Koefoedgotfredsen2706

Sequence databases on Schistosoma mansoni have revealed micro-exon gene (MEGs) families. Many of these genes are highly expressed in parasite life cycle stages associated with the mammalian host infection and appear to be involved in immune evasion by schistosomes. So, we believe that MEG-coding proteins would make potential candidates for vaccine development or diagnosis for schistosomiasis. Here, we study MEG-3.2 and MEG-3.4, members of the MEG-3 family. Recombinant (r) proteins were produced and formulated with Freund's adjuvant for vaccination of mice. Immunization with recombinant MEG-3.2 or MEG-3.4 formulation generated high levels of IgG1 antibodies. Additionally, vaccination also induced a mixed Th1/Th2/Th17-type of response, since IFN-γ, IL-5 and IL-17 cytokines were detected in the supernatant of spleen cell cultures; however it failed to induce reduction in parasitic worm burden. Finally, the recombinant proteins were evaluated in a serological assay using human samples. Schistosome-infected individuals showed higher levels of both IgG and IgM against rMEG-3.2 compared to non-infected individuals, while only IgM anti-rMEG-3.4 antibodies were elevated in infected patients. Therefore, between both studied molecules, MEG-3.2 protein is the antigen that shows potential to compose a serological diagnosis test for schistosomiasis. In Venezuela, areas endemic for schistosomiasis are of low transmission, with low parasite loads. Immunological tests often lack specificity and cannot differentiate past from present infections. Molecular tests are an alternative, although validation studies in endemic areas are needed. The aim of this study was to determine the performance of parasitological, immunological and molecular tests for the diagnosis of Schistosoma mansoni infection in low-transmission settings. A cross-sectional study was carried out in a rural community located in a schistosomiasis-endemic area of Venezuela to determine the prevalence and diagnostic performance of the Kato-Katz (KK) technique, Circumoval Precipitin Test (COPT), ELISA based on soluble egg antigen (ELISA-SEA) with and without treatment with sodium metaperiodate (ELISA-SEA-SMP), and PCR for amplification of the 121 bp highly repeated sequence of Schistosoma mansoni in faeces, urine and serum samples. The highest prevalence rates were obtained with ELISA-SEA (38.7%), COPT (33.3%), ELISA-SEA-SMP (31.5%), PCR on faeces (21.6%), and KK (17.1%), whereas PCR-based prevalence in urine was 6.2% and no positivity was detected in serum samples. Results showed that ELISA-SEA is the best method for the diagnosis of both current and former infections and that PCR on faeces is the best method for detecting recent transmission. The use of different tests that complement one another also allowed for a better diagnosis of Schistosoma mansoni infection, revealing a relatively high prevalence (33.8%) of schistosomiasis in a community of low transmission. With U.S. healthcare expenditures leading and social service spending trailing other developed nations, patients, caregivers, and employers are insisting on improved value in health and healthcare for communities. Yet, health systems struggle to understand how to best invest existing funding or savings to reach these goals. We share the experience of Los Angeles County's health system that has invested in housing through their Housing for Health Program (HFH) to address the needs of high cost populations within communities. The approach rested on four key program strategies including having partnerships with various housing facilities, a whole person approach with broad community-based resources, a local footprint in community health services, and a robust jail and prison transitions program. HFH also relied on three key implementation strategies including having dynamic funding sources, stakeholder alignment, and continuous improvement. This case report describes these program and implementation strategies plus challenges and lessons learned navigating homeless individuals through the regulations of various funding contracts, maintaining service provider capacity, maintaining local culture in implementation, and persistent gaps in affordable housing availability. Future policies can incentivize similar efforts and infrastructure to transfer healthcare dollars into public services to improve housing and value for communities. Upregulation of nerve growth factor (NGF) in parenchymal hepatocytes has been shown to exert hepatoprotective function during cholestatic liver injury. However, the modulatory role of NGF in regulation of liver autophagy remains unclear. This study aimed to scrutinize the regulatory role of NGF in hepatic expression of farnesoid X receptor (FXR), a bile acid (BA)-activated nuclear receptor, and to determine its cytoprotective effect on BA-induced autophagy and cytotoxicity. Livers of human hepatolithiasis and bile duct ligation (BDL)-induced mouse cholestasis were used for histopathological and molecular detection. The regulatory roles of NGF in autophagy flux and FXR expression, as well as its hepatoprotection against BA cytotoxicity were examined in cultured hepatocytes. FXR downregulation in human hepatolithiasis livers showed positive correlation with hepatic NGF levels. NGF administration upregulated hepatic FXR levels, while neutralization of NGF decreased FXR expression in BDL-induced cholestatic mouse livers. Acalabrutinib In vitro studies demonstrated that NGF upregulated FXR expression, increased cellular LC3 levels, and exerted hepatoprotective effect in cultured primary rat hepatocytes. Conversely, autophagy inhibition abrogated NGF-driven cytoprotection under BA exposure, suggesting involvement of NGF-modulated auophagy flux. Although FXR agonistic GW4064 stimulation did not affect auophagic LC3 levels, FXR activity inhibition significantly potentiated BA-induced cytotoxicity and increased cellular p62/SQSTM1 and Rab7 protein in SK-Hep1 hepatocytes. Moreover, FXR gene silencing abolished the protective effect of NGF under BA exposure. These findings support that NGF modulates autophagy flux via FXR upregulation and protects hepatocytes against BA-induced cytotoxicity. NGF/FXR axis is a novel therapeutic target for treatment of cholestatic liver diseases.