A public health e-learning master's programme with a focus on health workforce development targeting francophone Africa: the University of Geneva experience.

BACKGROUND: Shortage of a competent public health workforce is as a worldwide problem. The situation is especially bad in sub-Saharan Africa. In 2008, the World Health Organization and the Global Health Workforce Alliance launched a call for proposals for a public health training programme with an emphasis on health workforce development specifically targeting Africa. Our article presents the development, implementation and evaluation of an e-learning Master of Advanced Studies in Public Health on Workforce Development. The project was developed in collaboration with academic partner institutions of 10 French-speaking African countries and local/regional/HQ WHO offices. METHODS: A five-step approach was adopted. First, a needs assessment study was done in the target countries, with identification of priority health issues. Second, student and tutor selection was done in collaboration with local WHO offices, health authorities and partner universities. Third, the e-platform was developed and a training workshop for tutors was organized. Fourth, the learning objectives were derived from the needs assessment study and an interactive educational approach was adopted. Fifth, the participation of students, their perception of the programme, their performance on assignments and community outcomes were monitored. RESULTS: The needs assessment allowed the identification of 12 priority health issues (trauma related to road accidents, maternal and child health, HIV/AIDS, mental heath, food and malnutrition, health resource management, infectious diseases, access to essential drugs, chronic diseases, health promotion, ageing and violence/conflicts) of which 10 were studied through the lens of the key public health disciplines (epidemiology, human resources, health project/service planning, health policy, communication, health economics/management, informatics and ethics/human rights), each validated through a certifying examination. Student participation, measured through connection hits (total: 58 256; mean: 168/student/module) and posted messages (total: 5994; mean: 18/student/module), was good, and global satisfaction was high (7.7/10). Twenty-nine students out of 37 obtained their master's degree from the University of Geneva. Outcomes reported include career development, strengthening of inter-country networks and common projects. CONCLUSIONS: Keys to the success of the programme were the enthusiasm and commitment of students, the availability of the coordination team, the simplicity of the electronic platform and the support of local/regional/WHO offices. Yet, the sustainability of the programme is not assured.

Neutrophil Granulopoiesis Optimized Through Ex Vivo Expansion of Hematopoietic Progenitors in Engineered 3D Gelatin Methacrylate Hydrogels.

Neutrophils are the first line of defense of the innate immune system. In response to methicillin-resistant Staphylococcus aureus infection in the skin, hematopoietic stem, and progenitor cells (HSPCs) traffic to wounds and undergo extramedullary granulopoiesis, producing neutrophils necessary to resolve the infection. This prompted the engineering of a gelatin methacrylate (GelMA) hydrogel that encapsulates HSPCs within a matrix amenable to subcutaneous delivery. The authors study the influence of hydrogel mechanical properties to produce an artificial niche for granulocyte-monocyte progenitors (GMPs) to efficiently expand into functional neutrophils that can populate infected tissue. Lin-cKIT+ HSPCs, harvested from fluorescent neutrophil reporter mice, are encapsulated in GelMA hydrogels of varying polymer concentration and UV-crosslinked to produce HSPC-laden gels of specific stiffness and mesh sizes. Softer 5% GelMA gels yield the most viable progenitors and effective cell-matrix interactions. Compared to suspension culture, 5% GelMA results in a twofold expansion of mature neutrophils that retain antimicrobial functions including degranulation, phagocytosis, and ROS production. When implanted dermally in C57BL/6J mice, luciferase-expressing neutrophils expanded in GelMA hydrogels are visualized at the site of implantation for over 5 days. They demonstrate the potential of GelMA hydrogels for delivering HSPCs directly to the site of skin infection to promote local granulopoiesis.

Autoimmune Lupus Enteritis with Pan Gastrointestinal Involvement in an Adult Patient with Systemic Lupus Erythematosus: Complete Response to Belimumab.

Autoimmune lupus enteritis in systemic lupus erythematosus (SLE) is a rare manifestation that comprises of gastrointestinal tract inflammation with supportive images and/or biopsy findings. We report a unique case of widespread lupus enteritis occurring late in the disease process and in isolation without additional features of active SLE but in the presence of SLE serological activity. There was no clear evidence of active mesenteric vasculitis, intestinal pseudo-obstruction, protein-losing enteropathy, or coagulopathy by imaging or histopathology. This is the first reported case of an SLE patient with pan-gastrointestinal involvement of lupus enteritis responding to Belimumab, with complete resolution of the gastrointestinal syndrome and no further recurrence of gastrointestinal events. Rapid diagnosis and prompt immunomodulatory treatment of lupus-related enteritis are critical to avoid potentially life-threatening complications.

A Call To Action: Cholangiocarcinoma in the Setting of Sustained Hepatitis C Virologic Response - Case Report and Review of Literature.

The incidence of cholangiocarcinoma, an aggressive malignancy with poor prognosis, is increasing. Hepatitis B and C have been well established as predisposing factors for this malignancy. The availability and efficacy of treatment for hepatitis C infection has led to a substantial reduction in viral hepatitis-related cholangiocarcinoma mortality. Despite treatment, the potential for developing cholangiocarcinoma continues to exist for patients with underlying cirrhosis. We present a patient who was effectively treated for hepatitis C with direct-acting antiviral therapy eight years prior. He presented with malaise, fatigue, and an unintentional weight loss of 40 pounds. Imaging revealed a metastatic malignancy, and a liver biopsy confirmed the diagnosis of cholangiocarcinoma and the absence of underlying cirrhosis in the background liver. This case highlights the persistent risk of developing cholangiocarcinoma despite achieving sustained virological response to treatment for hepatitis C. We review the associated literature and briefly discuss the predisposing conditions that might result in such an outcome. We also encourage the need for long-term surveillance for such patients and the importance of conducting more multi-center studies to identify at-risk patients and develop cost-effective screening protocols.

Esophageal Perforation Unveiling the Diagnosis of Zollinger-Ellison Syndrome.

Gastrinomas are the most common neuroendocrine tumors worldwide and cause a clinical syndrome known as Zollinger-Ellison Syndrome (ZES). Increased acid production resulting from elevated gastrin levels contributes to symptoms such as abdominal pain, heartburn, and diarrhea. However, the non-specificity and overlap in the symptoms with idiopathic peptic ulcer disease and gastroesophageal reflux disease (GERD) can lead to delayed diagnosis. In this case, we describe a patient with a past medical history of GERD and a perforated gastric ulcer who continued to experience symptoms of dyspepsia and had a subsequent esophageal perforation, despite H. pylori eradication and high-dose proton pump inhibitor (PPI) therapy. Multiple ulcers were visualized in the first portion of the duodenum, and metastatic lesions were demonstrable in the liver. Serum gastrin level was elevated to 433 pg/mL. Histology of liver biopsy showed a well-differentiated neuroendocrine tumor, supporting the diagnosis of ZES. This article underscores the significance of considering ZES in the differential in cases of refractory gastric hyperacidity and the importance of early diagnosis with serum gastrin testing to prevent complications such as gastric obstruction, perforation, hemorrhage, esophageal strictures, or rupture and to minimize the risk of metastasis. It is noteworthy that while perforations in cases of ZES typically occur in the duodenum, this particular case is atypical as it had involved the stomach. Furthermore, it was associated with esophageal perforation, likely resulting from forceful and prolonged vomiting caused by persistent dyspepsia.

Gastrointestinal Bleeding as Initial Manifestation of Injection Drug Use-Associated Amyloidosis.

Systemic amyloidosis has been reported in the context of injection drug use, usually related to ongoing chronic inflammation and persistent cutaneous infections. The kidneys are almost always the first organs affected in that setting. Involvement of the gastrointestinal tract is less common and rarely the initial site of presentation. We present a case of systemic amyloidosis that primarily manifested in the gastrointestinal tract, occurring in the setting of chronic injection drug use. The patient's hemoglobin level dropped progressively over time due to ongoing, slow gastrointestinal bleeding, prompting an endoscopic examination that ultimately confirmed the presence of gastrointestinal amyloidosis. As the overall prognosis for gastrointestinal amyloidosis is poor, early diagnosis and treatment are essential to decelerate the progression of the disease.

Thermodynamic principles for the engineering of pH-driven conformational switches and acid insensitive proteins.

The general thermodynamic principles behind pH driven conformational transitions of biological macromolecules are well understood. What is less obvious is how they can be used to engineer pH switches in proteins. The acid unfolding of staphylococcal nuclease (SNase) was used to illustrate different factors that can affect pH-driven conformational transitions. Acid unfolding is a structural transition driven by preferential H(+) binding to the acid unfolded state (U) over the native (N) state of a protein. It is the result of carboxylic groups that titrate with more normal pK(a) values in the U state than in the N state. Acid unfolding profiles of proteins reflect a balance between electrostatic and non-electrostatic contributions to stability. Several strategies were used in attempts to turn SNase into an acid insensitive protein: (1) enhancing global stability of the protein with mutagenesis or with osmolytes, (2) use of high salt concentrations to screen Coulomb interactions, (3) stabilizing the N state through specific anion effects, (4) removing Asp or Glu residues that titrate with depressed pK(a) values in the N state, and (5) removing basic residues that might have strong repulsive interactions in the N state at low pH. The only effective way to engineer acid resistance in SNase is not through modulation of pK(a) values of Asp/Glu but by enhancing the global stability of the protein. Modulation of pH-driven conformational transitions by selective manipulation of the electrostatic component of the switch is an extremely difficult undertaking.