Clinical inertia in poorly controlled elderly hypertensive patients: a cross-sectional study in Spanish physicians to ascertain reasons for not intensifying treatment

Background Clinical inertia, the failure of physicians to initiate or intensify therapy when indicated, is a major problem in the management of hypertension and may be more prevalent in elderly patients. Overcoming clinical inertia requires understanding its causes and evaluating certain factors, particularly those related to physicians. Objective The objective of our study was to determine the rate of clinical inertia and the physician-reported rea- sons for it. Conclusion Physicians provided reasons for not intensi- fying treatment in poorly controlled patients in only 30 % of instances. Main reasons for not intensifying treatment were borderline BP values, co-morbidity, suspected white coat effect, or perceived difficulty achieving target. nJCI was associated with high borderline BP values and car- diovascular diseas

Retinal Degeneration Progression Changes Lentiviral Vector Cell Targeting in the Retina

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina

Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient ' s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients

Advertising, earnings prediction and market value: An analysis of persistent UK advertisers

YesThis paper examines whether major media advertising expenditures help in predicting future earnings. We consider the role of media advertising in firms’ marketing efforts and posit that persistent advertisers are more likely to benefit from advertising activities in creating long‐lived intangible assets. Employing a sample of persistent UK advertisers over the period 1997–2013, we find that advertising expenditures are significantly positively associated with firms’ future earnings and market value. We also report size and sector‐based differences in the association between advertising and firms’ future earnings. Our additional analysis provides support for the arguments that despite the recent rise in digital advertising budgets, traditional advertising media are still effective in positively influencing firms’ performance. Overall, the results of this study are consistent with the view that advertising expenditures produce intangible assets, at least for firms in certain sectors. These findings have implications for marketers in providing evidence of the value generated by firms’ advertising budgets, for investors in validating the relevance of advertising information in influencing future earnings, and for accounting regulators in relation to the provision of useful insights for any future deliberations on financial reporting policies for advertising expenditures

Effects of calcium buffering on glucose-induced insulin release in mouse pancreatic islets: an approximation to the calcium sensor

The properties of the calcium sensor for glucose-induced insulin secretion have been studied using cell-permeant Ca2+ buffers with distinct kinetics and affinities. In addition, submembrane cytosolic Ca2+ distribution has been modelled after trains of glucose-induced action potential-like depolarizations.Slow Ca2+ buffers (around 1 mmol l−1 intracellular concentration) with different affinities (EGTA and Calcium Orange-5N) did not significantly affect glucose-induced insulin release. Modelling showed no effect on cytosolic Ca2+ concentrations at the outermost shell (0.05 μm), their effects being observed in the innermost shells dependent on Ca2+ affinity.In contrast, fast Ca2+ buffers (around 1 mmol l−1 intracellular concentration) with different affinities (BAPTA and Calcium Green-5N) caused a 50% inhibition of early insulin response and completely blocked the late phase of glucose-induced insulin response, their simulations showing a decrease of [Ca2+]i at both the inner and outermost shells.These data are consistent with the existence in pancreatic β-cells of a higher affinity Ca2+ sensor than that proposed for neurons. Moreover, these data are consistent with the proposed existence of two distinct pools of granules: (i) ‘primed’ vesicles, colocalized with Ca2+ channels and responsible of the first phase of insulin release; and (ii) ‘reserved pool’ vesicles, not colocalized and responsible for the second phase

Ca2+ channel clustering with insulin-containing granules is disturbed in type 2 diabetes

Loss of first-phase insulin secretion is an early sign of developing type 2 diabetes (T2D). Ca2+ entry through voltage-gated L-type Ca2+ channels triggers exocytosis of insulin-containing granules in pancreatic β cells and is required for the postprandial spike in insulin secretion. Using high-resolution microscopy, we have identified a subset of docked insulin granules in human β cells and rat-derived clonal insulin 1 (INS1) cells for which localized Ca2+ influx triggers exocytosis with high probability and minimal latency. This immediately releasable pool (IRP) of granules, identified both structurally and functionally, was absent in β cells from human T2D donors and in INS1 cells cultured in fatty acids that mimic the diabetic state. Upon arrival at the plasma membrane, IRP granules slowly associated with 15 to 20 L-type channels. We determined that recruitment depended on a direct interaction with the synaptic protein Munc13, because expression of the II-III loop of the channel, the C2 domain of Munc13-1, or of Munc13-1 with a mutated C2 domain all disrupted L-type channel clustering at granules and ablated fast exocytosis. Thus, rapid insulin secretion requires Munc13-mediated recruitment of L-type Ca2+ channels in close proximity to insulin granules. Loss of this organization underlies disturbed insulin secretion kinetics in T2D