18272 research outputs found
Sort by
Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet
Full text linkThe physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PP). The importance of PP for inhibiting arterial calcification has been reinforced by the protective effects of PP in various mouse models displaying ectopic calcifications. Besides PP, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or -deficient mice develop spontaneous calcification of the arterial media. Whereas PP and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification
Metabo-lipidomics of Fibroblasts and Mitochondrial-Endoplasmic Reticulum Extracts from ALS Patients Shows Alterations in Purine, Pyrimidine, Energetic, and Phospholipid Metabolisms
Full text linkAmyotrophic lateral sclerosis (ALS) is characterized by a wide metabolic remodeling, as shown by recent metabolomics and lipidomics studies performed in samples from patient cohorts and experimental animal models. Here, we explored the metabolome and lipidome of fibroblasts from sporadic ALS patients (n = 13) comparatively to age- and sex-matched controls (n = 11), and the subcellular fraction containing the mitochondria and endoplasmic reticulum (mito-ER), given that mitochondrial dysfunctions and ER stress are important features of ALS patho-mechanisms. We also assessed the mitochondrial oxidative respiration and the mitochondrial genomic (mtDNA) sequence, although without yielding significant differences. Compared to controls, ALS fibroblasts did not exhibit a mitochondrial respiration defect nor an increased proportion of mitochondrial DNA mutations. In addition, non-targeted metabolomics and lipidomics analyses identified 124 and 127 metabolites, and 328 and 220 lipids in whole cells and the mito-ER fractions, respectively, along with partial least-squares-discriminant analysis (PLS-DA) models being systematically highly predictive of the disease. The most discriminant metabolomic features were the alteration of purine, pyrimidine, and energetic metabolisms, suggestive of oxidative stress and of pro-inflammatory status. The most important lipidomic feature in the mito-ER fraction was the disturbance of phosphatidylcholine PC (36:4p) levels, which we had previously reported in the cerebrospinal fluid of ALS patients and in the brain from an ALS mouse model. Thus, our results reveal that fibroblasts from sporadic ALS patients share common metabolic remodeling, consistent with other metabolic studies performed in ALS, opening perspectives for further exploration in this cellular model in ALS
Prevalence of and Predictive Factors for Burnout Among French Urologists in Training
Full text linkThe burnout rate among young doctors currently seems to be increasing [1]. It is essential to be able to diagnose and prevent this condition to better take care of young caregivers. Burnout is defined as a “feeling of intense exhaustion, loss of control and inability to achieve concrete results at work” according to the World Health Organisation. The assessment questionnaire used most often is the Maslach Burnout Inventory (MBI), which covers (1) emotional exhaustion, (2) depersonalisation, and (3) personal accomplishment [2]
A new electron paramagnetic resonance device to measure transcutaneous oxygen in humans
Full text linkEfficient Semi-Synthesis of Natural δ-(R)-Tocotrienols from a Renewable Vegetal Source
Full text linkRecent studies have highlighted the biological potential of tocotrienols, a vitamin E subfamily. The major natural sources of tocotrienols are complex mixtures requiring particularly challenging purification processes. The present study describes efficient semi-synthetic strategies toward relevant δ-( R)-tocotrienol derivatives, using as a starting material δ-( R)-garcinoic acid, the major vitamin E derivative isolated from Garcinia kola nuts, a renewable vegetal source
Pediatric Evans syndrome is associated with a high frequency of potentially damaging variants in immune genes
Full text linkEvans syndrome (ES) is a rare severe autoimmune disorder characterized by the combination of autoimmune hemolytic anemia and immune thrombocytopenia. In most cases, the underlying cause is unknown. We sought to identify genetic defects in pediatric ES (pES), based on a hypothesis of strong genetic determinism. In a national, prospective cohort of 203 patients with early-onset ES (median (range) age at last follow-up: 16.3 years (1.2-41.0)) initiated in 2004, 80 non-selected consecutive individuals underwent genetic testing. The clinical data were analyzed as a function of the genetic findings. Fifty-two patients (65%) received a genetic diagnosis (the M+ group): 49 carried germline mutations, and 3 carried somatic variants. Thirty-two (40%) had pathogenic mutations in one of 9 genes known to be involved in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS), whereas 20 patients (25%) carried probable pathogenic variants in 16 genes that had not previously been reported in the context of autoimmune disease. Lastly, no genetic abnormalities were found in the remaining 28 patients (35%, the M- group). The M+ group displayed more severe disease than the M- group, with a greater frequency of additional immunopathologic manifestations and a greater median number of lines of treatment. Six patients (all from the M+ group) died during the study. In conclusion, pES was potentially genetically determined in at least 65% of cases. Systematic, wide-ranging genetic screening should be offered in pES; the genetic findings have prognostic significance and may guide the choice of a targeted treatment
Die Österreichische Schule als Gegenprogramm zur Standardökonomik
Full text linkIn this article we outline the special position of the Austrian School (AS) among the numerous currents of modern economics, and distinguish it methodologically from mainstream economics (ME). The AS has largely remained true to classical economics in its approach and conclusions, whereas modern ME has become a “new economics” that emulates the methods of the natural sciences. The methodological instrumentalism of ME proclaims empirical prediction as the primary goal of science. The latter remains secondary in the tradition of the AS. Like classical economics, it pursues a methodological realism. It holds that theory precedes empirical analysis. Economic theory, despite all of its mistakes and incompleteness, is a priori according to the AS. Empirical analysis, on the other hand, is understood as purely descriptive. It describes the phenomena that need to be explained causally. But there is no way from empirical analysis to the realization of general causal connections. One of the most important contributions of the AS to modern economic research is the elaboration of the unsuitability of empirical prediction as methodological guiding criterion in the social sciences
Decision-Making Measured by the Iowa Gambling Task in Patients with Alcohol Use Disorders Choosing Harm Reduction versus Relapse Prevention Program
Full text linkAIMS: Two main therapeutic programs were offered to patients suffering from alcohol use disorders (AUDs): avoid the alcohol by abstinence or controlling their consumption. After information and motivational sessions, the patient chooses his own therapeutic plan. However, patients with AUD exhibit poor decision-making. The purpose of this study was to investigate the decision-making in AUD by comparing patients who chose to reduce and control their consumption to those who chose abstinence program.
METHODS: Sixty-seven subjects with alcohol use disorder were included (AUD group) for treatment, choosing either a relapse prevention program (RPP) or a harm reduction program (HRP). Patients were compared to a healthy control group (n = 31). Cognitive skills were assessed through the Montreal Cognitive Assessment test, the National Adult Reading Test, the Trail Making Test and the Iowa Gambling Task (IGT).
RESULTS: Thirty-seven patients with AUD chose the RPP while 30 followed a HRP. The AUD group performed worse than controls on the IGT. The RPP group had significantly lower performance than both HRP and control groups (these later groups being not statistically different). No correlation was observed between the available clinical, cognitive and intellectual measures.
CONCLUSION: This study confirms that the decision-making process of patients with an alcohol use disorder is impaired. However, the 2 groups differ on the IGT scores, despite comparable clinical and cognitive profiles. The patients\u27 decision-making abilities could be a useful guide when developing therapeutic programs
Qui meurt après une néphrectomie pour cancer ? Étude des facteurs de risque de décès, des causes de décès et des réunions de morbi-mortalité (étude UroCCR-33)
Full text linkBACKGROUND AND METHODS: Nephrectomy is the treatment for renal cell cancer from T1-4 tumors but remains at risk. To determine the thirty-day mortality rate after nephrectomy for cancer and to identify causes and risk factors of death in order to find clinical applications. From 2014 to 2017, we performed a retrospective multicentric analysis of prospectively collected data study involving the French network for research on kidney cancer (UroCCR). All patients who died after nephrectomy for cancer during the first thirty days were identified. Patients\u27 characteristics, causes of death and morbidity and mortality reviews reports were analyzed for each death.
RESULTS AND LIMITATIONS: In total, 2578 patients underwent nephrectomy and 35 deaths occurred. The thirty-day mortality rate was 1.4%. In univariate analysis, symptoms at diagnosis (P=0.006, OR=2.56 IC (1.3-5.03)), c stage superior to cT1 (P<0.0001, OR=6.13 IC (2.8-13.2)), cT stage superior to cT2 (P<0.0001, OR=8.8 IC (4.39-17.8)), nodal invasion (P<0.0001, OR=4.6 IC (1.9-10.7)), distant metastasis (P=0.001, OR=4.01 IC (1.7-8.9)), open surgery (P<0.0001, OR=0.272 IC (0.13-0.54)) and radical nephrectomy (P=0.007, OR=2.737 IC (1.3-5.7)) were risk factors of thirty-day mortality. In a multivariable model, only cT stage superior to T2 (P=0.015, OR=3.55 IC (1.27-10.01)) was a risk factor of thirty-day mortality. The main cause of postoperative death was pulmonary (n=15; 43%). The second cause was postoperative digestive sepsis for 7 patients (20%). Only 2 morbidity and mortality reviews had been done for the 35 deaths. Limitations are related to the thirty-day mortality criteria and descriptive study design.
CONCLUSIONS: Symptomatic patients, stage cTNM and type and techniques of surgery are determinants of thirty-day mortality after nephrectomy for cancer. The first cause of postoperative death is pulmonary. Morbidity and mortality reviews should be considered to better understand causes of death and to reduce early mortality after nephrectomy for cancer.
LEVEL OF EVIDENCE: 4