Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.

Meibomian gland (MG) dysfunction is the leading cause of evaporative dry eye and it leads to inflammation of the ocular surface. Eicosanoids may be involved in inflammation of dry eye. This study aimed to profile tear eicosanoid levels in healthy individuals and those with MG dysfunction, and to examine if these levels are associated with clinical factors and expressibility of MG. Forty participants with MG dysfunction and 30 healthy controls were recruited in this study. Clinical signs of MG dysfunction were assessed, and tear lactoferrin concentration was evaluated. Tear eicosanoids were extracted from Schirmer’s strips and analyzed using mass spectrometry. We were able to quantify 38 tear eicosanoids and levels were increased in older individuals. In participants with MG dysfunction, higher 5-HETE, LTB4, 18-HEPE, 12-HEPE and 14-HDoHE were associated with poorer MG expressibility. The eicosanoids PGF2α, 18-HEPE, 20-HDoHE and 17-HDoHE were elevated with increased corneal staining; higher 5-HETE, LTB4 were associated with lower tear lactoferrin levels. The receiver-operating-characteristics analysis shows higher levels of 5-HETE, LTB4 and 18-HEPE were able to predict poor expressibility of MGs. In conclusion, tear eicosanoid levels are age-dependent and specific eicosanoids may be indicators of clinical obstruction of MG or the severity of ocular surface damage.

BackgroundGlobally, anemia in pregnancy increases maternal, fetal and neonatal mortality and morbidity. According to 2011 Ethiopian Demographic and Health Survey, 22% of pregnant women in Ethiopia were reported to be anemic. However, since the Ethiopian population is diverse with regard to culture, religion and other characteristics, this evidence may not represent the condition in our study area. So, we aimed to determine the prevalence of anemia and its associated factors among women receiving Antenatal Care (ANC) in Debre Berhan Town Hospitals and Clinics.MethodsWe conducted an institution based cross sectional study among women receiving ANC at hospitals and clinics in Debre Berhan Town, Ethiopia from September to November, 2013. Antenatal care providers in the respective health facilities collected the data by interview and observation using closed and open-ended questions. We computed frequencies and percentages to describe the data. We performed bivariate and multivariable binary logistic regression analyses to identify factors associated with anemia in pregnancy. STATA version 12 was used to carry out the analyses.ResultsA total of 295 participants completed the study, with a response rate of 89%. This study demonstrated a 10% prevalence of anemia out of which 64.3%, 32% and 4% of the respondents were with mild, moderate and severe anemia respectively. Anemia was statistically significantly associated with education and occupation.ConclusionThe prevalence of anemia in our study area is lower than previous studies’ findings. Literacy and job status of the women were predictors of anemia in pregnancy. Since this study was conducted on women who had an opportunity to visit health facilities, it is more valuable to conduct community based research to better understand the problem in the study area and thus propose future deliverable.

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