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Sökning: WFRF:(Tadele T)

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  • Amouzou, A, et al. (författare)
  • Health service utilisation during the COVID-19 pandemic in sub-Saharan Africa in 2020: a multicountry empirical assessment with a focus on maternal, newborn and child health services
  • 2022
  • Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 7:5
  • Tidskriftsartikel (refereegranskat)abstract
    • There are concerns about the impact of the COVID-19 pandemic on the continuation of essential health services in sub-Saharan Africa. Through the Countdown to 2030 for Women’s, Children’s and Adolescents’ Health country collaborations, analysts from country and global public health institutions and ministries of health assessed the trends in selected services for maternal, newborn and child health, general service utilisation.MethodsMonthly routine health facility data by district for the period 2017–2020 were compiled by 12 country teams and adjusted after extensive quality assessments. Mixed effects linear regressions were used to estimate the size of any change in service utilisation for each month from March to December 2020 and for the whole COVID-19 period in 2020.ResultsThe completeness of reporting of health facilities was high in 2020 (median of 12 countries, 96% national and 91% of districts ≥90%), higher than in the preceding years and extreme outliers were few. The country median reduction in utilisation of nine health services for the whole period March–December 2020 was 3.9% (range: −8.2 to 2.4). The greatest reductions were observed for inpatient admissions (median=−17.0%) and outpatient admissions (median=−7.1%), while antenatal, delivery care and immunisation services generally had smaller reductions (median from −2% to −6%). Eastern African countries had greater reductions than those in West Africa, and rural districts were slightly more affected than urban districts. The greatest drop in services was observed for March–June 2020 for general services, when the response was strongest as measured by a stringency index.ConclusionThe district health facility reports provide a solid basis for trend assessment after extensive data quality assessment and adjustment. Even the modest negative impact on service utilisation observed in most countries will require major efforts, supported by the international partners, to maintain progress towards the SDG health targets by 2030.
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  • Basic, Vladimir T., 1982-, et al. (författare)
  • Chronic cigarette smoke exposureimpairs skeletal muscle regenerative capacity in murineCOPD/emphysema model.
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Cigarette smoke (CS) is a well established risk factor in the development of COPD and irreversible airflow limitation. In contrast, the extent to which CS exposure contributes to development of peripheral skeletal muscle dysfunction and wasting remains largely unknown. Decline in skeletal muscle regenerative capacity has been previously reported in COPD patients.Methods: To investigate effects of chronic CS exposure on skeletal muscle regenerative capacity, 129/SvJ mice were exposed to CS for 6 months. The expression levels of myogenin, Jarid2, Znf496, Notch1, Pax7, Fgf1 and Myh3, which are known to regulate skeletal muscle myogenesis, were studied. Additionally, number of fibers with central nuclei, myonuclei number and mean fiber cross-sectional area were assessed.Results: Compared to controls, skeletal muscles from CS-exposed mice exhibited significantly decreased expression of Jarid2, coupled with enhanced expression of Znf496, Notch1, Pax7, Fgf1 and Myh3. Expression of myogenin, a marker of terminally differentiated myofibers, was reduced. Furthermore, reduced muscle fiber crosssectional area, increased number of fibers with central nuclei and reduced myonuclei number were also observed in CS-exposed animals.Conclusions: Taken together, current results provide evidence linking chronic CS exposure and an ongoing damage/repair process as well as impaired regenerative capacity in skeletal muscles of CS-exposed mice.
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  • Basic, Vladimir T., et al. (författare)
  • Cigarette smoke exposure up-regulates Ubiquitin specific protease 19 in murine skeletal muscles as an adaptive response to prolonged ER stress
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Enhanced protein degradation via ubiquitin proteolytic system (UPS) was demonstrated to play an important role in the pathogenesis of cachexia syndrome and muscle wasting in patients with COPD and animal models of the disease. The role of cigarette smoke (CS) exposure in eliciting these abnormalities remains largely unknown. Usp19 is a member of UPS suggested to be involved in progressive muscle wasting in different catabolic conditions. However, factors regulating Usp19 expression, activity and correlation/s with CS-induced muscle atrophy remainunclear.Methods: To address these questions, 129 SvJ mice were exposed to cigarette smoke for 6 months and the gastrocnemius muscles were collected. Expression levels of Usp19 as well as pivotal mediators of ER stress response have been studied using PCR, qPCR, western blot and immunofluorescence. Factors regulating muscle Usp19 expression were studied using in-silico analysis of Usp19 promoter as well as by stimulating C2C12 myocytes with different inducers of ER stress including hypoxia, TNF and tunicamycin. Finally, Usp19 expression was depleted in C2C12 myocytes using specific Usp19 siRNA quadriplex and the expression of pivotal myogenic regulators were analyzed.Results: Usp19 mRNA expression was enhanced in skeletal muscles of CS-exposed mice. Concurrently, ER stress-associated Caspase 12 and Caspase 3 were activated in the CS-exposed group. Analysis of Usp19 promoter sequence revealed binding sites for ER stress response transcription factors such as HSF, STRE1 and AML1-α. Exposure of C2C12 myocytes to tunicamycin but not hypoxia elevated expression levels of Usp19. TNFstimulation elevated Usp19 protein expression but inhibited its RNA transcription in a dose- and time-dependent manner. Finally, Usp19 overexpression in tunicamycin-treated myocytes was accompanied by reduced expression of myosin heavy chain and tropomyosin and their levels were increased after knocking down Usp19 in C2C12 myocytes.Conclusions: In summary, our data demonstrated elevated expression of Usp19 in skeletal muscles of CS-exposed 129 SvJ mice. Moreover, Usp19 overexpression was associated with muscle adaptations to ER stress and suppression of myogenesis. Taken together; our results might provide further insight into molecular mechanisms underlying development and progression of skeletal muscle abnormalities in response to chronic cigarette smoke exposure.
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  • Gebreyesus, TD, et al. (författare)
  • Efficacy and safety of praziquantel preventive chemotherapy in Schistosoma mansoni infected school children in Southern Ethiopia: A prospective cohort study
  • 2023
  • Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 14, s. 968106-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The World Health Organization recommends efficacy and safety surveillance of anti-helminths used in mass drug administration campaigns. We evaluated the effectiveness of single-dose praziquantel against Schistosoma mansoni infection, and the safety of praziquantel plus albendazole preventive chemotherapy (PC) in Schistosoma mansoni infected school children (n = 512) in Southern Ethiopia.Method: Stool examinations were done using thick smear Kato-Katz at baseline, week-4, and week-8 of post-Mass drug administration (MDA) to assess praziquantel efficacy. Participants were followed for MDA-associated adverse events up to day 7 of post-MDA. The primary and secondary study outcomes were praziquantel efficacy (parasitological cure and egg reduction rates) and MDA-associated adverse events (AEs), respectively.Result: The overall cure rates at week-4 and week-8 were 89.1% (95%CI = 86.1–91.7) and 87.5% (95%CI = 83.6–90.8), respectively. Cure rates among moderate-to-heavily infected children were significantly lower (p = 0.001) compared to those with light infection at week-4 (84.4% vs. 91.1%, p = 0.03) and week-8 (78.6% vs. 91.9%, respectively). Older children had a higher cure rate than younger ones at week-8 (90.1% vs. 79.5%, p = 0.01). Among those who were Schistosoma egg-free (cured) at week 4, 7.8% became egg-positive at week 8. The overall egg reduction rate (ERR) at week-4 and week-8 were 93.5% and 91.3%, respectively, being lower among the 5–9 years old age groups (p = 0.01) at week-8. The proportion of children who remained schistosoma egg-positive throughout the study follow-up period was 4.6%, and their ERR at week-4 and week-8 was 50% and 51%, respectively, which is below the 90% World Health Organization threshold for efficacy. The incidence of experiencing at least one type of MDA-associated AEs were 17.0% (95%CI = 13.8%–20.5%); abdominal pain, headache, and vomiting were the most common. The proportion of mild, moderate, and severe AEs was 63.2%, 26.3%, and 10.5%, respectively. Females experienced more AEs than males (p = 0.03).Conclusion: Single-dose praziquantel is still effective for the treatment of intestinal schistosomiasis. Praziquantel and albendazole preventive chemotherapy is safe and tolerable, and associated AEs are mostly mild-to-moderate and transient. However, the reduced PZQ effectiveness in moderate-to-heavy infection and observed AEs in about one-fifth of infected children underscores the need for better treatment strategies and surveillance for early detection of parasite resistance and management of AEs.
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  • Gebreyesus, TD, et al. (författare)
  • Prevalence, Intensity, and Correlates of Schistosomiasis and Soil-Transmitted Helminth Infections after Five Rounds of Preventive Chemotherapy among School Children in Southern Ethiopia
  • 2020
  • Ingår i: Pathogens (Basel, Switzerland). - : MDPI AG. - 2076-0817. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Preventive chemotherapy (PC) is a WHO-recommended strategy to control and eliminate schistosomiasis and soil-transmitted helminths (STHs). We assessed the prevalence, intensity, and correlates of schistosomiasis and STH infection after five rounds of PC in southern Ethiopia. A total of 3162 school children from four schools in Wondo Gennet and Hawella Tula districts were screened for Schistosoma mansoni and STHs infection. The overall prevalence of S. mansoni infection was 25.8% (range between schools 11.6% to 54.1%), with light (19.1%), moderate (5.3%), and heavy (1.4%) infection intensities. A total of 61.6% S. mansoni-infected children were STH co-infected. The overall prevalence of STHs infection was 54.7% (range between schools 30.6–71.0%), with moderate-to-heavy intensity infections being 16.3%. Ascaris lumbricoides was the most prevalent 45% (95% CI, 43.5–47) followed by Trichuris trichiura 25.3% (95% CI, 23.8–26.9) and hookworm 6.1% (95% CI, 5.3–7). A total of 33.7% of STHs-infected children had A. lumbricoides and T. trichiura co-infections. S. mansoni infection was significantly associated with school and STHs co-infection (p < 0.001). STH infection was correlated with school and younger age (p < 0.001). Despite repeated PC, S. mansoni and STH infection remain significant health problems, and the WHO target to control schistosomiasis and eliminate STH by 2020 may not be achieved. Intensified control and prevention measures, including drug efficacy surveillance, is recommended.
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  • Gebreyesus, TD, et al. (författare)
  • Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring
  • 2022
  • Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5–15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5–14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ2 = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas.
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