Thyroid hormone status in Ghanaian patients with chronic kidney disease

Introduction: There is limited data on the prevalence of thyroid dysfunction in Ghanaian individuals with chronic kidney disease (CKD). Studies exploring the effect of thyroid hormones on renal function decline are also scanty. Unrecognized thyroid dysfunction in CKD may increase the burden of adverse health outcomes. The aim of this study was to determine thyroid hormone status and lipid profiles in patients with CKD attending the Renal Unit of the Korle-Bu Teaching Hospital. Methods: 60 clinically euthyroid patients with CKD, and 65 clinically euthyroid subjects without CKD were recruited for this study. Estimation of effective glomerular filtration rate (eGFR) was done using the 4-variable Modification of Diet in Renal Disease (MDRD) formula with subsequent staging of CKD (stages 2-4). Collected venous blood samples from all study participants were analyzed for creatinine, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) and triglycerides (TG). Results: Levels of TC, HDL, LDL, and TSH levels did not differ significantly between the two study groups. However, TG, VLDL, FT3 and FT4 levels were significantly higher in CKD patients than in the control group. TC, TG, HDL, LDL, VLDL and TSH levels were not significantly different between stages of CKD in study subjects, although FT4 and FT3 levels were significantly different between all stages of CKD. Conclusion: Higher levels of FT3 and FT4 but not TSH, are associated with the incidence of CKD and eGFR decline in Ghanaian CKD patients

Thyroid hormone profile in preeclampsia patients: a case control study

Objective: Preeclamptic women are reported to have a higher incidence of thyroid dysfunction that correlates with the severity of preeclampsia. The aim of this study was to assess thyroid hormone profiles in in pregnant women with preeclampsia and gestational hypertension and the risk for thyroid dysfunction.Methods: In this study, age-matched pregnant females in the second trimester of pregnancy, diagnosed with preeclampsia (PE), gestational hypertension (GH), as cases, and apparently healthy normotensive (NT) pregnant woman as controls were recruited. Blood samples were drawn for the assessment of thyroid hormone (TSH, FT3 and FT4) levels and thyroid dysfunction.Results: Out of the total of 133 pregnant women recruited for this study, sub-clinical hypothyroidism was the only thyroid dysfunction common to all study groups, with a prevalence of 3.3% in both PE and NT groups, and 4.3% in the GH group. 1% of women in the PE group had sub-clinical hyperthyroidism, compared to 3.3% in the NT group. Although TSH and FT3 were elevated in normotensives, mean differences between the three groups were not statistically significant. However, mean FT4 levels in the GH group (12.99 ± 1.24) and PE group (12.33 ± 2.26), when compared to the control group (11.55 ± 1.94), were significantly higher (p < 0.05).Conclusion: Undiagnosed subclinical hypothyroidism was found in all the categories of pregnant women studied, which if uncontrolled, could increase the risk of pregnancy-related complications, especially in pregnant women with preeclampsia and gestational hypertension

Immune responses to P falciparum antibodies in symptomatic malaria patients with variant hemoglobin genotypes in Ghana

Abstract Background Haemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite (Plasmodium falciparum surface protein 230 (Pfs230) and Plasmodium falciparum erythrocyte binding antigen 175 region-3 (PfEBA175-3R)) and vector (on the An. gambiae Salivary Gland Protein-6 peptide 1 (gSG6-P1)) antigens in individuals with variants Hb genotypes. This study assessed antibody (IgG) responses against malaria parasite, Pfs230 and PfEBA175-3R and vector, gSG6-P1 in febrile individuals with variant Hb genotypes. Methods The study was conducted on symptomatic malaria patients attending various healthcare facilities throughout Ghana. Microscopy and ELISA were used to determine the natural IgG antibody levels of gSG6-P1, PfEBA175-3R & Pfs230, and Capillarys 2 Flex Piercing was used for Hb variants determination. Results Of the 600 symptomatic malaria patients, 50.0% of the participants had malaria parasites by microscopy. The majority 79.0% (398/504) of the participants had Hb AA, followed by HbAS variant at 11.3% (57/504) and HbAC 6.7% (34/504). There were significantly (p < 0.0001) reduced levels of gSG6-P1 IgG in individuals with both HbAC and HbAS genotypes compared to the HbAA genotype. The levels of gSG6-P1 IgG were significantly (p < 0.0001) higher in HbAS compared to HbAC. Similarly, Pfs230 IgG and PfEBA-175-3R IgG distributions observed across the haemoglobin variants were significantly higher in HbAC relative to HbAS. Conclusion The study has shown that haemoglobin variants significantly influence the pattern of anti-gSG6-P1, Pfs230, and PfEBA-175 IgG levels in malaria-endemic population. The HbAS genotype is suggested to confer protection against malaria infection. Reduced exposure to infection ultimately reduces the induction of antibodies targeted against P. falciparum antigens

Prospecting for Breast Cancer Blood Biomarkers: Death-Associated Protein Kinase 1 (DAPK1) as a Potential Candidate

Background. Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. Aim. To investigate DAPK1 as a blood biomarker for breast cancer. Methods. Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p≤0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. Conclusion. DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development

Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women

Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p-value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young ( <35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade (r = 0.696, p < 0.05) but weakly correlated with tumour stage (r = 0.420, p < 0.05). Patient's age correlated with DAPK1 concentration (r = 0.393, p < 0.05). DAPK1 serum levels weakly correlated with cancer duration (r = 0.098, p = 0.27) and tumour size (r = 0.40, p < 0.05). Serum concentration of Vimentin and DAPK1 are elevated in Ghanaian breast cancer patients. This may be partly responsible for aggressive nature of the disease among the population. Vimentin and DAPK1 should be explored further as potential breast cancer biomarkers in African

Lineage specific markers of influenza B HA gene.

Multiple sequence alignment was carried out using ClustalW in BioEdit with a boostrap replicates of 1000 in line with Edgar [16]. Influenza B/Brisbane/60/2008 was used as the reference sequence for B/Victoria lineages while B/Wisconsin/1/2010, Clade 3 and B/Massachusetts/2/2012, Clade 2 were used as the reference sequence for B Yamagata lineages. Influenza B virus lineage-specific markers (nts 522, 540–542, 548, 549, 555, 558 and 568) are shown in yellow, whereas the clade specific markers (nts 538, 562 and 589) have been highlighted as green.</p

Details of primers used for this research.

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Phylogenetic analysis of influenza B Victoria lineage using HA genes.

Bootstrap values over 80% are indicated on the tree. Red represents the WHO vaccine candidate virus genome, pink represents reference Ghanaian specimens sequenced at the Francis Crick Institute, blue represents the sequences obtained from our retrospective analysis, green represents the deletion sub-group, Amino acid changes in black represent those within HA1, with violet representing changes in the HA2.</p

A sample gel image.

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A schematic of primer locations on the influenza B HA gene.

A schematic representation of the influenza B HA gene showing overlapping fragments and their expected sizes in base pairs. All sixteen primers and their corresponding eight fragments are shown. Red and green colors indicate fragment numbers and expected sizes, respectively.</p