Competencies for Transformational Leadership in Public Health-An International Delphi Consensus Study.

Objectives: This Delphi study intended to develop competencies for transformational leadership in public health, including behavioral descriptions (descriptors) tailored to individuals and their contexts. Methods: The study involved five rounds, including online "e-Delphi" consultations and real-time online workshops with experts from diverse sectors. Relevant competencies were identified through a literature review, and experts rated, ranked, rephrased, and proposed descriptors. The study followed the Guidance on Conducting and REporting DElphi Studies (CREDES) and the COmpeteNcy FramEwoRk Development in Health Professions (CONFERD-HP) reporting guidelines. Results: Our framework comprises ten competencies for transformational public health leadership (each with its descriptors) within four categories, and also describes a four-stage model for developing relevant competencies tailored to different contexts. Conclusion: Educators responsible for curriculum design, particularly those aiming to align curricula with local goals, making leadership education context-specific and -sensitive, may benefit from the proposed framework. Additionally, it can help strengthen links between education and workforce sectors, address competency gaps, and potentially reduce the out-migration of graduates in the health professions.

Transformed through the CARTA experience: changes reported by CARTA fellows about their PhD journey.

Transformative learning occurs when a person, group, or larger social unit encounters ideas that are at odds with their prevailing perspective. This discrepant perspective can lead to an examination of previously held beliefs, values, and assumptions. The Consortium for Advanced Research Training in Africa (CARTA) has since 2011 been training and supporting faculty from different African universities, to become more reflective and productive researchers, research leaders, educators, and change agents who will drive institutional changes in their institutions. As part of a mid-term evaluation of CARTA, an open-ended question was posed to the CARTA fellows asking them to describe any changes they had experienced in their professional lives as a result of the CARTA Programme. The 135 responses were inductively coded and analysed using qualitative thematic analysis. These themes were subsequently mapped onto Hoggan's typology of transformative learning outcomes. CARTA fellows reported shifts in their sense of self; worldviews; beliefs about the definition of knowledge, how it is constructed and evaluated; and changes in behaviour/practices and capacities. This paper argues that the changes described by the CARTA fellows reflect transformative learning that is embedded in CARTA's Theory of Change. The reported transformation was enabled by a curriculum intentionally designed to facilitate critical reflection, further exploration, and questioning, both formally and informally during the fellows' PhD journey with the support of CARTA facilitators. Documenting and disseminating these lessons provide a guide for future practice, and educators wishing to revitalise their PhD training may find it useful to review the CARTA PhD curriculum.

Resilience of research capacity strengthening initiatives in Africa during crises: the case of CARTA during COVID.

Background: Several research capacity strengthening (RCS) initiatives have been established in Africa over the past decade. One such initiative is the Consortium for Advanced Research Training in Africa (CARTA) that has gained traction over the years and has been proven as an effective multidisciplinary approach to strengthen research capacity to address public and population health in Africa. Objectives: In this article, we document the experiences and management-related interventions that cushioned the CARTA programme and enabled it to remain resilient during the COVID pandemic. We further make recommendations on the enablers of resilience and optimal performance of such RCS initiatives during crises and beyond. Methods: We used routine information gathered by the CARTA secretariat from consortium correspondence, meeting minutes, reports and other related documents produced in the year 2020 in order to consolidate the experiences and interventions taken by the programme at programmatic, institutional and fellowship levels. Results: We identified a series of management-related cyclic phases that CARTA went through during the pandemic period, which included immobilisation, reflection, brainstorming, decision-making, intervening and recovery. We further identified strategic management-related interventions that contributed to the resilience of the programme during the pandemic including assessment and monitoring, communication management, policy and resource management, making investments and execution. Moreover, we observed that the strength of the leadership and management of CARTA, coupled with the consortium´s culture of collaboration, mutual trust, respect, openness, transparency, equitability, ownership, commitment and accountability, all contributed to its success during the pandemic period. Conclusion: We conclude that RCS initiatives undergo a series of phases during crises and that they need to promptly adopt and adapt appropriate management-related strategic interventions in order to remain resilient during such periods. This can be significantly realised if RCS initiatives build a culture of trust, commitment and joint ownership, and if they invest in strong management capacity.

Attenuation of Seizures, Cognitive Deficits, and Brain Histopathology by Phytochemicals of Imperata cylindrica (L.) P. Beauv (Poaceae) in Acute and Chronic Mutant Drosophila melanogaster Epilepsy Models.

Imperata cylindrica is a globally distributed plant known for its antiepileptic attributes, but there is a scarcity of robust evidence for its efficacy. The study investigated neuroprotective attributes of Imperata cylindrica root extract on neuropathological features of epilepsy in a Drosophila melanogaster mutant model of epilepsy. It was conducted on 10-day-old (at the initiation of study) male post-eclosion bang-senseless paralytic Drosophila (parabss1) involved acute (1-3 h) and chronic (6-18 days) experiments; n = 50 flies per group (convulsions tests); n = 100 flies per group (learning/memory tests and histological examination). Administrations were done in 1 g standard fly food, per os. The mutant flies of study (parabss1) showed marked age-dependent progressive brain neurodegeneration and axonal degeneration, significant (P < 0.05) bang sensitivity and convulsions, and cognitive deficits due to up-regulation of the paralytic gene in our mutants. The neuropathological findings were significantly (P < 0.05) alleviated in dose and duration-dependent fashions to near normal/normal after acute and chronic treatment with extract similar to sodium valproate. Therefore, para is expressed in neurons of brain tissues in our mutant flies to bring about epilepsy phenotypes and behaviors of the current juvenile and old-adult mutant D. melanogaster models of epilepsy. The herb exerts neuroprotection by anticonvulsant and antiepileptogenic mechanisms in mutant D. melanogaster due to plant flavonoids, polyphenols, and chromones (1 and 2) which exert antioxidative and receptor or voltage-gated sodium ion channels' inhibitory properties, and thus causing reduced inflammation and apoptosis, increased tissue repair, and improved cell biology in the brain of mutant flies. The methanol root extract provides anticonvulsant and antiepileptogenic medicinal values which protect epileptic D. melanogaster. Therefore, the herb should be advanced for more experimental and clinical studies to confirm its efficacy in treating epilepsy.

A Scientometric Analysis of Africa's Health Science Journals Indexed in International and Regional Databases: A Comparative Analysis.

Objectives: This study aimed to compare the geographic coverage, citation impact, subject trends and authorship collaboration pattern of African health science journals indexed in international and regional databases. Methods: Data was collected from Ulrichs web serials directory, Web of Science (WoS), Scopus, PubMed, Google scholar, African Index Medicus (AIM) and African Journals Online (AJOL) between February 2023 and May 2023. Data was analysed using summary descriptive statistics such as percentages and interquartile ranges, and through network visualisation. Results: More than 40 African countries had no any health science journal indexed in WoS, whereas 20 African countries did not have any health science journal indexed in AJOL and AIM. The Journal of Advanced research was the top performing journal on almost all journal metric lists such as Google scholar's H5-Index, SNIP, Journal Impact Factor, and Citescore, except Journal Citation indicator. Conclusion: The coverage of African health science journals by international citation databases is still limited which result in low scientific impact of many African health science journals. Authorship collaboration is related to historical ties among countries.

Considerations for an integrated population health databank in Africa: lessons from global best practices.

Background: The rising digitisation and proliferation of data sources and repositories cannot be ignored. This trend expands opportunities to integrate and share population health data. Such platforms have many benefits, including the potential to efficiently translate information arising from such data to evidence needed to address complex global health challenges. There are pockets of quality data on the continent that may benefit from greater integration. Integration of data sources is however under-explored in Africa. The aim of this article is to identify the requirements and provide practical recommendations for developing a multi-consortia public and population health data-sharing framework for Africa. Methods: We conducted a narrative review of global best practices and policies on data sharing and its optimisation. We searched eight databases for publications and undertook an iterative snowballing search of articles cited in the identified publications. The Leximancer software © enabled content analysis and selection of a sample of the most relevant articles for detailed review. Themes were developed through immersion in the extracts of selected articles using inductive thematic analysis. We also performed interviews with public and population health stakeholders in Africa to gather their experiences, perceptions, and expectations of data sharing. Results: Our findings described global stakeholder experiences on research data sharing. We identified some challenges and measures to harness available resources and incentivise data sharing.  We further highlight progress made by the different groups in Africa and identified the infrastructural requirements and considerations when implementing data sharing platforms. Furthermore, the review suggests key reforms required, particularly in the areas of consenting, privacy protection, data ownership, governance, and data access. Conclusions: The findings underscore the critical role of inclusion, social justice, public good, data security, accountability, legislation, reciprocity, and mutual respect in developing a responsive, ethical, durable, and integrated research data sharing ecosystem.

Institutionalizing research capacity strengthening in LMICs: A systematic review and meta-synthesis.

Background: Evidence on effective strategies to ensure sustainability of research capacity strengthening interventions in low- and middle-income country (LMIC) institutions is lacking. This systematic review identified publications describing research capacity building programs and noted their effect, their contexts, and the mechanisms, processes and social actors employed in them. Methods: We searched online databases for the period 2011-2018. Inclusion criteria were that the publications 1) described the intervention; 2) were implemented in LMICs; 3) were based in, or relevant to, university staff or post docs; 4) aimed to improve research capacity; 5) aimed to effect change at the institutional level. Two reviewers screened titles, abstracts and full text in consecutive rounds, a third resolved disagreements. Two people extracted the data of each full text using a data extraction tool covering data relevant to our question. Results: In total 4052 citations were identified and 19 papers were included, which referred to 14 interventions. Only three interventions mentioned using a conceptual framework to develop their approach and none described using a theory of change to assess outcomes. The most frequent inputs described were some method of formal training, promotion of a research-conducive environment and establishment of research support systems. A range of outcomes were reported, most frequently an increased number of publications and proportion of staff with PhDs. When factors of success were discussed, this was attributed to a rigorous approach to implementation, adequate funding, and local buy-in. Those who mentioned sustainability linked it to availability of funds and local buy-in. The lack of a common lexicon and a framework against which to report outcomes made comparison between initiatives difficult. Conclusions: The reduced number of interventions that met the inclusion criteria suggests that programs should be well-described, evaluated systematically, and findings published so that the research capacity strengthening community can extract important lessons.

Gender responsive multidisciplinary doctoral training program: the Consortium for Advanced Research Training in Africa (CARTA) experience.

Doctoral training has increasingly become the requirement for faculty in institutions of higher learning in Africa. Africa, however, still lacks sufficient capacity to conduct research, with just 1.4% of all published research authored by African researchers. Similarly, women in Sub-Saharan Africa only constitute 30% of the continent's researchers, and correspondingly publish little research. Challenging these gendered inequities requires a gender responsive doctoral program that caters for women's gender roles that likely affect their enrollment in, and completion of, doctoral programs. In this article, we describe a public and population health multidisciplinary doctoral training program - CARTA and its approach to supporting women. This has resulted in women's enrollment in the program equaling men's and similar throughput rates. CARTA has achieved this by meeting women's practical needs around childbearing and childrearing and we argue that this has produced some outcomes that challenge gender norms, such as fathers being child minders in support of their wives and creating visible female role models.

Resveratrol prolongs lifespan and improves 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative damage and behavioural deficits in Drosophila melanogaster.

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) is a neurotoxin that causes Parkinson's disease in animals via mechanisms linked with oxidative stress and inflammation. Resveratrol is a natural polyphenol and a phytoalexin with antioxidative and antiinflammatory properties. Here, we investigated the rescue role of resveratrol on MPTP-triggered toxicity in Drosophila melanogaster for the first time. D. melanogaster (Harwich strain, 1-to 3- days old) were first orally exposed to resveratrol (0, 7.5, 15, 30, 60 and 120 mg/kg diet) and MPTP (0, 250, 500, 1000, 2000, and 3000 µM) for longevity and 7 days survival assays respectively. Consequently, we selected resveratrol (30 and 60 mg/kg diet) to evaluate its rescue role on MPTP (250 and 500 µM)-induced toxicity in D. melanogaster after 3 days of oral treatment. Specifically, we evaluated markers of neurotoxicity (acetylcholinesterase and negative geotaxis), inflammation (nitric oxide), oxidative stress-antioxidant status (hydrogen peroxide, total thiol, catalase and glutathione-S-transferase), cell viability and fecundity. The data showed that resveratrol increased lifespan of D. melanogaster in a dose-dependent manner up to 60 mg/kg diet. Further, resveratrol restored MPTP-induced inhibition of catalase, glutathione-S-transferase and acetylcholinesterase activities in D. melanogaster. Moreover, resveratrol ameliorated MPTP-triggered cell death, histological alterations, behavioural deficits and accumulation of nitric oxide and hydrogen peroxide levels in flies (p < 0.05). Conclusively, the lifespan extension effects of resveratrol and its rescue role on MPTP- mediated toxicity in the flies may be due to its antioxidant and anti-inflammatory properties.

Drosophila Upf1 and Upf2 loss of function inhibits cell growth and causes animal death in a Upf3-independent manner.

Nonsense-mediated RNA decay (NMD) is a surveillance mechanism that degrades transcripts containing nonsense mutations, preventing the translation of truncated proteins. NMD also regulates the levels of many endogenous mRNAs. While the mechanism of NMD is gradually understood, its physiological role remains largely unknown. The core NMD genes upf1 and upf2 are essential in several organisms, which may reflect an important developmental role for NMD. Alternatively, the lethality of these mutants might arise from their function in NMD-independent processes. To analyze the developmental importance of NMD, we studied Drosophila mutants of the other core NMD gene, upf3. We compare the resulting upf3 phenotype with those defects observed in upf1 and upf2 loss-of-function mutants, as well as with flies expressing a mutant Upf2 protein unable to bind Upf3. Our results show that Upf3 is an NMD effector in the fly but, unlike Upf1 and Upf2, plays a peripheral role in the degradation of most NMD targets and is not required for development or viability. Furthermore, Upf1 and Upf2 loss-of-function inhibits cell growth and induces apoptosis through a Upf3-independent pathway. Accordingly, disruption of Upf2-Upf1 interaction causes death, while the Upf2-Upf3 complex is dispensable for viability. Our findings suggest that NMD is essential for cell growth and animal development, and that the lethality of upf1 and upf2 mutants is not due to disrupting their roles during NMD-independent processes, but to their function in the degradation of specific mRNAs by the NMD pathway. Furthermore, our results show that Upf3 is not always essential in NMD.

Nonsense-mediated mRNA decay and development: shoot the messenger to survive?

NMD (nonsense-mediated mRNA decay) is a surveillance mechanism that degrades transcripts containing nonsense mutations, preventing the translation of potentially harmful truncated proteins. Although the mechanistic details of NMD are gradually being understood, the physiological role of this RNA surveillance pathway still remains largely unknown. The core NMD genes Upf1 (up-frameshift suppressor 1) and Upf2 are essential for animal viability in the fruitfly, mouse and zebrafish. These findings may reflect an important role for NMD during animal development. Alternatively, the lethal phenotypes of upf1 and upf2 mutants might be due to their function in NMD-independent processes. In the present paper, we describe the phenotypes observed when the NMD factors are mutated in various organisms, and discuss findings that might shed light on the function of NMD in cellular growth and development of an organism.

Genetic and chemical modifiers of a CUG toxicity model in Drosophila.

Non-coding CUG repeat expansions interfere with the activity of human Muscleblind-like (MBNL) proteins contributing to myotonic dystrophy 1 (DM1). To understand this toxic RNA gain-of-function mechanism we developed a Drosophila model expressing 60 pure and 480 interrupted CUG repeats in the context of a non-translatable RNA. These flies reproduced aspects of the DM1 pathology, most notably nuclear accumulation of CUG transcripts, muscle degeneration, splicing misregulation, and diminished Muscleblind function in vivo. Reduced Muscleblind activity was evident from the sensitivity of CUG-induced phenotypes to a decrease in muscleblind genetic dosage and rescue by MBNL1 expression, and further supported by the co-localization of Muscleblind and CUG repeat RNA in ribonuclear foci. Targeted expression of CUG repeats to the developing eye and brain mushroom bodies was toxic leading to rough eyes and semilethality, respectively. These phenotypes were utilized to identify genetic and chemical modifiers of the CUG-induced toxicity. 15 genetic modifiers of the rough eye phenotype were isolated. These genes identify putative cellular processes unknown to be altered by CUG repeat RNA, and they include mRNA export factor Aly, apoptosis inhibitor Thread, chromatin remodelling factor Nurf-38, and extracellular matrix structural component Viking. Ten chemical compounds suppressed the semilethal phenotype. These compounds significantly improved viability of CUG expressing flies and included non-steroidal anti-inflammatory agents (ketoprofen), muscarinic, cholinergic and histamine receptor inhibitors (orphenadrine), and drugs that can affect sodium and calcium metabolism such as clenbuterol and spironolactone. These findings provide new insights into the DM1 phenotype, and suggest novel candidates for DM1 treatments.

Drosophila muscleblind is involved in troponin T alternative splicing and apoptosis.

BACKGROUND: Muscleblind-like proteins (MBNL) have been involved in a developmental switch in the use of defined cassette exons. Such transition fails in the CTG repeat expansion disease myotonic dystrophy due, in part, to sequestration of MBNL proteins by CUG repeat RNA. Four protein isoforms (MblA-D) are coded by the unique Drosophila muscleblind gene. METHODOLOGY/PRINCIPAL FINDINGS: We used evolutionary, genetic and cell culture approaches to study muscleblind (mbl) function in flies. The evolutionary study showed that the MblC protein isoform was readily conserved from nematods to Drosophila, which suggests that it performs the most ancestral muscleblind functions. Overexpression of MblC in the fly eye precursors led to an externally rough eye morphology. This phenotype was used in a genetic screen to identify five dominant suppressors and 13 dominant enhancers including Drosophila CUG-BP1 homolog aret, exon junction complex components tsunagi and Aly, and pro-apoptotic genes Traf1 and reaper. We further investigated Muscleblind implication in apoptosis and splicing regulation. We found missplicing of troponin T in muscleblind mutant pupae and confirmed Muscleblind ability to regulate mouse fast skeletal muscle Troponin T (TnnT3) minigene splicing in human HEK cells. MblC overexpression in the wing imaginal disc activated apoptosis in a spatially restricted manner. Bioinformatics analysis identified a conserved FKRP motif, weakly resembling a sumoylation target site, in the MblC-specific sequence. Site-directed mutagenesis of the motif revealed no change in activity of mutant MblC on TnnT3 minigene splicing or aberrant binding to CUG repeat RNA, but altered the ability of the protein to form perinuclear aggregates and enhanced cell death-inducing activity of MblC overexpression. CONCLUSIONS/SIGNIFICANCE: Taken together our genetic approach identify cellular processes influenced by Muscleblind function, whereas in vivo and cell culture experiments define Drosophila troponin T as a new Muscleblind target, reveal a potential involvement of MblC in programmed cell death and recognize the FKRP motif as a putative regulator of MblC function and/or subcellular location in the cell.