Daviesarsenault9723

These effects were abolished in cells with ERβ knockdown by silencing receptor expression or by using specific receptor antagonists. Our observations support the hypothesis that estrogen-like molecules may be useful in LHON prophylactic therapy. This is particularly important for lifelong disease prevention in unaffected LHON mutation carriers. Current strategies attempting to combat degeneration of RGCs during the acute phase of LHON have not been very effective. Implementing a different and preemptive approach with a low risk profile may be very helpful.

Studies in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) have revealed promising biomarkers. The aim of our study was to validate the most encouraging markers of granulomatosis with polyangiitis and microscopic polyangiitis identified by literature search and to create biomarker panels.

A systematic literature review was performed and we identified 161 marker molecules that were ranked by their quantitative differential expression between active and inactive disease. Enzyme-linked immunosorbent assays were used to validate the results in a cross-sectional cohort of patients with renal involvement. Active vasculitis as assessed by the Birmingham Vasculitis Score version 3 (BVAS v3) was defined as BVAS v3 ≥1 and inactive disease as BVAS v3 = 0. Statistical analysis was performed with SPSS version 21 and the Salford Predictive Modeler 7.0 was used to generate a predictive biomarker panel.

The review indicated abundant expression of sC5bC9, C3a, C5a and monocyte chemotactic protein (iability to predict disease relapses.

We identified promising biomarkers in a literature-based review that were in part corroborated as has been shown for CRP, C3a, C5a, IL-18BP in blood and MCP-1 and C5a in urine samples. Moreover, we propose a biomarker panel comprising CRP and urinary MCP-1 in patients with AAV and renal involvement. Further investigations to confirm our preliminary results are clearly warranted, including the reliability to predict disease relapses.

In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population.

We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up.

The correlations between eGFR and mGFR were only moderate, with r-values ranging from 0.55 preoperatively to 0.82 during follow-up. Most importantly, the level of agreement between eGFR and mGFR was very low for all three estimates, with percentage errors ranging from 93.3 to 157.3%. Also, the percentage of patients with eGFR within 30% of mGFR (P30) rarely reached the National Kidney Foundation recommended minimum level of 75%.

We argue that the accuracy and the precision of the most commonly used estimation equations for assessment of kidney function are unacceptably low and we believe that mGFR should be used liberally as the basis for clinical decision-making both before and after HTx when eGFR is subnormal.

We argue that the accuracy and the precision of the most commonly used estimation equations for assessment of kidney function are unacceptably low and we believe that mGFR should be used liberally as the basis for clinical decision-making both before and after HTx when eGFR is subnormal.Strait et al. described a novel mouse model of cryoglobulinaemia by challenging mice deficient in the immunoglobulin (Ig)G1 subclass (γ1(-) mice) with goat anti-mouse IgD [5]. The phenotype of wild-type mice was not remarkable, whereas γ1(-) mice developed IgG3 anti-goat IgG cryoglobulins as well as severe and lethal glomerulonephritis. Renal phenotype could not be rescued in γ1(-) mice by the deletion of C3, fragment crystalline γ receptor (FcγR) or J chain. On the other hand, early injection of IgG1, IgG2a or IgG2b inhibited the pathogenic effects of IgG3 in an antigen-dependent manner even in the absence of the FcγRIIb, an anti-inflammatory receptor. The authors concluded that the pathogenic role of IgG3 and the protective characteristic of IgG1 in this model were not explained by their abilities to bind to FcRs or effector molecules but are rather due to structural discrepancies enhancing the precipitation properties/solubility of IgG3/IgG1-containing immune complexes. The present article aims to discuss the current knowledge on IgG biology and the properties of IgGs explaining their differential propensity to acquire cryoglobulin activity.

Marine n-3 polyunsaturated fatty acids (PUFAs) may exert beneficial effects on inflammation, fibrosis, endothelial function, lipid profile and blood pressure that may prevent graft loss.

In this observational cohort study in Norwegian renal transplant recipients (n = 1990), transplanted between 1999 and 2011, associations between plasma marine n-3 PUFA levels and graft loss were assessed by multivariable Cox proportional hazard regression analysis. Plasma phospholipid fatty acid composition was determined by gas chromatography and individual fatty acids recorded as weight percentage (wt%) of total fatty acids in a stable phase 10 weeks after transplantation.

During a median follow-up time of 6.8 years, 569 (28.6%) renal allografts were lost, either due to patient death (n = 340, 59.8% of graft loss) or graft loss in surviving patients (n = 229, 40.2%). Plasma marine n-3 PUFA levels ranged from 1.35 to 23.87 wt%, with a median level of 7.95 wt% (interquartile range 6.20-10.03 wt%). When adjusting for established graft loss risk factors, there was a 11% reduced risk of graft loss for every 1.0 wt% increase in marine n-3 PUFA level [adjusted hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.84-0.93], and a 10% reduced risk of graft loss in surviving patients (adjusted HR 0.90; 95% CI 0.84-0.97).

High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival.

High levels of plasma marine n-3 PUFAs were associated with better renal allograft survival.Sodium balance is achieved within a matter of days and everything that enters should come out; sodium stores are of questionable relevance and sodium accumulation is accompanied by weight gain. Careful balance studies oftentimes conflicted with this view, and long-term studies suggested that total body sodium (TBNa) fluctuates independent of intake or body weight. We recently performed the opposite experiment in that we fixed sodium intake for weeks at three levels of sodium intake and collected all urine made. We found weekly (circaseptan) patterns in sodium excretion that were inversely related to aldosterone and directly related to cortisol. TBNa was not dependent on sodium intake, but instead exhibited far longer (greater than or equal to monthly) infradian rhythms independent of extracellular water, body weight or blood pressure. To discern the mechanisms further, we delved into sodium magnetic resonance imaging (Na-MRI) to identify sodium storage clinically. We found that sodium stores are greater in men than in women, increase with age and are higher in hypertensive than normotensive persons. AZD9291 We have suggestive evidence that these sodium stores can be mobilized, also in dialysis patients. The observations are in accordance with our findings that immune cells regulate a hypertonic interface in the skin interstitium that could serve as a protective barrier. Returning to our balance studies, we found that due to biological variability in 24-h sodium excretion, collecting urine for a day could not separate 12, 9 or 6 g/day sodium intakes with the precision of tossing a coin. Every other daily urine sampling correctly classified a 3-g difference in salt intake less than half the time, making the gold standard 24-h urine collection of little value in predicting salt intake. We suggest that wobbles in expected outcomes can lead to novel clinical insights even with respect to banal salt questions.

A consistent association between low serum sodium measured at a single-point-in-time (baseline sodium) and higher mortality has been observed in hemodialysis patients. We hypothesized that both low and high time-varying sodium levels (sodium levels updated at quarterly intervals as a proxy of short-term exposure) are independently associated with higher death risk in hemodialysis patients.

We examined the association of baseline and time-varying pre-dialysis serum sodium levels with all-cause mortality among adult incident hemodialysis patients receiving care from a large national dialysis organization during January 2007-December 2011. Hazard ratios were estimated using multivariable Cox models accounting for case-mix+laboratory covariates and incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose.

Among 27 180 patients, a total of 7562 deaths were observed during 46 194 patient-years of follow-up. Median (IQR) at-risk time was 1.4 (0.6, 2.5) years. In baseline analyses erm risk in this population.Polyether ether ketone (PEEK) as a high-performance, thermoplastic implant material entered the field of medical applications due to its structural function and commercial availability. In bone tissue engineering, the combination of mesenchymal stem cells (MSCs) with PEEK implants may accelerate the bone formation and promote the osseointegration between the implant and the adjacent bone tissue. In this concept the question how PEEK influences the behaviour and functions of MSCs is of great interest. Here the cellular response of human adipose-derived MSCs to PEEK was evaluated and compared to tissue culture plate (TCP) as the reference material. Viability and morphology of cells were not altered when cultured on the PEEK film. The cells on PEEK presented a high proliferation activity in spite of a relatively lower initial cell adhesion rate. There was no significant difference on cell apoptosis and senescence between the cells on PEEK and TCP. The inflammatory cytokines and VEGF secreted by the cells on these two surfaces were at similar levels. The cells on PEEK showed up-regulated BMP2 and down-regulated BMP4 and BMP6 gene expression, whereas no conspicuous differences were observed in the committed osteoblast markers (BGLAP, COL1A1 and Runx2). With osteoinduction the cells on PEEK and TCP exhibited a similar osteogenic differentiation potential. Our results demonstrate the biofunctionality of PEEK for human MSC cultivation and differentiation. Its clinical benefits in bone tissue engineering may be achieved by combining MSCs with PEEK implants. These data may also provide useful information for further modification of PEEK with chemical or physical methods to regulate the cellular processes of MSCs and to consequently improve the efficacy of MSC-PEEK based therapies.