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

Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance

BACKGROUND: Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE PRESENTATION: During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery

Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics

BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO). Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood. METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed. Twelve patients with irritable bowel syndrome were studied as controls. RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05). Colony counts ranged from 3 × 10(2 )to 10(15 )(median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003). 21/50 (42%) patients had counts ≥10(5 )CFU/ml in MAS and none of controls (p < 0.05). Aerobes were isolated in 34/34 and anaerobe in 1/34. Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively. The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs. tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs. tetracycline, p = ns). CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment. This needs to be proved further by a randomized controlled trial

Gastric adenocarcinoma in a patient re-infected with H. pylori after regression of MALT lymphoma with successful anti-H. pylori therapy and gastric resection: a case report

BACKGROUND: Helicobacter pylori (H. pylori) has been etiologically linked with primary gastric lymphoma (PGL) and gastric carcinoma (GC). There are a few reports of occurrence of both diseases in the same patient with H. pylori infection. CASE PRESENTATION: We report a patient with PGL in whom the tumor regressed after surgical resection combined with eradication of H. pylori infection. However, he developed GC on follow up; this was temporally associated with recrudescence / re-infection of H. pylori. This is perhaps first report of such occurrence. CONCLUSIONS: Possible cause and effect relationship between H. pylori infection and both PGL and GC is discussed. This case also documents a unique problem in management of PGL in tropical countries where re-infection with H. pylori is supposed to be high

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4–5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1–3, 3–5, 5–8, 8–10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25–3.35) and 4.28 ± 0.40 years (95% CI: 3.51–5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate

Abrogated Inflammatory Response Promotes Neurogenesis in a Murine Model of Japanese Encephalitis

Japanese encephalitis virus (JEV) induces neuroinflammation with typical features of viral encephalitis, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. The detrimental effects of inflammation on neurogenesis have been reported in various models of acute and chronic inflammation. We investigated whether JEV-induced inflammation has similar adverse effects on neurogenesis and whether those effects can be reversed using an anti-inflammatory compound minocycline.Here, using in vitro studies and mouse models, we observed that an acute inflammatory milieu is created in the subventricular neurogenic niche following Japanese encephalitis (JE) and a resultant impairment in neurogenesis occurs, which can be reversed with minocycline treatment. Immunohistological studies showed that proliferating cells were replenished and the population of migrating neuroblasts was restored in the niche following minocycline treatment. In vitro, we checked for the efficacy of minocycline as an anti-inflammatory compound and cytokine bead array showed that production of cyto/chemokines decreased in JEV-activated BV2 cells. Furthermore, mouse neurospheres grown in the conditioned media from JEV-activated microglia exhibit arrest in both proliferation and differentiation of the spheres compared to conditioned media from control microglia. These effects were completely reversed when conditioned media from JEV-activated and minocycline treated microglia was used.This study provides conclusive evidence that JEV-activated microglia and the resultant inflammatory molecules are anti-proliferative and anti-neurogenic for NSPCs growth and development, and therefore contribute to the viral neuropathogenesis. The role of minocycline in restoring neurogenesis may implicate enhanced neuronal repair and attenuation of the neuropsychiatric sequelae in JE survivors

Disease-Free Survival after Hepatic Resection in Hepatocellular Carcinoma Patients: A Prediction Approach Using Artificial Neural Network

Background: A database for hepatocellular carcinoma (HCC) patients who had received hepatic resection was used to develop prediction models for 1-, 3- and 5-year disease-free survival based on a set of clinical parameters for this patient group. Methods: The three prediction models included an artificial neural network (ANN) model, a logistic regression (LR) model, and a decision tree (DT) model. Data for 427, 354 and 297 HCC patients with histories of 1-, 3- and 5-year disease-free survival after hepatic resection, respectively, were extracted from the HCC patient database. From each of the three groups, 80 % of the cases (342, 283 and 238 cases of 1-, 3- and 5-year disease-free survival, respectively) were selected to provide training data for the prediction models. The remaining 20 % of cases in each group (85, 71 and 59 cases in the three respective groups) were assigned to validation groups for performance comparisons of the three models. Area under receiver operating characteristics curve (AUROC) was used as the performance index for evaluating the three models. Conclusions: The ANN model outperformed the LR and DT models in terms of prediction accuracy. This study demonstrated the feasibility of using ANNs in medical decision support systems for predicting disease-free survival based on clinical databases in HCC patients who have received hepatic resection

Gastric cancers of Western European and African patients show different patterns of genomic instability

<p>Abstract</p> <p>Background</p> <p>Infection with <it>H. pylori </it>is important in the etiology of gastric cancer. Gastric cancer is infrequent in Africa, despite high frequencies of <it>H. pylori </it>infection, referred to as the African enigma. Variation in environmental and host factors influencing gastric cancer risk between different populations have been reported but little is known about the biological differences between gastric cancers from different geographic locations. We aim to study genomic instability patterns of gastric cancers obtained from patients from United Kingdom (UK) and South Africa (SA), in an attempt to support the African enigma hypothesis at the biological level.</p> <p>Methods</p> <p>DNA was isolated from 67 gastric adenocarcinomas, 33 UK patients, 9 Caucasian SA patients and 25 native SA patients. Microsatellite instability and chromosomal instability were analyzed by PCR and microarray comparative genomic hybridization, respectively. Data was analyzed by supervised univariate and multivariate analyses as well as unsupervised hierarchical cluster analysis.</p> <p>Results</p> <p>Tumors from Caucasian and native SA patients showed significantly more microsatellite instable tumors (p < 0.05). For the microsatellite stable tumors, geographical origin of the patients correlated with cluster membership, derived from unsupervised hierarchical cluster analysis (p = 0.001). Several chromosomal alterations showed significantly different frequencies in tumors from UK patients and native SA patients, but not between UK and Caucasian SA patients and between native and Caucasian SA patients.</p> <p>Conclusions</p> <p>Gastric cancers from SA and UK patients show differences in genetic instability patterns, indicating possible different biological mechanisms in patients from different geographical origin. This is of future clinical relevance for stratification of gastric cancer therapy.</p

Post-Covid-19 Irritable Bowel Syndrome

Objectives The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p < 0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls