Biomembrane Modelling in Planar Chromatographic Determination of Lipophilicity Using Olive and Castor Oils

BackgroundLipophilicity is a crucial physicochemical parameter that predicts in vivo pharmacokinetics and should be reliably estimated in early stage drug discovery to reduce incidence of attrition. Previous methodologies for its measurement often lead to technically incorrect decisions due to simplistic architecture and poor biomimetic attributes. Significantly, a certain seed oil, used for biomembrane modelling on planar chromatographic platform, was reported to be sufficiently biomimetic and fit for purpose.ObjectivesTo evaluate olive oil (OL) and olive-castor oil (OL-C) equi-mixture as lipids for biomembrane simulation on planar chromatographic platform.Material and MethodRetention behavior of nabumetone, a model compound was used to optimize these potential lipid membranes using a thin film engineered from 5% Liquid paraffin (LP) as benchmark, while halofantrine, nabumetone , α-naphthol and β-naphthol representing varying molecular polarities, were used for validation studies. The validation involved 2-way analysis of variance (ANOVA) associated with variability in Basic lipophilicity parameter (Rmw), and Specific hydrophobic surface area (SHSA) for the optimized surfaces, relative to LP and octadecylsilane (ODS) Further validation entailed correlation of the lipophilicity descriptor i.e. isocratic chromatographic hydrophobicity index (ICHI) on OL, OL-C, ODS and LP with experimental Log P(octanol/water).ResultsOptimized film thicknesses were produced by 5% OL and 1.25% OL-C (p > 0.05). The 2-way ANOVA revealed great variability in performance characteristics of the surfaces (p < 0.0001), and the new surfaces also gave poorer correlation with Log P values (R2= 0.502 and 0.449 respectively).ConclusionThe 1.25 % OL-C demonstrated a higher biomimetic attribute and warrants further validation studies to ascertain biorelevance, of lipophilicity measurement on this platform, in predicting oral drug absorption. Keywords: Lipophilicity, Reversed-phase Thin Layer Chromatography, Retention behaviour, Olive oil, Castor oi

Evaluating the impact of neurosurgical rotation experience in Africa on the interest and perception of medical students towards a career in neurosurgery : a protocol for a continental, cross-sectional study

Introduction Africa has the second highest neurosurgical workforce deficit globally. Despite the many recent advancements in increasing neurosurgical access in Africa, published reports have shown that the vast majority of undergraduate students have little or no exposure to neurosurgery. The lack of exposure may pose a challenge in reducing the neurosurgical workforce deficit, which is one of the long-term strategies of tackling the unmet burden of disease. Students may also miss the opportunity to appreciate the specialty and its demands as well as nurture their interest in the field. This study aims to assess the impact of a neurosurgical rotation during medical school in shaping the perception and interest of students towards a career in neurosurgery. Methods The cross-sectional study will be conducted through the dissemination of a self-administered e-survey hosted on Google Forms from 21st February 2021 to 20th March 2021. The survey will contain five-point Likert scale, multiple-choice and free-text questions. The structured questionnaire will have four sections with 27 items: (i) socio-demographic background, (ii) neurosurgical experience, (iii) perception towards a neurosurgical career and (iv) interest in a neurosurgical career. All consenting medical students in African medical schools who are in their clinical years (defined as fourth to sixth years or higher years of study) will be eligible. Odds ratios and their 95% confidence intervals, Wilcoxon rank-sum test, Welch t-test and adjusted logistic regression models will be used to test for associations between independent and dependent variables. Statistical significance will be accepted at P < 0.05

Evaluating the impact of neurosurgical rotation experience in Africa on the interest and perception of medical students towards a career in neurosurgery : a continental, multi-centre, cross-sectional study

Objective: Africa has the second highest neurosurgical workforce deficit globally and many medical students in Africa lack exposure to the field. This study aims to assess the impact of a neurosurgical rotation during medical school in shaping the perception and interest of students toward a career in neurosurgery. Study Design: Cross-sectional study. Methods: A Google form e-survey was disseminated to African clinical medical students between February 21st and March 20th, 2021. Data on exposure and length of neurosurgical rotation and perception of, and interest in, neurosurgery were collected. Data was analyzed using descriptive statistics and adjusted logistic regression modeling. Results: Data was received from 539 students in 30 African countries (30/54, 55.6%). The majority of participants were male and were from Kenya, Nigeria and South Africa. Most students had undertaken a formal neurosurgery rotation, of which the majority reported a rotation length of 4 weeks or less. Students who had more than 4 weeks of neurosurgical exposure were more likely to express a career interest in neurosurgery than those without [odds ratio (OR) = 1.75, p < 0.04] and men were more likely to express interest in a neurosurgical career compared to women (OR = 3.22, p < 0.001), after adjusting for other factors. Conclusion: Neurosurgical exposure is a key determinant in shaping the perception and interest of medical students toward a career in neurosurgery. Our findings support the need: i) for a continent-wide, standardized curriculum guide to neurosurgical rotations and ii) to advocate for gender inclusivity in education and policy-making efforts across the African continent

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Accidental denture ingestion in two teaching hospitals in Lagos

Background: Accidental foreign body ingestion is a common cause for emergency treatment. Dentures can be accidentally ingested.Objective: This study investigated accidental denture ingestion, and management outcome.Materials and Methods: A prospective study involving patients at 2 teaching hospitals in south-west Nigeria, who presented in the emergency room within a period of two years (2016-2018) with a previous history of wearing dentures were included. Information collected included patients' demography, presenting complaints, investigations done, type of dentures/prostheses, surgical procedure performed and outcome.Results:&nbsp;A total of 20 cases were seen during the period of the study. The age range was from 28-75 years. More males 16 (80.0%) presented than females 4(20.0%). Patients presented with pain on swallowing 9(45.0%), while 11(55.0%) gave a positive history of ingesting dentures. Dentures ingestion occurred more frequently while taking medications 12(60.0%). Most patients (80.0%) presented with denture impaction in the upper oesophagus, while 3 (15.0%) were lodged in the hypopharynx. All dentures ingested were more often upper dentures 13(65.0%) and made of acrylic with no metallic attachment. Most dentures were used for more than five years (76.5%). Radiographs showed widened prevertebral shadow in 13(65.0%) patients, air trapping and widening of hypopharynx in 3(15.0%). Seventeen of the 20 ingested dentures were successfully removed without complication. Complications included oesophageal perforation with secondary mediastinitis, and oesophageal mucosal tear without perforation.Conclusion: Denture use after more than 5years, with or without signs of lack of retention have a higher tendency to be ingested accidentally, leading to impaction in the upper oesophagus. The impacted denture can be successfully removed through oesophagoscopy. Key words: Dentures, Accidental Ingestion, Impaction