB concentrations from other exposure sources (food, dust, air). The estimated total PCB concentrations in children's blood at different ages were compared with threshold PCB concentrations of 500, 700 and 1000 ng·glipid-1 in serum proposed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) and the German Environment Agency (UBA), above which possible adverse health effects may be expected. We estimated that up to 20.6% of Slovak children and up to 45.7% of Czech children at two years of age exceeded the threshold value of 700 ng·glipid-1 in blood. Mean TEDIs leading to values of 500 ng·glipid-1 in blood for children up to two years ranged between 110 and 220 ng·kg-1·bw·day-1, varying according to breastfeeding duration. Breast milk and prenatal exposure contributed to 71%-85% of PCBs exposure at two years of age. In contrast, the contributions of PCBs from dust and indoor air were negligible.

Sensorineural hearing loss and ulcerative colitis in remission.

INTRODUCTION: Sensorineural hearing loss (SNHL) has been reported in association with inflammatory bowel disease (IBD). However, SNHL as an extraintestinal manifestation of IBD is frequently underreported. In the present study, we compared the prevalence and severity of SNHL among patients with IBD-ulcerative colitis (IBD-UC) in remission with controls to find out any association between SNHL and IBD-UC in remission compared to controls. METHODS: This single-center hospital-based prospective observational study included outdoor patients with IBD-UC in remission and healthy age- and sex-matched controls. Eligible patients and healthy participants were subjected to a battery of audiological tests (otoscopy, tympanometry and pure tone audiometry [PTN]) after thorough systemic and ear, nose and throat (ENT) examination. RESULTS: A total of 100 patients were enrolled in the study: 50 in IBD-UC in the remission group and 50 in the control group. None of the demographic variables (age, gender, residence and habits) were significantly different between the two groups. Otoscopy and tympanometry were normal in all patients and controls. The difference between the two groups in respect to frequency and severity of SNHL on PTA and in respect to unilateral and bilateral distribution of the hearing loss was not statistically significant. CONCLUSION: There is no statistically significant difference in frequency and severity of SNHL between patients with ulcerative colitis in remission and healthy age- and sex-matched controls.

Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease.

Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.

Gastric Outlet Obstruction: Don't Miss Duodenal Tuberculosis.

We report a case of isolated duodenal tuberculosis (TB) in a patient who presented with features of gastric outlet obstruction. The diagnosis was made on repeat endoscopic duodenal biopsy after initial histopathology failed to reveal the diagnosis. The patient recovered with antitubercular therapy. The index of suspicion has to be high in TB endemic countries as clinical, radiological, and endoscopic features are nonspecific.

Agro-morphological and molecular diversity in different maturity groups of Indian cauliflower (Brassica oleracea var. botrytis L.).

The present study analysed the molecular and agro-morphological diversity in a set of 92 diverse cauliflower genotypes and two each of cabbage and broccoli. Field evaluation of the genotypes was done in randomized block design (RBD) at two locations (i.e. IARI, New Delhi and ICAR-RC-NEH Region, Barapani) during Rabi2019-20. Genotypes showed variation for all the eight observed traits at both locations and, the differences in early and snowball groups were distinct. Pusa Meghna, DC-33-8, Pusa Kartiki and CC-14 were earliest for curd initiation. Genotypes showed higher values for curd traits at Delhi. Molecular diversity was detected with 90 polymorphic simple sequence repeats (SSR). Number of alleles ranged from 1 to 9 with mean value of 2.16 and the highest polymorphic information content (PIC) value was observed for primer BoGMS0742 (0.68) with a mean value of 0.18. Cluster analysis using agro-morphological traits substantiated classification of the genotypes for maturity groups. However, SSR analysis revealed four clusters and with a composite pattern of genotype distribution. STRUCTURE analysis also supported the admixture and four subpopulations. The studyindicates for introgression of genetic fragments across the maturity groups, thereby, potential for use in further genetic improvement and heterosis breeding.