Development of a combined database / in silico pipeline for the investigation of novel approaches for precision medicine

This project investigates how integrated in silico approaches can be developed to advance precision medicine. A novel bioinformatics database was created and implemented. This database was able to output gene and variant information of all the known human protein drug targets, while also retrieving information on compounds, disorders and drugs associated with each protein. This database was created by writing code, in Linux, that was able to web-scrape multiple databases for information and store it in the pipeline database. The databases that were scraped were UniProt, ClinVar, PubChem, chEMBL, guide to pharmacology, MedGen and the therapeutic target database. These databases were selected as they provided the largest and most reliable data, that could be web-scraped, for each section they were scraped for. Once coded, the full pharmacology set (a set of 720 pharmacologically relevant proteins, whose pharmacological mechanism is known) was added to the pipeline, meaning all their information was downloaded and stored in the pipeline. This bioinformatics pipeline proved to be very effective as an investigative tool for identifying new avenues for personalised medicine as it was able to retrieve and integrate all the requested information on proteins, variants, diseases, and compounds when called upon. In the proof-of-concept study, the database was used to gather key information that allowed for an investigation into the effect of pathogenic variants on drug binding in proteins. This investigation was conducted by simulating the binding of a protein’s wild type to two of its known drug ligands. 10 benign variants and 10 pathogenic variants of the protein were also bound to 2 drug ligands associated with the protein; their relative binding energies were collected. This allowed for comparisons to be made between the effect of pathogenic variants and benign variants on a protein’s binding ability. Analysis from the docking simulations showed that in 3 of the 5 proteins studied (60%), more pathogenic mutations returned a binding energy with at least a 15% deviation from the wildtype binding energy than benign mutations. These results suggest that the binding interactions of a protein could be affected by polymorphic variation, especially pathogenic variation, although in this case study the difference between the two groups did not show statistical significance

Effect of Prednisolone on the Lymhpoid Tissue of Small Intestine of Adult Wistar Rats

Peyers patches are central to mucosal immunity as they play a major role in the gastrointestinal tract; they modulate intestinal immune and inflammatory responses or tolerance and they are subject to other factors that influences immunity. This study aims at assessing the immunosuppressive effect of prednisolone on the histology of peyers patches of adult wistar rats. Twenty eight adult albino wistar rats weighing between 190g to 300g were randomly assigned seven groups A, B, C, E, F & G of four rats each. Group A animals served as the control and were given distilled water only; Group B received 2mg/kg of prednisolone for two weeks, Group C received 4mg/kg of prednisolone for two weeks, Group D received 6mg/kg of prednisolone for two weeks, Group E received 2mg/kg of predisolone for four weeks, Group F received 4mg/kg of prednisolone for four weeks and Group G received 6mg/kg of prednisolone for four weeks. The oral administration was in two phases; short term (two weeks) and long term (four weeks) which lasted for twenty eight days. Body weight result showed general increase in body weight in all the groups. Histological examination revealed significantly increased influx of lymphocytes in peyers patches into the lumen in groups F & G compared with the control while other groups B, C, D, & E were not affected when compared with the control group. The groups given prednisolone for a longer period showed reduction in numbers of peyers patches and lymphoid follicles, suggesting that  higher doses of prednisolone tend to lower the number of peyers patches. Keywords: Prednisolone, Lymphoid tissue, Small intestine, Peyers patches, Wistar rat

Correlation of ultrasound measured testicular volume with waist circumference, hip circumference, waist-hip ratio and conicity index in Nigerian adults

Background: Accurate testicular volume measurement is one way to assess testicular function. Some obese males exhibit altered levels of circulating sex steroids; decreased levels of total testosterone (T) and sex hormone binding globulin (SHBG) and increased estrogens levels. Some anthropometric measurements are markers for obesity.Objective: This study aims to evaluate the correlation of testicular volume measured by ultrasound with some anthropometric measurements: Waist circumference, Hip circumference, Waist-Hip Ratio (WHR), and Conicity Index in adult males.Methodology: One hundred and twenty-five adult male subjects comprising staff and students of a University Teaching Hospital, were recruited. The subjects' height, weight, waist circumference and hip circumference were measured and used to calculate the WHR and Conicity Index. Ultrasound measurement of the length, width and height of both testes were done and used to calculate the volumes.Results: The age of the subjects ranged from 19 to 29 years with a mean of 23.48±2.26. The mean ultrasound testicular volumes for the right and left testes were: 15.38±3.29ml and 15.29±3.89ml using the first formula; 22.86±5.43ml and 23.54±6.88ml for second formula; 21.20±5.28ml and 20.87±5.35ml for the third formula respectively. The calculated mean for height, weight, Waist circumference, Hip circumference, WHR and Conicity Index were: 174.64±6.36cm, 68.68±8.25kg, 77.51±5.44cm, 88.76±4.46cm, 0.87±0.40 and 1.14±0.05 respectively. The left, right and combined testicular volumes showed weak negative correlation with the Waist circumference, Hip circumference, WHR and Conicity Index.Conclusion: Ultrasound measured testicular volume showed weak negative correlation with the Waist circumference, Hip circumference, WHR and Conicity Index in Nigerian adults.Key words: Ultrasound, testicular volumes, waist-hip ratio, conicity index, Nigerian adult

Patterns of antiepileptic drug use and seizure control among people with epilepsy in a suburban community in Southeast Nigeria

Background Epilepsy is characterized by episodic and unpredictable seizure recurrences which are often amenable to medical treatment. Simple and readily available medications can be used to control seizures in epilepsy. However, in many communities in developing countries seizure control among people living with epilepsy is still poor. Method We assessed the patterns of antiepileptic drug use and seizure control among persons living with epilepsy in a suburban community in Southeast Nigeria found in a two phase cross-sectional study. Detailed information on epilepsy treatment, seizure control and patterns of antiepileptic drug use (AED) by those diagnosed with epilepsy was determined by use of a semi-structured interviewer administered questionnaire. Further verification of the type of antiepileptic drugs (AEDs) was done by drug inspection. Result The total of 29 cases of active epilepsy comprising 16 (55.2%) males and 13 (44.8%) females were found. Those receiving AEDs at the time of survey were 7 (24.1%), 11(37.9%) who had previously used AEDs had stopped and the remaining 11 (37.9%) were AEDs naïve. Carbamazepine monotherapy was used by 57.1% (n=4) while phenobarbitone was used by 42.9% (n=3). The antiepileptic drugs were prescribed in all these cases by medical personnel. Over 82% of the persons with active epilepsy found were having more than one seizure per month. Conclusion Active epilepsy was prevalent in this suburban community with only 24.1% (n=7) of them receiving treatment with AEDs. Seizure control was poor even among those receiving AEDs and carbamazepine monotherapy was most commonly used AEDs

Serum lipid and glucose concentration in relation to some physiological varibles in college students from Nnewi, Nigeria

Background: Serum lipid and glucose levels are largely determined by and or related to certain physical, physiological and biochemical parameters/variables. This study therefore, is aimed at determining the levels of serum lipid and glucose and the relationship between the serum lipid and glucose concentrations and the physical and physiological parameters/variables of apparently healthy individuals. Method: The blood samples of twenty-five medical students in the age range of 20 and 25 years were analyzed, for the serum glucose, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDLc) levels after overnight fast, and LDLc calculated.Result: The mean serum glucose, HDLc, TC and LDLc were not significantly different in females and males students. The serum TG was however significantly lower in females than in the males (90.22 ± 25.17 vs. 116.93 ± 21.54 mg/dl;

Exercise performance in relation to glucose drink and their effect on some biochemical parameters

This study was designed to determine the effect of glucose drink on marathon running and on some biochemical parameters. Seven untrained athletes (male students) participated in this study and were engaged in marathon running with and without intake of glucose drink (1g/kg body weight) in a double blind procedure. Blood samples were collected at 0, 30, 60 and 150 minutes for serum glucose, triglyceride, cholesterol and PCV estimation. There were significant increases in serum glucose (F=13.01;

Safety Evaluation of Potential Toxic Metals Exposure from Street Foods Consumed in Mid-West Nigeria

Objective. Street-vended foods offer numerous advantages to food security; nevertheless, the safety of street food should be considered. This study has investigated the level of potential toxic metal (Pb, Cd, Hg, Sb, Mn, and Al) contamination among street-vended foods in Benin City and Umunede. Methods. Twenty street food samples were purchased from vendors at bus stops. Metals were analyzed with atomic absorption spectrophotometry. The methods developed by the US EPA were employed to evaluate the potential health risk of toxic metals. Results. The concentrations of the toxic metals in mg/kg were in the range of Pb (0.014–1.37), Cd (0.00–0.00017), Hg (0.00–0.00014), Sb (0.00–0.021), Mn (0.00–0.012), and Al (0.00–0.22). All the toxic metals except Pb were below permissible limit set by WHO, EU, and USEPA. The daily intake, hazard quotient, and hazard index of all toxic metals except for Pb in some street foods were below the tolerable daily intake and threshold value of 1, indicating an insignificant health risk. Total cancer risk was within the priority risk level of 1.0E-04 but higher than the acceptable risk level of 1E-06. Conclusion. Consumption of some of these street foods is of public health concern

REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis

Serum Lipid and Glucose Concentration in Relation to Some Physiological Varibles in College Students From Nnewi, Nigeria

Background: Serum lipid and glucose levels are largely determined by and or related to certain physical, physiological and biochemical parameters/variables. This study therefore, is aimed at determining the levels of serum lipid and glucose and the relationship between the serum lipid and glucose concentrations and the physical and physiological parameters/variables of apparently healthy individuals. Method: The blood samples of twenty-five medical students in the age range of 20 and 25 years were analyzed, for the serum glucose, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDLc) levels after overnight fast, and LDLC calculated. Result: The mean serum glucose, HDLc, TC and LDLc were not significantly different in females and males students. The serum TG was however significantly lower in females than in the males (90.22 \ub1 25.17 vs. 116.93 \ub1 21.54 mg/dl; P< 0.05). Furthermore, females are significantly lower in weight than the males (61.2 \ub1 6.91 vs. 69.96 \ub1 9.30 kg; P< 0.05). Significant correlations were also recorded. Conclusion: The results presented showed that the slight difference seen in males and females was a factor of growth and diet and activity.Introduction :S\ue9rum lipide et niveau du glucose sont en grande partie d\ue9termin\ue9s par ou li\ue9s aux certains physique physiologique et variables/param\ue8tres biochimiques. Donc, l'objet de cette \ue9tude est de d\ue9terminer les niveaux de s\ue9rum lipide et du glucose et le rapport entre le s\ue9rum lipide et concentration du glucose et des variables/param\ue8tres physiques et physiologiques des individus apparemment en tr\ue8s bonne sant\ue9. M\ue9thodes : La prise de sang de vingt cinq \ue9tudiants en m\ue9decine dans la tranche d'\ue2ge de 20 - 25 ans ont \ue9t\ue9 \ue9tudi\ue9s pour le s\ue9rum glucose, cholest\ue9rol total (CT) triglyc\ue9ride (TG), et les niveaux de la densit\ue9 \ue9lev\ue9e du cholest\ue9rol lipoprot\ue9ines (HDLc) apr\ue8s un je\ufcne d'une nuit, et LDLc calcul\ue9. R\ue9sultats : Le s\ue9rum glucose, HDLc, TC et LDLc moyen n'\ue9taient pas sensiblement diff\ue9rents chez des \ue9tudiants du sexe f\ue9minin et masculin. Le s\ue9rum TG toutefois \ue9tait sensiblement inf\ue9rieur chez le sexe f\ue9minin et le sexe masculin (90,22+- 25,17 contre 116, 93+-21,54mg/dl ; P<0,05). Par ailleurs sexe f\ue9minin sont sensiblement inf\ue9rieurs en poids plus que chez le sexe masculin. (61,2+-6,91 contre 69,96+-9,30kg : P<0,05). Des corr\ue9lations importantes ont \ue9t\ue9 \ue9galement not\ue9es. Conclusion :À travers des r\ue9sultats, nous notons que la diff\ue9rence l\ue9g\ue8re vue chez le sexe masculin et le sexe f\ue9minin \ue9tait un facteur d'activit\ue9, d'alimentation et de la croissance