LEAD MOLECULE IDENTIFICATION FROM VITEX TRIFOLIA LINN FOR HELMINTHIASIS USING IN VITRO AND IN SILICO METHODS

Objective: The study was an attempt to discover a lead molecule to treat helminthiasis using Vitex trifolia. Linn (V. folia Linn) through sterile effect, in vitro and in silico evaluation. Methods: The antibacterial activity was done by Kirby-Bauer disc diffusion method in three different concentrations of extract and in vitro anthelmintic activity was carried out by petri dish and organ bath method. Further, the in silico docking studies were carried out by 11 phytoconstituents against phosphoethanolamine methyltransferase (4FGZ) using Auto Dock 4.2, it was working based on the principle of Lamarckian genetic algorithm. In docking studies, three important parameters such as binding energy, inhibition constant and intermolecular energy are determined. Results: The extracts showed an antibacterial effect in three different concentrations. At 16 mcg/disc a significant effect was observed when compared to blank and ciprofloxacin 5 mcg/disc. The anthelmintic activity in the petri dish method, means paralyzing time of Pheretimaposthuma with the dose of 25, 50 and 100 mg/ml were 13.78, 5.79 and 4.57 min respectively and Piperazine citrate (10 mg/ml) showed paralysis in 21.58 min. In the organ bath method, the time for paralysis of the worm was recorded on a slow-moving Sherrington rotating drum and the study report showed that paralyzing time was decreased at increasing concentrations of the extract. The results of in silico studies exhibited a binding energy of-10.25kcal/mol, inhibitory constant (Ki) 30.91nM, intermolecular energy,-10.84kcal/mol for abietatriene-3-ol which is lesser than the standard ligand phosphoethanolamine (-6.03kcal/mol, 38.29µM,-7.82kcal/mol) respectively. Conclusion: The study reports conclude that the active constituents in V. folia Linn having better anthelmintic activity, thus the active constituents may be optimized and make way to a new moiety for the treatment of helminthiasis

Neuro-Protective Effect of Ethanolic Extract of Trombidium Grandissimum Koch Against Aluminium Chloride (Alcl3) Induced Neurotoxicity in Albino Rats

The current goal of this investigation is to assess the ethanolic extract of T. grandissimum (EETG) against AlCl3-initiated neurotoxicity, where AlCl3 (100 mg/kg/p.o) is administered for 42 days by provoking oxidative stress followed by neurotoxicity. The evaluation of behavioural parameters such as locomotor activity, elevated plus maze, and motor incoordination, as well as biochemical parameters such as reduced glutathione, lipid peroxidation, Superoxide dismutase (SOD), Catalase (CAT), total Protein, and Acetylcholinesterase in the brain, was performed. According to the study report, behavioural changes such as dropped locomotor movements, enhanced transfer latency, and muscle weakness were often noted. Significant rising of lipid peroxides and AChE activity in rat brain tissue was observed, and activity of antioxidant enzymes like SOD, Catalase, and Reduced Glutathione decreased substantially in alcl3 treated rats compared to control, whereas EETG at both dose and standard treated rats showed a significant reduction in LPO, AChE activity and significant elevation in SOD, CAT, and GSH in brain tissues compared to AlCl3 treated rats. The findings are further supported by histopathology of the brain. This is due to the extract's enormous amount of bioactive components. Through in-silico analysis, isolation, and characterisation, future research will be required to pinpoint the chemical component responsible for the extract's observed biological effect

Biomedical research in developing countries: Opportunities, methods, and challenges

Health research is essential for improving global health, health equity, and economic development. There are vast differences in the disease burden, research budget allocation, and scientific publications between the developed and the low-middle-income countries, which are the homes of 85% of the world's population. There are multiple challenges, as well as opportunities for health research in developing countries. One of the primary reasons for reduced research output from the developing countries is the lack of research capacity. Many developing countries are striving to build their research capacity. They are trying to understand their needs and goals to solve their fundamental health problems, but the opportunity for research education and training remains low. The first joint research meeting of the Bangladesh Gastroenterology Society and the British Society of Gastroenterology took place in February 2020 at the Bangabandhu Sheikh Mujib Medical University in Dhaka, Bangladesh, aimed at providing an overview of medical research for young, aspiring medical researchers. This review article provides an outline of the research day and covers a number of useful topics. This review aims to provide a basic guide for early career researchers, both within the field of gastroenterology and, more generally, to all spheres of medical research

Monitoring vegetation dynamics using multi-temporal Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) images of Tamil Nadu

Vegetation indices serve as an essential tool in monitoring variations in vegetation. The vegetation indices used often, viz., normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) were computed from MODIS vegetation index products. The present study aimed to monitor vegetation's seasonal dynamics by using time series NDVI and EVI indices in Tamil Nadu from 2011 to 2021. Two products characterize the global range of vegetation states and processes more effectively. The data sources were processed and the values of NDVI and EVI were extracted using ArcGIS software. There was a significant difference in vegetation intensity and status of vegetation over time, with NDVI having a larger value than EVI, indicating that biomass intensity varies over time in Tamil Nadu. Among the land cover classes, the deciduous forest showed the highest mean values for NDVI (0.83) and EVI (0.38), followed by cropland mean values of NDVI (0.71) and EVI (0.31) and the lowest NDVI (0.68) and EVI (0.29) was recorded in the scrubland. The study demonstrated that vegetation indices extracted from MODIS offered valuable information on vegetation status and condition at a short temporal time period

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.

BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). CONCLUSIONS: Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2-4% at 1 year in these high-risk patients. TRIAL REGISTRATION NUMBER: ISRCTN93069556

Machine Learning Creates a Simple Endoscopic Classification System that Improves Dysplasia Detection in Barrett's Oesophagus amongst Non-expert Endoscopists

INTRODUCTION: Barrett’s oesophagus (BE) is a precursor to oesophageal adenocarcinoma (OAC). Endoscopic surveillance is performed to detect dysplasia arising in BE as it is likely to be amenable to curative treatment. At present, there are no guidelines on who should perform surveillance endoscopy in BE. Machine learning (ML) is a branch of artificial intelligence (AI) that generates simple rules, known as decision trees (DTs). We hypothesised that a DT generated from recognised expert endoscopists could be used to improve dysplasia detection in non-expert endoscopists. To our knowledge, ML has never been applied in this manner. METHODS: Video recordings were collected from patients with non-dysplastic (ND-BE) and dysplastic Barrett’s oesophagus (D-BE) undergoing high-definition endoscopy with i-Scan enhancement (PENTAX®). A strict protocol was used to record areas of interest after which a corresponding biopsy was taken to confirm the histological diagnosis. In a blinded manner, videos were shown to 3 experts who were asked to interpret them based on their mucosal and microvasculature patterns and presence of nodularity and ulceration as well as overall suspected diagnosis. Data generated were entered into the WEKA package to construct a DT for dysplasia prediction. Non-expert endoscopists (gastroenterology specialist registrars in training with variable experience and undergraduate medical students with no experience) were asked to score these same videos both before and after web-based training using the DT constructed from the expert opinion. Accuracy, sensitivity, and specificity values were calculated before and after training where p < 0 05 was statistically significant. RESULTS: Videos from 40 patients were collected including 12 both before and after acetic acid (ACA) application. Experts’ average accuracy for dysplasia prediction was 88%. When experts’ answers were entered into a DT, the resultant decision model had a 92% accuracy with a mean sensitivity and specificity of 97% and 88%, respectively. Addition of ACA did not improve dysplasia detection. Untrained medical students tended to have a high sensitivity but poor specificity as they “overcalled” normal areas. Gastroenterology trainees did the opposite with overall low sensitivity but high specificity. Detection improved significantly and accuracy rose in both groups after formal web-based training although it did it reach the accuracy generated by experts. For trainees, sensitivity rose significantly from 71% to 83% with minimal loss of specificity. Specificity rose sharply in students from 31% to 49% with no loss of sensitivity. CONCLUSION: ML is able to define rules learnt from expert opinion. These generate a simple algorithm to accurately predict dysplasia. Once taught to non-experts, the algorithm significantly improves their rate of dysplasia detection. This opens the door to standardised training and assessment of competence for those who perform endoscopy in BE. It may shorten the learning curve and might also be used to compare competence of trainees with recognised experts as part of their accreditation process

Systematic assessment with I-SCAN magnification endoscopy and acetic acid improves dysplasia detection in patients with Barrett's esophagus

BACKGROUND AND STUDY AIMS: Enhanced endoscopic imaging with chromoendoscopy may improve dysplasia recognition in patients undergoing assessment of Barrett's esophagus (BE). This may reduce the need for random biopsies to detect more dysplasia. The aim of this study was to assess the effect of magnification endoscopy with I-SCAN (Pentax, Tokyo, Japan) and acetic acid (ACA) on dysplasia detection in BE using a novel mucosal and vascular classification system. METHODS: BE segments and suspicious lesions were recorded with high definition white-light and magnification endoscopy enhanced using all I-SCAN modes in combination. We created a novel mucosal and vascular classification system based on similar previously validated classifications for narrow-band imaging (NBI). A total of 27 videos were rated before and after ACA application. Following validation, a further 20 patients had their full endoscopies recorded and analyzed to model use of the system to detect dysplasia in a routine clinical scenario. RESULTS: The accuracy of the I-SCAN classification system for BE dysplasia improved with I-SCAN magnification from 69 % to 79 % post-ACA (P = 0.01). In the routine clinical scenario model in 20 new patients, accuracy of dysplasia detection increased from 76 % using a "pull-through" alone to 83 % when ACA and magnification endoscopy were combined (P = 0.047). Overall interobserver agreement between experts for dysplasia detection was substantial (0.69). CONCLUSIONS: A new I-SCAN classification system for BE was validated against similar systems for NBI with similar outcomes. When used in combination with magnification and ACA, the classification detected BE dysplasia in clinical practice with good accuracy.Trials registered at ISRCTN (58235785)

A deep learning system for detection of early Barrett's neoplasia:a model development and validation study

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus.METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs).FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p&lt;0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p&lt;0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p&lt;0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video).INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases.FUNDING: Olympus.</p

BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia

OBJECTIVES: Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD). METHODS: We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations. RESULTS: In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients. CONCLUSIONS: In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response