Replicative senescence of human dermal fibroblasts affects structural and functional aspects of the Golgi apparatus

It is well recognized that the world population is ageing rapidly. Therefore, it is important to understand ageing processes at the cellular and molecular levels to predict the onset of age‐related diseases and prevent them. Recent research has focused on the identification of ageing biomarkers, including those associated with the properties of the Golgi apparatus. In this context, Golgi‐mediated glycosylation of proteins has been well characterized. Additionally, other studies show that the secretion of many compounds, including pro‐inflammatory cytokines and extracellular matrix–degrading enzymes, is modified during ageing, resulting in physical and functional skin degradation. Since the Golgi apparatus is a central organelle of the secretory pathway, we investigated its structural organization in senescent primary human dermal fibroblasts using confocal and electron microscopy. In addition, we monitored the expression of Golgi‐related genes in the same cells. Our data showed a marked alteration in the Golgi morphology during replicative senescence. In contrast to its small and compact structure in non‐senescent cells, the Golgi apparatus exhibited a large and expanded morphology in senescent fibroblasts. Our data also demonstrated that the expression of many genes related to Golgi structural integrity and function was significantly modified in senescent cells, suggesting a relationship between Golgi apparatus function and ageing.     

Effects of Price,Information, and Transactions Cost Interventions to Raise Voluntary Enrollment in a Social Health Insurance Scheme: A Randomized Experiment in the Philippines

A cluster randomized experiment was undertaken testing two sets of interventions encouraging enrollment in the Individually Paying Program (IPP), the voluntary component of the Philippines' social health insurance program. In early 2011, 1037 unenrolled IPP‐eligible families in 179 randomly selected intervention municipalities were given an information kit and offered a 50% premium subsidy valid until the end of 2011; 383 IPP‐eligible families in 64 control municipalities were not. In February 2012, the 787 families in the intervention sites who were still IPP‐eligible but had not enrolled had their vouchers extended, were resent the enrollment kits and received SMS reminders. Half the group also received a ‘handholding’ intervention: in the endline interview, the enumerator offered to help complete the enrollment form, deliver it to the insurer's office in the provincial capital, and mail the membership cards. The main intervention raised the enrollment rate by 3 percentage points (ppts) (p = 0.11), with an 8 ppt larger effect (p < 0.01) among city‐dwellers, consistent with travel time to the insurance office affecting enrollment. The handholding intervention raised enrollment by 29 ppts (p < 0.01), with a smaller effect (p < 0.01) among city‐dwellers, likely because of shorter travel times, and higher education levels facilitating unaided completion of the enrollment form. Copyright © The World Bank Health Economics © 2015 John Wiley & Sons, Ltd.     

Sensitivity and specificity of a self-administered questionnaire for familial screening of adult-onset dystonia.

We developed a self-administered questionnaire for screening the most common adult-onset dystonias. It was tested in 90 first-degree relatives of 22 adult-onset dystonia patients, yielding 79% sensitivity and 94% specificity. Simulation of a case-finding procedure based on serial application of the questionnaire and clinical examination of both subjects screening positive and subjects screening negative who had < 8 years of schooling increased sensitivity to 95% and specificity to 100%. This questionnaire may be an important screening resource for familial aggregation studies to be used in the context of a complex case-finding procedure.     

Lecithin: cholesterol-acyltransferase (LCAT) activity in alcoholic liver disease

The activity of LCAT (the controlling enzyme for cholesterol esterification in plasma) is known to be reduced in alcoholic cirrhosis, while little is known about early stage (liver steatosis) alcoholics. In this study, LCAT activity was assayed by Stokke and Norum's method, before and after a 15-day sobriety period, in liver steatosis and in cirrhosis alcoholics. Before alcohol withdrawal, LCAT activity was depressed in both groups. After the sobriety period, LCAT activity was significantly raised in liver steatosis patients, but was still lower than in controls; in cirrhosis patients, it was increased, but not significantly. According to our results, LCAT activity impairment in alcoholic liver disease is sustained by both the hypothesized mechanisms, alcohol-related metabolic disorders and lowered LCAT-enzyme production, but to different degrees, depending on the stage of the disease. In liver steatosis, metabolic disorders play a major role, as a liver-impairment-induced decrease in LCAT production seems rather unlikely, and increased LCAT activity is more likely to be sustained by metabolic normalisation than by any recovery of the damaged liver. However, the lack of improvement in about 20% of patients, and the fairly wide scattering of individual data, suggest a minor LCAT production impairment in liver steatosis too. In cirrhosis, the major role seems to be played by a permanent decrease in LCAT production, as no significant rise in LCAT activity was observed after alcohol withdrawal. However the restored LCAT activity observed in some patients could be related to improvement in the metabolic disorder, thus confirming the effectiveness of this mechnism in cirrhosis too.(ABSTRACT TRUNCATED AT 250 WORDS)