Building One Health through School-Community-University Model in Sierra Leone

Project 1808, Inc. is a multi-generational and multi-layered One Health based school-community-university partnership model for sustainable development in Sierra Leone. The country, Sierra Leone has faced successive years of war, a deadly Ebola outbreak, and in 2017 severe environmental disasters in the form of floods and landslides. It was precisely for these reasons that Project 1808, Inc. was conceived in 2011 to help break these logjams of community challenges and build sustained health by engaging, exciting, empowering youths with tools that foster community well-being in Sierra Leone. Building resilient and thriving communities in Sierra Leone is central to the Project 1808 Model and embodies the One Health concept of the interdependence of health (and disease) among humans, domestic and free-ranging animals, and our shared ecosystems. Our One Health concept further embodies an integrated, holistic, multidisciplinary life cycle of programs from school to university that aims to tackle significant global or public health problems. We draw upon the global thinking and local action akin to a World Without Borders, where our collective thoughts and efforts are used to develop tools that enable the individuals, families, and their local communities to empower themselves, sustainably manage and utilize their natural resources, and at the same time ability to adapt, anticipate, and better respond to changes in their environment. To this end, we engage and connect students, teachers, community members through small pointed and targeted projects that address disconnects between learning and community problem-solving in Kabala, Koinadugu Districts and Freetown, Western Area of Sierra Leone

PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model

7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM) leading to mature cell losses as replenishment fails. These losses are mediated by Cyp1b1, independent of the AhR, despite induction of Cyp1b1. BM mesenchymal progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is minimally induced. PreB colony forming unit activity (PreB CFU) is lost within 24 hours in isolated BM cells (BMC) unless cocultured with cells derived from primary MPC (BMS2 line). The mouse embryonic OP9 line, which provides more efficient coculture support, shares similar induction-resistant Cyp1b1 characteristics. This OP9 support is suppressed by DMBA, which is then prevented by Cyp1b1 inhibitors. OP9-enriched medium partially sustains CFU activities but loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1. PreB CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA. BMC gene expression profiles identified cytokines and developmental factors that are substantially changed in Cyp1b1-ko mice. DMBA had few effects in WT mice but systematically modified many clustered responses in Cyp1b1-ko mice. Typical BMC AhR-responsive genes were insensitive to Cyp1b1 deletion. TCDD replicated Cyp1b1 interventions, suggesting alternative AhR mediation. Cyp1b1 also diminishes oxidative stress, a key cause of stem cell instability

Principal component analysis.

<p>Principal component analysis (PCA) using gene expression measurements from 592 genes selected based on significance level (<i>P</i><0.01). Control samples (CO) clustered effectively separated from the estradiol-17β (E2), progesterone (P4) and estradiol-17β+progesterone (E2P4T) treated samples.</p

Histogram of <i>P</i>-Values.

<p>Using the ANOVA analysis, a histogram of P-values was generated based on the treatment effects for genes present in at least one array (18,603 genes). It is observed a higher than expected (under the null hypothesis of no treatment effects) number of genes with low <i>P</i>-Values.</p

Hierarchical clustering analysis of significant genes by treatment.

<p>Unsupervised hierarchical clustering analysis produced five main clusters. The clusters correspond to upregulated genes in all treatments (Cluster 1, n = 172), downregulated genes in all treatments (Cluster 2, n = 173), synergized downregulated genes (Cluster 3, n = 69), marked P4 downregulated genes that were moderately downregulated by estradiol-17β and estradiol-17β+progesterone (Cluster 4, n = 47), and genes that were downregulated by estradiol-17β and progesterone alone and antagonized by the combined treatment (Cluster 5, n = 24). An extensive similarity of magnitude and direction of expression can be observed between significantly regulated genes.</p

Venn diagrams.

<p>Venn diagrams of all genes regulated by estradiol-17β (E2T), progesterone (P4T) and the combined treatment (E2P4T) (A); genes up-regulated (B) and down-regulated (C) by all treatments; the highlighted intersection represents genes that were commonly regulated by all treatments. Each of the circles represents a different treatment. The numbers in the intersection of the circles represent the number of transcripts that were affected in the treatments represented by those respective circles. The numbers in the outer portion of each circle represent the number of transcripts that were exclusively affected in the treatment represented by that particular circle. There was a total of 578 differentially expressed genes (A); 202 upregulated genes (B) and 382 downregulated genes (C) compared to controls, considering the following stringency: fold change >1.25 and <i>P</i><0.05.</p

Examples of genes significantly regulated by estradiol-17β (E2T), progesterone (P4T) and estradiol-17β+progesterone (E2P4T) treatment, grouped in 5 distinct clusters.

<p>Examples of genes significantly regulated by estradiol-17β (E2T), progesterone (P4T) and estradiol-17β+progesterone (E2P4T) treatment, grouped in 5 distinct clusters.</p

Designing a leadership and management training curriculum for undergraduate health professions students: Lessons from the University of Sierra Leone

Leadership by health professionals is key in any health system, but health leadership training programmes are varied in their conceptualisation, learning objectives, and design. This paper describes an undergraduate leadership and management module for health students at the University of Sierra Leone and provides lessons from the design process. Our methods included an initial scoping review and qualitative study, followed by a co-design process of 10 workshops and 17 consultation meetings. The result was a curriculum with learning outcomes emphasising leadership identity, proactiveness, management of people and of change, and the formation of peer relationships. Learning methods included group teaching, team quality improvement projects, mentoring, and reflective practice. Lessons from the design process included the importance of support from university leadership and extensive consultation. Virtual workshops enabled broader participation but limited relationship building. Integrating doctoral research into the process facilitated inclusion of evidence and theory but risked reducing ownership by faculty. The importance of interprofessionalism and management skills in leadership training emerged during the process, illustrating the effectiveness of a co-design approach. Our programme is broadly aligned with other health leadership frameworks and is distinctive due to its undergraduate focus, offering insights for leadership training design in other settings