Myocardial asynchronism is a determinant of changes in functional mitral regurgitation severity during dynamic exercise in patients with chronic heart failure due to severe left ventricular systolic dysfunction.

AIMS: Functional mitral regurgitation (MR) and myocardial asynchronism occur commonly in patients with dilated cardiomyopathy and affect adversely their prognosis and symptoms. The aim of this study was to evaluate the mechanisms of changes in MR severity during dynamic exercise in patients with chronic heart failure (CHF). METHODS AND RESULTS: Seventy patients with CHF due to left ventricular (LV) systolic dysfunction [LV ejection fraction (EF) <40%] and functional MR were studied. All were in sinus rhythm. Medications were left unchanged for the study. Each patient performed a maximal symptom-limited exercise test with continuous 2D-Doppler echocardiography. Mitral regurgitant volume (RV) and effective regurgitant orifice (ERO) were determined at rest and during exercise. LV asynchrony using Doppler tissue imaging and interventricular asynchrony using conventional pulsed-Doppler were evaluated at rest. Resting LV EF averaged 25+/-8%. Mean resting LV and interventricular mechanical delays were 56+/-50 and 43+/-37 ms, respectively. The overall median values for mitral ERO and RV did not significantly change during dynamic exercise (11 [7-16] vs. 11 [6-21] mm2 and 14 [10-22] vs. 12 [9-23] mL, respectively). However, changes in mitral ERO and RV were individually variable and significantly correlated with the degree of LV asynchronism (r=0.66, P<0.0001 and r=0.66, P<0.0001, respectively). CONCLUSION: Changes in MR are variable during dynamic exercise. LV asynchronism at rest substantially contributes to worsening of functional MR during dynamic exercise in patients with CHF due to LV systolic dysfunction.     

Control of cholesterolemia in Spain, 2000. A tool for cardiovascular prevention

The document "Cholesterolemia Control in Spain, 2000: A Tool for Cardiovascular Disease Prevention" reviews the current evidence on cardiovascular disease prevention and the therapeutic advances achieved in recent years, in order to aid risk-based clinical decision-making. Cardiovascular diseases rank as the first cause of death in Spain. Their demographic, health and social impact is increasing and it is likely to continue to do so in the next decades. Appropriate treatment for high blood cholesterol and other major risk factors is crucial in cardiovascular disease prevention. Individual risk stratification is essential to determine follow-up periodicity and treatment. Priorities for the control of cholesterolemia and the consequent cardiovascular risk are based on risk stratification. In primary prevention, the therapeutic objective in high risk patients has been established as LDL-cholesterol < 130 mg/dl. In secondary prevention, drug treatment is indicated when LDL-cholesterol > or = 130 mg/dl and the therapeutic objective is LDL-cholesterol < 100 mg/dl. Statins are first line drugs for treatment of high blood cholesterol. In moderate-severe hypertriglyceridemia or low HDL-cholesterol, fibrates are preferred. In acute coronary syndrome, hypolipemiant treatment, should be started as soon as possible, when indicated. Secondary prevention programmes that continually provide good clinical and risk factor control should be provided to coronary heart disease patients.     

Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2

BACKGROUND/AIMS: Lysyl-oxidases catalyze the oxidation of lysine residues in collagen and elastin thereby promoting their polymerization. We have studied here the expression of four lysyl-oxidases in normal and diseased human liver. METHODS: The expression of the different lysyl-oxidases in paraffin embedded liver sections was studied using in-situ hybridization and immunohistochemistry. The enzymatic activity of lysyl-oxidase like protein-2 (Loxl2 or LOR-1) using a previously described lysyl-oxidase assay. RESULTS: We have found that the four lysyl-oxidases which we examined are not significantly expressed in the normal liver. By contrast, Wilson's disease and primary biliary cirrhosis (PBC) patients express lysyl-oxidase (Lox) and lysyl-oxidase like protein-2 (Loxl2 or LOR-1) in hepatocytes, and the expression is accompanied by collagen deposition around the hepatocytes. Lysyl-oxidases are also expressed in additional fibrotic liver diseases such as hepatitis B and C but in these diseases the expression is confined to the fibrotic lesions and collagen does not accumulate around hepatocytes. We have found that Loxl2 is able to oxidize lysine residues of collagen, and behaves in that respect similarly to Lox. The copper chelator D-penicillamine inhibits Loxl2 induced oxidation of collagen but the Lox inhibitor beta-aminopropionitrile did not inhibit the oxidation using a BAPN concentration at which Lox activity was completely inhibited. Loxl2 also catalyzed the oxidation of cell surface proteins on HepG2 hepatoblastoma cells and inhibited their proliferation. CONCLUSIONS: Upregulation of Lox and Loxl2 in hepatocytes of Wilson's disease and PBC patients may contribute to liver damage by various mechanisms. The upregulation of Lox and Loxl2 in Wilson's disease could perhaps be utilized for diagnostic purposes since their expression is up-regulated in hepatocytes even before the onset of fibrosis.     

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade

ObjectivesDuring the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain.MethodsData from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006–7 cohort study was performed between October 2006 and March 2007, and the 2016–17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression.ResultsOverall, 1262 episodes of BSI were included, 563 (44.6%) in 2006–7 and 699 (55.3%) in 2016–17. Multivariate models selected the following changes in patients' features in 2016–17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01–1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26–0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71–0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32–0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18–8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03–8.86).ConclusionsWe found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.     

Support system for decision making in the identification of risk for body dysmorphic disorder: A fuzzy model

PurposeTo develop a fuzzy linguistic model to quantify the level of distress of patients seeking cosmetic surgery. Body dysmorphic disorder (BDD) is a mental condition related to body image relatively common among cosmetic surgery patients; it is difficult to diagnose and is a significant cause of morbidity and mortality. Fuzzy cognitive maps are an efficient tool based on human knowledge and experience that can handle uncertainty in identifying or grading BDD symptoms and the degree of body image dissatisfaction. Individuals who seek cosmetic procedures suffer from some degree of dissatisfaction with appearance.MethodsA fuzzy model was developed to measure distress levels in cosmetic surgery patients based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostic criterion B for BDD. We studied 288 patients of both sexes seeking abdominoplasty, rhinoplasty, or rhytidoplasty in a university hospital.ResultsPatient distress ranged from “none” to “severe” (range = 7.5–31.6; cutoff point = 18; area under the ROC curve = 0.923). There was a significant agreement between the fuzzy model and DSM-IV criterion B (kappa = 0.805; p < 0.001).ConclusionThe fuzzy model measured distress levels with good accuracy, indicating that it can be used as a screening tool in cosmetic surgery and psychiatric practice.     

A new finite element approach for near real‐time simulation of light propagation in locally advanced head and neck tumors

Background and Objectives

Several clinical studies suggest that interstitial photodynamic therapy (I‐PDT) may benefit patients with locally advanced head and neck cancer (LAHNC). For I‐PDT, the therapeutic light is delivered through optical fibers inserted into the target tumor. The complex anatomy of the head and neck requires careful planning of fiber insertions. Often the fibers' location and tumor optical properties may vary from the original plan therefore pretreatment planning needs near real‐time updating to account for any changes. The purpose of this work was to develop a finite element analysis (FEA) approach for near real‐time simulation of light propagation in LAHNC.

Methods

Our previously developed FEA for modeling light propagation in skin tissue was modified to simulate light propagation from interstitial optical fibers. The modified model was validated by comparing the calculations with measurements in a phantom mimicking tumor optical properties. We investigated the impact of mesh element size and growth rate on the computation time, and defined optimal settings for the FEA. We demonstrated how the optimized FEA can be used for simulating light propagation in two cases of LAHNC amenable to I‐PDT, as proof‐of‐concept.

Results

The modified FEA was in agreement with the measurements (P = 0.0271). The optimal maximum mesh size and growth rate were 0.005–0.02 m and 2–2.5 m/m, respectively. Using these settings the computation time for simulating light propagation in LAHNC was reduced from 25.9 to 3.7 minutes in one case, and 10.1 to 4 minutes in another case. There were minor differences (1.62%, 1.13%) between the radiant exposures calculated with either mesh in both cases.

Conclusions

Our FEA approach can be used to model light propagation from diffused optical fibers in complex heterogeneous geometries representing LAHNC. There is a range of maximum element size (MES) and maximum element growth rate (MEGR) that can be used to minimize the computation time of the FEA to 4 minutes. Lasers Surg. Med. 47:60–67, 2015. © 2015 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.     

Characterization of the expression of MHC proteins in human embryonic stem cells

Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers both in vivo and in vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase on in vitro or in vivo differentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN-gamma but not with IFN-alpha or -beta. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells, we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation.