METTL3-mediated m6A modification of circGLIS3 promotes prostate cancer progression and represents a potential target for ARSI therapy.

BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported. METHODS: Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3. RESULTS: CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide. CONCLUSIONS: METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.

Appropriate definition of non-metastatic castration-resistant prostate cancer (nmCRPC) and optimal timing of androgen receptor signaling inhibitor (ARSI).

BACKGROUND: Defined by rising PSA levels under androgen deprivation therapy (ADT) despite no visible metastases on conventional imaging, non-metastatic castration-resistant prostate cancer (nmCRPC) represents a complex clinical challenge. A significant subset of these patients rapidly develops metastatic disease, negatively impacting survival. We examined the difference in prognosis of nmCRPC patients according to the timing of therapeutic interventions with androgen receptor signaling inhibitor (ARSI). METHODS: We examined 102 nmCRPC patients treated with ARSI. We divided patients according to their PSA levels when ARSI was administered: Cohort A (PSA 0.5-2.0 ng/mL), Cohort B (PSA 2.0-4.0 ng/mL), and Cohort C (PSA > 4.0 ng/mL). Utilizing the Kaplan-Meier method for survival analysis, our analytical starting point was the moment when PSA levels exceeded 0.5 ng/mL post-ADT nadir, ensuring a fair comparison and minimizing lead-time bias. RESULTS: After excluding 5 patients whose PSA nadir after ADT > 0.5 ng/mL, patient distribution across Cohort A, Cohort B, and Cohort C was 32, 24, and 41 patients, respectively. Kaplan-Meier survival analysis highlighted a 2-year metastasis-free survival rate of 97% for Cohort A, 87% for Cohort B, and 73% for Cohort C. A marked statistical difference emerged when comparing Cohort A with Cohorts B and C, with a p-value of 0.043. CONCLUSION: The timely initiation of ARSI is paramount in nmCRPC management. Our findings strongly advocate for consideration of ARSI administration in nmCRPC patients before their PSA levels exceed 2.0 ng/mL. Our results indicated a PSA threshold of 1.0 ng/mL for nmCRPC definition which is more reasonable to administer ARSI without delay.

Magnitude of malaria and associated factors among febrile adults in Siraro District Public Health facilities, West Arsi Zone, Oromia, Ethiopia 2022: a facility-based cross-sectional study.

BACKGROUND: Despite significant efforts made to control malaria in Ethiopia, the disease remains one of the top public health problems in the country. Baseline malaria prevalence and associated factor at high malaria area is important to guide malaria control interventions, there was paucity of information regarding the study area. Therefore, the aim of this study was to determine prevalence of malaria and associated factors among febrile adults in Siraro district health facilities, West Arsi Zone, Oromia, Ethiopia. METHODS: Institution-based cross-sectional study was conducted among 317 febrile adult patients at Siraro district health facilities. Structured pre-tested questionnaires were used to collect data. Epi-data version 3.1 and SPSS version 23 were used for data entry and analysis respectively. In order to identify factors associated with malaria infection bivariable and multivariable binary logistic regression analysis was employed, The Adjusted Odds Ratio (AOR) with a 95% confidence interval (CI) and p-value of < 0.05 was computed to show the strength of the association. RESULTS: The overall prevalence of malaria at the study area was 130 (41.0%) [(95% CI 35.3-46.7)]. Occupation (being farmer) [(AOR = 6.05; 95% CI 1.38, 26.49)], having poor knowledge on malaria transmission [(AOR = 2.95 95%; CI 1.48-5.88)], house with wood wall [(AOR = 2.71; 95% CI 1.34-5.49)], and number of windows (≥ 3) in the house [(AOR = 6.82; 95% CI 1.05, 44.40)] were identified to be significantly associated with magnitude of malaria in the study area. CONCLUSION: The prevalence of malaria at the study area was high as compared with the national wide figures. Being farmer, having poor knowledge on malaria transmission, and housing condition (house with wood wall and houses with three and above windows) were found to be significantly associated with malaria infection in the study area. Therefore, there has to be an emphasis on addressing the factors by providing sustainable health education for the communities to improve their housing condition and knowledge of community on the way of malaria prevention.

Determinants of defaulter to full vaccination among children aged 12-23 months in Siraro district, West Arsi zone, Oromia, Ethiopia: a case-control study.

BACKGROUND: Vaccination is one of the most cost-effective global public health interventions to reduce childhood morbidity and mortality. Defaulters to full vaccination can put children at greater risk of acquiring vaccine-preventable disease outbreaks. The reason for not receiving full vaccination is not well explored, and hence, there is limited evidence about defaulters of vaccination in Ethiopia. OBJECTIVES: To identify determinants of defaulter to full vaccination among children aged 12-23 months in Siraro District, West Arsi Zone, Oromia Region, Ethiopia. METHODS: A community-based unmatched case-control study was conducted among children aged 12-23 months from March 20 to April 30, 2022, with a total sample size of 444 (148 cases and 296 controls). Cases were children aged 12-23 months who had missed at least one routine vaccination dose, while controls were children who had received all of the recommended routine vaccinations. Consecutive sampling and simple random sampling techniques were used to select representative cases and controls respectively. Data were collected using a structured questionnaire, entered into Epi-data version 4.6, and exported to Statistical Package for Social Sciences version 26 for analysis. Logistic regression was used to identify determinants of the defaulter to full vaccination and the variables with p-value < 0.25 were recruited for multivariable analysis, and an adjusted odds ratio with a 95% confidence interval and a p-value of ≤ 0.05 was used to declare the statistical significance of the association. RESULT: Of the assessed determinants of the defaulter to full vaccination; inadequate knowledge of mothers/caretakers (AOR = 4.32, 95% CI:2.78-6.70), educational status of a father unable to read and write (AOR = 3.66, 95% CI:1.29-10.39), time to reach health facility ≥ 30 minutes (AOR = 2.45, 95% CI:1.51-3.97), not told about the type of vaccine received (AOR = 2.37, 95% CI;1.27-4.45), no parents discussion on vaccination (AOR = 2.16, 95% CI:1.24-3.79), home delivery (AOR = 2.43, 95% CI:1.39-4.25) and not participated in pregnant mother conference (AOR = 2.47, 95% CI = 1.35-4.49) were the identified determinants of the defaulter to full vaccination. CONCLUSION: Mother's' knowledge, father's education, place of delivery, time to reach a health facility, health workers who told the type of vaccine received, participation in pregnant mother conference, and parents' discussion on vaccination were the determinants of the defaulter to full vaccination status. Thus, the district health office should work on defaulters of vaccination by strengthening immunization service delivery and improving maternal knowledge on vaccination through pregnant mother conference participation.

The psychological impact and coping of Covid-19 pandemic among Arsi University students -Ethiopia.

The foremost initiative of this investigation was to scrutinize the psychological influence of COVID-19 pandemic and the coping strategies of Arsi university students. Descriptive survey method was applied to investigate the intended variables. Data for this study was collected via an internet of 420 students (245 females and 175 males) from those whose email addresses were randomly accessed. Data was collect through questionnaires. Mean, standard deviation and t-test were used to analysis the collected data. The findings revealed that the psychological impacts of covid-19 on both male and female students were high. The results also showed that there was statistically significant difference between males and females in terms of every mean item. Therefore, it is recommended to engage actively in different activities, and relying on reliable sources of information, taking rests and the like are some of the mentioned coping strategies of the students. Finally, besides the transmitting of educational programs through TV, motivational speech, mass consultation/education through mass media like radio and television to reach those students who were dispersed to different parts of the country incorporates additional dimension of combating the psychological pressure of COVID-19.

Predictors of time to recovery from uncomplicated severe acute malnutrition among 6-59 months children treated in out patient treatment in health posts of Nagele Arsi district: a retrospective cohort study.

BACKGROUND: Access to outpatient therapeutic feeding programs (OTP) for all children who have uncomplicated severe acute malnutrition (SAM) remains a global public health priority. Identifying predictors that determine time-to-recovery from severe acute malnutrition optimize therapeutic success. However, reliable evidence on the determinants of time to recovery at health posts was not available in Nagele Arsi district of South Ethiopia. OBJECTIVE: This study was aimed to identify determinants of time-to-recovery from uncomplicated SAM among children aged (6-59) months treated at an OTP in health posts of Nagele Arsi district, Southern Ethiopia. METHODS: Institutional based retrospective cohort study was conducted among 357 children treated in Negele Arsi district from July1, 2018 to June 30, 2020. The children were selected using simple random sampling from 20 health posts. SAM treatment outcomes were compared against international SPHERE standards. The average time-to-recovery was estimated using Kaplan-Meier survival curve and the independent predictors of time to recovery were determined using multivariable Cox-proportional hazard model. The strength of the association was done using adjusted hazard ratio (AHR) with 95% confidence intervals. Statistical significance was declared at p value < 0.05. The results were presented by text, tables and figures. RESULT: A total of 284 (79.6%) children recovered during follow up. The mean weight gain for recovered children was 4.7 + 2.4 g/kg/day. The median time-to-recovery was 44 days 95% CI (42.7-45.3). Children who received Amoxicillin, AHR =2.574, 95% CI (1.879-3.525); de-wormed, AHR = 1.519, 95% CI (1.137-2.031); received Vitamin A, AHR = 2.518, 95% CI, (1.921-3.301) and new admissions, AHR = 1.823, 95%CI, (1.224-2.715) were more likely to recover. However, those who admitted with non-edema, AHR = 0.256, 95% CI, (0.189-0.346); had cough at admission, AHR = 0.513, 95 CI, (0.366-0.719) and had diarrhea at admission AHR = 0.5, 95% CI, 0.5 (0.350-0.712) were less likely to recover. CONCLUSION AND RECOMMENDATION: The recovery rate was within the acceptable ranges of International Sphere Standards. Those children who had cough and diarrhea should be given due attention from health extension workers and program planners. Appropriate provision of routine medication and timely intervention of co-morbidity are needed to increase chance of early recovery.

Arylsulfatase I is a prognostic biomarker for head and neck squamous cell carcinoma and Pan-cancer.

BACKGROUND: Sulfatase gene family members mediate various biological functions in tumor stroma and tumor cell environments. However, the expressions and prognostic value of Arylsulfatase I (ARSI), a sulfatase gene family member, in head and neck squamous cell carcinoma (HNSC) have not been fully established. METHODS: Arylsulfatase I expressions in pan-cancer were profiled using publicly available databases. Then, univariate Cox regression, Kaplan-Meier, and the Pearson's correlation analyses were performed to determine correlations between ARSI expressions and cancer prognosis, immune cell status, and drug sensitivity. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to assess the potential mechanisms underlying ARSI functions in HNSC. RESULTS: Arylsulfatase I was highly expressed in 15 cancer types, with significant expressions in HNSC. Elevated ARSI levels were associated with worse prognostic outcomes in HNSC patients. In addition, GSVA and GSEA showed that ARSI was highly involved in tumor cell escape and inflammatory responses. Expressions of ARSI negatively correlated with tumor mutation burden or microsatellite instability and positively correlated with immune-related genes. Elevated ARSI expressions conferred poor tolerance to daporinad and sinularin, but increased cell sensitivity to dasatinib and XAV939. CONCLUSION: Arylsulfatase I is a promising prognostic and therapeutic target for HNSC.

Evaluation of health-related quality of life of Covid-19 patients: a hospital-based study in South Central Ethiopia.

BACKGROUND: Covid-19 causes a wide range of symptoms in patients, ranging from mild manifestations to severe disease and death. This study assessed the health-related quality of life (HRQOL) and associated factors of Covid-19 patients using primary data from confirmed cases in South Central Ethiopia. METHODS: We employed a facility-based, cross-sectional study design and conducted the study at the Bokoji Hospital Covid-19 treatment centre. A structured questionnaire and the EQ-5D-3L scale were used to collect the data for analysis. The HRQOL results measured by the EQ-5D-3L tool were converted to a health state utility (HSU) using the Zimbabwe tariff. The average health utility index and HSU-visual analogue scale across diverse sociodemographic and clinical characteristics were compared using the Mann-Whitney U test or Kruskal-Wallis test. We employed a multiple linear regression to examine factors associated with HSU values simultaneously. The data were analysed using STATA version 15. RESULTS: The overall mean HSU score from the EQ-5D was 0.688 (SD: 0.285), and the median was 0.787 (IQR 0.596, 0.833). The mean HSU from the visual analogue scale score was 0.69 (SD: 0.129), with a median of 0.70 (IQR 0.60, 0.80). Those who received dexamethasone and intranasal oxygen supplement, those with comorbidity, those older than 55 years and those with a hospital stay of more than 15 days had significantly lower HSU scores than their counterparts (p < .001). CONCLUSION: Covid-19 substantially impaired the HRQOL of patients in Ethiopia, especially among elderly patients and those with comorbidity. Therefore, clinical follow-up and psychological treatment should be encouraged for these groups. Moreover, the health utility values from this study can be used to evaluate quality adjusted life years for future cost-effectiveness analyses of prevention and treatment interventions against Covid-19.

Performance of Arsi-Bale sheep fed urea treated maize cob as basal diet and supplemented with graded levels of concentrate mixture.

The experiment was conducted using 20 yearling intact male Arsi-Bale sheep with a mean body weight of 20.56 ± 0.45 (mean ± SD) to investigate the performance and economic benefit of graded levels of concentrate supplementation to urea-treated maize cob (UTMC)-based diet. The experiment consisted of 7 days of digestibility trial and subsequent 90 days of feeding trial. Before the commencement of the experiment, sheep were vaccinated against common infectious diseases, dewormed, and disinfected against internal and external parasites, respectively. The experimental design was randomized complete block design. The sheep were grouped into five blocks of four animals based on their initial body weight, and one animal from each block was randomly assigned to one of the four treatments. The treatments included ad libitum feeding of UTMC (T1) and supplementation with a concentrate mixture composed of wheat bran (WB) and noug seed cake (NSC) in 2:1 ratio, which were offered at 150 g (T2), 250 g (T3), and 350 g (T4) DM/head/day. The CP content of the UTMC was 9.3% on DM basis. The daily DM intake of UTMC was higher (P < 0.001) for T4 (614.6 g) compared to T1 (505.1 g), T2 (538.9 g), and T3 (590.3 g). Total DM intake was higher (P < 0.001) for supplemented treatments T2 (688.4 g), T3 (844.1 g), and T4 (966.9 g). Supplementation did not improve (P > 0.05) digestibility of DM, OM, NDF, and ADF, except CP digestibility which was significant (P < 0.001) across treatments. Supplementation increased (P < 0.001) final body weight (FBWT), feed conversion efficiency (FCE), and average daily weight gain (ADG). The average daily gain (ADG) was highest (P < 0.001) in T4 (80.8 ± 7.74 g/day) followed by T3 (33.3 ± 7.74 g/day) and T2 (23.1 ± 0.95 kg) whereas the un-supplemented animals lost about 9.2 g/day. The highest total return, net income, and marginal rate of return were observed in higher level supplemented sheep than the control. Therefore, T4 improved biological performance and marginal rate of return than the other treatments and can be considered as better alternative feed supplement in UTMC-based feeding of Arsi-Bale sheep in Ethiopia.

Effects of feeding different varieties of faba bean (Vicia faba L.) straws with concentrate supplement on feed intake, digestibility, body weight gain and carcass characteristics of Arsi-Bale sheep.

OBJECTIVE: A study was conducted to evaluate the varietal differences among faba bean straws and also to assess the potentials of faba bean straws supplemented with concentrate fed at the rate 70% straws and 30% concentrate mixture on feed intake, digestibility, body weight gain and carcass characteristics of the animals. METHODS: Forty yearling Arsi-Bale sheep with initial body weight of 19.85±0.29 kg (mean± standard deviation) were grouped in a randomized complete block design into eight blocks of five animals each based on their initial body weight. Straws included in the study were from Mosisa (T1M), Walki (T2W), Degaga (T3D), Shallo (T4S), and local (T5L) varieties of faba bean and concentrate (2:1 ratio of wheat bran to "noug" seed cake). The experiment consisted of seven days of digestibility and 90 days of feeding trials followed by evaluation of carcass parameters at the end. RESULTS: Local variety had lower (p<0.05) in grain and straw yield compared to improved varieties but higher in crude protein, metabolizable energy contents and in vitro organic matter digestibility. The apparent digestibility of dry matter and crude protein of sheep fed Walki and Mosisa straws were higher than (p<0.05) straws from Shallo varieties. Sheep fed Walki straw had greater (p<0.05) dry matter intake, average daily gain and feed conversion efficiency than sheep fed local and Shallo straws. Slaughter body weight and empty body weight were higher (p<0.05) for sheep fed Mosisa and Walki straws as compared to sheep fed Shallo straws. Apart from this, the other carcass components were not affected (p>0.05) by variety of the faba bean straws. CONCLUSION: There is significant varietal differences between faba bean straws both in quality and quantity. Similarly, significant variation was observed in feed intake, digestibility, body weight gain and feed conversion efficiency among sheep fed different straws of faba bean varieties with concentrate supplement. Based on these results, Walki and Mosisa varieties could be recommended as pulse crop rotation with cereals in the study area.

Prevalence and Incidence of Smear-Positive Pulmonary Tuberculosis in the Hetosa District of Arsi Zone, Oromia Regional State of Central Ethiopia.

BACKGROUND: The real burden of smear-positive (PTB+) and bacteriologically confirmed tuberculosis (BCTB) in Ethiopia is not known. Thus, the aim of this community-based study was to measure the prevalence and incidence of tuberculosis in the Hetosa District of Oromia Region, Ethiopia. METHODS: First, a population-based cross-sectional survey was conducted on a total of 33,073 individuals aged ≥ 15 years to determine the prevalence of PTB+ and BCTB cases. Then, in order to determine the incidence, a prospective follow-up was carried out on 32,800 individuals found to be either free from symptoms suggestive of TB (SSTB) during the baseline survey or had symptoms suggestive of TB but yielded negative bacteriological examination results. We identified 1,041 presumptive TB cases at the baseline survey, and 1,468 in the follow-up study. Each participants with cough of more than two weeks were provided spot and morning sputum samples for acid-fast bacilli sputum microscopy and culture. RESULTS: At the baseline survey, 43 BCTB cases were identified. Thirty six of these were both smear- and culture-positive while seven were only culture-positive. In the follow-up study, however, 76 BCTB cases were diagnosed and 70 of these were found to be both smear- and culture-positive while six were culture-positive only. The adjusted prevalence of PTB+ and BCTB in the study area was 109 and 132/100,000 persons, respectively. Moreover, the incidences of PTB+ and BCTB were 214 and 232/100,000 persons per year (py), respectively. The ratio of the passive to active case finding was 1:0.96 (45/43). For every TB case identified through the existing passive case diagnosis, there was an almost equal number (0.96) of undiagnosed infectious TB cases in the community. A family history of TB contact was independently associated with a high risk of TB (TB prevalence, AOR, 13; 95% CI: 6.55-15.33) and (TB incidence, aIRR 4.11, 95% CI: 2.18-7.77). CONCLUSIONS AND RECOMMENDATIONS: The prevalence and incidence of smear-positive and bacteriologically confirmed TB cases were high in the study area. For every case of smear-positive TB receiving treatment, there was an almost equal (0.96) number of undetected infectious bacteriologically confirmed TB case in the community. The high proportion of undetected infectious TB cases in the community could possibly be due to the sub-optimal performance of Directly Observed Treatment Short-course (DOTS) in detecting 70% of infectious TB cases, as well as attaining a cure rate of 85% in the study area. Family history of TB contact has substantaially increased the risk of developing the disease, and there is a need to improve ways of identifying TB cases and intensify mechanisms of tracing contacts among household members of PTB+ cases.

Outcomes of First-Line Abiraterone Acetate or Enzalutamide for Older Adults With Metastatic Castration-Resistant Prostate Cancer According to Use of Upfront Docetaxel for Metastatic Castration-Sensitive Prostate Cancer in an International Multicenter Registry: A SPARTACUSS-Meet-URO 26 Study.

BACKGROUND: Managing metastatic castration-resistant prostate cancer (mCRPC) in men aged ≥ 75 is challenging due to limited data. Regardless of age, in real-world clinical practice, most mCRPC still derive from failure of androgen deprivation therapy (ADT) with or without docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC). As abiraterone acetate plus prednisone (AA) and enzalutamide (Enza) are common first-line treatments for mCRPC. The impact of prior use of D for mCSPC on the efficacy and safety of AA or Enza in this older population remains unclear. METHODS: A cohort of patients aged ≥ 75 years starting AA or Enza as first-line therapy for mCRPC from January 2015 to April 2019 was identified from the registries of 10 institutions. Patients were categorized into 2 groups based on previous use of D for mCSPC. Primary endpoints were cancer-specific survival (CSS) from AA or Enza start, CSS from ADT onset, and safety. We used Kaplan-Meier method to estimate the endpoints distribution, including median values with 95% confidence intervals (95% CI). RESULTS: Of the 337 patients identified, 24 (7.1%) received ADT+D and 313 (92.9%) received ADT alone for mCSPC. Median follow-up from AA/Enza start was 18.8 months. Median CSS from ADT or AA/Enza was not significantly different between ADT+D and ADT alone cohorts (71.9 vs. 52.7 months, P = .97; 25.4 vs. 27.2 months, P = .89, respectively). No statistically significant difference in adverse events (AEs) of any grade rate (58.3% vs. 52.1%, respectively; P = .67) or grade ≥ 3 (12.5% vs. 15.7%, respectively; P = 1.0) was found between ADT+D and ADT alone cohorts. CONCLUSIONS: Despite the innate limitations of a retrospective design and relatively small size of the ADT+D cohort, this analysis suggests that elderly men receiving AA or Enza as first-line therapy for mCRPC have similar survival outcomes and tolerability, regardless of previous D for mCSPC.

Importance of 3ß-hydroxysteroid dehydrogenases and their clinical use in prostate cancer.

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3ß-hydroxysteroid dehydrogenases (3ßHSDs) play critical roles in extragonadal androgen synthesis, especially 3ßHSD1. Increased expression of 3ßHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3ßHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3ßHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3ßHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3ßHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

Hemiparesis Caused by Cerebral Venous Sinus Thrombosis during the Postpartum Period: A Case Report; Negelle Arsi General Hospital and Medical College, Ethiopia.

Background: Although rare, cerebral venous sinus thrombosis (CVT) can result in significant neurological complications, particularly after childbirth. Early diagnosis poses a challenge due to symptom overlap with other conditions. Limited publications and underdiagnosis of CVT are prevalent in developing nations, notably in Ethiopia. Case: A 29-year-old mother, having given birth four times, presented to the emergency department in her second month postpartum with complaints of persistent headaches and blurred vision over three weeks. Additionally, she reported sudden weakness on her right side for one day. Despite previous treatments for migraine headaches, she was diagnosed with CVT after magnetic resonance imaging/venography revealed blockage in the right anastomotic vein and the posterior segment of the superior sagittal sinus. Treatment commenced with the anticoagulant enoxaparin. During hospitalization, she experienced one episode of generalized seizures, leading to transfer to the intensive care unit where phenytoin was added. Subsequent diagnosis of papilledema occurred. After a 16-day hospital stay, she was discharged with warfarin, phenytoin, and acetazolamide. Oral anticoagulation and other medications ceased after six months of treatment, considering the postpartum period as a temporary risk factor for CVT. The patient currently maintains good health and has resumed normal activities. Conclusion: Maintaining a high index of suspicion for CVT during the postpartum period and promptly conducting imaging scans are crucial for early diagnosis. This approach can halt neurological decline and facilitate immediate recovery through early therapeutic interventions.

Nutritional knowledge, nutritional status and associated factors among pregnant adolescents in the West Arsi Zone, central Ethiopia.

When pregnancy occur among teenagers; there is a competition for nutrients between the still-growing adolescent mother and her fetus. Pregnant adolescents' nutrition issues are not addressed well and changes are too slow in Ethiopia. This study aimed to study, nutrition knowledge, nutritional status and associated factors among pregnant adolescents in West Arsi , central Ethiopia. We conducted a cross-sectional study of 426 pregnant adolescents between January 1 and January 25, 2023. Data were collected using kobo collect and analyzed using SPSS version 25. We performed linear regression to identify independent predictors of nutritional status and multivariable logistic regression analyses to identify nutritional knowledge. Odds ratios (ORs) with 95% confidence intervals were estimated to show the strength of the association. Magnitude of good nutrition knowledge was 23.7%, 95% CI (21.4-25.3%), and the odds of having good nutrition knowledge was 7.5 times higher among participants whose education level was above college compared with illiterate participants [(AOR = 7.5, 95% CI = (5.27-9.38)],the odds of having good nutrition knowledge was 8 times higher among adolescent who had ANC visits, [(AOR = 8, 95% CI = (3.63-13.85)], and the odds of having good nutrition knowledge was 5 times higher among adolescents who received nutrition education [(AOR = 5, 95% CI = (3.67- 13.53)]. Receiving nutrition education (ß = 0.25, P = 0.002) and good nutrition knowledge (ß = 0.08, P < 0.001) were positively associated with nutritional status; however, food insecurity (ß = - 0.93, P < 0.001) was negatively associated with nutritional status. The nutrition knowledge of pregnant adolescents was suboptimal; educational status, ANC visits and nutrition education were associated with good nutrition knowledge, whereas food insecurity, low nutrition knowledge, and not receiving nutrition education were predictors of poor nutritional status. Nutritional education interventions, increasing utilization of ANC, and interventions for improving food security are strongly recommended.

Integrating PARP Inhibitors in mCRPC Therapy: Current Strategies and Emerging Trends.

Metastatic castrate-resistant prostate cancer (mCRPC) is associated with poor prognosis. DNA damage response (DDR) genes are commonly altered in mCRPC rendering them as promising therapeutic targets. Poly (ADP ribose) polymerase inhibitors (PARPi) demonstrated antitumor activity in mCRPC patients with DDR gene mutations through synthetic lethality. Multiple clinical trials with PARPi monotherapy exhibited encouraging clinical outcomes in selected patients with mCRPC. More recently, three Phase III randomized clinical trials (RCTs) combining PARPi with androgen receptor signaling inhibitors (ARSIs) demonstrated improved antitumor activity compared to ARSI monotherapy in mCRPC patients as the first-line therapy. Clinical benefit was more pronounced in patients harboring DDR alterations, specifically BRCA1/2. Interestingly, antitumor activity was also observed irrespective of DDR gene mutations, highlighting BRCAness phenotype with androgen receptor blockade resulting in synergistic activity between ARSIs and PARPi. In this review, we discuss the clinical efficacy and safety data of the combination of PARPi plus ARSI in all Phase 3 randomized controlled trials (RCTs), emphasizing strategies for patient selection and highlighting emerging trends based on clinical trial data.

Prevalence of burnout and associated factors among midwives, 2023: institution-based cross-sectional study.

Background: One of the main characteristics of the mental health condition known as burnout syndrome is an overwhelming feeling of physical and emotional tiredness, particularly with regard to one's work. Midwives are the group most prone to burnout because they work in emergency situations to save two lives at a time, share the stress of laboring women, and put in extra hours without enough payment. Besides this, there is little information on burnout among Ethiopian midwives. Objectives: To assess burnout and associated factors among midwives working in public health facilities in West Arsi Zone, Ethiopia. Methods and materials: A census method cross-sectional study was conducted among all 467 midwives working in public health facilities found in the West Arsi Zone, Ethiopia, from September 1 and 30, 2023. A pretested, validated face-to-face interviewer-administered structured questionnaire was used to collect data. Then, binary logistic regression was used for analysis. Bi-variable and multivariable logistic regression analyses were employed to identify factors associated with burnout. The level of statistical significance was declared at p < 0.05 with a 95% CI. Results: Overall, the prevalence of burnout among midwives was 47.10% (95% CI: 42.55, 51.75%). Marital status not in union 2.03 (95% CI: 1.32-3.13), working more than 40 h per week 2.00 (95% CI: 1.29-3.08), conflict with their metron 2.33 (95% CI: 1.54-3.54), not satisfied with their current job 2.39 (95% CI: 1.56-3.66) and having depression symptoms 1.71 (95% CI: 1.06-2.74) were factors significantly associated with burnout. Conclusion: This study found that in the study area, almost half of the midwives experienced burnout. Thus, it is recommended that midwives should develop respectful interactions with both their mentors and colleagues. Secondly, we suggest that zonal health offices set up systems that by shortening working hours and boost job satisfaction by creating conducive working environment, provide opportunities for career advancement and increase employee engagement.

Radiographic Progression at Castration-Resistant Prostate Cancer Diagnosis: A Prognostic Indicator of Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: The critical role of radiographic assessment at the time of castration-resistant prostate cancer (CRPC) diagnosis is underscored by this study. We performed a retrospective analysis of radiographic changes in metastasis from the time of diagnosis of metastatic hormone-sensitive prostate cancer (mHSPC) to CRPC diagnosis. We also explored its impact on prognosis post-CRPC. MATERIALS AND METHODS: We retrospectively analyzed 98 men who underwent radiographic examinations (bone scans and computed tomography [CT]) at the time of CRPC diagnosis. When radiographic studies demonstrated progression at CRPC diagnosis, patients were assigned to the radiographic progressive disease (rPD) group. The remaining patients were placed in the "non-rPD" group. The overall survival (OS) post-CRPC was compared between the 2 groups. RESULTS: The median OS post-CRPC was significantly shorter in the rPD group (n = 50) compared to the non-rPD group (n = 48) (32 months vs. not reached, P = .0124). Multivariate analysis showed that radiographic progression and shorter time to CRPC were associated with a shorter OS post-CRPC (hazard ratio [HR] = 3.14; 95% confidence interval [CI], 1.21-8.12, P = .019). CONCLUSION: Radiographic progression at the point of CRPC diagnosis independently predicts a shorter OS post-CRPC in patients with mHSPC. Therefore, assessing radiographic changes at the time of CRPC diagnosis could be instrumental in managing CRPC in patients with mHSPC.

Combination of the PARPi and ARSi in advanced castration resistant prostate cancer: a review of the recent phase III trials.

Tumors with an impaired ability to repair DNA double-strand breaks by homologous recombination, including those with alterations in breast cancer 1 and 2 (BRCA1 and BRCA2) genes, are very sensitive to blocking DNA single-strand repair by inhibition of the poly (ADP-ribose) polymerase (PARP) enzyme. This provides the basis for a synthetic deadly strategy in the treatment of different types of cancer, such as prostate cancer (PCa). The phase 3 PROfound study was the first to lead to olaparib approval in patients with metastatic castration resistant PCa (mCRPC) and BRCA genes mutations. In recent years, the benefit of combination therapy consisted of a PARP inhibitor (PARPi) plus an androgen receptor signalling inhibitor (ARSi), was evaluated as first-line treatment of mCRPC, regardless of the mutational state of genes, participating in the homologous recombination repair (HRR). This review explores the role of PARPi in PCa and analyses the data of latest clinical trials exploring the PARPi-ARSi combinations, and how these results could change our clinical practice.

Ethnobotanical study of wild edible plants in Arsi Robe district of East Arsi Zone, Ethiopia.

BACKGROUND: Wild edible plants (WEPs) are usually considered to constitute all plant resources that are neither cultivated nor domesticated but are used as nutritional supplements by local people. WEPs play a vital role in ensuring food and livelihood security for countless families and communities around the world. The objective of the study was to assess and document wild edible plants used by communities in the Arsi Robe district as food. METHODS: Semi-structured interviews, market surveys, and guided field walks were employed as data collection tools. The data were analyzed using preference ranking, direct matrix ranking, and Jaccard's similarity index. RESULTS: The present study revealed various types of wild edible plants consumed by local communities in the Arsi Robe district of the East Arsi Zone. This could be justified by the documentation of 36 different wild edible plants in the study area. These WEPs belong to 31 genera and 25 families. Most of the growth forms of the edible wild plants in the district were shrubs (16, 44.44%) and trees (14, 38.88%). Amaranthus caudatus and Bridelia micrantha are the most preferred WEPs in the study area. The finding of the study also revealed that Lepidotrichilia volkensii and Premna schimperi are among the novel WEPs that had not before been documented as food items in other areas. Olea europaea subsp. cuspidata, Ficus sycomorus, Cordia africana, and Ficus sur are species with multiple uses. Agricultural expansion, charcoal production, the construction of different materials, making agricultural tools, deforestation, and other factors were the top prioritized threats affecting the abundance and diversity of wild edible plants. CONCLUSION: Along with the sustainable utilization and conservation of the existing WEPs of the study district, priority should be given to the urgent collection, domestication, and cultivation of multiuse wild edible plant species such as Olea europaea subsp. cuspidata, Ficus sycomorus, Cordia africana, and Ficus sur in the study area.