Multiple sclerosis (MS) is an in ammatory demyelinating disease of the central nervous system (CNS) mediated by aberrant immune responses. The current immune modulatory therapies are unable to protect and repair the brain damage caused by the immune attack. One of the therapeutic targets for MS is the sphingosine-1-phosphate (S1P) pathways, which signals via sphingosine-1-phosphate receptors 1-5 (S1P 1-5 ), in the CNS and immune cells. In light of the potential neuro-protective properties of S1P signaling, we utilized the S1P 1 -GFP (Green uorescent protein) reporter mice in the cuprizone-induceddemyelination model, to investigate the in vivo S1P-S1P 1 signaling in the CNS. We observed S1P 1 signaling in a subset of neural stem cells in the subventricular zone (SVZ) during demyelination. Additionally, oligodendrocyte progenitor cells in the SVZ and mature oligodendrocytes in the medial corpus callosum (MCC) expressed S1P 1 signaling during remyelination. We did not observe S1P 1 signaling in neurons and astrocytes in the cuprizone model. This approach was unable to determine S1P 1 -GFP signaling in the myeloid cells because of their aberrant GFP expression in GFP reporter mice.Signi cant S1P 1 signaling was observed in lymphocytes during demyelination and in ammation. Our ndings reveal β-arrestin dependent S1P 1 signaling in oligodendrocyte lineage cells, indicating a role of S1P 1 signaling during remyelination.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) mediated by aberrant immune responses. The current immune modulatory therapies are unable to protect and repair the brain damage caused by the immune attack. One of the therapeutic targets for MS is the sphingosine-1-phosphate (S1P) pathways, which signals via sphingosine-1-phosphate receptors 1-5 (S1P1-5), in the CNS and immune cells. In light of the potential neuro-protective properties of S1P signaling, we utilized the S1P1-GFP (Green fluorescent protein) reporter mice in the cuprizone-induced-demyelination model, to investigate the in vivo S1P- S1P1 signaling in the CNS. We observed S1P1 signaling in a subset of neural stem cells in the subventricular zone (SVZ) during demyelination. Additionally, oligodendrocyte progenitor cells in the SVZ and mature oligodendrocytes in the medial corpus callosum (MCC) expressed S1P1 signaling during remyelination. We did not observe S1P1 signaling in neurons and astrocytes in the cuprizone model. This approach was unable to determine S1P1-GFP signaling in the myeloid cells because of their aberrant GFP expression in GFP reporter mice. Significant S1P1 signaling was observed in lymphocytes during demyelination and inflammation. Our findings reveal β-arrestin dependent S1P1 signaling in oligodendrocyte lineage cells, indicating a role of S1P1 signaling during remyelination.

BackgroundHospitals in the United States often have an abundance of unused medical supplies and equipment while many developing countries are in considerable need of these resources. Many nongovernmental organizations (NGOs) have donated medical equipment to health centers in low-resource settings to rectify this issue; however, studies show many of these donations are not usable by the facilities that receive them. To better serve the partner hospitals of our NGO, Oasis Medical Relief, we investigated the perspectives and insights of Ethiopian healthcare workers (HCWs) on the medical equipment distribution paradigm of the country. MethodologyQualitative analysis including semi-structured, open-ended interviews was conducted. Semi-structured interviews (n = six) were conducted with HCWs (four physicians and two hospital administrators) working in hospitals in Addis Ababa and Southern Nations, Nationalities, and Peoples' Region (SNNPR) of Ethiopia. Interviews were recorded and transcribed. Categorical content analysis was utilized to develop themes. The topical areas addressed by our questions include populations served, prevalence of diseases, laws, and strategies guiding medical equipment distribution, funding and budget for medical equipment, etc. ResultsThree themes related to perspectives and insights of HCWs on the current medical equipment distribution paradigm in Ethiopia interviewed include: (1) state of healthcare concerns, (2) medical equipment scarcity, and (3) policy shaping medical distribution paradigm. ConclusionsPre-donation assessments utilized to understand equipment needs are recognized by the World Health Organization to more effectively address medical equipment/supply. However, to further strengthen such efforts, qualitative interviews with HCWs are a tool that can be utilized to better understand the intricacies of Ethiopia's complex medical distribution paradigm. This can potentially lead to more effective partnerships between NGOs and their partner hospitals. Furthermore, increasing decentralized methods of procuring medical equipment should be further explored to mitigate issues with national distribution of medical supplies.