The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population.

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44+/CD24-/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes. METHOD: Tissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44+/CD24-/low/ALDH1+ and the clinicopathological phenotypes were also studied. RESULTS: A high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751-12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841-16.662, p = 0.001) but not associated with CD44+/CD24-/low (r = 0.134, OR- 2.720 95%CI- 0.959-7.710, p = 0.052). CD44+/CD24-/ALDH1+ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147-6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339-175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421-10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217-7.536). There was no association between CD44+/CD24-/ALDH1+ and the molecular subtypes. CONCLUSION: The high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44+/CD24-/ALDH1+ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.

Evaluating the Contribution of Nocardia spp. and Mycobacterium tuberculosis to Pulmonary Infections among HIV and Non-HIV Patients at the Komfo Anokye Teaching Hospital, Ghana.

Tuberculosis (TB) is a major cause of human mortality particularly in association with the human immunodeficiency virus (HIV). Nocardia spp. has emerged as an opportunistic infection especially in HIV patients. The high prevalence of TB and HIV coupled with the lack of a definitive laboratory diagnosis for Nocardia spp. could lead to misdiagnosed pulmonary TB. This study determined the prevalence of pulmonary infections due to Nocardia spp. and Mycobacterium tuberculosis in sputum of HIV and non-HIV patients with suspected pulmonary tuberculosis at KATH. A total of sixty sputum samples were obtained from HIV and non-HIV patients with suspected pulmonary tuberculosis. Samples were examined by fluorescence based Ziehl-Neelsen staining, culture, and PCR methods. The prevalence of Nocardia spp. and Mycobacterium tuberculosis was 18.3% and 20%, respectively, with the latter having the highest rate among patients aged 21-40 years (P=0.075). The prevalence of Nocardia spp. among HIV patients was 90.9% whilst 16.7% of the patients had HIV/Nocardia spp. coinfection. Detection of Mycobacterium tuberculosis by fluorescence-based Ziehl-Neelsen staining, culture, and PCR yielded 9 (15%), 11 (18.3%), and 12 (20%), respectively. There is a high prevalence of nocardiosis especially in HIV patients. PCR is a better diagnostic method that detects both Nocardia spp. and Mycobacterium tuberculosis and should be incorporated into routine diagnosis for pulmonary infections.

Association between Interleukin-6 Gene Polymorphism (rs1800795 and rs1800796) and Type 2 Diabetes Mellitus in a Ghanaian Population: A Case-Control Study in the Ho Municipality.

Background: There is no conclusive evidence on the association between interleukin- (IL-) 6 gene polymorphism and type 2 diabetes mellitus (type 2 DM). Thus, this study is aimed at evaluating the role of rs1800795 and rs1800796 polymorphisms in the pathogenesis of type 2 DM among Ghanaians in the Ho Municipality. Materials and Methods: We recruited into this hospital-based case-control study 174 patients with type 2 DM (75 DM alone and 99 with DM+HTN) and 149 healthy individuals between 2018 and 2020. Demographic, lifestyle, clinical, anthropometric, and haemodynamic variables were obtained. Fasting blood samples were collected for haematological, biochemical, and molecular analyses. Genomic DNA was extracted, amplified using Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique, and genotyped for IL-6 gene polymorphism. Logistic regression analyses were performed to assess the association between IL-6 gene polymorphism and type 2 DM. Results: The minor allele frequency (MAF) of the rs1800795 and rs1800796 polymorphisms was higher in DM alone (57.5%, 62.0%) and DM with HTN groups (58.3%, 65.3%) than controls (33.1%, 20.0%). Carriers of the rs1800795GC genotype (aOR = 2.35, 95% CI: 1.13-4.90, p = 0.022) and mutant C allele (aOR = 2.41, 95% CI: 1.16-5.00, p = 0.019) as well as those who carried the rs1800796GC (aOR = 8.67, 95% CI: 4.00-18.90, p < 0.001) and mutant C allele (aOR = 8.84, 95% CI: 4.06-19.26, p = 0.001) had increased odds of type 2 DM. For both polymorphisms, carriers of the GC genotype had comparable levels of insulin, HOMA-IR, and fasting blood glucose (FBG) with those who carried the GG genotype. IL-6 levels were higher among carriers of the rs1800796GC variant compared to carriers of the rs1800796GG variant (p = 0.023). The rs1800796 polymorphism, dietary sugar intake, and exercise status, respectively, explained approximately 3% (p = 0.046), 3.2% (p = 0.038, coefficient = 1.456), and 6.2% (p = 0.004, coefficient = -2.754) of the variability in IL-6 levels, suggesting weak effect sizes. Conclusion: The GC genotype and mutant C allele are risk genetic variants associated with type 2 DM in the Ghanaian population. The rs1800796 GC variant, dietary sugar intake, and exercise status appear to contribute significantly to the variations in circulating IL-6 levels but with weak effect sizes.

Performance of Body Adiposity Index and Relative Fat Mass in Predicting Bioelectric Impedance Analysis-Derived Body Fat Percentage: A Cross-Sectional Study among Patients with Type 2 Diabetes in the Ho Municipality, Ghana.

Objective: The study sought to determine the diagnostic accuracy of body adiposity index (BAI) and relative fat mass (RFM) to predict BIA-derived BFP among patients with type 2 diabetes in the Ho municipality. Materials and Method. This hospital-based cross-sectional study involved 236 patients with type 2 diabetes. Demographic data, including age and gender were obtained. Height, waist circumference (WC), and hip circumference (HC) were measured using standard methods. BFP was estimated on a bioelectrical impedance analysis (BIA) scale. The validity of BAI and RFM as alternative estimates for BIA-derived BFP was evaluated based on mean absolute percentage error (MAPE), Passing-Bablok regression, Bland-Altman plots, receiver-operating characteristic curve (ROC), and kappa statistics analyses. A p value less than 0.05 was considered statistically significant. Results: BAI showed systematic bias in estimating BIA-derived BFP in both genders, but this was not evident between RFM and BFP among females (t = -0.62; p = 0.534). While BAI showed "good" predictive accuracy in both genders, RFM exhibited "high" predictive accuracy for BFP (MAPE: 7.13%; 95% CI: 6.27-8.78) among females according to MAPE analysis. From the Bland-Altman plot analysis, the mean difference between RFM and BFP was acceptable among females [0.3 (95% LOA: -10.9 to 11.5)], but both BAI and RFM recorded large limits of agreement and low Lin's concordance correlation coefficient with BFP (Pc < 0.90) in the two gender populations. The optimal cut-off, sensitivity, specificity, and Youden index for RFM were >27.2, 75%, 93.75%, and 0.69, respectively, while those of BAI were >25.65, 80%, 84.37%, and 0.64, respectively, among males. Among females, the values for RFM were >27.26, 92.57%, 72.73%, and 0.65, whereas those of BAI were >29.4, 90.74%, 70.83%, and 0.62, respectively. The accuracy of discriminating between BFP levels was higher among females [BAI (AUC: 0.93) and RFM (AUC: 0.90)] compared to males [BAI (AUC: 0.86) and RFM (AUC: 0.88)]. Conclusion: RFM had a better predictive accuracy of BIA-derived BFP in females. However, both RFM and BAI failed as valid estimates for BFP. Furthermore, gender-specific performance in the discrimination of BFP levels for RFM and BAI was observed.

Vitamin D Deficiency Is Common in Ghana despite Abundance of Sunlight: A Multicentre Comparative Cross-Sectional Study.

BACKGROUND: Vitamin D is a steroid hormone important for the normal functioning of the body. It is produced through skin exposure to sunlight and from the diet. Although Ghana is located in the tropics where sunlight is abundant, factors like culture, diet, skin pigmentation, variation in the ozone layer, and geographical area influence the optimization of vitamin D concentration. It is imperative to evaluate the interplay between sunshine exposure, proinflammatory cytokines, and mediators of vitamin D metabolism and their relationship to vitamin D status in three geographical sections among apparent healthy Ghanaians. METHODS AND RESULTS: In a cross-sectional study, a total of five hundred (500) healthy blood donors from three geographical areas in Ghana were enrolled. Their age ranged from 17 to 55 years with a mean age of 27.97 ± 8.87 years. The overall prevalence rate of vitamin D deficiency was 43.6% (218/500), with 41.2% (91/221), 45.3% (63/139), and 45.7% (64/140) of vitamin D deficiency being recorded in participants from the Northern Sector (NS), Middle Belt (MB), and Southern Sector (SS), respectively. However, there were no significant differences in the proportions of vitamin D deficiency across various geographical sectors. The median 25-hydroxyvitamin D serum levels were compared among geographical areas (NS, MB, and SS) and there were no significant differences (P=0.275) after adjusting for confounding factors. 25-Hydroxyvitamin D correlated positively with corrected ionized calcium (rs = 0.622, P ≤ 0.001) and phosphorus (rs = 0.299, P ≤ 0.001) and negatively correlated with SBP (rs = -0.092, P=0.039), vitamin D binding protein (VDBP) (rs = -0.421, P ≤ 0.001), intact parathyroid hormone (iPTH) (rs = -0.0568, rs ≤ 0.001), IFN-gamma (rs = -0.684, P ≤ 0.001), and TNF-alpha (rs = -0.600, P ≤ 0.001). After adjusting for possible confounders, not having knowledge about vitamin D foods, taking fewer vitamin D foods, and higher levels of IF-γ and IL-10 were associated with a higher risk of having vitamin D deficiency. CONCLUSION: The prevalence of 25-hydroxyvitamin D deficiency is high among the general adult population in Ghana despite the abundance of sunlight. Increasing knowledge on vitamin D diet coupled with a daily intake of vitamin D dietary supplements is likely to reduce the risk of developing 25-hydroxyvitamin D deficiency.

Developing a Modified Low-Density Lipoprotein (M-LDL-C) Friedewald's Equation as a Substitute for Direct LDL-C Measure in a Ghanaian Population: A Comparative Study.

Despite the availability of several homogenous LDL-C assays, calculated Friedewald's LDL-C equation remains the widely used formula in clinical practice. Several novel formulas developed in different populations have been reported to outperform the Friedewald formula. This study validated the existing LDL-C formulas and derived a modified LDL-C formula specific to a Ghanaian population. In this comparative study, we recruited 1518 participants, derived a new modified Friedewald's LDL-C (M-LDL-C) equation, evaluated LDL-C by Friedewald's formula (F-LDL-C), Martin's formula (N-LDL-C), Anandaraja's formula (A-LDL-C), and compared them to direct measurement of LDL-C (D-LDL-C). The mean D-LDL-C (2.47±0.71 mmol/L) was significantly lower compared to F-LDL-C (2.76±1.05 mmol/L), N-LDL-C (2.74±1.04 mmol/L), A-LDL-C (2.99±1.02 mmol/L), and M-LDL-C (2.97±1.08 mmol/L) p < 0.001. There was a significantly positive correlation between D-LDL-C and A-LDL-C (r=0.658, p<0.0001), N-LDL-C (r=0.693, p<0.0001), and M-LDL-C (r=0.693, p<0.0001). M-LDL-c yielded a better diagnostic performance [(area under the curve (AUC)=0.81; sensitivity (SE) (60%) and specificity (SP) (88%)] followed by N-LDL-C [(AUC=0.81; SE (63%) and SP (85%)], F-LDL-C [(AUC=0.80; SE (63%) and SP (84%)], and A-LDL-C (AUC=0.77; SE (68%) and SP (78%)] using D-LDL-C as gold standard. Bland-Altman plots showed a definite agreement between means and differences of D-LDL-C and the calculated formulas with 95% of values lying within ±0.50 SD limits. The modified LDL-C (M-LDL-C) formula derived by this study yielded a better diagnostic accuracy compared to A-LDL-C and F-LDL-C equations and thus could serve as a substitute for D-LDL-C and F-LDL-C equations in the Ghanaian population.