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

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 1; peer review: 1 approved, 1 approved with reservations]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. / Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) language and publishing online. / Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. / Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Delivering Behaviour Change Interventions: Development of a Mode of Delivery Ontology [version 2; peer review: 2 approved]

Background: Investigating and improving the effects of behaviour change interventions requires detailed and consistent specification of all aspects of interventions. An important feature of interventions is the way in which these are delivered, i.e. their mode of delivery. This paper describes an ontology for specifying the mode of delivery of interventions, which forms part of the Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Mode of Delivery Ontology was developed in an iterative process of annotating behaviour change interventions evaluation reports, and consulting with expert stakeholders. It consisted of seven steps: 1) annotation of 110 intervention reports to develop a preliminary classification of modes of delivery; 2) open review from international experts (n=25); 3) second round of annotations with 55 reports to test inter-rater reliability and identify limitations; 4) second round of expert review feedback (n=16); 5) final round of testing of the refined ontology by two annotators familiar and two annotators unfamiliar with the ontology; 6) specification of ontological relationships between entities; and 7) transformation into a machine-readable format using the Web Ontology Language (OWL) and publishing online. Results: The resulting ontology is a four-level hierarchical structure comprising 65 unique modes of delivery, organised by 15 upper-level classes: Informational, Environmental change, Somatic, Somatic alteration, Individual-based/ Pair-based /Group-based, Uni-directional/Interactional, Synchronous/ Asynchronous, Push/ Pull, Gamification, Arts feature. Relationships between entities consist of is_a. Inter-rater reliability of the Mode of Delivery Ontology for annotating intervention evaluation reports was a=0.80 (very good) for those familiar with the ontology and a= 0.58 (acceptable) for those unfamiliar with it. Conclusion: The ontology can be used for both annotating and writing behaviour change intervention evaluation reports in a consistent and coherent manner, thereby improving evidence comparison, synthesis, replication, and implementation of effective interventions

Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p> Methods: An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p> Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p> Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p&gt

Is there a clinically significant seasonal component to hospital admissions for atrial fibrillation?

BACKGROUND: Atrial fibrillation is a common cardiac dysrhythmia, particularly in the elderly. Recent studies have indicated a statistically significant seasonal component to atrial fibrillation hospitalizations. METHODS: We conducted a retrospective population cohort study using time series analysis to evaluate seasonal patterns of atrial fibrillation hospitalizations for the province of Ontario for the years 1988 to 2001. Five different series methods were used to analyze the data, including spectral analysis, X11, R-Squared, autocorrelation function and monthly aggregation. RESULTS: This study found evidence of weak seasonality, most apparent at aggregate levels including both ages and sexes. There was dramatic increase in hospitalizations for atrial fibrillation over the years studied and an age dependent increase in rates per 100,000. Overall, the magnitude of seasonal difference between peak and trough months is in the order of 1.4 admissions per 100,000 population. The peaks for hospitalizations were predominantly in April, and the troughs in August. CONCLUSIONS: Our study confirms statistical evidence of seasonality for atrial fibrillation hospitalizations. This effect is small in absolute terms and likely not significant for policy or etiological research purposes

The relationship of primary health care use with persistence of insomnia: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Prevalence of insomnia symptoms in the general population is high. Insomnia is linked with high health care use and within primary care there are a number of treatment options available. The objective of this study was to determine the association of persistence and remission of insomnia with primary health care using a longitudinal study.</p> <p>Methods</p> <p>A postal survey of registered adult (over 18 years) populations of five UK general practices, repeated after 1 year, linked to primary care records. Baseline survey responders were assessed for persistence of insomnia symptoms at 12 months. The association of primary care consultation or prescription for any mood disorder (defined as anxiety, depression, stress, neurosis, or insomnia) in the 12 months between baseline and follow-up surveys with persistence of insomnia was determined.</p> <p>Results</p> <p>474 participants reporting insomnia symptoms at baseline were followed up at 12 months. 131(28%) consulted for mood problem(s) or received a relevant prescription. Of these 100 (76%) still had insomnia symptoms at one year, compared with 227 (66%) of those with no contact with primary care for this condition (OR 1.37; 95% CI 0.83, 2.27). Prescription of hypnotics showed some evidence of association with persistence of insomnia at follow-up (OR 3.18; 95% CI 0.93, 10.92).</p> <p>Conclusion</p> <p>Insomniacs continue to have problems regardless of whether or not they have consulted their primary care clinician or received a prescription for medication over the year. Hypnotics may be associated with persistence of insomnia. Further research is needed to determine more effective methods of identifying and managing insomnia in primary care. There may however be a group who have unmet need such as depression who would benefit from seeking primary health care.</p

A forced titration study of the antioxidant and immunomodulatory effects of Ambrotose AO supplement

Background Oxidative stress plays a role in acute and chronic inflammatory disease and antioxidant supplementation has demonstrated beneficial effects in the treatment of these conditions. This study was designed to determine the optimal dose of an antioxidant supplement in healthy volunteers to inform a Phase 3 clinical trial. Methods The study was designed as a combined Phase 1 and 2 open label, forced titration dose response study in healthy volunteers (n = 21) to determine both acute safety and efficacy. Participants received a dietary supplement in a forced titration over five weeks commencing with a no treatment baseline through 1, 2, 4 and 8 capsules. The primary outcome measurement was ex vivo changes in serum oxygen radical absorbance capacity (ORAC). The secondary outcome measures were undertaken as an exploratory investigation of immune function. Results A significant increase in antioxidant activity (serum ORAC) was observed between baseline (no capsules) and the highest dose of 8 capsules per day (p = 0.040) representing a change of 36.6%. A quadratic function for dose levels was fitted in order to estimate a dose response curve for estimating the optimal dose. The quadratic component of the curve was significant (p = 0.047), with predicted serum ORAC scores increasing from the zero dose to a maximum at a predicted dose of 4.7 capsules per day and decreasing for higher doses. Among the secondary outcome measures, a significant dose effect was observed on phagocytosis of granulocytes, and a significant increase was also observed on Cox 2 expression. Conclusion This study suggests that Ambrotose AO® capsules appear to be safe and most effective at a dosage of 4 capsules/day. It is important that this study is not over interpreted; it aimed to find an optimal dose to assess the dietary supplement using a more rigorous clinical trial design. The study achieved this aim and demonstrated that the dietary supplement has the potential to increase antioxidant activity. The most significant limitation of this study was that it was open label Phase 1/Phase 2 trial and is subject to potential bias that is reduced with the use of randomization and blinding. To confirm the benefits of this dietary supplement these effects now need to be demonstrated in a Phase 3 randomised controlled trial (RCT)

Effect of time of administration on cholesterol-lowering by psyllium: a randomized cross-over study in normocholesterolemic or slightly hypercholesterolemic subjects

BACKGROUND: Reports of the use of psyllium, largely in hypercholesterolemic men, have suggested that it lowers serum cholesterol as a result of the binding of bile acids in the intestinal lumen. Widespread advertisements have claimed an association between the use of soluble fibre from psyllium seed husk and a reduced risk of coronary heart disease. Given the purported mechanism of cholesterol-lowering by psyllium, we hypothesized that there would be a greater effect when psyllium is taken with breakfast than when taken at bedtime. Secondarily, we expected to confirm a cholesterol-lowering effect of psyllium in subjects with "average" cholesterol levels. METHODS: Sixteen men and 47 women ranging in age from 18 to 77 years [mean 53 +/- 13] with LDL cholesterol levels that were normal or slightly elevated but acceptable for subjects at low risk of coronary artery disease were recruited from general gastroenterology and low risk lipid clinics. Following a one month dietary stabilization period, they received an average daily dose of 12.7 g of psyllium hydrophilic mucilloid, in randomized order, for 8 weeks in the morning and 8 weeks in the evening. Change from baseline was determined for serum total cholesterol, LDL, HDL and triglycerides. RESULTS: Total cholesterol for the "AM first" group at baseline, 8 and 16 weeks was 5.76, 5.77 and 5.80 mmol/L and for the "PM first" group the corresponding values were 5.47, 5.61 and 5.57 mmol/L. No effect on any lipid parameter was demonstrated for the group as a whole or in any sub-group analysis. CONCLUSION: The timing of psyllium administration had no effect on cholesterol-lowering and, in fact, no cholesterol-lowering was observed. Conclusions regarding the effectiveness of psyllium for the prevention of heart disease in the population at large may be premature

Our past creates our present: a brief overview of racism and colonialism in Western paleontology

As practitioners of a historical science, paleontologists and geoscientists are well versed in the idea that the ability to understand and to anticipate the future relies upon our collective knowledge of the past. Despite this understanding, the fundamental role that the history of paleontology and the geosciences plays in shaping the structure and culture of our disciplines is seldom recognized and therefore not acted upon sufficiently. Here, we present a brief review of the history of paleontology and geology in Western countries, with a particular focus on North America since the 1800s. Western paleontology and geology are intertwined with systematic practices of exclusion, oppression, and erasure that arose from their direct participation in the extraction of geological and biological resources at the expense of Black, Indigenous, and People of Color (BIPOC). Our collective failure to acknowledge this history hinders our ability to address these issues meaningfully and systemically in present-day educational, academic, and professional settings. By discussing these issues and suggesting some ways forward, we intend to promote a deeper reflection upon our collective history and a broader conversation surrounding racism, colonialism, and exclusion within our scientific communities. Ultimately, it is necessary to listen to members of the communities most impacted by these issues to create actionable steps forward while holding ourselves accountable for the past