Colorectal cancer disease profile and treatment patterns at an urban tertiary hospital in Rwanda.

Background: The incidence of colorectal cancer (CRC) in sub-Saharan Africa (SSA) is rising, due to improving cancer registration efforts on one hand and an increasing westernisation of diets and lifestyle on the other as well as increasing rates of comorbidities. Methods: We present data for the clinical characteristics, pathology, treatments received, and survival outcomes of patients diagnosed with CRC at King Faisal Hospital (KFH) between January 2019 and May 2023. KFH is an urban tertiary hospital in Rwanda that provides chemotherapy and surgery to cancer patients. The data were extracted from electronic medical records, imaging and histopathology reports from the patient's time of diagnosis. We plotted Kaplan-Meier estimation of survival, defined as the time from presentation to death, within the study period (2019-2023). Results: Seventy-four patients diagnosed with CRC with complete information were identified in the KFH oncology records. The mean age at diagnosis was 54.6 years, with ages ranging between 22 and 81 years. At diagnosis, 24 (32.4%) patients were less than 50 years old and 29 (39.2%) were females. The rectum (36.5%) was the most common tumour location, and 58.1 tumours were left-sided. Most patients presented with Stage III (41.9%) or IV (35.1%) disease. Adenocarcinoma was the most common histological type (98.6%) including adenocarcinoma not otherwise specified (NOS) (86.5%), mucinous adenocarcinoma (10.8%), signet ring cell carcinoma (1.4%) and followed by squamous cell carcinoma (1.4%). In terms of treatment, 19 (25.7%) patients received only chemotherapy, 43 (58.1%) patients received neo-adjuvant or adjuvant chemotherapy, 9 (12.2%) of patients received both neo-adjuvant and adjuvant chemotherapy, 49 patients (66.2%) underwent surgery and 17 (23%) patients also received radiation. At the end of the follow up period, 63 (85.1%) patients remained in surveillance, 10 (13.5%) patients died, and 1 (1.3%) patient was lost to follow up. Mean overall survival was 45.5 (SD ± 2.0) months. Conclusion: CRC patients presented at an advanced stage and required complex treatment regimens at KFH. Further epidemiologic and molecular research is needed to characterise CRC incidence and presentation at a national level in Rwanda as increasing westernisation continues to change the face of CRC in urban areas of SSA.

Awareness, attitudes towards genetic diseases and acceptability of genetic interventions among pregnant women in Burera district, Rwanda.

Approximately 3% of all pregnancies are associated with conditions linked with disability, either mild or severe congenital diseases. This is a consequence of environmental and genetic exposures. Complications and poor management of these diseases arise due to limited knowledge, awareness about the disease, and limited resource settings. The current study assessed awareness, attitudes towards genetic diseases, and acceptability of genetic interventions among pregnant women. This was a cross-sectional study that was conducted among 664 pregnant women in six selected health centers in Burera district using a detailed questionnaire. The data were analysed using STATA Version 15 and entailed univariate, bivariate, and multivariable analyses. The level of significance was set at p < 0.05. The mean age of the study participants was 28, and most of them were in the age range of 21 to 30 (50%). Most of the participants were married (91.1%), Christians (98.4%), farmers (92.7%), used public health coverage (96.6%), and attained primary studies (66.1%). The findings from this study showed that among participants, adequate awareness was at 29.5%, inadequate awareness at 70.5%, positive attitudes at 87.1%, negative attitudes at 12.9%, high acceptability at 97.1%, and low acceptability at 2.9%. While there was no significant difference between awareness and acceptability, there was a statistical significance between attitudes towards genetic diseases and acceptability towards the use of genetic services (p < 0.01). There was no statistical significance between sociodemographic or obstetric characteristics and the acceptability of genetic interventions. Participants with positive attitudes towards genetic diseases were more likely to develop a high level of acceptability and willingness towards the use of genetic interventions (OR: 5.3 [2.1-13.5]). Improving awareness about genetic diseases and establishing genetic interventions in healthcare facilities are needed.

Immunohistochemistry versus PCR Technology for Molecular Subtyping of Breast Cancer: Multicentered Expereinces from Addis Ababa, Ethiopia.

The application of immunohistochemistry (IHC) for molecular characterization of breast cancer (BC) is of paramount importance; however, it is not universally standardized, subject to observer variability and quantifying is a challenge. An alternative molecular technology, such as endpoint reverse transcription (RT)-PCR gene expression analysis, may improve observer variability and diagnostic accuracy. This study was intended to compare IHC with the RT-PCR based technique and assess the potential of RT-PCR for molecular subtyping of BC. In this comparative cross-sectional study, 54 BC tissues were collected from three public hospitals in Addis Ababa and shipped to Gynaecology department at Martin-Luther University (Germany) for laboratory analysis. Only 41 samples were qualified for IHC and RT-PCR investigation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 protein expression analysis. Kappa statistics was used to assess the concordance between the two techniques. The overall percent agreement between RT-PCR and IHC was 68.3% for ER (positive percent agreement [PPA] 71.1%; negative percent agreement [NPA] 33.3%), 39.0% for PR (PPA 14.3%; NPA 92.3%), and 82.9% for HER2 (PPA 62.5%; NPA 87.9%). Cohen's κ-values of 0.018 (< 0.20), 0.045 (< 0.200), and 0.481 (0.41-0.60) were generated for ER, PR, and HER2, respectively. Concordance for molecular subtypes was only 56.1% (23/41) and 0.20 kappa value. IHC and endpoint RT-PCR techniques have shown to be discordant for 43% samples. Molecular subtyping using endpoint RT-PCR was fairly concordant with IHC. Thus, endpoint RT-PCR may give an objective result, and can be applied for BC subtyping.

Estimating prognostic relevant cutoff values for a multiplex PCR detecting BCR::ABL1 in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy in resource-limited settings.

The prognosis of chronic myeloid leukemia (CML) on tyrosine kinase inhibitor (TKI) treatment is based on the quantification of BCR::ABL1 fusion gene transcript copy number, harmonized by an international scale (IS) based on TaqMan-based real-time quantitative PCR (qRT-PCR). In Ethiopia, as in most low- and middle-income countries (LMICs), access to standard diagnostic, follow-up, and prognostic tools is very limited, and it has been challenging to strictly follow international guidelines. This seriously compromises clinical outcome, despite the availability of TKIs through the Glivec International Patient Assistance Program (GIPAP). Multiplex PCR (mpx-PCR), conventionally regarded as a "screening tool," offers a potential solution to this problem. A total of 219 samples from confirmed CML patients were assayed. In reference to qRT-PCR, the AUC of ROC curve for mpx-PCR was 0.983 (95% CI: 0.957 to 0.997). At the optimum cut-off value, equivalent to BCR::ABL1 (IS) transcript copy number of 0.6%, the specificity and sensitivity were 93% and 95%, respectively, with 94% accuracy. Albeit the sensitivity and accuracy of mpx-PCR decrease below the optimum cutoff of 0.6% (IS), the specificity at 0.1% (IS) was 100%, making it an attractive means to rule-out relapse and drug non-adherence at later stages of treatment, which is particularly an issue in a low income setting. We conclude that the relative simplicity and low cost of mpx-PCR and prognostic relevant cutoff values (0.1-0.6% IS) should allow its use in peripheral clinics and thus maximize the positive impact of TKIs made available through GIPAP in most LMICs.

Detection and isolation of intestinal muscle relaxant substances from the root of Taverniera abyssinica A. Rich.

ETHNOPHARMACOLOGICAL RELEVANCE: In Ethiopian traditional medicine the root of Taverniera abyssinica A.Rich is known as a remedy for sudden gastrointestinal cramping and fever. In this study we have isolated and identified the bioactive principle of Taverniera abyssinica that exerts effects on isolated smooth muscle tissues of the rabbit duodenum and guinea-pig ileum. AIM OF THE STUDY: To isolate and purify the bioactive principle from the root of Taverniera abyssinica A.Rich by bioassay-guided fractionation, HPLC purification and masspectrometry, with further investigation of its bioactivity on isolated smooth muscle strips. MATERIALS AND METHODS: Roots of Taverniera abyssinica A.Rich extracted in 75% methanol/water were fractioned with a reverse phase column and then subjected to HPLC purification. Each fraction collected from the HPLC was tested for its bioactivity using electric field stimulation-evoked contractions of the rabbit duodenum and guinea-pig ileum. Finally, detailed structural analysis of the fraction displaying significant bioactivity was made by mass spectrometry. RESULTS: Through bioassay-guided fractionation and HPLC purification the bioactive fractions were identified. These were tested for bioactivity on isolated smooth muscle strips which showed about 80% inhibition of contractions evoked by electric field stimulation. These compounds were identified as formononetin, afrormosin and tectorigenin by using masspectrometry applying relevant standards for detection. CONCLUSION: The traditionally claimed smooth muscle-relaxing effect of the roots of Taverniera abyssinica A.Rich is essentially due the three isolated and purified the two isoflavones formononetin, afrormosin as well as the metoxyisoflavone tectorigenin, along with possibly other not yet purified bioactive substances, however with similar smooth muscle-relaxing properties.

Red blood cell folate level and associated factors of folate insufficiency among pregnant women attending antenatal care during their first trimester of pregnancy in Addis Ababa, Ethiopia.

Objective: Folate is an essential vitamin for de novo DNA synthesis and cell proliferation. Folate insufficiency at the time of conception and during the first trimester of pregnancy is associated with unintended pregnancy and birth outcomes, particularly neural tube defects. Hence, this study aimed to assess folate status and associated factors of folate insufficiency among pregnant women attending antenatal care during their first trimester of pregnancy in Addis Ababa, Ethiopia. Materials and methods: A cross-sectional study was conducted from 8 August 2017 to 3 January 2018 in Addis Ababa. In this study, 160 participants were enrolled via the convenience sampling method. Red blood cell folate was measured by the electrochemiluminescence binding assay method. Data were entered into Epi-Data version 3.1 and analyzed by SPSS version 22.0. Descriptive statistics were used to describe demographic characteristics and to determine the magnitude of folate deficiency. Logistic regression was used to identify the risk factors for folate deficiency. A p-value of less than 0.05 was considered statistically significant. Results: In this study, 44/160 (27%) participants had red blood cell folate level <400 ng/mL, insufficient to prevent neural tube defect. Multivariate regression showed that regular vegetable consumption was an independent determinant factor for red blood cell folate level (adjusted odds ratio: 0.41, confidence interval: 0.18-0.93). Conclusion: This study shows that a large magnitude of the first-trimester pregnant women had red blood cell folate concentrations below levels that are maximally protective against neural tube defects. Folic acid supplementation and supplemental nutrition containing green leafy vegetables should be promoted during the periconceptional period. In addition, the policymakers should set rules for mandatory folic acid fortification.

Towards Improved Management of Tuberculous Bloodstream Infections: Pharmacokinetic Considerations with Suggestions for Better Treatment Outcomes.

Mycobacterium tuberculosis is the leading cause of sepsis among HIV-infected adults, yet effective treatment remains a challenge. Efficacy of antituberculous drugs is optimized by high Area Under Curve to Minimum Inhibitory Concentration (AUC/MIC) ratios, suggesting that both the drug concentration at the disease site and time above MIC are critical to treatment outcomes. We elaborate on sepsis pathophysiology and show how it adversely affects antituberculous drug kinetics. Expanding distribution volumes secondary to an increased vascular permeability prevents the attainment of target Cmax concentrations for nearly all drugs. Furthermore, sepsis-induced metabolic acidosis promotes protonation, which increases renal clearance of basic drugs such as isoniazid and ethambutol, and hence AUCs are substantially reduced. Compared with the treatment of non-sepsis TB disease, these distorted kinetics underlie the poor treatment outcomes observed with bloodstream infections. In addition to aggressive hemodynamic management, an increase in both the dose and frequency of drug administration are warranted, at least in the early phase of treatment.

African Medical Educators and Anatomy Teachers' Perceptions and Acceptance of the Anatomage Table as an EdTech and Innovation: A Qualitative Study.

Background: This article presents a qualitative study of African anatomists and anatomy teachers on the Anatomage Table-a modern medical education technology and innovation, as an indicator of African anatomy medical and anatomy educators' acceptance of EdTech. The Anatomage Table is used for digital dissection, prosection, functional anatomy demonstration, virtual simulation of certain functions, and interactive digital teaching aid. Materials and Methods: Anatomy teachers [n=79] from 11 representative African countries, Ghana, Nigeria [West Africa], Ethiopia, Kenya, Rwanda [East Africa], Namibia [South Africa], Zambia [Southern Africa], Egypt [North Africa], and Sudan [Central Africa], participated in this study. Focus group discussions [FGDs] were set up to obtain qualitative information from stakeholders from representative institutions. In addition, based on the set criteria, selected education leaders and stakeholders in representative institutions participated in In-depth Interviews [IDIs]. The interview explored critical issues concerning their perceptions about the acceptance, adoption, and integration of educational technology, specifically, the Anatomage Table into the teaching of Anatomy and related medical sciences in the African continent. Recorded interviews were transcribed and analyzed using the Dedoose software. Results: African anatomists are generally technology inclined and in favor of EdTech. The most recurring opinion was that the Anatomage Table could only be a "complementary teaching tool to cadavers" and that it "can't replace the real-life experience of cadavers." Particularly, respondents from user institutions opined that it "complements the traditional cadaver-based approaches" to anatomy learning and inquiry, including being a good "complement for cadaveric skill lab" sessions. Compared with the traditional cadaveric dissections a majority also considered it less problematic regarding cultural acceptability and health and safety-related concerns. The lifelikeness of the 3D representation is a major factor that drives acceptability.

Folate, Vitamin B12, and Homocysteine Levels in Women With Neural Tube Defect-Affected Pregnancy in Addis Ababa, Ethiopia.

Background: Neural tube defects (NTDs) are prevalent congenital defects associated with pre-pregnancy diet with low levels of maternal folate. They are linked to severe morbidity, disability, and mortality, as well as psychological and economic burdens. Objective: The goal of this study was to determine the levels of folate, vitamin B12, and homocysteine in the blood of women who had a pregnancy impacted by NTDs. Subjects and Methods: A hospital-based case-control study was undertaken between September 2019 and August 2020. The study comprised a total of 100 cases and 167 controls. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of folate, vitamin B12, and homocysteine in the serum. Results: Only 39% of the cases and 54.5% of control mothers reported periconceptional use of folic acid/multivitamin, which indicated a statistically significant difference (p = 0.014). Logistic regression indicated that periconceptional use of folic acid/multivitamin was associated with NTDs (p = 0.015, OR = 1.873, 95% CI: 1.131-3.101). We found that 57% of the cases and 33.5% of controls, as well as 43% of cases and 20.4% of controls had serum folate and vitamin B12 levels below the cut-off value, respectively. Twenty-seven percent of the cases and 6.6% of controls had hyperhomocysteinemia (HHcy). The median concentrations of folate, vitamin B12, and homocysteine in cases and controls were 4.78 and 8.86 ng/ml; 266.23 and 455 pg/ml; 13.43 and 9.7 µmol/l, respectively. The median concentration of folate (p < 0.001) and vitamin B12 (p < 0.001) were significantly lower in the cases than controls, while the homocysteine concentration (p < 0.001) was significantly lower in the controls than cases. Folate [OR (95% CI) = 1.652 (1.226-2.225; p = 0.001)], vitamin B12 [OR (95% CI) = 1.890 (1.393-2.565; p < 0.001], and homocysteine [OR (95% CI) = 0.191 (0.09-0.405; p < 0.001)] levels were associated with NTDs. Conclusion: Folate and vitamin B12 are deficient in both cases and control mothers. The lower levels of folate and vitamin B12 with an elevated homocysteine level in NTD-affected pregnancy may be an indication that these biochemical variables were risk factors for NTDs. Folate/multivitamin supplementation and/or food fortification should be promoted.

Cytotoxic and other bioactivities of a novel and known sesquiterpene lactones isolated from Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke in breast cancer cell lines.

Vernonia leopoldi (Sch. Bip. ex Walp.) Vatke (Asteraceae) is one of the widely used anti-cancer traditional medicinal plants in Ethiopia, despite the lack of data to support its therapeutic efficacy. Here we describe the isolation of compounds from the plant and the investigation of their cytotoxicity and other bioactivities. We identified the novel sesquiterpene lactone (SL) 11ß,13-dihydrovernodalol along with the three other SLs (vernomenin, vernolepin, and 11ß,13-dihydrovernodalin) and three flavonoids (apigenin, eriodyctiol, and luteolin) isolated from this plant for the first time. The structures of all the compounds were established based on extensive analysis of nuclear magnetic resonance spectroscopic data and confirmed by high-resolution electrospray ionization mass spectrometry. We then studied the biological activities of the SLs and found that all were cytotoxic at low µM ranges against MCF-7 and JIMT-1 breast cancer cells as well as against the normal-like MCF-10A breast epithelial cells evaluated in a spectrophotometric assay. All the SLs significantly reduced JIMT-1 cell migration after 72 h of treatment with 2 µM concentrations in a wound healing assay. Treatment with all SLs reduced the aldehyde dehydrogenase expressing cancer stem cell sub-population of the JIMT-1 cells significantly, evaluated by flow cytometry. Only 11ß,13-dihydrovernodalin resulted in a significant inhibition of tumor necrosis factor-α-induced translocation of nuclear factor κB to the cell nucleus. In addition, we show that the reporter fluorophore nitrobenzoxadiazole (NBD) can successfully be conjugated with an SL and that this SL-NBD conjugate is taken up efficiently in JIMT-1 cells. Therefore, the overall bioactivities of the SL compounds and specifically their effects against the stemness of breast cancer cells make them prime candidates for further in-depth investigation.

A Study of Anatomy Teachers' Perception and Acceptance of the Anatomage Table Technology and Digital Teaching Materials in the Training of Medical and Allied Health Students.

BACKGROUND: The Anatomage Table is a modern technology that is used to enhance the teaching of human anatomy and related basic medical sciences to medical and allied health students. Its use is gaining popularity. This study considered anatomy teachers' perception and acceptance of the Anatomage Table technology and digital teaching materials in the training of medical and allied health students in African countries. MATERIALS AND METHODS: Validated questionnaires were used. Altogether, 79 respondents fully participated in the study, with all African regions being represented as follows: Ghana, Nigeria (West Africa), Ethiopia Kenya Rwanda (East Africa), Namibia, South Africa, Zambia (Southern Africa), Egypt (North Africa), and Sudan (Central Africa). Responses were obtained from the electronic Google form, organized on Excel spreadsheets, and analyzed using the SPSS statistical software version 23.0 (IBM Corp, Armonk, NY). RESULTS: In terms of proportion, 29.1% of respondents reported that they had some level of mastery in using the Anatomage Table; with 6.3% of all the participants reportedly having a high mastery of this technology, 12% and 6% reported that they had an average mastery and low mastery levels, respectively. Participants' rating of their level of agreement with whether the Anatomage Table is a useful EdTech showed that 54.4% of them strongly agreed while 27.8% just agreed. The majority considered the use of the Anatomage as a means of embracing the global culture of technology-in-medical sciences (87.3%). CONCLUSION: Most respondents would accept the technology as a complementary tool to support the existing traditional practices, especially cadaveric.

Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women.

BACKGROUND: Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women. METHODS: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link. RESULTS: Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39. CONCLUSION: The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.

Cardiometabolic syndrome and associated factors among Ethiopian public servants, Addis Ababa, Ethiopia.

Non-communicable diseases (NCDs) are increasingly becoming the global cause of premature death encompassing cardiovascular diseases (CVDs), cancer, respiratory diseases and diabetes mellitus. However, cardiometabolic risk factors in the general population, especially among the high-risk groups have rarely been assessed in Ethiopia. The study aimed to assess the prevalence of metabolic syndrome, its components and associated factors among staff in the Ethiopian Public Health Institute (EPHI). An institutional-based cross-section study was conducted from March to June 2018 among EPHI staff members. A total of 450 study participants were involved in the study, and the World Health Organization NCD STEPS survey instrument version 3.1 was used for the assessment. The biochemical parameters were analyzed by using COBAS 6000 analyzer. Statistical package for the social science (SPSS) version 20 was used for data analysis. Both bivariate and multivariate logistic regression analyses were used to identify associated risk factors. p value < 0.05 was considered for statistical significance. The overall prevalence of metabolic syndrome was 27.6% and 16.7% according to IDF and NCEP criteria respectively, with males having greater prevalence than females (35.8% vs 19.4%). Central obesity, low high-density lipoprotein (HDL) and hypertension had a prevalence of 80.2%, 41.3%, and 23.6%, respectively. In multivariate analysis increasing age and having a higher body mass index (25-29.9) were significantly associated with metabolic syndromes. The magnitude of metabolic syndrome was relatively high among public employees. Preventive intervention measures should be designed on the modification of lifestyle, nutrition and physical activities, and early screening for early identification of cardiometabolic risks factors should be practised to reduce the risk of developing cardiovascular diseases.

Serum level of high sensitive C-reactive protein and IL - 6 markers in patients with treatment-resistant schizophrenia in Ethiopia: a comparative study.

BACKGROUND: Accumulating evidence indicates that schizophrenia is accompanied by significant activation of the immune system; however, there is limited data from low and middle-income countries (LMIC). Inflammatory markers may be more relevant in LMIC settings where infectious conditions are more prevalent and may thus play some role in the causation and maintenance of schizophrenia. The aim of this study was to assess the level of inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with schizophrenia. MATERIALS AND METHODS: The study population consisted of a total of 132 study participants; 82 participants with schizophrenia and 50 controls. hsCRP and IL-6 were measured using Cobas Integra 400 Plus and Cobas e 411 analysers respectively. RESULTS: The levels of hsCRP and IL-6 were significantly increased among participants with schizophrenia compared to controls: hsCRP mean value 2.87 ± 5.6 vs 0.67 ± 0.6 mg/L; IL-6 mean value 6.63 ± 5.6 vs 3.37 ± 4.0 pg/ml. Controlling for potential confounders (age, sex and body mass index), having a diagnosis of schizophrenia remained significantly associated with increased hsCRP and IL-6. CONCLUSION: The results confirm that inflammatory processes may have a role in the pathophysiology of schizophrenia regardless of setting. Despite failure of some interventions with anti-inflammatory properties, interventions to reduce inflammation are still worth pursuing.

Effect of 70% Ethanol Extract and its Solvent Fractions of Artemisia afra (Jacq. Ex Willd.) against Pentylenetetrazole-Induced Seizure in Mice.

INTRODUCTION: Artemisia afra (Jacq. ex Willd.), commonly called African wormwood, is a highly aromatic perennial herb and a well-known medicinal plant, claimed to be effective and safe in the treatment of epilepsy. The whole-plant extract is traditionally used as an antiepileptic agent in Ethiopia. Aim of the Study. The aim of this study was, therefore, to evaluate the anticonvulsant effect of the hydroethanolic extract and solvent fractions of A. afra whole part in mice. MATERIALS AND METHODS: The effects of A. afra hydroethanolic extract and its solvent fractions were evaluated against pentylenetetrazole- (PTZ-) induced convulsions in mice. The onset and duration of PTZ-induced convulsions were determined with hydroethanolic A. afra extract and its solvent fractions. Data were analyzed using a one-way analysis of variance (ANOVA) followed by post hoc Tukey's multiple comparisons test. p < 0.05 was considered statistically significant. RESULTS: The hydroethanolic extract of A. afra, with all the three doses of 250, 500, and 1000 mg/kg, showed a significant delay (504.833 ± 62.835 ∗ s; p < 0.05 ∗ ; 551.833 ± 47.69 ∗∗ s; p < 0.01 ∗∗ ; and 808.333 ± 64.8 ∗∗∗ s; p < 0.001 ∗∗∗ , respectively) in the mean onset of convulsion and a decrease (17.000 ± 1.88 ∗∗∗ s, p < 0.05 ∗ ; 13.000 ± 1.8 ∗∗ s, p < 0.01 ∗∗ ; and 7.833 ± 1.07 ∗∗∗ s, p < 0.001, respectively) in the mean duration of convulsion against PTZ-induced convulsion in a dose-dependent manner compared to the control (92.833 ± 13.006 s; 34.167 ± 3.683 s), and its anticonvulsant activity was significantly less compared to that of diazepam (1001.167 ± 68.430 s; 4.500 ± 0.619 s). The solvent fractions, however, did not show anticonvulsant activity against PTZ-induced convulsion. CONCLUSION: Crude extract of A. afra has an anticonvulsant effect in mice. This might be attributed to the synergistic effects of two or more active ingredients present in the herb.

Genetic Mutations Associated with Hormone-Positive Breast Cancer in a Small Cohort of Ethiopian Women.

In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER+) breast cancer. This is surprising given (1) that patients have late-stage breast cancer at the time of diagnosis, (2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and (3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched tumor and normal adjacent tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and that from white patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.

Serum Lipid Profiles of Patients Taking Efavirenz-Based Antiretroviral Regimen Compared to Ritonavir-Boosted Atazanavir with an Optimized Background at Zewditu Memorial Hospital, Addis Ababa, Ethiopia.

BACKGROUND: Dyslipidemia represents significant health care concerns in patients taking antiretroviral therapy due to their association with cardiovascular disease risk. There is limited data regarding the effects of boosted atazanavir (ATV/r) treatment in the lipid profiles of Ethiopian HIV patients. Thus, this study compares the mean values of lipid profile differences of HIV patients on ATV/r-based regimen compared to efavirenz (EFV)-based regimen, while the background is Tenofovir Disoproxil Fumarate/lamivudine. MATERIALS AND METHODS: A comparative hospital-based cross-sectional study was conducted among adult HIV-infected patients at Zewditu Memorial Hospital, Addis Ababa, Ethiopia, from July-September 2017. An equal number of EFV and ATV/r-treated patients (n=90 each) receiving for 1-year and over were included in the study. Serum total cholesterol (TC), triglyceride (TG), gigh-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were measured. Data comparison used chi-square test, Student's t-test and Mann-Whitney U-test. Multivariate logistic regression analysis and p-value<0.05 were used to identify associated factors of serum lipid profiles. RESULTS: In the present study, the ATV/r-treated group results were significantly higher in the median values of TG [207 (56-1094) vs 145 (42-768) mg/dL; p=0.001] and the mean value of TG/HDL-c (6.6 vs 4.4; p=0.001) as compared to the EFV-treated group. The EFV-treated group showed significantly higher in the mean value of HDL-c (44.7 vs 38.7 mg/dL; p=0.001) as compared to the ATV/r-treated group. Body mass index was associate with LDL and HDL. CD4 was associated with TC. Current antiretroviral therapy was associated with TG. Duration of HIV since first diagnosis and duration of ART were associated with HDL. CONCLUSION: ATV/r is associated with elevated in TG and TG/HDL-C, but low HDL as compared to EFV. Differences in LDL or HDL that were found were of unclear clinical significance. The long-term significance is unknown.

Distribution and determinants of serum high-sensitivity C-reactive protein in Ethiopian population.

BACKGROUND: C-reactive protein (CRP) is an important inflammatory marker associated with different disease conditions, and its concentration differs among ethnicity. This study aimed to determine the distribution and determinants of serum high-sensitive method CRP (hsCRP) that can measure the typically low concentrations, among the Ethiopian population, for which there is no data. METHODS: A cross-sectional community-based study was conducted in April-June 2015. A total of 5162 individuals aged 15-69 were included. Behavioral, physical, and biochemical measurements were taken using the WHO STEPS non-communicable diseases (NCDs) risk factors assessment tool. Serum hsCRP was determined using Cobas Integra 400 Plus (Roche). Factors associated with hsCRP levels were also considered. RESULTS: median hsCRP was 0.80 mg/L (Interquartile range, 0.19-2.12) (males: 0.91 mg/L, females: 0.74 mg/L). More than 18% of the study participants had hsCRP greater than 3 mg/L according to the American Heart Association and Centers for Diseases Control and Preventions cut off value. Higher BMI, living in Somali and in Dire Dawa region, and not consuming of fruit or vegetables were independent risk factors for high hsCRP levels. CONCLUSION: Serum hsCRP levels distribution is comparable to other studies. Until now, no data have been reported in the literature about the Ethiopian population.

BCR-ABL Transcript Level as Compared to LDH and Uric Acid Among Chronic Myeloid Leukemic Patients.

BACKGROUND: Chronic myeloid leukemia is characterized by the presence of the Philadelphia chromosome, which is caused by the breakpoint cluster region-Abelson fusion or joined gene. A high concentration of BCR-ABL transcripts level can strongly forecast cytogenetic and hematologic reversion in CML patients. However, the molecular test for BCR-ABL is costly and hardly available in developing countries with low and middle-income. Owing to this, it is required to examine other cost-effective and best diagnostic (prognostic) biomarkers. OBJECTIVE: The present study aimed to estimate the total LDH and uric acid level as compared to BCR-ABL transcript level among treated and treatment-naive Chronic Myeloid Leukemia (CML) patients. METHODS: A comparative cross-sectional study design was used to include eighty-one (81) CML patients tested for BCR-ABL by GeneXpert RT-PCR transcript level at Tikur Anbessa Specialized Hospital. The current study correlates LDH with BCR-ABL and hematological parameters using the spearman correlation, Mann-Whitney U test, and roc curve data analysis tool. RESULTS: A total of 81 CML patients were assayed; 46(56.8%) of them were in the medically treated group, and the remaining 35 (43.2%) were treatment-naive patients. Significant positive correlations were observed between LDH and BCR-ABL (r=0.79, P<0.001).The correlation coefficient value of uric acid (r=0.295, p<0.008) with BCR-ABL showed a weak correlation between the two test parameters. There was a statistically noteworthy (p<0.05) difference in the median level of BCR-ABL and LDH among patients in the treatment group (median=21%, 350 U/L) and the treatment- naive group (median=57%, 1246 U/L), respectively. For uric acid, there was no statistically significant (p<0.542) difference between the study group. The AUC for LDH, Basophil, and WBC was 0.881, 0.889, and 0.748, respectively, which showed better performance for the follow-up of patients with CML than uric acid (0.695) and platelets (0.70). CONCLUSION: The CML LDH value strongly correlated with BCR-ABL transcript level, whereas uric acid was weakly correlated with BCR-ABL. Hence, in parallel with the BRC-ABL transcript level, these findings could be a patent for confirming the capability of LDH as an alternative cost-- effective diagnostic, prognostic biomarker, and a novel therapeutic target in CML disease.

Assessment of serum electrolytes and kidney function test for screening of chronic kidney disease among Ethiopian Public Health Institute staff members, Addis Ababa, Ethiopia.

BACKGROUND: Chronic kidney disease (CKD), which is characterized by its asymptomatic nature until an end stage, is one of the most common public health problems in the world. Thus, a regular checkup, especially for those individuals with high risk groups is inevitably important, and the screening has been done with laboratory findings. However, in developing countries, including Ethiopia screening for CKD are rarely done, and it is becoming common to hear sudden death from the kidney failure. Therefore, we aimed to screen serum electrolyte levels and estimated glomerular filtration rate (eGFR) among Ethiopian Public Health Institute (EPHI) staff members for an early detection of CKD and to identify the factors associated with it. METHODS: A cross-sectional study was conducted from July 1 to October 28, 2018 among EPHI staff members. The level of serum creatinine and electrolytes were measured using COBAS 6000 analyzer. Then, eGFR was calculated using MDRD and CKD-EPI equations. Data analysis were done using SPSS version 20, and the factors associated with the outcome variable were assessed using logistic regression. P values < 0.05 were considered as statistically significant. RESULTS: This study found that 3.6 and 1.9% of the study participants were at CKD stage II by MDRD and CKD-EPI equations, respectively. Out of the total study participants, 9.5% had hyperkalemia (serum potassium level > 5.0 mmol/L) and 8.5% had hypocalcemia (serum calcium level < 2.15 mmol/L). An older age (P = 0.006), high BMI (P = 0.045) and previous history of CVDs (P = 0.033) were found to be significantly associated factors with reduced glomerular filtration rate. Nine percent of the study participants were obese, 6.1% had family history of kidney failure, 18% self-reported history of hypertension, 3.4% diabetic and 5.3% had CVDs. About 51.2% of the study participants were males, and the majorities, (66%) of the study participants were found to be alcohol consumers. CONCLUSIONS: The prevalence of a stage II kidney disease was relatively low and none of the participants was under serious kidney disease (GFR < 60 mmol/min/1.73m2). An older age, high BMI and previous history of CVDs were significantly associated with reduced GFR. Hyperkalemia and hypokalemia were the major electrolyte disorders in the study participants.