Class 3 PI3K coactivates the circadian clock to promote rhythmic de novo purine synthesis.

Metabolic demands fluctuate rhythmically and rely on coordination between the circadian clock and nutrient-sensing signalling pathways, yet mechanisms of their interaction remain not fully understood. Surprisingly, we find that class 3 phosphatidylinositol-3-kinase (PI3K), known best for its essential role as a lipid kinase in endocytosis and lysosomal degradation by autophagy, has an overlooked nuclear function in gene transcription as a coactivator of the heterodimeric transcription factor and circadian driver Bmal1-Clock. Canonical pro-catabolic functions of class 3 PI3K in trafficking rely on the indispensable complex between the lipid kinase Vps34 and regulatory subunit Vps15. We demonstrate that although both subunits of class 3 PI3K interact with RNA polymerase II and co-localize with active transcription sites, exclusive loss of Vps15 in cells blunts the transcriptional activity of Bmal1-Clock. Thus, we establish non-redundancy between nuclear Vps34 and Vps15, reflected by the persistent nuclear pool of Vps15 in Vps34-depleted cells and the ability of Vps15 to coactivate Bmal1-Clock independently of its complex with Vps34. In physiology we find that Vps15 is required for metabolic rhythmicity in liver and, unexpectedly, it promotes pro-anabolic de novo purine nucleotide synthesis. We show that Vps15 activates the transcription of Ppat, a key enzyme for the production of inosine monophosphate, a central metabolic intermediate for purine synthesis. Finally, we demonstrate that in fasting, which represses clock transcriptional activity, Vps15 levels are decreased on the promoters of Bmal1 targets, Nr1d1 and Ppat. Our findings open avenues for establishing the complexity for nuclear class 3 PI3K signalling for temporal regulation of energy homeostasis.

Knowledge, attitude, and practices toward chronic kidney disease among care providers in Jimma town:cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a common and growing health problem that requires adequate Knowledge by health care providers to reduce the progress of the disease. Thus, this study aimed to assess the care provider's Knowledge, attitude, and practices toward CKD. METHOD: A cross-sectional study conducted among 326 care providers at Jimma University Specialized hospital and three medium to higher clinics found in Jimma Town. Collected data entered into Epi-Data version 3.1 and exported to SPSS version 21 for windows for data analysis. Descriptive statistics and generalized linear modal used to analyze the data. RESULT: The mean age and service year of the participants were 29.68(±4.877) and 4.28(±4.561), respectively. The overall weighted Knowledge, attitude, and practice score of the study participant were 9.0971(8.77, 9.42), 2.53(2.4, 2.65), 10.14(9.94, 10.33) respectively. Over half of the care providers had the awareness to use eGFR to assess kidney function and patient referral to Nephrologists. Also, many care providers knew the five-stage of CKD and the risk factors of CKD, such as diabetes, long-term alcohol consumption, anemia, and cardiovascular disorders, respectively. Care providers had an understanding of late detection, and referral of CKD would increase kidney disease complications. Besides, 275(84.4%) of them are worried about treatment costs related to CKD. Over half of the care providers, 238(73.0%), believed that the Ethiopian ministry of health gave less attention to the problem. Furthermore, 234(71.8%) are interested in studying more on CKD management. Majority 256(78.5%), very likely or likely refer the patient to senior physician and Nephrologist. CONCLUSION: Care providers showed enough Knowledge, a favorable attitude, and practice toward CKD.

Knowledge, attitude and willingness to donate organ among medical students of Jimma University, Jimma Ethiopia: cross-sectional study.

BACKGROUND: The lack of organ donors has become a limiting factor for the development of organ transplantation programs. Many countries are currently facing a severe shortage of organs for transplantation. Medical students, as future doctors can engage in the role of promoting organ donation by creating awareness and motivating the community to donate their organs besides their voluntary organ donation. The aim of this study is to assess the knowledge, attitude and willingness of undergraduate medical students' towards organ donation at Jimma University. METHODS: A cross-sectional study was conducted among 320 medical students from year I to internship using questionnaire in order to assess their knowledge, attitude and willingness regarding organ donation. Data collected was entered using epidata and analyzed using Statistical Package for Social Sciences (SPSS) software version 20. RESULTS: Mean (±SD = standard deviation) age of participants was 23.48 ± 17.025 years. 57.8% of the study subjects were male. There was a statistically significant interaction effect between gender and year of study on the combined knowledge questions (dependent variables) F(25,062) = 1.755,P = 0.014, Wilk's Λ = .033. Variables which were related to a positive attitude towards organ donation were: being of the male sex (Odds Ratio = 1.156); having awareness about organ donation (Odds Ratio = 2.602); not having a belief on the importance of burying intact body (Odds Ratio = 5.434); willingness to donate blood (Odds Ratio = 4.813); and willingness to donate organ (Odds Ratio = 19.424). CONCLUSION: High level of knowledge but low level of positive attitude and willingness was noticed among the study participants toward organ donation.

Care Provider's Knowledge and Attitude Toward Organ Donation in Jimma Town, Ethiopia: Cross-Sectional Study.

INTRODUCTION: Ethiopia is a country in sub-Saharan Africa with a population of 100 million people. The incidence and prevalence of end-stage organ failure seems to be a growing health problem in the country. Transplant legislation was drafted years ago by the federal minster of health in Ethiopia, but the number of donors is still low. Thus, we aimed to assess care providers' knowledge and attitude toward organ donation so they will be volunteer advocates for the public to increase organ donation in the country. METHOD: A cross-sectional survey was conducted at 3 main higher private clinics and at Jimma University Specialized Hospital (JUSH) in Ethiopia from February 25, 2018, to June 21, 2018. Knowledge measuring questions had 2 possible answers (yes or no). The attitudes domain was measured with an "Agree" and "Disagree" categorical response scale. Data was entered to Epi-Data version 3.1 and exported to SPSS version 21 for Windows (IBM-SPSS Statistics 21, IBM, Armonk, NY) for data analysis. Descriptive statistics and a generalized linear model were used to analyze the data. RESULTS: In total, 326 care providers were involved in the study. The mean age and service year of the participants were 29.68 (± 4.877) and 4.28 (± 4.561), respectively. The overall weighted knowledge and practices scores were 4.344 (4.214, 4.473) and 5.64 (5.39, 5.89), respectively. Majority care providers had an understanding about brain death and the definition of organ donation. Over half of the care providers agreed to donate organs in the future; additionally, they believed there was no strict association between religion and organ donation. Furthermore, many care providers believed in the advertisement and promotion of organ donation to raise public awareness. CONCLUSION: Care providers showed good knowledge and attitudes toward organ donation. The findings may encourage health care workers to provide better counseling to improve organ donation.

Health sciences students knowledge, attitude and practices with chronic kidney disease in Jimma University, Ethiopia: cross-sectional study.

OBJECTIVE: The objective of this study was to assess knowledge, attitude and practices of undergraduate health sciences students toward chronic kidney disease at Jimma University. RESULTS: The overall weighted knowledge, attitude and practices score of the students were 8.6042 (8.26, 8.95), 6.23 (5.93, 6.53) and 2.51 (2.35, 2.67). Many students knew the basic function, symptoms and risk factors of chronic kidney disease. However, the same number of students showed a lack of diagnosis knowledge. Generally, students showed a favorable attitude and practice toward chronic kidney disease. However, they had a poor habit of a hospital visit for routine kidney checkup because of the socio-economic factors. The current study concludes that, despite students showed a good level of knowledge, attitude, and practices toward chronic kidney disease poor knowledge of kidney diagnosis methods and poor practice of visit to biomedical clinics for regular kidney checkup observed.

Non-Alcoholic Fatty Liver Disease and Associated Factors among Type 2 Diabetic Patients in Southwest Ethiopia.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic fatty liver disease and associated factors among type 2 diabetic patients in Southwestern Ethiopia attending Diabetic Clinic of Jimma University Specialized Hospital (JUSH). METHODS: Facility based cross-sectional study design was used. Anthropometry, fatty liver (using utrasonography), liver enzymes, and lipid profiles were measured among type 2 diabetic patients who fulfilled the inclusion criteria. Socio-demographic and clinical characteristics were assessed using standard questionnaires. RESULTS: Ninety-six (96) type 2 diabetic patients were enrolled and non-alcoholic fatty liver disease prevalence was 73%. Of non-alcoholic fatty Liver disease documented patients, 35.4%, 31.3% and 6.3% exhibited mild, moderate and severe fatty liver diseases, respectively. Alanine aminotransferase (p ≤0.001), Triacyglycerol (p ≤0.001), total bilirubin (p ≤0.05), direct bilirubin (p ≤0.05) and diabetic duration (p ≤0.01) were significantly associated with non-alcoholic fatty liver disease among type 2 diabetic patients. The Aspartate aminotransferase/Alanine aminotransferase ratio among non alcoholic fatty liver disease patients was greater than one. CONCLUSIONS: The magnitude of non-alcoholic fatty liver disease is high among study groups and it needs urgent action by healthcare systems. Therefore, targeted treatment approach inclusive of non-alcoholic fatty liver disease should be designed.

Association of trace metal elements with lipid profiles in type 2 diabetes mellitus patients: a cross sectional study.

BACKGROUND: It is well known that dyslipidemia and chronic hyperglycemia increase the onset of diabetes and diabetic complication. The aim of this study is to see the association of trace metals elements and lipid profile among type 2 diabetes mellitus patients. METHODS: The study was conducted on 214 type 2 diabetic patients at Jimma University Specialized Hospital, Jimma, Ethiopia. All the eligible study participants responded to the structured interviewer administered questionnaire and fasting venous blood was drawn for biochemical analysis. Trace metal elements (zinc(Zn+2), magnesium(Mg+2), chromium(Cr+3), calcium(Ca+2), phosphorus(Po4-3), manganese(Mn+2), copper(Cu+2), and iron(Fe+3)) and lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), and triglycerides (TG)) were measured by atomic absorption spectrophotometry and enzymatic determination method respectively. Data were analyzed by SPSS version 24 software for windows. Bonferroni correction for multiple statistical comparisons was used and a p-value less than 0.01 were accepted as a level of significance. RESULT: The mean age of study participants was 42.95(±12.6) with an average of 5.83(±3.1) years being diagnosed with diabetes mellitus. The BMI of female (27.1(±4.9)) was significantly higher than male (25.21(±4.2)). BMI shows positive and significant (p < 0.01) association with lipid profiles (TC, LDL-C, and TG) among type 2 diabetic patients in the liner regression model. In addition, WH-R was positively associated with TG. In Pearson partial correlation adjusted for sex and age, Za+2 shown to have statistically significant and negative correlations with TC, LDL-C and with TG. Mg+2 and Cr+2 negatively and significantly correlated with the lipid profile TC and LDL-C. Ca+2 negatively correlated with TC and TG. Po-34 positively correlated with HDL-C; iron negatively correlated with TC. However, in the liner regression model, only calcium positively and significantly (Beta = -0.21, p < 0.01) associated with TG. CONCLUSION: In the current study, a negative correlation was observed between trace metal elements (Zn+2, Mg+2, Cr+3, Ca+2 and Fe+3) and lipid profile (TC, LDL-C and TG) among type 2 diabetes mellitus patients. In addition, Ca+2 observed to be associated with TG. Future studies are highly advised to uncover the bidirectional association between trace metal element and dyslipidemia in diabetic patients.

Burden and associated factors of anemia among pregnant women attending antenatal care in southern Ethiopia: cross sectional study.

BACKGROUND: Anemia is a condition in which the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiologic needs, which varies by age, sex, altitude, smoking, and pregnancy status. The study aim is to determine the prevalence and factors associated with anemia among pregnant women attending a hospital in southern Ethiopia using a structured interview administered questionnaire. METHODS: Facility-based cross-sectional study was conducted from March 01-April 30 2015 at Butajira General Hospital, Ethiopia. A total of 217 women responded to the questionnaire and provided blood and stool samples for analysis. Data were analyzed using Statistical packages for social sciences version 20 for windows. RESULT AND CONCLUSIONS: The overall burden of anemia in this study was 27.6%. Residence, ANC follow up, history of excess menstrual bleeding and interpregnancy interval were statistically associated with anemia among the pregnant women. Therefore, working in the identified gaps could reduce the current burden of anemia among pregnant women in the study area.

Association between thyroid hormone parameters and dyslipidemia among type 2 diabetes mellitus patients: Comparative cross-sectional study.

BACKGROUND: The relationship between thyroid function and lipid profile has been documented in T2DM and healthy subjects. The aim of the current study was to assess the association between thyroid hormone parameters and dyslipidemia in T2DM and non-diabetic study participants. METHOD AND MATERIALS: In this comparative cross-sectional study, 214 type 2 diabetic and 214 non-diabetic study participants were enrolled. Clinical and anthropometric data were collected from all study participants. After overnight fasting, 10ml of whole blood samples were drawn for the measurement of serum TSH, free thyroxine (fT4), free triiodothyronine (fT3), serum reactive C-protein levels, as well as for lipid profile test and glucose. RESULT: The burden of hypothyroidism and subclinical hypothyroidism among T2DM study participants were 73 (17.05%) and 13 (3.04%) respectively. Comparatively, T2DM study participants had significantly higher serum lipid level than non-diabetics. Stratified by TSH, hypothyroid T2DM study participants had increased lipid level than euthyroid subjects. T2DM serum TSH have shown a positive significant correlation with all lipid profile parameters except HDL-C. In the final model (multivariate linear regression), diabetics serum TSH significantly and positively associated with TG and BMI. Diabetic serum fT3 and fT4 negatively associated with body mass index. In addition, diabetics serum fT3 negatively and serum fT4 positively associated with TC and HDL-C respectively. CONCLUSION: T2DM study subjects had significantly higher lipid level than nondiabetic and We identified that TSH was positively associated with serum TG and BMI among T2DM study participants.

Evaluation of serum ferritin and some metal elements in type 2 diabetes mellitus patients: comparative cross-sectional study.

BACKGROUND: The chronic hyperglycemia of diabetes has been associated with an imbalance of some trace metal elements in the blood sample of type 2 diabetes patients. AIM: To evaluate the status of serum ferritin and some selected metal elements among type 2 diabetes mellitus (T2DM) patients. METHODS: Facility-based comparative cross-sectional study was conducted from February 15, 2015 to October 30, 2015, at Jimma University Specialized Hospital, Ethiopia. A total of 428 type 2 diabetes and nondiabetes study subjects were recruited to the study. After overnight fasting, 10 mL of venous blood samples were taken for biochemical and trace metal element analysis. Data were entered into EpiData version 3.5.1 and exported to SPSS version 20 for Windows for analysis. RESULTS: Serum concentration of Zn+2, Mg+2, Cr+3, ferritin, and Fe+3 in patients with type 2 diabetes was significantly lower (p<0.0001) than nondiabetes patients. In contrast, serum Cu+2 was significantly higher (p<0.0001) in type 2 diabetes patients than nondiabetics. In addition, significant differences were not seen in both groups with regard to serum Mn+2, Ca+2, and Po4-3. Waist-to-hip ratio (WHR), serum Fe+3, ferritin, and Mn+2 were significantly higher among oral hypoglycemic agent users of type 2 diabetes patients than the injectable insulin users. Serum Zn+2 had significant positive correlation with serum Mg+2 (r=0.738), Cr+3 (r=0.233), Ca+2 (r=0.238), and Po4-3 (r=0.222). In addition, serum Zn+2 had shown significant and negative correlation with body mass index (BMI, r=-0.331), WHR (r=-0.340), and fasting blood glucose (FBG, r=-0.186). Likewise, serum Mg+2 and Po4-3 are significantly and negatively correlated with BMI, WHR, and FBG. CONCLUSION: The imbalance of trace metal elements in the blood sample of diabetes is uncertain. Thus, we recommend a prospective cohort study to find out the principal factors behind the problem.