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rogression of cardiac disease. At present, the role of troponin and brain natriuretic peptide in monitoring and therapy remains unclear. Orthotopic heart transplantation is feasible in case of severe disease, even if the experience is limited in -EGPA, and optimal post-transplantation immunosuppressive strategy has yet to be defined.The importance of proper diet in primary and secondary cardiovascular prevention is now quite clear several recent studies, e.g. on fat and saturated fat intake, on sodium, and on dietary cholesterol, are being discussed by the lay press and by professionals. This paper reviews the most solid published evidence on diet and cardiovascular risk, to provide clinicians (namely, cardiologists) with a useful tool to be discussed with patients. Where evidence was strong enough, we discussed the cardiovascular actions of specific nutrients and of dietary patterns. Particular attention was paid to dietary fat, carbohydrates (in terms of glycemic index), and functional, polyphenol-rich foods. Of note, we critically review the available evidence in light of the Italian dietary patterns, to draw practical conclusions applicable to this country.Hypertension is common and occurs in the majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end-stage renal disease. The pathogenesis of hypertension in ADPKD is complex and depends on many factors that influence each other. High expression of PKD1 and PKD2 genes is present in the cilia of tubular epithelial cells, in endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin-1 or -2 expression is associated with abnormal vascular structure and function. PKD1/PKD2 deficiency results in reduced nitric oxide levels, altered endothelial response to shear stress with attenuation in vascular relaxation. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased nitric oxide production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the renin-angiotensin-aldosterone system occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to end-stage renal disease. Inhibition of the angiotensin-aldosterone system is possible with angiotensin-converting enzyme inhibitors and seems to be the first-line treatment for hypertension in these subjects. As suggested by the HALT-PKD study, an aggressive blood pressure control is safe and recommended and is associated with preservation of kidney function and a reduction in total kidney volume over time. A collaborative multidisciplinary approach between nephrologists and cardiologists is necessary for the monitoring of kidney and heart complications.The differences in terms of cardioembolic risk of permanent and paroxysmal atrial fibrillation are reviewed. On the basis of the available literature, the authors suggest that their equivalence reported in the recent guideline for the management of patients with atrial fibrillation represents an oversimplification.The exponential increase in publications focusing on important clinical issues represents a major challenge for patients, physicians, and decision-makers, despite the braggadocio of many experts. Meta-analysis, when conducted within the context of a systematic review, offers an efficient and potent tool to summarize the clinical evidence accrued on a specific clinical question. Despite their many strengths, which include statistical precision, external validity, and the opportunity to analyze subgroups and moderators, meta-analyses also have many limitations. In addition, they are criticized because potentially an exercise in "mega-silliness", mixing "apples and oranges", unable to improve the quality of primary studies (in keeping with the say "garbage in-garbage out"), and focusing on an "average patient" who is only hypothetical. Yet, it is evident that meta-analyses will continue to play a key role in informing decision making whenever the best approach is not self-evident. Thus, it is mandatory to know their main features in order to use them critically and constructively, without being dominated nor scared.Using an asymmetrical set of vernier stimuli (-15″, -10″, -5″, +10″, +15″) together with reverse feedback on the small subthreshold offset stimulus (-5″) induces response bias in performance (Aberg & Herzog, 2012; Herzog, Eward, Hermens, & Fahle, 2006; Herzog & Fahle, 1999). These conditions are of interest for testing models of perceptual learning because the world does not always present balanced stimulus frequencies or accurate feedback. Here we provide a comprehensive model for the complex set of asymmetric training results using the augmented Hebbian reweighting model (Liu, Dosher, & Lu, 2014; Petrov, Dosher, & Lu, 2005, 2006) and the multilocation integrated reweighting theory (Dosher, Jeter, Liu, & Lu, 2013). The augmented Hebbian learning algorithm incorporates trial-by-trial feedback, when present, as another input to the decision unit and uses the observer's internal response to update the weights otherwise; block feedback alters the weights on bias correction (Liu et al., 2014). Asymmetric training with reversed feedback incorporates biases into the weights between representation and decision. The model correctly predicts the basic induction effect, its dependence on trial-by-trial feedback, and the specificity of bias to stimulus orientation and spatial location, extending the range of augmented Hebbian reweighting accounts of perceptual learning.Studies have revealed complex interactions between bone and fat, however there are few studies about this crosstalk in patients with chronic kidney disease. This study investigated possible relationship between bone mineral density (BMD) and body composition in patients who underwent hemodialysis. Twenty patients were enrolled in a cross-sectional study (47.0 [42.3-56.8] years, body mass index 26.0 ± 4.2 kg/m, dialysis vintage of 48.5 [26.7-95.7] months). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. Leptin and parathormone levels were analyzed using Multiplex kits (R&D System Inc). Low bone mass in the femoral neck was reported in 54.8% of patients. Total BMD and total T-score were positively correlated with lean mass (r = 0.46, P = 0.04; r = 0.47, P = 0.04, respectively), but not with leptin or body fat mass. In conclusion, lean body mass is probably important to maintain bone health in male patients who underwent hemodialysis.

Chronic pain is common, costly and leads to significant morbidity in older adults, yet there are limited data on medication safety. Selleckchem LY333531 The authors sought to evaluate the association of incident high-risk medication in the elderly (HRME) with mortality, emergency department (ED) or hospital care among older adults with chronic pain.

A retrospective Veterans Health Administration cohort study was conducted examining older veterans with chronic pain diagnoses and use of incident HRME (opioids, skeletal muscle relaxants, antihistamines and psychotropics). Outcomes evaluated included all-cause mortality, ED visits or inpatient hospital care. Descriptive statistics summarized variables for the overall cohort, the chronic pain cohort and those with and without HRME. Separate generalized linear mixed-effect regression models were used to examine the association of incident HRME on each outcome, controlling for potential confounders.

Among 1,807,404 veterans who received Department of Veterans Affairs care in 2005 f drugs in this vulnerable population.

Renal hypouricemia (RHUC) is a heterogeneous inherited disorder characterized by impaired tubular uric acid (UA) transport with severe complications, such as acute kidney injury. Type 1 is caused by a mutation in the SLC22A12 gene (URAT1) and type 2 in the SLC2A9 gene (GLUT9). In this article, the authors present a coexpression functional characterization of variants responsible for RHUC type 1 in a Czech family with polycystic kidney disease (PKD).

The serum UA concentration in the proband was 1.1 mg/dL and was expressed as an increase in the fractional excretion of UA (43%). The URAT1 allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. Linkage analysis using a panel of 4 CA-repeat flanking markers for chromosome 16 and a panel of 3 CA-repeat flanking markers for chromosome 4 was performed, which carry the PKD1 and PKD2 genes, respectively.

Coexpression results showed that p.G366R and p.R477H suppressed urate transport by wild types. Colocalization studies showed an accumulation of URAT1 in the endoplasmic reticulum of the p.G366R variant and mainly retention of wild-type protein by variants p.G366R and p.R477H.

The findings suggest that not only loss-of-function mutation of URAT1 but also the dominant-negative effect cause RHUC through loss of UA absorption, partly due to protein misfolding caused by accumulation of URAT1 protein in the endoplasmic reticulum.

The findings suggest that not only loss-of-function mutation of URAT1 but also the dominant-negative effect cause RHUC through loss of UA absorption, partly due to protein misfolding caused by accumulation of URAT1 protein in the endoplasmic reticulum.In the simplest ionic liquid, ethylammonium nitrate (EAN), ionogels with high mechanical strength were prepared from a surfactant with a disaccharide polar head. Phase structures from closely packed bilayers to right-handed twisted ribbons were determined via freeze-fracture transmission electron microscopy (FF-TEM) observations. The phase transition mechanism was investigated deeply and systematically. The temperature contributes to suitable tail chain conformations of surfactant molecules for adapting to different self-assembled structures including right-handed twisted ribbons and bilayers. Two different arrays were revealed for different bilayers by the small-angle X-ray scattering (SAXS) measurements. The rheological and tribological properties of the ionogels were investigated. The better lubricating property and antiwear capability of the ionogels compared to the EAN may be attributed to the structure characteristics and the good thixotropic properties.Cystic Fibrosis (CF) is a lethal, genetic disease caused by mutations to the CFTR chloride channel. The most common CF causing mutation is the deletion of F508 from the first Nucleotide Binding Domain (F508del-NBD1). This mutation leads to a thermally unstable domain and a misfolded, nonfunctioning CFTR. Replica Exchange MD simulations were used to simulate seven NBD1 constructs including wt and F508del-NBD1 both alone and in the presence of known rescuing mutations as well as F508del-NBD1 in complex with a known small (ligand) stabilizer. Analyzing the resulting trajectories suggests that differences in the biochemical properties of the constructs result from local and coupled differences in their dynamic profiles. A comparative analysis of these profiles as well as of the resulting trajectories reveals how the different perturbations exert their deleterious, rescuing, and stabilizing effects on NBD1. These simulations may therefore be useful for the design and mechanism-of-action analysis of new NBD1 stabilizers.

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