During human skin development, embryonic-and fetal-specific periderm cells and incompletely keratinized cells are replaced by keratinocytes that differentiate while stratifying to form the fully functional epidermis. Proliferating basal cells of fetal skin also develop into epidermal appendages such as hair follicles and glands. We demonstrate that programmed cell death, not emphasized in conventional epidermal biology, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localization of transglutaminases in fetal periderm, intermediate epidermal cells, and within appendages coincides with DNA fragmentation indicating that apoptosis is involved in deletion of these stagespecific cells and remodeling of appendages. The data also suggest that terminal differentiation of epidermal cells might be a specialized form of apoptosis. The pattern of expression of bcl-2, a gene associated with survival of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific morphogenetic events in hair follicles and eccrine sweat glands, and its presence in single cells of the hair follicle bulge suggests that Bcl-2 may be a stem cell marker.

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Normal human keratinocytes synthesize and release nerve growth factor (NGF) and express both the low- and the high-affinity NGF receptor. Because NGF has been shown to rescue certain cell types from programmed cell death, we investigated the role of endogenous NGF in preventing keratinocyte apoptosis. We report here that apoptosis is induced in normal human keratinocytes in culture by blocking endogenous NGF signaling with either anti-NGF neutralizing antibody or K252, a specific inhibitor of the tyrosine kinase high-affinity NGF receptor. Apoptosis was assessed by DNA laddering, electron microscopy, and in situ nick end labeling technique. In anti-NGF-treated keratinocytes, the apoptotic process starts at 96 h, and is maximal at 120 h. After K252 treatment, apoptosis starts at 48 h and peaks at 120 h. Because the product of the bcl-2 proto-oncogene protects many cell types from apoptosis, we measured the levels of this protein in apoptotic keratinocytes. We found that both K252 and anti-NGF antibody strikingly downregulate bcl-2 expression, starting at 72 h. Furthermore, HaCat keratinocytes stably transfected with a plasmid containing bcl-2 cDNA fail to undergo apoptosis when treated with K252. These findings show that autocrine NGF acts as a survival factor for human keratinocytes in vitro through its high-affinity NGF receptor, possibly by maintaining constant levels of Bcl-2.

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BackgroundLack of access to health and medical education resources for doctors in the developing world is a serious global health problem. In Rwanda, with a population of 11 million, there is only one medical school, hence a shortage in well-trained medical staff. The growth of interactive health technologies has played a role in the improvement of health care in developed countries and has offered alternative ways to offer continuous medical education while improving patient's care. However, low and middle-income countries (LMIC) like Rwanda have struggled to implement medical education technologies adapted to local settings in medical practice and continuing education. Developing a user-centered mobile computing approach for medical and health education programs has potential to bring continuous medical education to doctors in rural and urban areas of Rwanda and influence patient care outcomes.ObjectiveThe aim of this study is to determine user requirements, currently available resources, and perspectives for potential medical education technologies in Rwanda.MethodsInformation baseline and needs assessments data collection were conducted in all 44 district hospitals (DHs) throughout Rwanda. The research team collected qualitative data through interviews with 16 general practitioners working across Rwanda and 97 self-administered online questionnaires for rural areas. Data were collected and analyzed to address two key questions: (1) what are the currently available tools for the use of mobile-based technology for medical education in Rwanda, and (2) what are user's requirements for the creation of a mobile medical education technology in Rwanda?ResultsGeneral practitioners from different hospitals highlighted that none of the available technologies avail local resources such as the Ministry of Health (MOH) clinical treatment guidelines. Considering the number of patients that doctors see in Rwanda, an average of 32 patients per day, there is need for a locally adapted mobile education app that utilizes specific Rwandan medical education resources. Based on our results, we propose a mobile medical education app that could provide many benefits such as rapid decision making with lower error rates, increasing the quality of data management and accessibility, and improving practice efficiency and knowledge. In areas where Internet access is limited, the proposed mobile medical education app would need to run on a mobile device without Internet access.ConclusionsA user-centered design approach was adopted, starting with a needs assessment with representative end users, which provided recommendations for the development of a mobile medical education app specific to Rwanda. Specific app features were identified through the needs assessment and it was evident that there will be future benefits to ongoing incorporation of user-centered design methods to better inform the software development and improve its usability. Results of the user-centered design reported here can inform other medical education technology develo...