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BackgroundDespite the effectiveness of antiretroviral treatment (ART) in reducing morbidity and mortality, children and adolescents with co-infections face an elevated risk of death due to their young age and compromised immune systems. While risk factors for tuberculosis (TB) and adverse TB outcomes in HIV-infected adults are well-documented for mortality estimation, understanding mortality risks among HIV-infected children and adolescents, especially in the era of test and treatment and universal ART for all HIV-infected persons, remains limited. This study aimed to estimate the mortality rate among TB and HIV-co-infected children in Sub-Saharan African countries using SRM.MethodsWe systematically searched relevant studies from seven international electronic databases. Articles were searched using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article searching included six electronic databases including PubMed/MEDLINE (N = 1287), Scopus (N = 447), Web of Science (N = 174), Science Direct (N = 749, Cochran (N = 57), and Google Scholar and research repository bases searching (N = 42). The quality of primary studies was evaluated using Joanna Briggs Institute (JBI) checklist. The pooled mortality rate was estimated using a weighted inverse variance random-effect meta-analysis. Heterogeneity among studies was assessed using Cochran's Q test and estimated using I2 statistic. This document is registered in Prospero (CRD420251012913).ResultIn this SRM, 16 individual studies were included. During the co-infected mortality screening of 5,098 participants, 657 deaths were reported after co-treatment started. The pooled mortality burden was estimated at 12.96% (95% CI: 8.94 to 16.98, I2 = 92.6%, P = 0.001). The majority of TB co-infected cases were newly diagnosed after ART started. The final weighted inverse variance random-effect regression indicated WHO stages III and IV (pooled HR = 4.34), poor/ fair ART adherence (pooled HR = 3.11), missed Isoniazid preventive therapy (IPT) (pooled HR = 3.07), hemoglobin levels ≤ 10 mg/dL (pooled HR = 2.84), bedridden functional status (pooled HR = 3.19), below threshold CD4 count (pooled HR = 1.80), and missed cotrimoxazole preventive therapy (CPT) (pooled AOR = 1.58) were predictors of premature death during co-infection.ConclusionIn this review, the overall pooled burden of mortality in HIV-infected children in SSA countries was high compared with the End TB Strategy target estimation. Significant predictors of mortality included WHO clinical stages III and IV, poor or fair ART adherence, missed Isoniazid preventive therapy (IPT), and hemoglobin levels ≤ 10 mg/dL. Therefore, counseling on antiretroviral therapy adherence should be strengthened; early screening and treating of anemia, screening and scaling up of IPT, critical ART drug, and nutritional counseling should be done during regular visits for caregivers to prevent premature deaths among children, youths, and adolescents during co-infection in SSA.

IntroductionOwing to the activation of the endogenous fibrinolytic system, spontaneous restoration of coronary blood flow in the infarcted artery may seldom occur without thrombolysis or primary coronary intervention. Spontaneous reperfusion is associated with less myocardial damage, a tremendous in-hospital outcome, and a better overall prognosis compared with patients requiring reperfusion therapy to achieve a thrombolysis in myocardial infarction grade 3 patency. We present an intriguing case of spontaneous recanalization succeeding a subtotal left anterior descending occlusion in a 46-year-old male from Tanzania with neither positive history of cardiovascular disease nor apparent coronary artery disease risk.Case presentationA 46-year-old man of African origin was referred from central Tanzania for revascularization. He had presented with a 2-day history of ongoing central chest pain, crushing in nature and radiating to the left arm. His past medical history was unremarkable and had no apparent risk factors for coronary artery disease. Cardiac markers were found to be elevated, while electrocardiographic and echocardiographic evaluation revealed features in keeping with anterior wall myocardial infarction. He was prescribed the standard precatheterization medications and subsequently underwent an urgent coronary angiography. Catheterization revealed a 99% occlusion of the proximal left anterior descending with a thrombolysis in myocardial infarction grade 1 flow. Due to an intraprocedural machine fault and a lack of technical support, percutaneous coronary intervention could not be done in the same setting, and the patient was referred to Dar es Salaam for revascularization. The patient continued to be symptomatic for 5 days postcatheterization but came to Jakaya Kikwete Cardiac Institute (JKCI) free from symptoms on the ninth day since the onset of chest pain. He had stable hemodynamics and was in Killip class I. Cardioselective enzymes, a 12-lead electrocardiogram, and two-dimensional echocardiography done at this point revealed essentially normal findings, but the patient underwent a second catheterization for revascularization of a tight proximal left anterior descending lesion. Unexpectedly, coronary angiography revealed a patent left anterior descending vessel. Based on the clinical presentation, cardiac markers, and electrocardiographic and angiographic evolution, a diagnosis of spontaneous recanalization following subtotal proximal left anterior descending occlusion was entertained.ConclusionSpontaneous recanalization in patients with significant coronary lesions may seldom occur and portend a favorable prognosis. In light of the increasing incidence of acute coronary syndrome in Sub-Saharan Africa, it is crucial for primary physicians to recognize this potentially fatal entity timely and offer or refer for appropriate reperfusion therapy promptly. Parallel to this, efforts to raise public awareness, improve health-seeking behaviors, and strengthen emergency services are of utmost importance.

Benign prostatic hyperplasia (BPH) is a prevalent progressive age-related disorder in men, yet its etiopathophysiology remains poorly understood. Current treatments like finasteride (Fin) have limited long-term efficacy, necessitating alternative therapies. Hydroxychloroquine (HCQ), a safe antimalarial agent, possesses anti-inflammatory, immunomodulatory, and antiproliferative activities, however, its therapeutic effect in BPH has not been investigated. Accordingly, we examined its therapeutic potential and underlying mechanisms, alone or combined with Fin, in testosterone-induced BPH in rats. In BPH-induced rats, HCQ markedly reduced prostate weight and index, and PSA, testosterone, dihydrotestosterone, pro-inflammatory cytokines (TNF-α, κ and IL-6), and the transcription factor “NF-κB” levels, while improving histological abnormalities in epithelial and stromal tissues. HCQ reduced the mRNA expression of AR and ERK1/2, and decreased the protein levels of EGFR and STAT3. Additionally, HCQ increased the mRNA expression of FOXO1 and promoted apoptosis through both intrinsic and TRAIL-mediated pathways. This was evidenced by the upregulation of pro-apoptotic Bax and the downregulation of anti-apoptotic Bcl-2 and Bcl-XL levels in the intrinsic pathway, as well as the reduction in mRNA expression of DR4 and DR5 in the TRAIL-mediated pathway. Notably, combining HCQ with Fin enhanced these effects. Molecular docking revealed HCQ’s strong interactions with androgen receptor (AR), EGFR, ERK1/2, FOXO, and TRAIL death receptors (DR4/DR5), comparable to Fin except for STAT3. Our findings suggest that HCQ modulates BPH progression by targeting STAT3/FOXO1/TRAIL and EGFR/ERK/AR pathways, offering a promising therapeutic strategy for BPH, either alone or in combination with Fin.

BackgroundThe United Nations Convention on the Rights of the Child affirms the human right of children to have their voices heard about issues affecting their lives. The One Chance to be a Child (One Chance) report provided an evidence-informed data profile of the well-being of children and youth in Nova Scotia (NS). To promote the report, we engaged youth from across the province in a knowledge mobilization (KMb) project. The purpose of this research is to outline the methods of the project, as well as the priority areas identified by youth.Methods10 NS youth (grades 7–12) were recruited to take part in a three-phased KMb approach: (1) A sense-making workshop to learn and discuss the report, (2) The planning and delivery of a youth-led forum to engage decision-makers in dialogue around the report, and (3) A participatory data analysis workshop to identify priority areas from the report. Data were collected through audio-recordings, note-taking, and pictures of all materials.ResultsFive priority areas were identified by youth: (1) Access to Care– high-quality care in a timely manner, (2) Community Care– inclusive community solutions, (3) Open Minded Education– school curricula that reflects their needs, (4) Quality of Life and Basic Needs– living wages and healthy workplace policies, and (5) Youth Empowerment– youth voice embedded throughout all actions.ConclusionEngaging youth around the findings of the One Chance report supported their voices being heard, and their well-being needs to be considered by decision-makers.

The Event Horizon Telescope (EHT) Collaboration recently published the first images of the supermassive black holes in the cores of the Messier 87 and Milky Way galaxies. These observations have provided a new means to study supermassive black holes and probe physical processes occurring in the strong-field regime. We review the prospects of future observations and theoretical studies of supermassive black hole systems. Current ground-based very-long-baseline interferometry (VLBI) arrays like the EHT and proposed future extensions like the next-generation Event Horizon Telescope will greatly enhance the capabilities of black-hole imaging interferometry. These enhancements will open up several previously inaccessible avenues of investigation, thereby providing important new insights into the properties of supermassive black holes and their environments. This review describes the current state of knowledge for five key science cases, summarising the unique challenges and opportunities for fundamental physics investigations that future mm/sub-mm VLBI developments will enable.

Ticks, hematophagous ectoparasites, pose significant health risks to wildlife and humans as vectors for various pathogens. This study aims to assess the efficacy of Ailanthus altissima plant extract against Rhipicephalus (Boophilus) microplus and Hyalomma anatolicum ticks using both in vitro and in silico approaches. According to gas chromatography–mass spectrometry, 29 bioactive components with varying retention times have been identified in the methanol leaf extract of A. altissima. The plants methanolic extracts were prepared, subsequently diluted to concentrations of 25, 50, 75, and 100 mg/mL. Ticks underwent an adult immersion test (AIT) to evaluate extract effectiveness. AIT results were statistically analyzed via probit regression for lethal concentration (LC50 and LC90) and lethal time (LT50 and LT90) values. Three-dimensional structures of R. (B.) microplus acetylcholinesterase (RmAChE) and H. anatolicum glutathione S-transferase (HaGST) were modeled using homology modeling, validated through Ramachandran plots and ERRAT server. Molecular docking studies explored extract inhibitory mechanisms at the molecular level against RmAChE (4-Quinolinecarboxylic acid: − 6.6 kcal/mol) and HaGST (Gamma Tocopherol: − 6.6 kcal/mol). In vitro findings indicated superior efficacy of the plant extract compared to the positive control permethrin (a commercially available acaricide), a result supported by in silico studies showing several phytochemicals with inhibitory potential against these tick species.

Antimicrobial resistance (AMR) is a global public health concern, and the inappropriate use of antibiotics in animals and humans is considered a significant contributing factor. Para-veterinarians and veterinarians are vital in the fight against AMR. The study aimed to evaluate the knowledge, attitudes and practices of the para-veterinarians and veterinarians towards antimicrobial stewardship in Malawi. A cross-sectional questionnaire survey among the para-veterinarians and veterinarians was conducted from October 2024 to January 2025. A total of 69 participants, comprised of 42 para-veterinarians and 27 veterinarians, participated in this study, and the response rate for the survey was 44% (n = 158). The study used a predetermined cutoff of ≥ 55% to classify scores as having good knowledge, good practice, and a positive attitude. The study found that 85.5% of the respondents had good knowledge and 98.6% had good practices towards antimicrobial stewardship and prevention of AMR, while 92.8% had favorable attitude towards AMR and antimicrobial stewardship. The maximum obtainable scores for each construct were 11, 13 and 13 for knowledge, practice, and attitude, respectively. The overall mean scores for knowledge, practice and attitude were 11.25 ± 2.83, 8.71 ± 1.34 and 9.04 ± 1.64, respectively. These findings indicated that the respondents had good knowledge, good practices and favorable positive attitude towards AMR and antimicrobial stewardship. The study concludes that there is good level of knowledge, practice and favorable attitude among para-veterinarians and veterinarians towards antimicrobial stewardship which can be capitalized in the fight against AMR in Malawi. The veterinary professionals can be entrusted to comply with responsible antimicrobial prescriptions and use.

BackgroundThe option B+ prevention of mother to child transmission of human immunodeficiency virus is the lifelong provision of antiretroviral therapy for all human immunodeficiency virus positive pregnant and breastfeeding women regardless of immune status. In Ethiopia, the overall mother-to-child transmission rate of human immunodeficiency virus was 15.9%. This study assessed determinants of human immunodeficiency virus infection among infants born to human immunodeficiency virus positive women on option B + prevention of mother to child transmission of human immunodeficiency virus in Tigray, north Ethiopia.MethodsUnmatched case-control study was conducted in Tigray region from October 2023 to April 2024. A total of 43 cases and 129 controls were selected using simple random sampling technique. Multivariable logistic regression analysis was fitted to identify the factors associated with mother to child transmission of human immunodeficiency virus at P < 0.05. Multicolinearity was checked among predictor variables using Variance Inflation Factor and Tolerance test. Furthermore, the goodness of fit of the logistic model was tested using Hosmer-Lemshow test.ResultsThis study showed that rural residence (Adjusted Odds ratio: 33.3, 95% CI: 1.02–87.05), World Health Organization disease stage III (Adjusted Odds ratio: 57.4, CI: 9.25– 297.54) and IV (Adjusted Odds ratio: 78.9, CI: 12.64–345.62) during initiation of antiretroviral therapy and a child with mouth ulcer during exclusive breastfeeding (Adjusted Odds ratio: 65, IC: 6.39–456.23) were the factors significantly associated with mother to child transmission of human immunodeficiency virus. Besides, mothers’ educational status (Adjusted Odds ratio: 0.2, CI: 0.04, 0.35), late time of antiretroviral therapy initiation after human immunodeficiency virus diagnosis (Adjusted Odds ratio: 0.14, CI: 0.02–0.18) and absence of human immunodeficiency virus exposed infant follow up visit (Adjusted Odds ratio: 0.04, IC: 0.005–0.09) had significant association with the mother to child transmission of human immunodeficiency virus.ConclusionThe determinant factors significantly associated with mother to child transmission of human immunodeficiency virus were identified. Health care providers should strengthen option B + prevention mother to child transmission of human immunodeficiency virus services to reduce the mother to child transmission of human immunodeficiency virus.

IntroductionThe effectiveness of anthelmintics in controlling gastrointestinal parasitism in livestock is increasingly threatened by the emergence of drug resistance. To address this issue, biological control methods have been proposed as potential alternatives. This research aimed to evaluate the efficacy of nematophagous fungi isolated from soil samples against Haemonchus contortus infective larvae.Material and methodsSoil samples were collected from Ambo and Hawasa, representing the central and southern regions of Ethiopia, respectively. The fungi were cultured on 2% water agar using the soil sprinkling technique. Fungal identification was conducted based on conidial morphology and adhesive networking.ResultsArthrobotrys oligospora (AO), Arthrobotrys conoides (AC) and Monacrosporium species (MS) were isolated from the soil samples. In vitro tests on 2% water agar demonstrated that the trapping and killing of H. contortus L3 larvae began within 48 h of exposure. From second to 4th day of observation, significant difference in the number of dead larvae were observed between the untreated control (UTC) and treatment plates (P < 0.0001); mortality being 99.77 ± 0.38%, 96.74 ± 3.15%, 89.92 ± 4.31 and 9.92 ± 3.45% for AC, AO, MS and UTC groups. Monacrosporium species was less effective compared to both AC and AO (P > 0.05). When accounting for natural mortality (control), the contributions to larval deaths attributed to AC, AO, and MS were 90%, 89.7%, and 88.9%, respectively. The introduction of AC and AO spores to H. contortus egg-positive feces significantly decreased the number of live larvae recovered compared to the UTC (P < 0.0001) with percentage recovery of 1.6 ± 0.31%, 11.09 ± 1.41% and 49 ± 4.75% respectively. Sheep treated with conidia of AC and AO expelled varying numbers of conidia in the first 24 h post-treatment, with AO reducing larval development by 80–86% and AC by 84–87% when the natural reduction in the UTC plates is taken into account.ConclusionThis study for the first time has demonstrated the in vitro efficacy of nematode trapping fungal isolated from Ethiopian soil. Further research is needed to evaluate their performance on pasture.

HER2 is a membrane receptor tyrosine kinase overexpressed in 18–20% of gastric tumors. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) that targets HER2-positive (HER2+) cancer cells with a chemotherapeutic agent, emtansine. T-DM1 has low efficacy in HER2+ gastric cancer. This study explored the efficacy of combining drugs known to modulate HER2 internalization to enhance T-DM1 efficacy in gastric cancer. We used cholesterol-depleting drugs (lovastatin) to enhance HER2 membrane density. The irreversible pan-HER tyrosine kinase inhibitor neratinib was used to enhance the internalization of HER2-bound T-DM1. Therapy, pre-treatment and post-treatment positron emission tomography/computed tomography (PET/CT) were performed in both male and female mice. An enhancement of cell surface and internalized HER2 was observed after lovastatin and neratinib incubations, respectively. The combination of lovastatin with neratinib enhanced T-DM1 internalization in cancer cells. A decrease in HER2 protein levels and HER2 phosphorylation was detected in cells treated with T-DM1/lovastatin/neratinib when compared to control and T-DM1-only groups. PET/CT imaging of mice in the T-DM1/lovastatin/neratinib group showed a decrease in HER2 tumoral expression, which was associated with a decrease in tumor volume and sustained treatment efficacy in the T-DM1/lovastatin/neratinib group. This work demonstrates the therapeutic enhancement of T-DM1 using combination therapy with lovastatin/neratinib in gastric cancer. The treatment can be successfully monitored through PET/CT imaging.