In Silico Identification of a Potential TNF-Alpha Binder Using a Structural Similarity: A Potential Drug Repurposing Approach to the Management of Alzheimer's Disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder with no conclusive remedy. Yohimbine, found in Rauwolfia vomitoria, may reduce brain inflammation by targeting tumour necrosis factor-alpha (TNFα), implicated in AD pathogenesis. Metoserpate, a synthetic compound, may inhibit TNFα. The study is aimed at assessing the potential utility of repurposing metoserpate for TNFα inhibition to reduce neuronal damage and inflammation in AD. The development of safe and effective treatments for AD is crucial to address the growing burden of the disease, which is projected to double over the next two decades. Methods: Our study repurposed an FDA-approved drug as TNFα inhibitor for AD management using structural similarity studies, molecular docking, and molecular dynamics simulations. Yohimbine was used as a reference compound. Molecular docking used SeeSAR, and molecular dynamics simulation used GROMACS. Results: Metoserpate was selected from 10 compounds similar to yohimbine based on pharmacokinetic properties and FDA approval status. Molecular docking and simulation studies showed a stable interaction between metoserpate and TNFα over 100 ns (100000 ps). This suggests a reliable and robust interaction between the protein and ligand, supporting the potential utility of repurposing metoserpate for TNFα inhibition in AD treatment. Conclusion: Our study has identified metoserpate, a previously FDA-approved antihypertensive agent, as a promising candidate for inhibiting TNFα in the management of AD.

HBV Infection Is an Intermediate-Risk Disease, Whereas Anaemia Is a Mild-to-Moderate Public Health Problem in Young Ghanaian Adults: A Four-Year Retrospective Analysis of Students' Medical Records.

Background: In sub-Saharan Africa, malaria, chronic viral diseases, nutritional deficiencies, and haemoglobinopathies are common causes of anaemia. Continual surveillance data is required to situate the anaemia and infectious disease burden within a given population. This study determined the 4-year trends of anaemia, hepatitis B virus (HBV), and HCV infections and factors associated with anaemia in young Ghanaian adults. Methods: This retrospective study analysed the medical records of 21,716 fresh students at the University of Cape Coast. Data was presented as percentages and line graphs to show the yearly trends in anaemia, HBV, and HCV infections. Binary logistic regression was used to determine the increased odds of anaemia in participants. Results: Although the 4-year anaemia prevalence was 14.2% (95% CI: 0.1403-0.1498), anaemia prevalence in women and men were 24.1% (95% CI: 0.2387-0.2562) and 6.6% (95% CI:0.0616-0.0705), respectively. Anaemia prevalence consistently remained mild (males) and moderate (females) public health problem over the four-year period. Adolescents were more represented in the anaemic group (18.7% prevalence), 70.9% of them being females. The prevalence of HBV and HCV infections were 5.4% (95% CI:0.0506-0.0567) and 0.9% (95% CI: 0.0082-0.0108), respectively; only 0.1% of participants had HBV and HCV coinfection. Males were more represented in both HBV (71.2%) and HCV (63.7%) infection groups. Moreover, 15.8% of the participants who were seropositive for HBsAg self-reported having previously been vaccinated, suggesting a breakthrough infection and/or vaccine nonresponse. Furthermore, female (COR: 4.545; p < 0.001), teenagers (COR: 1.697; p < 0.001), 20-29 years (COR: 1.221; p = 0.035), and positive sickling slide test (COR: 1.176; p = 0.003) were statistically significantly associated with increased odds of anaemia. Conclusion: Intentional preventative public health campaigns regarding anaemia, HBV, and HCV infection should, respectively, target females and young adult males to increase chances of making real change in behavioural attitudes in these at-risk groups.

Establishing pregnancy-specific haematological reference intervals in Ghana; a three-center cross-sectional study.

BACKGROUND: Abnormal intra-pregnancy haematological variables are associated with adverse feto-maternal outcomes. However, the reference intervals (RIs) employed in sub-Saharan Africa to inform clinical decisions are generally imported. Since RIs are influenced by age, geographical location, and race, we hypothesized that context specific RIs should be established in Ghana to contextualize intra-pregnancy decision making. METHODS: This cross-sectional study retrospectively retrieved data of 333 pregnant women with no known clinically determined intra-pregnancy complications; 22 participants in their first trimester (T1; 1-13 weeks), 177 in their T2 (14-27 weeks), and 132 in T3 (28-41 weeks). RIs for haematological parameters were non-parametrically determined at 2.5th and 97.5th percentiles in accordance with CLSI guidance document EP28-A3c. Two-sample comparisons were undertaken using Wilcoxon rank-sum tests whereas more than two-sample comparisons were undertaken using Kruskal-Wallis test. Statistical significance was set at p <0.05 under the two-tailed assumptions. RESULTS: In accordance with WHO trimester-specific haemoglobin cutoffs, anaemia prevalence was a moderate (T1: 36.4%; 8/22 & T2: 31.6%; 56/177) to severe (T3:68.0%; 90/132) public health problem. Additionally, 9.3% (31/333) individuals had high gestational haemoglobin levels (Hb >13.0 g/dL). Moreover, haemoglobin (T2: 8.6-14.3 vs T3: 7.5-13.6 g/dL), MCH (T2: 22.5-69.8 vs T3: 21.6-31.9 pg), MCHC (T2: 30.2-51.8 g/L vs T3: 30.5-37.9 g/L), TWBC (T2: 4.0-13.4 vs T3: 4.1-13.0 x 109/L) required trimester specific RIs, compared to RBC (2.8-5.1 x 1012/L), MCV (66.2-100.2 fL), and platelet counts (106.3-388.3 x 109/L) that each required combined reference intervals. CONCLUSIONS: The intra-pregnancy haematological RIs determined have appreciable lower limits; there is the need to determine context-specific thresholds for haematological variables predictive of positive and/or adverse maternal and infant health outcomes.

A Review of African Medicinal Plants and Functional Foods for the Management of Alzheimer's Disease-related Phenotypes, Treatment of HSV-1 Infection and/or Improvement of Gut Microbiota.

Alzheimer's disease (AD), which is a progressive neurodegenerative disorder is the most common form of dementia globally. Several studies have suggested alteration in the gut microbiota and HSV-1 infection as contributing factors to the development of the disease. As at now, there are no AD attenuating agents and AD pharmacotherapy is focused on managing symptoms while plants used in ethnomedicine remain potential sources of drugs for the treatment of the condition. Here, we reviewed published databases for African ethnomedicinal plants and functional foods of African origin that are used in the management of AD-related phenotypes, treatment of herpes simplex virus -1 (HSV-1) and/or improvement of gut microbiota. A total of 101 unique plant species and 24 different types of traditionally prepared African functional foodstuff were identified. Of the 101 identified plant species, 50 species serve as functional foodstuffs. Twenty-three (23) of the ethnomedicinal plant families were successfully identified for the treatment and management of AD-related phenotypes and age-related dementia. Eighteen (18) African plant species from 15 families were also identified as potent remedies for HSV-1; while many African wild fruits (3 species), roots and tubers (7 species), leafy vegetables (14 species), and seaweeds (26 species) were functional foods for modifying AD-related phenotypes. It was concluded that African medicinal plants are potential sources of both AD attenuating agents and phytocompounds that may be used against HSV-1 infection and alteration of gut microbiota. Additionally, a number of African functional foods are important sources of prebiotics and probiotics.

Anaemia Prevalence More Than Doubles in an Academic Year in a Cohort of Tertiary Students: A Repeated-Measure Study in Cape Coast, Ghana.

BACKGROUND: The stress of academic life may predispose young adults to poor dietary habits, which could potentially precipitate nutritional deficiencies, such as iron deficiency. This study evaluated factors predictive of optimal iron stores as well as changes in haematological parameters over the course of an academic year in a cohort of tertiary students. MATERIALS AND METHODS: The repeated-measure cohort study recruited 117 undergraduate students from September 2018 to May 2019. Venous blood samples were drawn for full blood count estimation, qualitative glucose-6-phosphate dehydrogenase (G6PD) status, haemoglobin variants, and blood group determination during the first 2 weeks of semester 1. However, anthropometric parameters as well as full blood counts were determined for each participant during the first week and last week of semesters 1 and 2. Additionally, semistructured questionnaires were used to capture sociodemographic data. Also, serum ferritin was estimated for each participant using enzyme-linked immunosorbent assay. RESULTS: Overall, 23.1% and 15.5% of participants inherited G6PD defect (G6PDd) or haemoglobin variants, respectively. However, group O (68/117; 58.1%) was the predominant ABO blood group and an overwhelming 90.6% (106/117) inherited Rh D antigen. The prevalence of anaemia increased from 20% at the beginning of the first semester to 45.1% at the latter part of the second semester. G6PDd participants had significantly higher median serum ferritin than G6PD normal participants (p = 0.003). Also, a significantly higher proportion of females were iron depleted (25% vs. 2.3%) or iron deficient (14.3% vs. 9.3%) compared to males. Moreover, being male, G6PD deficient, or 21-25 years was associated with increased odds of participants having optimal serum ferritin levels. CONCLUSION: The progression of anaemia prevalence from mild to severe public health problem over the course of one academic year should urgently be addressed.

Poor haemoglobin-haematocrit agreement in apparently healthy adult population; a cross-sectional study in Cape Coast Metropolis, Ghana.

BACKGROUND: This study estimated total body water (TBW), daily water intake (DWI) and haemoglobin-haematocrit relationship in adults in a tropical environment where active lifestyles could precipitate plasma volume contraction. METHODS: This cross-sectional study recruited 170 participants, and was carried out between February 2018 and May 2018 at University of Cape Coast. Semi-structured questionnaires were used to obtain demographic data and DWI. Five ml of venous blood sample was drawn for full blood count, haemoglobin variant determination, serum sodium and potassium levels. TBW was estimated using Chumlea's anthropometric equation. Statistical significance was set at p < 0.05 under two-tail assumption. RESULTS: Whereas 72.3% had low haematocrit, only 22.4% were anaemic per haemoglobin cut-off demonstrating a poor haemoglobin-haematocrit correlation. Also, whereas 30% of participants had low TBW, 22.9% had hypernatraemia, with 97.1% reporting DWI of <3 L. Bland-Altman plot showed that calculated haematocrit (HCT = Hb∗3) underestimated HCT by a factor of 1.788 (p = 0.0314). A scatter-plot showed a trend towards higher haematocrit-haemoglobin deviations as haemoglobin increased. Furthermore, 32.6% of participants with normal haemoglobin levels had low TBW. Moreover, whereas haemoglobin and serum K+ significantly positively correlated to TBW, serum Na+ was inversely related to TBW. CONCLUSION: The low DWI is suggestive that measuring plasma volume and/or haemoglobin mass may be required to correctly diagnose anaemia.

Crude extracts from Allium cepa skin and Sorghum bicolor seed can provide as non-toxic and eco-friendly cytoplasmic stains.

INTRODUCTION: Staining is an important histological process; however, the use of non-toxic and environmentally friendly products is generally required. We explored the staining quality of two natural plants, Allium cepa skin and Sorghum bicolor seed extract on the cytoplasm. MATERIALS AND METHODS: Distilled water at 37 °C and 1% acid-ethanol were respectively used to extract the dyes from Allium cepa skin and Sorghum bicolor seed. RESULT: The application of these two dyes on rodent tissue showed an excellent cytoplasmic histomorphology. CONCLUSION: Allium cepa skin and Sorghum bicolor seed extracts are good cytoplasmic dyes when used as counterstain for haematoxylin.

Poor iron store recovery in voluntary blood donors in the northern zone of Ghana; a five-month three-centre cohort study.

OBJECTIVE: In Ghana, although iron deficiency is endemic, post blood donation iron supplementation is not routine. We sought to determine whether at five months post-donation of a single unit of whole blood, donors were able to recover iron stores. MATERIALS AND METHODS: This three-centre cohort study recruited 164 blood donors at the Lawra, Nandom, and Bimbila communities in the northern zone of Ghana. Venous blood samples were drawn at baseline to estimate full blood count (FBC), haemoglobin variants, qualitative G6PD status, and serum ferritin. Five months post-donation, venous blood samples were drawn for a repeat measurement of FBC and serum ferritin. Data were analysed using SPSS and GraphPad prism to assess recovery of iron stores. RESULTS: Whereas 26.8 % had inherited haemoglobin variants, 18.9 % of the donors had qualitative G6PD deficiency. Overall, mean difference between pre-donation and five months post donation iron stores significantly differed from zero (p < 0.001; one sample t-test). After five months post donation, 76.8 % of the blood donors could not achieve pre-donation iron stores. Whereas 6.1 % and 8.5 % blood donors had depleted iron stores and iron deficient erythropoiesis at baseline, these increased to 9.8 % and 21.3 % respectively at five-month post donation. Moreover, at five months post donation, 11 % of these blood donors would have been disqualified per haemoglobin screening cut off of 12.5 g/dl. CONCLUSION: Reliance on food intake to replenish iron store lost per blood donation may not adequately assure donor health in the study area; iron supplementation should be considered.

High Iodine Deficiency among Pregnant Women in Periurban Ghana: A Hospital-Based Longitudinal Study.

BACKGROUND: Iodine deficiency causes maternal hypothyroidism which can lead to growth, cognitive, and psychomotor deficit in neonates, infants, and children. This study examined the iodine status of pregnant women in a periurban setting in Ghana. METHODS: This longitudinal study recruited 125 pregnant women by purposeful convenience sampling from the antenatal clinic of the Sefwi Wiawso municipal hospital in Ghana. Urinary iodine concentration (UIC) was estimated by the ammonium persulfate method at an estimated gestational age (EGA) of 11, 20, and 32 weeks. Demographic information, iodized salt usage, and other clinical information were collected using a questionnaire. RESULTS: The prevalence of iodine deficiency among the pregnant women was 47.2% at EGA 11 and 60.8% at both EGA of 20 and 32, whereas only 0.8% of participants not using iodized salt had iodine sufficiency at EGA 32. 18.4%, 20%, and 24% of participants using iodized salt had iodine sufficiency at EGA 11, 20, and 32, respectively. CONCLUSION: A high prevalence of iodine deficiency was observed among our study cohort.

HER-2 Protein Overexpression in Patients with Gastric and Oesophageal Adenocarcinoma at a Tertiary Care Facility in Ghana.

The prognosis of gastric and oesophageal adenocarcinoma remains generally poor. However, mounting evidence suggests a positive role of human epidermal growth factor receptor-2 (HER-2) expression in the prognosis of patients with these cancers. In this work, the patterns of HER-2 protein expression were determined in patients with gastric or oesophageal adenocarcinoma. Retrospectively, we reviewed records of gastric and oesophageal biopsies received from 2008 to 2012 and their corresponding archived formalin-fixed paraffin-embedded tissue blocks selected for immunohistochemical analysis. The prevalence of gastric and oesophageal adenocarcinomas and their association with HER-2 protein overexpression were evaluated. Gastric adenocarcinoma made up 18.79% of the gastric biopsies reviewed, and majority of these cancers occurred in males. Regarding the tumour type, HER-2 overexpression was common in the intestinal subtype compared to the diffuse type. Although squamous cell carcinoma was observed to be the commonest (31%) tumour type in the oesophagus compared to adenocarcinoma (8.79%), HER-2 was overexpressed in 42.9% of oesophageal adenocarcinomas, like gastric adenocarcinoma (41.4%). There is a high prevalence of gastric and oesophageal adenocarcinoma, with significant overexpression of HER-2 in these tumours, a window of hope for the management of patients with these cancers.

TDP-43 self-interaction is modulated by redox-active compounds Auranofin, Chelerythrine and Riluzole.

Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disease, which is characterized by a rapid loss of lower and upper motor neurons. As a major neuropathological hallmark, protein aggregates containing the Transactivating Response Region (TAR) DNA Binding Protein (TDP-43) are detectable in about 95% of sporadic ALS patients. TDP-43 interacts with itself physiologically to form liquid droplets, which may progress to pathological aggregates. In this study, we established the NanoBit luciferase complementation assay to measure TDP-43 self-interaction and found the fusion of the split luciferase subunits to the N-terminus of the protein as the strongest interacting partners. A screen of pharmacologically active compounds from the LOPAC®1280 library identified auranofin, chelerythrine and riluzole as dose-dependent inhibitors of TDP-43 self-interaction. Further analysis of drug action of the gold-containing thioredoxin reductase inhibitor auranofin revealed a redistribution from insoluble TDP-43 protein pool to PBS-soluble protein pool in N2a cells. In addition, auranofin treatment diminished reduced glutathione as a sign for oxidative modulation.

Prevalence of helicobacter pylori infection among children living in a rural setting in Sub-Saharan Africa.

BACKGROUND: Helicobacter pylori infection affects more than half of the world's population. It is generally acquired during childhood with no symptoms but has long- term clinical sequelae. This study estimated the prevalence of H. pylori infection amongst children in a rural environment in Africa. METHODS: We conducted a cross-sectional study over a four (4)-month period within two rural communities. 240 asymptomatic children were tested using lateral flow immunochromatographic assay for the qualitative detection of H. pylori antigen in a fecal specimen. Statistical analysis and processing was done using Stata version 11. RESULTS: The mean age of the participants was 10.5 ± 2.7 years with the predominant age range being 8-10 years (34.6%), and a mean household size of 7.1 ± 1.7. The study population showed a female preponderance of 57.1%. 88% of the H. pylori positive children lacked pipe and borehole drinking water. All of the positive H. pylori children practiced open-air defecation. The overall prevalence of H. pylori infection among children in this study was at least 14.2%. CONCLUSION: Our study demonstrated a high prevalence of H. pylori infection among children in a rural setting. Educational status of parents did not affect H. pylori prevalence but increasing household numbers, female gender, source of drinking water other than pipe and borehole, open-air defecation and younger age were associated with a higher H. pylori prevalence.

Detection of Human Papillomavirus Genotypes and Epstein-Barr Virus in Nasopharyngeal Carcinomas at the Korle-Bu Teaching Hospital, Ghana.

Nasopharyngeal carcinomas (NPC) are endemic in Far East Asia and commonly harbour Epstein-Barr virus (EBV) which is known to serve as a key oncogenic promoter. Human papillomavirus (HPV) is known to contribute to the pathogenesis of NPC. However, in Ghana these two viruses have not been linked to NPC prevalence. This study was designed to determine the HPV genotypes and EBV involved in NPC tissue biopsies. A retrospective study design involving 72 formalin-fixed paraffin-embedded tissue (FFPET) samples of NPC from 2006 to 2012 were retrieved from the Department of Pathology, University of Ghana School of Biomedical and Allied Health Sciences. Sections were taken for histological analysis and for DNA lysate preparation. The DNA lysates were subjected to polymerase chain reaction (PCR) analysis to determine the presence of HPV genotypes and EBV. HPV specific primers were used to type for fourteen HPV genotypes (HPV-16, 18, 6/11, 31, 33, 35, 44, 42, 43, 45, 56, 52, 58, and 59). Out of the 72 NPC biopsies analyzed by PCR, EBV DNA was present in 18 (25%) cases and HPV DNA in 14 (19.23%). High risk HPV (HR-HPV) genotypes 18 and 31 were associated with the NPC. There were 3 (4.2%) cases of coinfection by both viruses. The EBV DNA present in the undifferentiated variant of the NPC and the histopathology of the NPC in Ghana is similar to the type described in endemic areas.

Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait among Prospective Blood Donors: A Cross-Sectional Study in Berekum, Ghana.

Background. Blood transfusion is a therapeutic procedure usually undertaken in patients with severe anaemia. In Ghana, severe anaemia is mostly due to malaria caused by severe Plasmodium falciparum infection, road traffic accidents, and haemoglobinopathy-induced acute haemolysis. Method. This cross-sectional study evaluated coinheritance of sickle cell haemoglobin variant and G6PD enzymopathy among individuals that donated blood at the Holy Trinity Hospital, Berekum, in the Brong-Ahafo Region, Ghana. Demographic data and other pertinent information were captured using questionnaire. Sickle cell haemoglobin variants were determined using cellulose acetate electrophoresis (pH 8.6). Qualitative G6PD status and quantitative G6PD enzyme activity were determined using methaemoglobin reduction and Trinity Biotech G6PD test kit, respectively. Results. Prevalence of sickle cell trait (SCT) and G6PD enzymopathy coinheritance was 7%. In addition, 19.5% of the donors had 10%-60% of normal G6PD enzyme activity suggesting that these donor units are prone to stressor-induced acute haemolysis when given to recipients. Mild G6PD activity (p = 0.03, OR: 2.410 (CI: 1.049-5.534)), commercial (p = 0.020, OR: 5.609 (CI: 1.309-24.035)), and voluntary (p = 0.034, OR: 2.404 (CI: 1.071-5.397)) donors were significantly associated with SCT. Conclusion. Screening for red cell pathologies must be incorporated into existing protocols for populations with high incidence of haemoglobinopathies to protect high-risk recipients.