The cholesterol content of the sperm membrane is regulated during both maturation in the epididymis and capacitation in the female tract, two processes required for the spermatozoa to acquire their fertilising ability. Because Niemann-Pick disease, type C2 (NPC2) protein is one of the most abundant components of the epididymal fluid and contains a functional cholesterol-binding site that can transfer cholesterol between membranes, it has been suggested for years that NPC2 could be involved in the regulation of cholesterol levels in spermatozoa during epididymal maturation. In the present study, western blot and immunohistochemistry analyses demonstrated significant levels of NPC2 in the mouse epididymal epithelium. Epididymal spermatozoa obtained from NPC2(-/-) mice were morphologically normal and had normal motility parameters, but had a reduced cholesterol content compared with that of wild-type (WT) spermatozoa, as determined by both biochemical and by flow cytometry analyses. These results suggest that NPC2 could be involved in regulating cholesterol levels in spermatozoa during epididymal maturation. To understand the relevance of epididymal NPC2 for sperm function, the ability of spermatozoa to undergo events influenced by epididymal maturation, such as capacitation and fertilisation, were compared between WT and NPC2(-/-) mice. Capacitated NPC2(-/-) spermatozoa exhibited defective tyrosine phosphorylation patterns and a reduced ability to fertilise cumulus-oocyte complexes compared with WT spermatozoa, supporting the relevance of mouse epididymal NPC2 for male fertility.
All studies attempting to find an association between vitamin D deficiency and cerebrovascular diseases have been conducted at latitudes far away from the Equator, where living conditions, cardiovascular risk factors, and sunshine exposure are different from tropical regions. We aimed to assess cerebrovascular correlates of vitamin D deficiency in community-dwelling older adults living in Atahualpa, a village located in rural coastal Ecuador. Out of 267 individuals enrolled in the neuroimaging substudy of the Atahualpa Project, 220 (82%) signed the informed consent. Mean age of participants was 70·9 ± 7·8 years, and 126 (57%) were women. Fifty-four (25%) persons have vitamin D levels <20 ng/ml, 47 (21%) had ischemic strokes, and 53 (24%) had moderate-to-severe white matter hyperintensities of presumed vascular origin. Exposure effect models constructed with vitamin D deficiency as the exposure, white matter hyperintensities and ischemic stroke as the outcomes, and confounders--age, gender, body mass index, physical activity, blood pressure, fasting glucose, total cholesterol, ionized calcium, phosphorus, intact parathormone, and serum creatinine--as independent variables revealed a significant association of vitamin D deficiency with white matter hyperintensities (P = 0·006) but not with ischemic strokes (P = 0·359). This study shows an association of vitamin D deficiency with diffuse subcortical brain damage in older adults living in a tropical region. Lack of awareness of the importance of vitamin D deficiency might be one of the factors influencing the high prevalence of white matter hyperintensities of presumed vascular origin in underserved Latin American populations.
Niemann-Pick C2 protein (NPC2) is a lysosomal soluble protein that is highly expressed in the liver; it binds to cholesterol and is involved in intracellular cholesterol trafficking, allowing the exit of lysosomal cholesterol obtained via the lipoprotein endocytic pathway. Thus, this protein may play an important role in controlling hepatic cholesterol transport and metabolism. The aim of this work was to study the relevance of NPC2 protein expression in hepatic cholesterol metabolism, biliary lipid secretion and gallstone formation by comparing NPC2 hypomorph [NPC2 (h/h)] and wild-type mice fed control, 2% cholesterol, and lithogenic diets. NPC2 (h/h) mice exhibited resistance to a diet-induced increase in plasma cholesterol levels. When consuming the chow diet, we observed increased biliary cholesterol and phospholipid secretions in NPC2 (h/h) mice. When fed the 2% cholesterol diet, NPC2 (h/h) mice exhibited low and high gallbladder bile cholesterol and phospholipid concentrations, respectively. NPC2 (h/h) mice fed with the lithogenic diet showed reduced biliary cholesterol secretion, gallbladder bile cholesterol saturation, and cholesterol crystal and gallstone formation. This work indicates that hepatic NPC2 expression is an important factor in the regulation of diet-derived cholesterol metabolism and disposal as well as in diet-induced cholesterol gallstone formation in mice.
Debido a la carga vocal a la que están expuestos los profesionales de la voz, como los profesores, son frecuentes los trastornos de voz y mal uso vocal en este grupo, lo que hace necesario poder contar con instrumentos de pesquisa rápidos y sencillos para un diagnóstico precoz de sintomatología vocal. El objetivo del presente estudio es realizar una adaptación y validación preliminar de la pauta “Vocal Tract Discomfort Scale (VTD)” al idioma español chileno en profesores. Se comenzó con la traducción al español del instrumento original por parte de dos expertos nativos y luego la retro-traducción por dos expertos en idioma inglés para determinar concordancias y discrepancias. Luego se continuó con la validación de apariencia y contenido realizada por valoración de grupo de expertos compuesto por dos metodólogos y cinco fonoaudiólogos con experiencia en el área vocal. La validez de criterio se obtuvo mediante la correlación entre la escala en estudio y el Voice Handicap Index en su versión validada al español como prueba gold-standard, para lo cual se aplicó en una muestra de 31 docentes. La validación de la escala VTD es fiable y deja a disposición de los fonoaudiólogos una herramienta sencilla y comprensible para el entendimiento del impacto generado en personas con disfonía, particularmente, en profesionales de la voz como los profesores.
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