Prof. Daniel Seifu
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Publication A Feasible Laboratory-Strengthening Intervention Yielding a Sustainable Clinical Bacteriology Sector to Support Antimicrobial Stewardship in a Large Referral Hospital in Ethiopia(Frontiers Media SA, 2020-06-23) ;Cedric P. Yansouni ;Daniel Seifu ;Michael Libman ;Tinsae Alemayehu ;Solomon Gizaw ;Øystein Haarklau Johansen ;Workeabeba Abebe ;Wondwossen AmogneMakeda SemretBackground: Access to clinical bacteriology in low resource settings (LRS) is a key bottleneck preventing individual patient management of treatable severe infections, detection of antimicrobial resistance (AMR), and implementation of effective stewardship interventions. We sought to demonstrate the feasibility of a practical bundle of interventions aimed at implementing sustainable clinical bacteriology services at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on cost and intensity of supervision. Methods: Starting in Dec 2015, an intervention based on the CLSI QMS01-A guideline was established, consisting of (i) an initial needs assessment, (ii) development of key standard operating procedures, (iii) adaptation of processes for LRS, (iv) training and supervision of laboratory staff via consultant visits and existing online resources, and (v) implementation of a practical quality systems approach. A guiding principle of the bundle was sustainability of all interventions post implementation. Outcomes and challenges: An initial investment of ~US$ 26,200 for laboratory reagents, and a total of 50 visit-days per year from three Canadian and Norwegian microbiologists were committed. Twelve SOPs, including antimicrobial susceptibility testing, were adapted, and an automated blood culture platform was donated (bioMerieux). In the first 18 months of implementation of the intervention, the average volume of specimens analyzed in the lab went from 15/day to 75/day. The number of blood cultures tested increased from an average of 2/day to over 45/day. Antimicrobial susceptibility testing was introduced and cumulative antibiograms were generated for the institution. Quality control was implemented for all procedures and quality assurance tools implemented included external quality assurance and proficiency testing of six technologists with longitudinal follow-up. The laboratory is on the path toward SLIPTA accreditation by the African Society for Laboratory Medicine. Reagent costs, staff training and retention, and engagement of clinical personnel with the lab proved to be manageable challenges. Key external challenges include in-country supply-chain management issues, lack of competition among distributors, and foreign-currency exchange distortions. Conclusions: Using a relatively low-intensity intervention based on existing training tools and accreditation schemes, we demonstrate that establishment of reasonable-quality clinical bacteriology is not only within reach but also a critical step toward assessing the burden of AMR in settings like this one and implementing effective stewardship strategies. - Some of the metrics are blocked by yourconsent settings
Publication Assessment of serum electrolytes and kidney function test for screening of chronic kidney disease among Ethiopian Public Health Institute staff members, Addis Ababa, Ethiopia(Springer Science and Business Media LLC, 2020-11-18) ;Meseret Derbew Molla ;Maria Degef ;Abebe Bekele ;Zeleke Geto ;Feyissa Challa ;Tadesse Lejisa ;Tigist Getahun ;Meron Sileshi ;Yosef Tolcha ;Genet AshebirDaniel SeifuBackground 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. - Some of the metrics are blocked by yourconsent settings
Publication Awareness, attitudes towards genetic diseases and acceptability of genetic interventions among pregnant women in Burera district, Rwanda(Springer Science and Business Media LLC, 2023-10-10) ;Jean Baptiste Niyibizi ;Erigene Rutayisire ;Monica Mochama ;Michael Habtu ;Zephanie NzeyimanaDaniel SeifuApproximately 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. - Some of the metrics are blocked by yourconsent settings
Publication Catha edulis Forsk and Ascorbic Acid Effects on Hematological Indices in Rat(Informa UK Limited, 2021-09-25) ;Abebaye Aragaw Leminie ;Tesfaye Tolessa Dugul ;Eyasu Makonnen EshetuDaniel Seyifu MelkaBackground: The prevalence of chewing Catha edulis Forsk and the use of ascorbic acid is increasing from time to time. Their subchronic effects on hematological indices are not well examined. The present study was aimed to investigate their subchronic effects on hematological indices in rats. Materials and methods: A total of 36 adult (7-8 weeks) wild-type rats weighing between 213 and 229g were used in this study. They received Catha edulis Forsk extract (Ce) (100 milligrams/kilogram, 200 milligram/kilogram and 300 milligram/kilogram b.w), Catha edulis Forsk juice (2.5 mL/kg), ascorbic acid (AA 200 milligram/kilogram), and 2% tween 80 in distilled water (T80W- v/v) for twelve weeks. Hematological indices were measured with Sysmex KX-21. Data were analyzed by SPSS version 21.0 and Microsoft Excel. Results: Neutrocytes (p < 0.01), lymphocytes (p < 0.05), plateletcrit (p < 0.05), average size of platelets (p < 0.05), platelet size variability (p < 0.01), platelet-large cell ratio (p < 0.05) and neutrocytes/lymphocytes ratio (p < 0.001) were significantly greater, while hemoglobin concentration per red blood cell (p < 0.05) and hemoglobin concentration per volume of red blood cells were significantly reduced (p < 0.05) in rats received khat. The red cell distribution width (p < 0.05), platelet size variability (p < 0.05) and platelet-large cell ratio (p < 0.01) were significantly greater in rats received ascorbic acid. Conclusion: Crude Catha edulis Forsk extract and juice changed some hematological indices and increased platelet activities. The platelet activity was also increased by ascorbic acid. The mechanisms for these changes need to be investigated. - Some of the metrics are blocked by yourconsent settings
Publication Colorectal cancer disease profile and treatment patterns at an urban tertiary hospital in Rwanda(Ecancer Global Foundation, 2024-03-28) ;Margaret Baldwin ;Brandon A Niyibizi ;Daniella Rangira ;Benita Rangira ;Madeleine K Kazindu ;Daniel Seifu ;Cristina Daniela Stefan ;Eulade RugengamanziAchille V C ManirakizaBackground: 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. - Some of the metrics are blocked by yourconsent settings
Publication CYP2J2∗7 Genotype Predicts Risk of Chemotherapy-Induced Hematologic Toxicity and Reduced Relative Dose Intensity in Ethiopian Breast Cancer Patients(Frontiers Media SA, 2019-05-14) ;Jemal Hussien Ahmed ;Eyasu Makonnen ;Getnet Yimer ;Daniel Seifu ;Abebe Bekele ;Mathewos Assefa ;Abraham Aseffa ;Rawleigh Howe ;Alan Fotoohi ;Moustapha HassanEleni AklilluChemotherapy-induced hematologic toxicity is the primary reasons of dose reductions and/or delays, low relative dose intensity (RDI), and predicts anticancer response. We investigated the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced RDI in Ethiopian breast cancer patients, and implication of pharmacogenetics variations. Breast cancer patients (n = 249) were enrolled prospectively to receive cyclophosphamide based chemotherapy. Hematological toxicity (neutropenia, anemia, and thrombocytopenia) were monitored throughout chemotherapy cycle. The primary and secondary outcomes were incidence of grade 3 or 4 toxicity and reduced RDI, respectively. CYP2B6∗6, CYP3A5∗3, CYP2C9 (∗2,∗3), CYP2C19 (∗2,∗3), CYP2J2∗7, POR∗28, and ABCB1 (rs3842) genotyping were done. Cox proportional hazard and logistic regression were used to estimate risk predictors of toxicity and reduced RDI, respectively. Majority (73.5%) of the patients were < 45 years of age. The incidence of grade 3 or 4 hematological toxicity was 51.0% (95% CI = 44.54-57.46%). Multivariate Cox proportional hazard regression indicated CYP2J2∗7 genotype [Hazard ratio (HR) = 1.82; 95% CI = 1.14-2.90], pretreatment grade 1 leukopenia (HR = 2.75; 95% CI = 1.47-5.15) or grade 1 or 2 neutropenia (HR = 2.75; 95% CI = 1.73-4.35) as significant predictors of hematologic toxicities. The odds of having hematologic toxicities was lower in CYP2C9∗2 or ∗3 carriers (p = 0.024). The prevalence of reduced RDI was 56.6% (95% CI = 50.3-62.9%). Higher risk of reduced RDI was associated with CYP2J2∗7 allele [Adjusted odds ratio (AOR) = 2.79; 95% CI = 1.21-6.46], BMI ≤ 18.4 kg/m2 (AOR = 5.98; 95% CI = 1.36-26.23), baseline grade 1 leukopenia (AOR = 6.09; 95% CI = 1.24-29.98), and baseline neutropenia (AOR = 3.37; 95% CI = 1.41-8.05). The odds of receiving reduced RDI was lower in patients with CYP2B6 ∗6/∗6 genotype (AOR = 0.19; 95% CI = 0.06-0.77). We report high incidence of chemotherapy-induced hematological toxicities causing larger proportion of patients to receive reduced RDI in Ethiopian breast cancer patients. Patients carrying CYP2J2∗7 allele and low baseline blood counts are at a higher risk for chemotherapy-induced hematologic toxicities and receiving reduced RDI, and may require prior support and close follow up during chemotherapy. - Some of the metrics are blocked by yourconsent settings
Publication Cysteine Cathepsins and Matrix Metalloproteases Among Breast Cancer Patients(Informa UK Limited, 2021-05-07) ;Solomon Tsegaye ;Mohammed Mehdi ;Wajana Lako LabissoDaniel Seifu MelkaBackground: Cellular proteases are thought to increase the likelihood of cancer cell infiltration and metastasis by degrading constituents of the extracellular matrix (ECM). Measuring activities of these proteases may be used as tumor markers for early diagnosis, prognosis, and as a possible target for treatment plan. Objective: The aim of the current study is to evaluate cysteine cathepsins (CTSK and CTSL) and matrix metalloproteases-2 (MMP-2) and 9 (MMP-9) activities in human breast tumor tissue. Methods: A comparative cross-sectional study plan was devised to study the enzymatic activities ofCTSK and CTSL andMMP-2 and MMP-9 via zymographic detection method. Sites of tissue sample collection were St Paul's Millennium Medical College, Menelik II Hospital and Zewditu Memorial Hospital, Addis Ababa, Ethiopia. A total of 36 breast cancer patients were recruited and tissue samples were collected for the study. Results: Activities of CTSK and CTSL were significantly elevated in cancerous tissue than the adjacent normal non-cancerous breast tissue of the same patients (n = 36, p ≤ 0.05). Also, activities ofMMP-2 and MMP-9 were increased significantly in tumor tissues than normal tissues (n = 36, P ≤ 0.05). Conclusion: It is found that there are different patterns of protease enzymatic activity expression between normal and tumor tissue using zymography. Compared with normal tissue samples, the protease enzymatic activity in cancerous tissue is higher. Thus, tissue proteases can be used in conjunction with histological techniques to identify patients in the same clinical group. - Some of the metrics are blocked by yourconsent settings
Publication 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(Elsevier BV, 2022) ;Nigatu Tuasha ;Zilma Escobar ;Daniel Seifu ;Endalamaw Gadisa ;Beyene Petros ;Olov SternerStina OredssonVernonia 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 MCF10A 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 indepth investigation. - Some of the metrics are blocked by yourconsent settings
Publication Detection and isolation of intestinal muscle relaxant substances from the root of Taverniera abyssinica A. Rich(Elsevier BV, 2023-08-10) ;Daniel Seifu ;Kristofer F. Nilsson ;Rajinder Chawla ;Solomon Genet ;Mikael Holst ;Asfaw DebellaPer M. HellströmEthnopharmacological 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. - Some of the metrics are blocked by yourconsent settings
Publication Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia: A cross sectional study(Public Library of Science (PLoS), 2020-05-06) ;Endale Hadgu ;Daniel Seifu ;Wondemagegnhu Tigneh ;Yonas Bokretsion ;Abebe Bekele ;Markos Abebe ;Thomas Sollie ;Christina Karlsson ;Mats G. KarlssonTomi F. AkinyemijuEvaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports. - Some of the metrics are blocked by yourconsent settings
Publication Effect of 70% Ethanol Extract and its Solvent Fractions of Artemisia afra (Jacq. Ex Willd.) against Pentylenetetrazole-Induced Seizure in Mice(Wiley, 2021-06-17) ;Teketel Eristu Kediso ;Tesfaye Tolessa ;Fikirte Getachew ;Eyasu Makonnen ;Daniel SeifuRoberto K. N. CumanIntroduction. 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. - Some of the metrics are blocked by yourconsent settings
Publication 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(Springer Science and Business Media LLC, 2023-05-22) ;Saifu Hailu ;Samuel Kinde ;Michael Cross ;Aster Tsegaye ;Tsehayneh Kelemu ;Daniel Seifu ;Dawit Alemayehu ;Azeb Tarekegn ;Gutema Jabessa ;Desalegn Abeje ;Markos Abebe ;Abdulaziz Sherif ;Fisihatsion Tadesse ;Uwe Platzbecker ;Rawleigh HoweAmha GebremedhinThe 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. - Some of the metrics are blocked by yourconsent settings
Publication Evaluation of Hydro-alcoholic Extract of Clerodendrum myricoides (Hochst. Vatke) Leaves and Its Solvent Fractionsin Pentylenetetrazole-Induced Convulsion in Mice(Sciencedomain International, 2020-09-03) ;Teketel Eristu Kediso ;Tesfaye Tolessa ;Fikirte Getachew ;Eyasu MakonnenDaniel SeifuIntroduction: Epilepsy is a chronic neurological disorder that affects people of all ages. Herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy. The low side effects of traditional herbal medicines have encouraged many types of research into antiepileptic activity. Clerodendrum myricoides is a plant whose leaves extract is traditionally used as an anticonvulsant in Ethiopia. Objective: The point of this investigation was to assess the anticonvulsant effect of the hydro-alcoholic extract and solvent fractions of C. myricoides leaves against pentylenetetrazole-induced seizures in mice. Methods: Comparison of mean latency to onset of convulsion, mean duration of convulsions, and the proportion of percentage protection against seizure of the plant extract was tested against PTZ-induced seizures. Three different doses were used by giving them orally 30 minutes before subcutaneous pentylenetetrazole (80 mg/kg) administration with the positive (diazepam 2 mg/kg) and negative (physiological saline 10 mg/kg) control groups. Data were presented as the mean ± standard error of the mean and analyzed using a one-way analysis of variance (ANOVA) and followed by post-hoc Tukey’s multiple comparisons test. Fisher’s exact test was used for the percentage protection. P < 0.05 was considered statistically significant. Results: The crude extract of C. myricoides, with the doses of 300, 600, 1,200 mg/kgshowed a significant delay in mean latency to onset of seizures [299.33±30.129 sec (p< 0.05); 387.167± 27.6 sec (p<0.01); 417.833±31.9 sec (p<0.001); respectively)]; decrease in the duration of convulsion [27.333±1.585 sec (p<0.05); 16.833±1.537 sec (p<0.01); 10.50±0.671 sec (p<0.001) respectively]; and a proportion of percentage protection of mice against seizure [16.33% (1/6) (p< 0.05); 33.33% (2/6) (p<0.01); 50% (3/6) (p<0.001) respectively] in a dose-dependent manner compared to the control group [92.833±13.006 sec; 34.167±3.683 sec, 0% respectively]. C. myricoides anticonvulsant activity was less than that of diazepam [1001.16± 68.430 sec, 4.500±0.619, 83.33 sec, 83.33% respectively for the doses]. Its solvent fractions, however, didn’tshow a significant anticonvulsant effect. Conclusion: The hydroalcoholic leaves crude extract of C. myricoides has anticonvulsant activity but its solvent fractions do not have comparable significant effects. - Some of the metrics are blocked by yourconsent settings
Publication Folate, Vitamin B12, and Homocysteine Levels in Women With Neural Tube Defect-Affected Pregnancy in Addis Ababa, Ethiopia(Frontiers Media SA, 2022-04-08) ;Winner Kucha ;Daniel Seifu ;Abenezer Tirsit ;Mahlet Yigeremu ;Markos Abebe ;Dawit Hailu ;Dareskedar TsehaySolomon GenetBackground: 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. - Some of the metrics are blocked by yourconsent settings
Publication Hyperuricemia and Its Associated Factors Among Adult Staff Members of the Ethiopian Public Health Institute, Ethiopia(Informa UK Limited, 2021-04-20) ;Meseret Derbew Molla ;Abebe Bekele ;Daniel Seifu Melka ;Maria Degef Teklemariam ;Feyissa Challa ;Birhanu Ayelign ;Tewodros Shibabaw ;Yonas AkaluZeleke GetoBackground: Hyperuricemia is related not only to an increased risk of gouty arthritis but also to an increased risk of cardiovascular diseases, resistant hypertension, insulin resistance and progression of type 2 diabetes mellitus. However, to the best of our knowledge, the prevalence of hyperuricemia and its associated factors have rarely been assessed in Ethiopian populations. Therefore, this study aimed to determine the prevalence of hyperuricemia and its associated factors among adult staff members of the Ethiopian Public Health Institute. Methods: An institution-based cross-sectional study was conducted from July 1 to October 28, 2018. A total of 402 study participants were selected using a simple random sampling technique. An interviewer-administered questionnaire was used to collect the data. A blood sample of approximately 5 mL was collected from each study participant after overnight fasting through standardized methods for biochemical tests, and analyses were carried out with an automated COBAS 6000 analyzer. Data analysis was performed by SPSS version 20 software. The factors associated with the outcome variable were identified by bivariable and multivariable logistic regression analyses, and a p value <0.05 was used to declare statistical significance. Results: The mean age of the study participants was 37.13±10.5 (mean ± SD), and 51.5% of the participants were male. The overall prevalence of hyperuricemia (>5.7 mg/dL for females and >7 mg/dL for males) was found to be 31.0%. The multivariable logistic analysis revealed that age (AOR=1.59, 95% CI 1.01-2.78), sex (AOR=1.66, 95% CI 1.02-2.70), cigarette smoking (AOR=2.05, 95% CI 1.01-4.19) and serum low-density lipoprotein (LDL) (AOR=1.70, 95% CI 1.01-2.87) were significantly associated with hyperuricemia. Conclusion: The prevalence of hyperuricemia was relatively high compared to similar studies. Early screening for hyperuricemia in the general population, especially in those who are smokers, of older age and with high serum LDL levels, is vital to control its adverse effects at an early stage. - Some of the metrics are blocked by yourconsent settings
Publication Immunohistochemistry-derived subtypes of breast cancer distribution in four regions of Ethiopia(Frontiers Media SA, 2023-11-09) ;Esmael Besufikad Belachew ;Adey Feleke Desta ;Tewodros Yalew Gebremariam ;Dinikisira Bekele Deneke ;Senait Ashenafi ;Melisachew Mulatu Yeshi ;Bizunesh Dires Fenta ;Alemwosen T/Hayimanot Alem ;Addisu Alemu ;Abdo Kedir Abafogi ;Tigist Desta ;Menberework Chanyalew ;Daniel Beshah ;Lesley Taylor ;Marcus Bauer ;Dareskedar Tsehay ;Selfu Girma ;Daniel Seifu Melka ;Tesfaye Sisay Tessema ;Eva J. KantelhardtRawleigh HowePurpose: Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions. Methods: A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers. Results: The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele. Conclusion: Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies. - Some of the metrics are blocked by yourconsent settings
Publication Investigation of the effect of coffee on body weight, serum glucose, uric acid and lipid profile levels in male albino Wistar rats feeding on high-fructose diet(Springer Science and Business Media LLC, 2019-12-18) ;Teka Obsa Feyisa ;Daniel Seifu Melka ;Menakath Menon ;Wajana Lako LabissoMezgebu Legesse HabteCoffee is one of the most commonly consumed beverages in the worldwide and is assumed to have protective effects against metabolic syndrome. The present study was aimed at investigating the effect of coffee on body weight, serum glucose, uric acid and lipid profile levels in male albino Wistar rats feeding on high fructose diet. A post-test experimental study was conducted on a total of 30 (9–10 weeks old) male albino Wistar rats. The rats were divided into 6 groups: group I (normal control)-fed on standard chow and plain tap water only; group II (fructose control)-fed on standard chow and 20% of fructose solution; group III–VI (treatment groups)-fed on standard chow, 20% of fructose solution and treated with 71, 142, 213 and 284 mg/kg body weight/day of coffee respectively for six weeks. At the end, body weight, serum glucose, uric acid and lipid profile levels were investigated. Data was entered and cleared by epi-data software version 3.1 and analyzed by one way ANOVA followed by Tukey post hoc multiple comparison tests using SPSS V. 23.00. Statistical significance was considered at p < 0.05. The results showed that body weight, fasting serum glucose and uric acid levels significantly lowered in rats treated with 213 (p = 0.047; 0.049; 0.026) and 284 (p = 0.035; 0.029; 0.010) mg/kg body weight/day of coffee compared to fructose control group. Fasting serum triglycide (TG) and low density lipoprotein (LDL-C) levels showed significant reduction in rats treated with 284 mg/kg body weight/day of coffee as compared to fructose control group (p = 0.031; 0.046) respectively. In conclusion, treating rats with coffee decreased body weight, fasting serum glucose, uric acid, TC, TG and LDL-C, and increased HDL-C in a dose dependent manner in rats feeding on high fructose diet, suggesting that coffee consumption may be helpful in ameliorating metabolic syndrome. - Some of the metrics are blocked by yourconsent settings
Publication Molecular and Immunological Diagnostic Techniques of Medical Viruses(Wiley, 2020-09-04) ;Daniel Hussien Reta ;Tesfaye Sisay Tessema ;Addis Simachew Ashenef ;Adey Feleke Desta ;Wajana Lako Labisso ;Solomon Tebeje Gizaw ;Solomon Mequanente Abay ;Daniel Seifu MelkaFisseha Alemu RetaViral infections are causing serious problems in human population worldwide. The recent outbreak of coronavirus disease 2019 caused by SARS-CoV-2 is a perfect example how viral infection could pose a great threat to global public health and economic sectors. Therefore, the first step in combating viral pathogens is to get a timely and accurate diagnosis. Early and accurate detection of the viral presence in patient sample is crucial for appropriate treatment, control, and prevention of epidemics. Here, we summarize some of the molecular and immunological diagnostic approaches available for the detection of viral infections of humans. Molecular diagnostic techniques provide rapid viral detection in patient sample. They are also relatively inexpensive and highly sensitive and specific diagnostic methods. Immunological-based techniques have been extensively utilized for the detection and epidemiological studies of human viral infections. They can detect antiviral antibodies or viral antigens in clinical samples. There are several commercially available molecular and immunological diagnostic kits that facilitate the use of these methods in the majority of clinical laboratories worldwide. In developing countries including Ethiopia where most of viral infections are endemic, exposure to improved or new methods is highly limited as these methods are very costly to use and also require technical skills. Since researchers and clinicians in all corners of the globe are working hard, it is hoped that in the near future, they will develop good quality tests that can be accessible in low-income countries. - Some of the metrics are blocked by yourconsent settings
Publication Polymorphisms in Maternal Selected Folate Metabolism-Related Genes in Neural Tube Defect-Affected Pregnancy(Medknow, 2023-06) ;Winner K. Dewelle ;Daniel S. Melka ;Abenezer T. Aklilu ;Mahlet Y. Gebremariam ;Markos A. Alemayehu ;Dawit H. Alemayehu ;Tamrayehu S. WoldemichaelSolomon G. GebreBackground: Neural tube defects (NTDs) are abnormalities of the brain and spinal cord, which occur as a result of failure in neural tube closure during embryogenesis. Causes of NTDs are complex and multiple, with hereditary, lifestyle, and environmental factors appearing to play a role. In spite of their impact on public health, the role genetics play on NTDs in Ethiopia is lacking. In this study, the role of polymorphisms in MTHFR 677C > T (rs1801133), MTHFR 1298A > C (rs1801131), MTRR 66A > G (rs1801394), RFC1 80A > G (rs1051266), and TCN2 776C > G (rs1801198) on the risk of having NTD-affected pregnancy was investigated. Materials and methods: One hundred women with NTD-affected pregnancy and 100 women with normal pregnancy were included in the study. DNA was extracted from saliva and genotyping for five polymorphisms in four genes was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The departure of the genotype's distribution from Hardy-Weinberg equilibrium (HWE) was evaluated using the x2 goodness-of-fit test. Frequencies of genotypes and alleles in case and control mothers were determined and differences between relative frequencies were evaluated by the x2 or the Fisher's exact test. Results: The statistically significant difference was absent in the genotype and allele frequencies for all the analyzed polymorphisms between cases and controls (P > 0.05). Conclusion: MTHFR 677C > T, MTHFR 1298A > C, MTRR 66A > G, RFC1 80A > G, and TCN2 776C > G polymorphisms lack association with the risk of having a pregnancy affected by NTD. The role of other genes or environmental factors in NTD etiology needs to be investigated. - Some of the metrics are blocked by yourconsent settings
Publication Prevalence of Hyperhomocysteinaemia and Associated Factors among Ethiopian Adult Population in a 2015 National Survey(Wiley, 2020-01-11) ;Feyissa Challa ;Tigist Getahun ;Meron Sileshi ;Bikila Nigassie ;Zeleke Geto ;Genet Ashibire ;Terefe Gelibo ;Solomon Teferra ;Daniel Seifu ;Yohannes Sitotaw ;Abebe Bekele ;Ebba Abate ;Kaleab BayeMarco SciosciaHyperhomocysteinaemia (HHcy) is an independent risk factor for major cardiovascular diseases, but data on the prevalence and predictors of HHcy in low- and middle-income countries like Ethiopia are scant. The aim of this study was to estimate the prevalence of HHcy and associated risk factors in the Ethiopian adult population. A cross-sectional survey on risks of noncommunicable diseases (NCDs) using the STEPwise approach to surveillance (STEPS) survey was conducted between April and June 2015. A total of 4,175 study participants were surveyed. Serum homocysteine (Hcy) and metabolic profile were determined using Cobas Integra 400 Plus and CardioChek PA analyzer, respectively. Factors associated with HHcy were determined using logistic regression. The mean serum tHcy concentration was 14.6 μmol/L, with 16.4 μmol/L in males and 13.4 μmol/L in females. Overall, 38% had HHcy, with figures in males (49%) higher than females (30%). Increased age, being male, and high blood pressure and/or taking blood pressure medication, as well as low consumption of fruit and/or vegetables, were independent risk factors for HHcy. In conclusion, the prevalence of HHcy among the adult Ethiopian population is alarmingly high. Improving diets through the promotion of fruit and vegetable consumption is needed to reduce the risk of NCDs.