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The highlighted local and international perspectives of school-based management (SBM) offer logical findings on its efficacy at the grassroots level. Despite some hindering factors, its impact along leadership and governance, curriculum and learning, accountability and continuous improvement, and resource management are commendable. After methodical scrutiny of data, this paper concludes that the improvements in schools triggered by SBM are responsiveness to the needs and challenges of schools; contextualization of curriculum; improvement of physical facilities and linkages; and stakeholders' awareness and involvement to school's programs, projects and activities (PPAs). Principals likewise implemented SBM in their respective schools by holding SBM planning with its stakeholders. In fact, the different programs and projects implemented in schools include SBM crafting and planning; implementation, monitoring, and documentation of student learning activities; and clean-up drive and transparency board installation. Researchers, therefore, recommend that responsiveness of SBM to the needs and challenges of schools; contextualization of curriculum; improvement of physical facilities and linkages; and stakeholders' awareness and involvement to school PPA be extensively maximized. Eventually, sound partnerships between schools and external stakeholders be cultivated.

Pre-messenger RNA splicing involves multi-step assembly of the large spliceosome complexes that catalyse the two consecutive trans-esterification reactions, resulting in intron removal. There is evidence that proof-reading mechanisms monitor the fidelity of this complex process. Transcripts that fail these fidelity tests are thought to be directed to degradation pathways, permitting the splicing factors to be recycled. While studying the roles of splicing factors in vivo, in budding yeast, we performed targeted depletion of individual proteins, and analysed the effect on co-transcriptional spliceosome assembly and splicing efficiency. Unexpectedly, depleting factors such as Prp16 or Prp22, that are known to function at the second catalytic step or later in the splicing pathway, resulted in a defect in the first step of splicing, and accumulation of arrested spliceosomes. Through a kinetic analysis of newly synthesized RNA, we observed that a second step splicing defect (the primary defect) was rapidly followed by the first step of splicing defect. Our results show that knocking down a splicing factor can quickly lead to a recycling defect with splicing factors sequestered in stalled complexes, thereby limiting new rounds of splicing. We demonstrate that this ‘feed-back’ effect can be minimized by depleting the target protein more gradually or only partially, allowing a better separation between primary and secondary effects. Our findings indicate that splicing surveillance mechanisms may not always cope with spliceosome assembly defects, and suggest that work involving knock-down of splicing factors or components of other large complexes should be carefully monitored to avoid potentially misleading conclusions.

ABSTRACTBackground: Access to essential malaria commodities is a cornerstone in malaria control. However optimal availability and access to essential malaria commodities remain a challenge in Tanzania. Therefore, this study aimed to explore the factors affecting the accessibility of malaria commodities in Tanzania.Methods: This was a mixed-method cross-sectional study using both quantitative and qualitative approaches. Data were collected between February and March 2023 from health facilities, health facility staff, and patients.Results: Availability of malaria commodities in government health facilities was 100% for all items while in the private and faith-based facilities, this ranged from 10% to 80%. The reasons for stockouts in Government facilities were related to delayed and inadequate quantity delivery while in private facilities the main reason was the lack of cash for procurement. Both private facilities’ clients and healthcare providers concurred that most people do not access complete treatment due to the high costs of prescribed medicines and poor stocking levels.Conclusion: The availability, hence the accessibility, of malaria commodities in private and faith-based health facilities is still sub-optimal. Logistic management needs to be improved to eliminate stockouts and malaria commodities high costs need a permanent solution.

Introduction Optimal adherence to recommended diets is crucial to achieving long-term glycaemic control among individuals with type 2 diabetes (T2D) individuals. However, there is limited evidence on the effectiveness of interventions that target dietary adherence through social networks. Since social networks can influence individuals’ health behaviours, it is important to thoroughly evaluate the impact of social network interventions on dietary adherence in adults with T2D. This systematic review protocol aimed to provide insights into future interventions and improve diabetes management strategies.Method and analysis PubMed, Embase, CINAHL Complete, Cochrane Central Register of Controlled Trials, ProQuest Dissertations and Theses and Google Scholar will be searched from inception to December 2023 for relevant randomised and non-randomised controlled trials of at least 3 months’ duration. In addition, studies that compared interventions involving the social networks (families, friends and peers) of adults with T2D with usual care, no intervention or an intervention with no explicit social network component will be included. Two reviewers will independently screen search outputs according to inclusion and exclusion criteria, critically evaluate the selected literature and extract data on the study setting, design, participants’ characteristics, interventions, controls, social network functions and duration of follow-up, using a standard data extraction form. Quantitative data analysis will be performed where studies are homogeneous in characteristics and provide adequate outcome data for meta-analysis. Otherwise, data will be synthesised using narrative synthesis. Finally, trials will be assessed for bias risk and overall evidence certainty using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.Ethics and dissemination Ethical approval is not required for literature-based studies. The results will be disseminated through peer-reviewed publications.PROSPERO registration number CRD42023441223.

Plant growth-promoting bacteria (PGPB) are of increased interest as they offer sustainable alternatives to the more common chemical fertilisers. Research, however, has increased into the use of PGPB as bioinoculants to improve yields. Legumes are known to interact with diazotroph PGPB which increase nutrient uptake, prevent pathogenic infections, and actively fix nitrogen. This study aimed to comprehensively describe PGPB associated with legumes grown in Namibia through analysis of the site-specific bacterial microbiomes. In the present study, we used the 16S rRNA sequencing approach to determine the structure of rhizosphere, root, and seed endosphere microbiomes of five drought-tolerant legume species: Macrotyloma uniflorum, Vigna radiata, Vigna aconitifolia, Vigna unguiculata and Lablab purpureus. Several important phyla were identified including Actinobacteriota, Bacteroidota, Firmicutes, Proteobacteria and Verrucomicrobiota. Overall, Proteobacteria was the most abundant phylum followed by Actinobacteria. The most important genera identified were Bacillus, Mesorhizobium, Pseudomonas, Bradyrhizobium and the Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium group. The relative abundance of these genera varied across sample types and legume species. This study identified important diazotrophs across all the legume species. Bacillus, an important PGPB, was found to be the most abundant genus among all the niches analysed and legume species, while Rhizobium spp. was particularly enriched in roots. This study ultimately provides previously undescribed information on legume-associated bacterial communities in Namibia.

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading. Astronauts are screened for a high level of physical fitness and health, are launched with high bone mineral densities, and perform exercise daily in space to combat skeletal atrophy as an adaptive response to reduced weight-bearing function, while the elderly display cellular and tissue pathology as a response to senescence and disuse. Current clinical testing for age-related bone change, applied to astronauts, may not be sufficient for fully understanding risks associated with rare and uniquely induced bone changes. This review aims to (i) highlight cellular analogies between spaceflight-induced and age-related bone loss, which could aid in predicting fractures, (ii) discuss why overreliance on terrestrial clinical approaches may miss potentially irreversible disruptions in trabecular bone microarchitecture induced by spaceflight, and (iii) detail how the cellular effects of the bisphosphonate class of drugs offer a prophylactic countermeasure for suppressing the elevated bone resorption characteristically observed during long-duration spaceflights. Thus the use of the bisphosphonate will help protect the bone from structural changes while in microgravity either along with exercise or alone when exercise is not performed, e.g. after an injury or illness.

With growing awareness of the environmental, economic, and social costs associated with food waste, there is a concerted effort on multiple scales to recover the nutrient value of discarded food. These developments are positive, but the rapid movement toward alternatives and the complexity of solving problems located at the intersection of economic, social, and environmental systems also have the potential to produce unanticipated risks. This paper draws upon long-term stakeholder-engaged research throughout New England, with a focus on Maine, to develop a transdisciplinary, systems-based model of the potential social, economic, and environmental risks of food waste nutrient cycling. Our effort is intended to help inform the creation of safe, functional, and environmentally benign circular food systems.

Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross-linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic-loading fatigue life, we conducted total-body, acute, gamma-irradiation experiments on skeletally mature (17-week-old) C57BL/6J male mice (n = 84). Mice were administered doses of either 0 Gy (sham), 1 Gy (motivated by cumulative exposures from a Mars mission), or 5 Gy (motivated by clinical therapy regimens) with retrieval of the lumbar vertebrae at either a short-term (11-day) or long-term (12-week) time point after exposure. Micro-computed tomography was used to assess trabecular and cortical quantity and architecture, biochemical composition assays were used to assess collagen quality, and mechanical testing was performed to evaluate vertebral compressive strength and fatigue life. At 11 days post-exposure, 5 Gy irradiation significantly reduced trabecular mass (p

Abstract Background Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples. Methods Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry. Results Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53 −/− colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53 +/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels. Conclusion BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.

Abstract Exercise training is a key countermeasure used to offset spaceflight-induced multisystem deconditioning. Here, we evaluated the effects of exercise countermeasures on multisystem function in a large cohort (N = 46) of astronauts on long-duration spaceflight missions. We found that during 178 ± 48 d of spaceflight, ~600 min/wk of aerobic and resistance exercise did not fully protect against multisystem deconditioning. However, substantial inter-individual heterogeneity in multisystem response was apparent with changes from pre to postflight ranging from −30% to +5%. We estimated that up to 17% of astronauts would experience performance-limiting deconditioning if current exercise countermeasures were used on future spaceflight missions. These findings support the need for refinement of current countermeasures, adjunct interventions, or enhanced requirements for preflight physiologic and functional capacity for the protection of astronaut health and performance during exploration missions to the moon and beyond.

Here, Parzych et al describe the development of a DNA-delivered SARS-CoV-2 mAb cocktail displaying synergistic RBD binding that confers broad neutralizing activity against variants of concern and prophylactic efficacy in multiple small animal models.