Ephrin and Eph receptor signaling in female reproductive physiology and pathology†.

Ephrins are ligands of Eph receptors (Ephs); both of which are sorted into two classes, A and B. There are five types of ephrin-As (ephrin-A1-5) and three types of ephrin-Bs (ephrin-B1-3). Also, there are 10 types of EphAs (EphA1-10) and six types of EphBs (EphB1-6). Binding of ephrins to the Eph receptors activates signaling cascades that regulate several biological processes such as cellular proliferation, differentiation, migration, angiogenesis, and vascular remodeling. Clarification of their roles in the female reproductive system is crucial to understanding the physiology and pathology of this system. Such knowledge will also create awareness regarding the importance of these molecules in diagnostic, prognostic, and therapeutic medicine. Hence, we have discussed the involvement of these molecules in the physiological and pathological events that occur within the female reproductive system. The evidence so far suggests that the ephrins and the Eph receptors modulate folliculogenesis, ovulation, embryo transport, implantation, and placentation. Abnormal expression of some of these molecules is associated with polycystic ovarian syndrome, ovarian cancer, tubal pregnancy, endometrial cancer, uterine leiomyoma (fibroids), cervical cancer, and preeclampsia, suggesting the need to utilize these molecules in the clinical setting. To enhance a quick development of this gradually emerging field in female reproductive medicine, we have highlighted some "gaps in knowledge" that need prospective investigation.

High prevalence of vitamin D deficiency among normotensive and hypertensive pregnant women in Ghana.

BACKGROUND: Hypovitaminosis D in pregnancy is associated with adverse health outcomes in mothers, newborns and infants. This study assessed the levels of 25-hydroxyvitamin D [25(OH)D] in normotensive pregnancies and in preeclampsia, evaluated the association between vitamin D deficiency and preeclampsia risk; and determined the foeto-maternal outcome in preeclamptic women with vitamin D deficiency. METHODS: This case-control study was conducted among pregnant women who visited the Comboni Hospital, in Ghana from January 2017 to May 2018 for antenatal care. A total of 180 pregnant women comprising 88 preeclamptic women (PE) and 92 healthy normotensive pregnant women (NP) were recruited. Socio-demographic, clinical and obstetric data were obtained using validated questionnaires. Blood pressure and anthropometrics were measured, and blood samples were collected for the estimation of 25- hydroxyvitamin D [25(OH)D] using enzyme-linked immunosorbent assay technique. Lipids (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were also estimated. RESULTS: A total of 81.7% of the study participants had vitamin D deficiency. Of these, 88.6% of the women with PE had vitamin D deficiency compared to 75.0% in the NP. Vitamin D levels were significantly reduced in the PE women compared to the normotensive pregnant women (p = 0.001). A higher proportion of the preeclamptic women who were vitamin D deficient had preterm delivery (p < 0:0001) and delivered low birth weight infants (p < 0:0001), and infants with IUGR (p < 0:0001) compared to the control group (p < 0:0001). Pregnant women with PE presented with significant dyslipidemia, evidenced by significantly elevated TC (p = 0.008), LDL (p < 0.0001), triglycerides (p = 0.017) and a significantly reduced HDL (p = 0.001) as compared to NP. In the preeclamptic women, serum 25(OH) D showed an inverse, but not significant association with TC (ß = - 0.043, p = 0.722, TG (ß = - 0.144, p = 0.210) and LDL (ß = - 0.076, p = 0.524) and a positive, but not significant association with HDL (ß = 0.171, p = 0.156). CONCLUSION: The prevalence of vitamin D deficiency is high in both normotensive pregnancies and pregnancies complicated by preeclampsia but amplified in preeclampsia. Higher proportion of pregnant women with hypovitaminosis D had preterm babies and delivered low birth weight neonates. Additional studies are needed to explore the potential benefits and optimal dosing of vitamin D use in pregnancy, especially in sub-Saharan Africa.

The role of adiponectin in placentation and preeclampsia.

Preeclampsia is not fully understood; and few biomarkers, therapeutic targets, and therapeutic agents for its management have been identified. Original investigative findings suggest that abnormal placentation triggers preeclampsia and leads to hypertension, proteinuria, endothelial dysfunction, and inflammation, which are characteristics of the disease. Because of the regulatory roles that it plays in several metabolic processes, adiponectin has become a cytokine of interest in metabolic medicine. In this review, we have discussed the role of adiponectin in trophoblast proliferation, trophoblast differentiation, trophoblast invasion of the decidua, and decidual angiogenesis, which are the major phases of placentation. Also, we have highlighted the physiological profile of adiponectin in the course of normal pregnancy. Moreover, we have discussed the involvement of adiponectin in hypertension, endothelial dysfunction, inflammation, and proteinuria. Furthermore, we have summarized the reported relationship between the maternal serum adiponectin level and preeclampsia. The available evidence indicates that adiponectin level physiologically falls as pregnancy advances, regulates placentation, and exhibits protective effects against the symptoms of preeclampsia and that while hyperadiponectinemia is evident in normal-weight preeclamptic women, hypoadiponectinemia is evident in overweight and obese preeclamptic women. Therefore, the clinical use of adiponectin as a biomarker, therapeutic target, or therapeutic agent against the disease looks promising and should be considered.

Predominant Complications of Type 2 Diabetes in Kumasi: A 4-Year Retrospective Cross-Sectional Study at a Teaching Hospital in Ghana.

Background and objectives: Diabetes mellitus type 2 (T2DM) has been associated with several microvascular and macrovascular complications. However, studies regarding the predominant complications of T2DM in Ghana have not been conducted. This study evaluated the prevalence and predominant complications of T2DM and assessed the sociodemographic factors associated with the development of diabetes-related complications in Kumasi, Ghana. Materials and Methods: This was a retrospective cross-sectional study conducted at Komfo Anokye Teaching Hospital (KATH), Kumasi, Ghana. A total of 1600 Ghanaian T2DM adults were included in this study. Patients' clinical data from 2012 to 2016 were retrieved from the hospital's archive. Results: The prevalence of macrovascular and microvascular complications of T2DM was 31.8% and 35.3% respectively. The prevalence of neuropathy, nephropathy, retinopathy, sexual dysfunction, diabetic keto-acidosis (DKA), and hypoglycemia were 20.8%, 12.5%, 6.5%, 3.8%, 2.0%, and 0.8% respectively. Sexual dysfunction was significantly associated with the male gender compared to females. Being employed: Informal (aOR = 0.479, p < 0.0001), and Formal (aOR = 0.475, p = 0.0008) was associated with lower age- and sex-adjusted odds of developing T2DM-related complications while having T2DM for 5-10 years (aOR = 1.550, p = 0.0009) and more than 10 years (aOR = 2.755, p < 0.0001) was associated with increased odds of developing complications. Conclusions: Microvascular complication is the most predominant among T2DM in Kumasi, Ghana. The most prevalent T2DM-related microvascular complication in Kumasi, Ghana is neuropathy. Sexual dysfunction is associated with male compared to female T2DM patients. Being employed reduces the chance of developing T2DM-related complications while increasing DM duration increases the risk of complications.

SERO-prevalence of herpes simplex virus type 1 and type 2 among women attending routine Cervicare clinics in Ghana.

BACKGROUND: Herpes simplex virus infection is a global health concern with disproportionately high burden in low and middle-income countries. There is a paucity of data on the prevalence of HSV infection in Ghana, which necessitated the present study. The aim of the study was to provide up-to-date data on sero-prevalence of HSV-1 and HSV-2 infection among women attending Cervicare clinics in Ghana. METHODS: This was a cross-sectional study in which 380 women attending routine Cervicare clinics at Regional Hospitals in Kumasi and Accra, Ghana were enrolled into the study. Serum HSV-1 IgG and HSV-2 IgG were determined by ELISA method. The Chi-square test was used to investigate the association between sero-prevalence of HSV-1 and HSV-2 and socio-demographic and behavioral factors using the Statistical Package for the Social Scientists (SPSS) version 22. Statistical significance was accepted at p < 0.05. RESULTS: The overall HSV-1 and HSV-2 sero-prevalence estimates were 99.2% (95% CI: 98.0-100%) and 78.4% (95% CI: 74.5-81.8%) respectively. The study observed 78.2% cross-positive prevalence of HSV-1 and HSV-2 among the studied participants. There was no association between the presence of HSV-1 and HSV-2 infection and age (χ2 = 2.351, p = 0.799 and χ2 = 1.655, p = 0.895 respectively). Our findings however, revealed association between the prevalence of HSV-2 and the age at coitarche (p = 0.021) as well as with number of sexual partners (p = 0.022). CONCLUSIONS: The sero-prevalence estimates of HSV-1 and HSV-2 among the study population of women in Ghana were found to be high. This high prevalence could be attributed to high endemicity and inadequate intervention in this population. There is the need to raise awareness through organized public health screening and education to ensure control.

Characterizing Breast Cancer in a Population with Increased Prevalence of Triple-Negative Breast Cancer: Androgen Receptor and ALDH1 Expression in Ghanaian Women.

BACKGROUND: The androgen receptor (AR) is a commonly-expressed hormone receptor in breast cancer and may be a marker of response to targeted anti-androgen therapy, a particularly attractive option for triple-negative breast cancer (TNBC). Gene expression studies suggest that ARs may distinguish a luminal/AR TNBC subtype from stem cell-like subtypes. TNBC frequency is two to three times higher in African American and African breast cancers compared with White American and European breast cancers, yet little is known regarding TNBC subtypes in high-frequency African-ancestry populations. We evaluated ARs and the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) among breast cancers from Ghana, Africa. METHODS: Overall, 147 formalin-fixed, paraffin-embedded invasive breast cancers from the Komfo Anoyke Teaching Hospital in Ghana were studied at the University of Michigan, and analyzed immunohistochemically for estrogen receptor (ER), progesterone receptor (PR), HER2/neu, ALDH1, and AR expression. RESULTS: The median age of patients was 45 years. Only 31 cases (21 %) were ER-positive, and 14 (10 %) were HER2-positive; 89 (61 %) were TNBCs. For the entire group, 44 % were AR-positive and 45 % were ALDH1-positive. ER/PR-positive tumors were more likely to be AR-positive compared with ER/PR-negative tumors (87 vs. 26 %; p < 0.0001), but there was no association between ALDH1 and AR expression. Among the TNBC cases, 45 % were ALDH1-positive and 24 % were AR-positive. ALDH1 positivity was associated with AR positivity within the subset of TNBC (36 vs. 14 %; p = 0.019). CONCLUSION: We confirmed other studies showing a high frequency of TNBC in Africa. Surprisingly, ALDH1 was found to correlate with AR expression among TNBC, suggesting that novel TNBC subtypes may exist among populations with African ancestry.

Interplay between vitamin D status, vitamin D receptor gene variants and preeclampsia risk in Ghanaian women: A case-control study.

BACKGROUND AND AIM: Preeclampsia (PE) is characterized by hypertension and proteinuria mostly after 20 weeks of gestation. It affects 2-8% of pregnancies worldwide, with detrimental consequences for both mother and foetus. Evidence, suggests that genetic factors, including vitamin D receptor (VDR) gene polymorphisms, could contribute to PE complexity. However, their role in the Ghanaian population remains underexplored. We assessed the interplay between Vitamin D, VDR gene variants and preeclampsia risk in Ghanaian women. METHODS: This unmatched case-control study was conducted at Kumasi South Hospital, Ghana, from June to November 2022. A total of 162 participants consisting of 62 PE cases and 100 normotensive controls were enrolled. Clinical and obstetric data were collected. Blood samples were also collected for DNA extraction and vitamin D assay. Genotyping of VDR Fok1 and Bsm1 gene variants was performed using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis whereas Vitamin D levels were estimated using sandwich ELISA. Statistical analyses were computed with SPSS version 25 and GraphPad prism version 8.0. A p-value of < 0.05 was considered statistically significant. RESULTS: Vitamin D concentration were significantly lower in the PE group (p < 0.0001). Vitamin D deficiency (aOR = 3.311, 95% CI: 1.584-6.921, p = 0.0010) was significantly associated with a three-fold increase in preeclampsia risk, whilst VDR gene variants, particularly the "bb" genotype (cOR = 0.227, 95% CI: 0.055-0.944, p = 0.0410) was associated with reduced risk of PE. There was no association between the distribution of Fok1 genotypes and PE. CONCLUSION: This study highlights a significant association between vitamin D deficiency and an increased risk of PE among Ghanaian women. However, the VDR gene variant, "bb", genotype, for Bsm1 reduces the risk of PE.

Alteration in maternal serum uric acid levels in pre-eclampsia and associated perinatal outcomes: a cross-sectional study in Ghana.

Introduction: pre-eclampsia (PE) is a multisystemic pregnancy-specific hypertensive disorder associated with significant adverse maternal and perinatal outcomes. Maternal serum uric acid level is hypothesized as a reliable marker for predicting the severity and adverse outcomes of pre-eclampsia and facilitating clinical decisions. This study explored the association between maternal serum uric acid and adverse pregnancy outcomes in pre-eclampsia. Methods: a cross-sectional study involving women diagnosed with pre-eclampsia was conducted at Korle-Bu Teaching Hospital (KBTH), a tertiary hospital in Ghana. Descriptive analyses were performed and multivariable logistic regression model was used to explore the association between maternal serum uric acid levels and pregnancy outcomes using R software. Results: we included 100 women with pre-eclampsia comprising 79% and 21% preterm and term pre-eclampsia respectively and with mean gestational age (GA) at diagnosis of 32.35±2.66 weeks and 35.96±1.94 weeks respectively. The mean maternal age of preterm and term pre-eclampsia groups was 29.81±5.29 years and 29.46±5.78 years respectively. Hyperuricemia (serum uric acid >375 µmol/L) occurred in 61% of the pre-eclamptic women. The mean gestational age (in weeks) at diagnosis was significantly lower in the pre-eclamptic women with hyperuricemia compared with those with normal levels of uric acid (33.51±3.03 versus 34.80±2.71). There was a significant negative association (moderate correlation) between maternal serum uric acid levels and birth weight (R= -0.34, p < 0.001) in pre-eclampsia; the statistical significance was limited to preterm only (Pearson R= -0.39, p-value <0.001) but not term pre-eclampsia. Hyperuricemia was significantly associated with low birth weight [aOR: 3.222 (95% CI: 1.098, 10.393)], caesarean section [aOR: 2.281 (95% CI: 1.084, 7.568)] and severe diastolic pressure at birth [aOR: 3.517 (95% CI: 1.123, 11.939)]. Conclusion: hyperuricemia in pre-eclampsia was significantly associated with both maternal (caesarean section and severe hypertension) and neonatal (low birth weight) adverse outcomes. Hyperuricemia seems clinically useful in predicting pregnancy outcomes, especially in preterm pre-eclampsia. Further longitudinal study is recommended in exploring the clinical significance of maternal uric acid levels and pregnancy outcomes in pre-eclampsia.

Advancing hypertensive disorders of pregnancy management: insights from the 5th preeclampsia scientific symposium in Ghana.

The 5th Preeclampsia Scientific Symposium (PSS2023) organized by Action on Preeclampsia (APEC) Ghana was themed: 'Realign, Refocus: Improving outcomes of Hypertensive Disorders of Pregnancy through Shared Decision Making, Research & Quality of Care'. It took place on the 18th and 19th of May 2023 at the Ghana College of Physicians and Surgeons (GCPS), Accra Ghana. This transdisciplinary symposium brought together a national representation of experts, policy makers, scientists, and healthcare professionals to discuss key priorities, opportunities, approaches, and strategies to improve the maternal and perinatal outcomes of hypertensive disorders of pregnancy (HDP) in Ghana and the sub-region. The symposium centered around three key themes: realigning/refocusing patient-doctor decision making processes to improve outcomes of HDP; realigning/refocusing clinical care to improve outcomes of HDP; and leveraging on research to predict, recognize and manage high-risk women.This report summarizes insights from the diverse presentations and discussions held at the #PSS2023. This will form a roadmap for future research, policy, and interventions to improve outcomes of HDP in Ghana and the sub-region. The symposium provided a wealth of evidence and knowledge from various experts, highlighting the need for women-centered care, equitable re-allocation of resources, multi-sectoral and innovative approaches, capacity strengthening. Other highlights include knowledge base development and increased stakeholder and community engagement with an overall aim of improving outcomes of HDP. The symposium also fostered inclusivity, welcoming survivors of HDP and their families at a scientific platform. They provided invaluable insights into the challenges faced and the lived experiences of those affected by the disease. Trainees and students also benefited from the symposium as it provided networking opportunities with fellow researchers, and a front row to gaining insights into cutting-edge research in Ghana.

Association between endothelial nitric oxide synthase (eNOS) gene variants and nitric oxide production in preeclampsia: a case-control study in Ghana.

Evidence suggests that a major cause of PE is endothelial dysfunction emanating from the reduced bioavailability of Nitric oxide (NO). Variants of endothelial nitric oxide synthase (eNOS) gene may lead to decreased NO levels. We explored the association between eNOS gene variants and nitric oxide levels among preeclamptic women in the Ghanaian population. This case-control study included 75 preeclamptic women and 75 healthy normotensive pregnant women attending antenatal care at the Nkawie-Toase Government Hospital, Ghana. A well-structured questionnaire was used to collect socio-demographic, obstetric and clinical data. Blood was obtained for DNA extraction; the gene variants were determined using PCR and RFLP. Preeclamptic women had significantly lower NO concentration compared to the normotensives (p < 0.0001) and was significantly different between VNTR variants (p < 0.0001). A significant difference in VNTR intron 4 distribution was also observed between the preeclamptic and normotensive women with 4c4c" (12.0%) and "4a4c" (1.3%) genotypes found predominantly in preeclamptic women (p < 0.0001). There was significantly higher distribution of "TC" genotype in preeclamptic women (44.0%) compared to normotensives (22.7%) (p = 0.019). However, possessing "4a4b" (cOR: 0.17, 95% CI 0.04-0.64) and "4b4b" (cOR: 0.09, 95% CI 0.02-0.38) significantly decreased the likelihood of experiencing preeclampsia by 83% and 91% respectively. Nitric oxide is reduced in preeclamptic women. NO levels in preeclampsia are altered by VNTR intron 4 variants but not T786C variants. Possessing VNTR intron 4 "4b" allele decreases the risk of PE while the "4c" allele increases the risk of PE. There is the need for eNOS variant screening and nitric oxide estimation among pregnant women for early prediction of women at risk of preeclampsia.

Evaluating circulating soluble markers of endothelial dysfunction and risk factors associated with PE: A multicentre longitudinal case control study in northern Ghana.

Serpin E1/PAI-1, N-terminal pro-brain natriuretic peptide (NTpro-BNP) and neuropilin-1 are markers which have been associated with endothelial dysfunction. However, data on the levels of these markers in PE is limited. The limited data on the pathophysiology of PE in relation to these markers necessitated the study. This was a multicentre case-control study conducted at the Obstetrics and Gynaecology Department of the Tamale Teaching Hospital, the Bawku Presbyterian Hospital and the Bolgatanga Regional Hospital. Out of 520 consenting pregnant women, 127 pregnant women met the inclusion criteria (53 with PE and 74 controls) and were included in this study. Venous, placental, cord and peripheral blood were collected for biomarker assay, haematological parameters and placental parasite determination. Placental tissue sections were obtained for placental malaria and histopathological lesions associated with hypoperfusion. Maternal heart rate and foetal umbilical artery Doppler impedance indices; resistance index (RI) and systolic diastolic (SD) ratio were determined to confirm utero-placental hypoperfusion. Significantly higher proportions of foeto-maternal complications; eclampsia, low birth weight (LBW), neonatal intensive care unit admissions (NICU), intrauterine growth restriction (IUGR), caesarian deliveries and early gestational age at delivery were associated with PE. Women with PE had lower concentrations of platelet (p = 0.02) whereas red cell distribution width (RDW) was markedly elevated (p = 0.01). NTPro-BNP concentration was markedly elevated (p = 0.01) in women with PE whereas neuropilin-1 concentration was lower (p = 0.03) compared to the non-PE group. Maternal heart rate was elevated in women with PE and Doppler resistance indices (RI and SD) were significantly elevated in foetuses of PE women than foetuses of the controls. Placental mal-perfusion lesions were higher in women with PE compared to the non-PE group. Women with PE had increased risk of adverse foeto-maternal complications, significantly associated with placental mal-perfusion lesions, had reduced platelet concentration and elevated RDW-CV levels. NTPro-BNP, RI and SD are elevated in women with PE whereas neuropilin-1 concentration is reduced. Significant changes in these pathological variables in PE women is indicative of significant derangement in endothelial function culminating in adverse maternal and perinatal outcomes of pregnancy.

Risk factors for the development of new-onset and persistent postpartum preeclampsia: A case-control study in Ghana.

BACKGROUND: Postpartum preeclampsia has been implicated in increasing hospital re-admissions, maternal morbidity, and mortality worldwide. The knowledge of the risk factors of postpartum preeclampsia would be helpful in formulating strategies to aid in the prevention, early diagnosis, and timely treatment of this disorder. Thus, this study aimed to identify the risk factors associated with the development of new-onset postpartum preeclampsia and persistent postpartum preeclampsia in the Ghanaian setting. METHODS: This case-control study was conducted at the Obstetrics and Gynecology units of Komfo Anokye Teaching Hospital and the Kumasi Regional Hospital, both located in the Ashanti Region of Ghana. A total of 65 postpartum preeclamptic women (33 new-onset postpartum preeclampsia and 32 persistent postpartum preeclampsia) and 65 normotensive postpartum mothers were recruited from 48 h to 6 weeks post-delivery. Questionnaires were administered to assess the socio-demographic, lifestyle, obstetric characteristics, and past medical history of the study participants. RESULTS: Physical inactivity (p < 0.0001), infrequent antenatal visits (p < 0.0001), analgesic use (p < 0.0001), and cesarean delivery (p = 0.021) were significantly associated with both the new-onset postpartum preeclampsia and persistent postpartum preeclampsia. Contraceptive use was significantly associated with the development of new-onset postpartum preeclampsia (p < 0.0001) while women with low-birthweight babies are also at high risk of developing persistent postpartum preeclampsia (p < 0.0001). CONCLUSION: Physical inactivity, infrequent antenatal visits, analgesic use, contraceptive use, and cesarean delivery are major predisposing risk factors for the development of postpartum preeclampsia. Screening using these risk factors, close monitoring and follow-up observation of women after delivery would be beneficial in identifying and managing postpartum preeclampsia.

Hematobiochemical variability and predictors of new-onset and persistent postpartum preeclampsia.

Preeclampsia (PE) can occur antepartum or postpartum. When it develops de novo after childbirth, it is termed new-onset postpartum PE (NOPPE). Often, antepartum PE disappears after childbirth; however, in some women it persists after childbirth. This form of PE is termed persistent PE (PPE). Thus, there are two forms of postpartum PE: NOPPE and PPE. The pathogenesis and pathophysiology of these diseases have not been fully characterized, and whether NOPPE and PPE are different or similar pathological conditions remains unexplored. Thus, we aimed to compare the haematological and biochemical characteristics of NOPPE and PPE, predict the occurrence of new-onset PE and identify lifestyles that predispose women to postpartum PE. A total of 130 women comprising 65 normotensive postpartum women, 33 NOPPE and 32 PPE women were recruited for this hospital-based case-control study. The socio-demographic and lifestyle characteristics of the participants were obtained through well-structured questionnaires. Haematological and biochemical indices were measured using automated analysers and ELISA. The prevalence of postpartum PE was 11.9%. Dyslipidaemia (p = < 0.0001), hypomagnesaemia (p = < 0.001), elevated serum levels of ALT, AST (p = < 0.0001), sVCAM-1 (p = < 0.0001) and sFlt-1 (p = < 0.0001) were more prevalent and severe in the PPE than in the NOPPE. Sedentary lifestyle was common among both groups of hypertensive women. Elevated ALT and AST were significant predictors of NOPPE. These findings indicate that preeclampsia exists after childbirth in a high percentage of women. NOPPE and PPE are different pathological conditions that require different clinical management. Combined glucose, lipid and liver assessment could be useful in predicting postpartum PE.

Urinary PCA3 a Superior Diagnostic Biomarker for Prostate Cancer among Ghanaian Men.

Introduction: Prostate cancer is one of the most commonly diagnosed cancers in men. Prostate-specific antigen (PSA) has been the biomarker of choice for screening and diagnosis of prostate cancer. However, inefficiencies exist with its diagnostic capabilities. This study thus evaluated the diagnostic and prognostic potential of urinary PCA3 as an alternative biomarker for prostate cancer in the Ghanaian population. Methods: A hospital-based cross-sectional study was conducted at the Urology Department of the 37 Military Hospital, Accra, Ghana. A total of 237 participants aged 40 years and above with any form of suspected prostate disorder were recruited into the study after written informed consent was obtained. Total serum PSA levels was measured using the electrochemiluminescence method and transrectal ultrasound-guided systematic core needle biopsies were obtained from each study participant. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracies of serum PSA, DRE, and PCA3 as diagnostic tools for prostate cancer. These three diagnostic tools were also evaluated in various combinations to ascertain the combinations with the best diagnostic accuracy. Results: Prostate cancer was diagnosed in 26.6% of the participants. Benign prostate hyperplasia and prostatitis were diagnosed in 48.5% and 24.9% participants, respectively. DRE had a sensitivity of 93.7% and a specificity of 12.1%. PSA had a sensitivity of 92.1% and a specificity of 16.1%. PCA3 had a sensitivity of 57.1% and a specificity of 85.6% and showed a better accuracy (AUC = 83.0) compared to PSA (AUC = 60.0) and DRE (AUC = 65.0) as individual diagnostic tools. The combination of DRE+PCA3 score had the best diagnostic accuracy (AUC = 0.80) with a sensitivity and specificity of 60.3% and 80.5%, respectively. Conclusion: The urinary PCA3 assay showed a better diagnostic performance compared to serum PSA and DRE. PCA3 as a stand-alone and in combination with DRE could be a suitable complimentary marker in diagnosis and management of prostate cancer.

Polymorphism of protein tyrosine phosphatase non-receptor type 22 and protein arginine deiminase 4 gene among Ghanaian rheumatoid arthritis patients: A case-control study.

AIM: Rheumatoid arthritis (RA) is an autoimmune disease which affects millions of lives globally characterized by chronic inflammation in the joints of the body. There is no known cause for RA; however, genetic predisposition has been associated with its occurrence. The association between genetic predisposition and RA has been reported largely among Caucasians and Asians. However, few studies with limited data have reported genome-wide association studies of RA in Africa, especially in Ghana. In addition, there is genetic heterogeneity that exists geographically among different populations. This study therefore investigated the association of protein arginine deiminase type 4 (PAD4) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) single nucleotide polymorphisms with susceptibility of RA among Ghanaians. METHODS: This case-control study included 75 RA patients and 75 healthy controls from the Komfo Anokye Teaching Hospital in Ghana. Validated questionnaires were used to obtain demographic data, and blood samples were collected and processed for DNA and polymerase chain reaction analysis. Statistical analysis was done using SPSS version 25.0. RESULTS: PTPN22 demonstrated a 100% minor allele frequency (GG) in both cases and healthy controls; however, an association could not be made for PTPN22 polymorphism with susceptibility of RA when comparing cases to controls. The homozygous minor allele (GG) of PAD4 was absent in the population. CONCLUSION: PAD4 polymorphism was absent, while PTPN22 was present in the Ghanaian population. The association between PTPN22 (rs2476601) and PAD4 (rs2240340) with RA susceptibility could not be established, thus may not contribute as risk factors for RA in the Ghanaian population.

Foeto-maternal complications associated with low birth weight: A prospective multicenter study in northern Ghana.

OBJECTIVE: The study evaluated the socio-demographic characteristics, obstetric variables and foeto-maternal complications associated with low birth weight (LBW) in order to provide better treatment and management options. METHODS: The prospective study conducted from February, 2019 to June, 2020 recruited 312 primigravid pregnant women who reported for antenatal care in three tertiary referral hospitals in northern Ghana. Their socio-demographic, obstetric and adverse foeto-maternal outcome information were obtained with a well-structured questionnaire according to the World Health Organisation (WHO) guidelines. Participants' blood samples were collected for haematological tests. Odds ratio [OR, 95% confidence interval (CI)] for the association between socio-demographic, obstetric characteristics, foeto-maternal complications and haematological tests in relation to LBW were assessed using logistic regression model. RESULTS: This study reported a LBW prevalence of 13.5%. Increasing maternal systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 1st visit, before and after delivery significantly increased the odds of LBW. Preterm delivery (PTD<37 weeks) (COR = 9.92, 95% CI (4.87-2020), p<0.001), preeclampsia (PE) (COR = 5.94, 95% CI (2.96-11.94), p<0.001), blood transfusion (COR = 14.11, 95% CI (2.50-79.65), p = 0.003), caesarian delivery (COR = 3.86, 95% CI (1.96-7.58), p<0.001) and male sex neonates (COR = 2.25, 95%CI (1.14-4.47), P = 0.020) presented with increased odds of LBW. Increasing gestational age at delivery presented with 28% reduced odds of LBW (COR = 0.72, 95% CI (1.12-4.40), P = 0.023). Upon controlling for potential confounders in multivariate logistic regression, only gestational age at delivery (AOR = 0.67, 95% CI (0.47-0.96), P = 0.030) remained significantly associated with reduced odds of LBW. CONCLUSION: This study found that high blood pressure at 1st visit, before and after delivery results in increased chances of delivering a baby with LBW. Furthermore, PTD<37 weeks, having PE in current pregnancy, and male sex potentiate the risk of LBW. On the other hand, increasing gestational age reduces the risk of LBW. Thus, we recommend that midwives should intensify education to pregnant women on the benefits of regular ANC visits to aid in the early detection of adverse foeto-maternal complications. We also recommend proper clinical management of pregnancies associated with an elevated blood pressure at registration. Also, maternal intrapartum blood pressure measurement could be used to predict LBW in low resourced settings.

Nexus between constructs of social cognitive theory model and diabetes self-management among Ghanaian diabetic patients: A mediation modelling approach.

The promotion of Diabetes Self-Management (DSM) practices, education, and support is vital to improving the care and wellbeing of diabetic patients. Identifying factors that affect DSM behaviours may be useful to promote healthy living among these patients. The study assessed the determinants of DSM practices among Type 2 diabetes mellitus (T2DM) patients using a model-based social cognitive theory (SCT). This cross-sectional study comprised 420 (T2DM) patients who visited the Diabetic Clinic of the Komfo Anokye Teaching Hospital (KATH), Kumasi-Ghana. Data was collected using self-structured questionnaires to obtain socio-demographic characteristics, T2DM-related knowledge, DSM practices, SCT constructs; beliefs in treatment effectiveness, level of self-efficacy, perceived family support, and healthcare provider-patient communication. Path analysis was used to determine direct and indirect effects of T2DM-related knowledge, perceived family support, and healthcare provider service on DSM practices with level of self-efficacy mediating the relationships, and beliefs in treatment effectiveness as moderators. The mean age of the participants was 53.1(SD = 11.4) years and the average disease duration of T2DM was 10 years. Most of the participants (65.5%) had high (>6.1mmol/L) fasting blood glucose (FBG) with an average of 6.93(SD = 2.41). The path analysis model revealed that age (p = 0.176), gender (p = 0.901), and duration of T2DM (p = 0.119) did not confound the relationships between the SCT constructs and DSM specified in the model. A significant direct positive effect of family and friends' support (Critical ratio (CR) = 5.279, p < 0.001) on DSM was observed. Self-efficacy was a significant mediator in this relationship (CR = 4.833, p < 0.001). There were significant conditional indirect effects (CIE) for knowledge of T2DM and family and friends' support at medium and high levels of belief in treatment effectiveness (p < 0.05) via level of self-efficacy on DSM practices. However, no evidence of moderated-mediation was observed for the exogenous variables on DSM. Diabetes-related knowledge of T2DM, family and friends' support, level of self-efficacy, and belief in treatment effectiveness are crucial in DSM practices among Ghanaian T2DM patients. It is incumbent to consider these factors when designing interventions to improve DSM adherence.

Evaluation of a real-time recombinase polymerase amplification assay for rapid detection of Schistosoma haematobium infection in resource-limited setting.

Accurate diagnosis of urogenital schistosomiasis is vital for surveillance/control programs as well as achieving the WHO 2012-2020 road map for the total eradication of schistosomiasis. Recombinase polymerase amplification (RPA) has emerged as a rapid and simple molecular tool adaptable for fewer resources with diagnostic accuracy similar to polymerase chain reaction (PCR). This rapid molecular assay employs the use of enzymes for the amplification of nucleic acid taget at a constant temperature. The aim of this study was to validate a real-time RPA assay targeting the Dra 1 repittitive sequence of Schistosoma (S.) haematobium and evaluate its use in urogenital schistosomiasis diagnosis. S. haematobium Dra 1 molecular DNA standard was applied to determine the assay's analytical sensitivity. DNA extracts of S. haematobium, other Schistosoma species, protozoa and bacteria species were used to determine the specificity of the RPA assay. Clinical performance of the assay was validated with a panel of 135 urine samples from volunteers of schistosomiasis endemic communities. The developed assay was evaluated with urine samples extracted by just boiling and with SpeedXtract® DNA extraction kit. A specific fragment of S. haematobium Dra 1 repetitive sequence was amplified within 15 minutes at a constant 42˚C using the developed S. haematobium RPA assay. The detection limit was 15 copies of Dra1 molecular DNA standard per reaction. There was no cross-reaction with other protozoan and bacterial species except Schistosoma species, S. mansoni and S. japonicum. Using 135 urine samples, Schistosoma RPA assay had a clinical sensitivity and specificity of 98.4% (95% CI, 91.6-100) and 100% (95% CI, 94.9-99) respectively when compared to S. haematobium Dra 1 qPCR assay. The diagnostic performance of S. haematobium real-time RPA assay was not affected by the use of crude DNA extracted samples. The S. haematobium RPA assay can serve as an alternative to PCR, especially in low resource settings.

A review of the racial heterogeneity of breast cancer stem cells.

Breast Cancer Stem Cells has become the toast of many breast cancer investigators in the past two decades owing to their crucial roles in tumourigenesis, progression, differentiation, survival and chemoresistance. Despite the growing list of research data in this field, racial or ethnic comparison studies on these stem cells remain scanty. This study is a comparative racial analysis of putative breast cancer stem cells. Research articles on the clinicopathological significance of breast cancer stem cells within a period of 17 years (2003-2020) were reviewed across 5 major races (African/Black American, Asian, Caucasian/White, Hispanic/Latino, and American). The associations between the stem cells markers (CD44+/CD24-/low, BMI1, ALDH1, CD133, and GD2) and clinicopathological and clinical outcomes were analysed. A total of 40 studies were included in this study with 50% Asian, 25% Caucasian, 10% African, 5% American and 2.5% Hispanic/Latino, and 7.5% other mixed races. CD44+/CD24-/low has been associated with TNBC/Basal like phenotype across all races. It is generally associated with poor clinicopathological features such as age, tumour size, lymph node metastasis and lymphovascular invasion. In Asians, CD44+/CD24-/low was associated with DFS and OS but not in Caucasians. ALDH1 was the most studied breast CSC marker (40% of all studies on breast cancer stem cell markers) also associated with poor clinicopathological features including size, age, stage, lymph node metastasis and Nottingham Prognostic Index. ALDH1 was also associated with DFS and OS in Asians but not Caucasians. Racial variations exist in breast cancer stem cell pattern and functions but ill-defined due to multiple factors. Further research is required to better understand the role of breast CSC.

Psychological impact of COVID-19 on diabetes mellitus patients in Cape Coast, Ghana: a cross-sectional study.

INTRODUCTION: COVID-19 pandemic has had a greater psychological impact on patients with chronic ailments such as diabetes mellitus, tuberculosis, and HIV/AIDS compared to those without chronic conditions. We explored the psychological impacts of COVID-19 among people living with diabetes mellitus in Ghana. METHODS: this study employed a hospital-based cross-sectional design involving 157 diabetes mellitus patients aged 20 years and above. We assessed diabetes distress by the seventeen-item diabetes stress (DDS17) scale and COVID-19 worries by 3 specific benchmarks: "worry about overly affected due to diabetes if infected with COVID-19", "worry about people with diabetes characterized as a risk group" and "worry about not able to manage diabetes if infected with COVID-19". A close-ended questionnaire was used in data collection. RESULTS: of 157 diabetic patients interviewed, the majority had type 2 diabetes mellitus with known complications and only 42.7% were managing COVID-19 symptoms. The participants showed moderate to high level of COVID-19 specific worry, moderate fear of isolation, and low level of diabetes-associated distress. About 33.8% of the study population expressed a sense of worry towards the pandemic. The logistic regression showed that age, employment status, and presence of other chronic diseases were significantly associated with worries about being overly affected if infected with COVID-19 due to their diabetes status. Age and sex were associated with worries about people with diabetes being characterized as a risk group and age, sex and employment status were associated with participants who were worried about not being able to manage diabetes if infected with COVID-19. CONCLUSION: the general trend indicates a sense of worry among diabetes patients during the COVID-19 pandemic which is associated with poorer psychological health. Clients' education and counseling on COVID-19 are necessary to address some of their concerns to minimize the level of anxiety and emotional stress in these individuals.