Plasma fibrin clot properties as determinants of bleeding time in human subjects : association with histidine-rich glycoprotein

Aims. Fibrin formation and histidine-rich glycoprotein (HRG) are involved in primary hemostasis and wound healing. Little is known regarding the relationship of clot characteristics, bleeding time, and wound healing. Methods and Results. We studied 154 patients with coronary artery disease (CAD) and 154 subjects free of CAD matched for age, obesity, and current smoking. We evaluated bleeding time (BT) using standardized skin incisions on a forearm, along with plasma clot permeability (s), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower s and 17% longer CLT as well as 50% lower HRG compared with controls (all ). After adjusting for potential confounders, s and HRG levels were independent predictors of prolonged BT in CAD patients (OR 23.70, 95% CI 4.65-120.8 and OR 10.27, 95% CI 2.05-51.31, respectively) and controls (OR 10.89, 95% CI 2.31-51.11 and OR 4.54, 95% CI 1.07-19.27, respectively). Scar formation (, 25.6%) was independently predicted by both short and prolonged BT in CAD cases (OR 21.87, 95% CI 7.41-64.55 and OR 10.17, 95% CI 2.88-35.97) and controls (OR 5.94, 95% CI 2.29-15.41 and OR 14.76, 95% CI 4.29-50.77, respectively). Conclusions. The study shows that plasma fibrin clot density and HRG may influence BT and that appropriate skin wound healing is associated with medium BT. Translational Perspective. Elucidation of the complex relationships between plasma fibrin clot phenotype and wound healing might have important practical implications

What is the initial work-up in the diagnosis of hypertension?

Patients with a new diagnosis of hypertension should be evaluated with a history and physical exam and the following initial studies: serum potassium and creatinine, fasting serum glucose and lipid panel, hematocrit, urinalysis, and electrocardiogram (strength of recommendation [SOR]: C, based on a consensus of expert opinion). Consensus is lacking for measuring serum sodium, calcium, and uric acid. Testing for microalbuminuria is optional in the work-up for a patient without diabetes (SOR: C, expert consensus). Some expert panels list limited echocardiography as another option

What treatments relieve arthritis and fatigue associated with systemic lupus erythematosus?

Q: What treatments relieve arthritis and fatigue associated with systemic lupus erythematosus? A: Hydroxychloroquine and chloroquine improve the arthritis associated with mild systemic lupus erythematosus (SLE)--producing a 50% reduction in arthritis flares and articular involvement--and have few adverse effects (strength of recommendation [SOR]: a, systematic review of randomized controlled trials [RCTs]). Methotrexate reduces arthralgias by as much as 79%, but produces adverse effects in up to 70% of patients (SOR: b, systematic review of RCTs with limited patient-oriented evidence). Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are often used for SLE joint pain (SOR: c, expert opinion). Omega-3 fatty acids may reduce arthritis symptoms by about 35% (SOR: b, RCTs with inconsistent evidence). Abatacept and dehydroepiandrosterone don't produce clinically meaningful improvements in fatigue associated with SLE, and abatacept causes significant adverse effects (SOR: b, posthoc analysis of a single RCT). Aerobic exercise may help fatigue (SOR: b, systematic review with inconsistent evidence)

Targeting proinflammatory cytokines ameliorates calcifying phenotype conversion of vascular progenitors under uremic conditions in vitro

Severe vascular calcification develops almost invariably in chronic kidney patients posing a substantial risk to quality of life and survival. This unmet medical need demands identification of novel therapeutic modalities. We aimed to pinpoint components of the uremic microenvironment triggering differentiation of vascular progenitors to calcifying osteoblast-like cells. In an unbiased approach, assessing the individual potency of 63 uremic retention solutes to enhance calcific phenotype conversion of vascular progenitor cells, the pro-inflammatory cytokines IL-1 beta and TNF-alpha were identified as the strongest inducers followed by FGF-2, and PTH. Pharmacologic targeting of these molecules alone or in combination additively antagonized pro-calcifying properties of sera from uremic patients. Our findings stress the importance of pro-inflammatory cytokines above other characteristic components of the uremic microenvironment as key mediators of calcifying osteoblastic differentiation in vascular progenitors. Belonging to the group of "middle-sized molecules", they are neither effectively removed by conventional dialysis nor influenced by established supportive therapies. Specific pharmacologic interventions or novel extracorporeal approaches may help preserve regenerative capacity and control vascular calcification due to uremic environment

Integrative analysis of extracellular and intracellular bladder cancer cell line proteome with transcriptome: improving coverage and validity of -omics findings

Characterization of disease-associated proteins improves our understanding of disease pathophysiology. Obtaining a comprehensive coverage of the proteome is challenging, mainly due to limited statistical power and an inability to verify hundreds of putative biomarkers. In an effort to address these issues, we investigated the value of parallel analysis of compartment-specific proteomes with an assessment of findings by cross-strategy and cross-omics (proteomics-transcriptomics) agreement. The validity of the individual datasets and of a “verified” dataset based on crossstrategy/omics agreement was defined following their comparison with published literature. The proteomic analysis of the cell extract, Endoplasmic Reticulum/Golgi apparatus and conditioned medium of T24 vs. its metastatic subclone T24M bladder cancer cells allowed the identification of 253, 217 and 256 significant changes, respectively. Integration of these findings with transcriptomics resulted in 253 “verified” proteins based on the agreement of at least 2 strategies. This approach revealed findings of higher validity, as supported by a higher level of agreement in the literature data than those of individual datasets. As an example, the coverage and shortlisting of targets in the IL-8 signalling pathway are discussed. Collectively, an integrative analysis appears a safer way to evaluate -omics datasets and ultimately generate models from valid observations

Analiza modalna stalowego zbiornika walcowego z dachem stałym przy różnym poziomie wypełnienia

In technical branches, such as chemical or petroleum industries, cylindrical steel tanks are essential structures used for storage of liquid products. Therefore, their safety and reliability is essential, because any failure might have dangerous consequences, in extreme cases may even lead to an environmental disaster. The aim of the presented paper is to show the results of the modal analysis concerning the cylindrical steel tank with self-supported roof which has been constructed in northern Poland. The investigation was carried out with the use of the FEM commercial computer program Abaqus. The values of natural frequencies, as well as the natural modes, for different levels of liquid filling (empty tank, partly filled and tank fully filled) were determined in the study. The results of the study clearly indicate that the increase in the liquid level leads to the substantial decrease in the natural frequencies of the structure.W branżach technicznych, takich jak przemysł chemiczny czy naftowy, stalowe zbiorniki walcowe są często wykorzystywane do magazynowania produktów płynnych. Z tego względu ich bezpieczeństwo i niezawodność to kluczowe aspekty, ponieważ ewentualne uszkodzenie konstrukcji może prowadzić do poważnych konsekwencji, a w skrajnych przypadkach nawet do katastrofy ekologicznej. Celem niniejszego referatu jest przedstawienie wyników badań numerycznych obejmujących szereg analiz modalnych dla modelu rzeczywistego zbiornika zlokalizowanego na terenie Polski. Badania przeprowadzone zostały w środowisku Abaqus. Celem wykonanych analiz było wyznaczenie wartości dominujących częstotliwości drgań własnych oraz odpowiadających im postaci drgań przy różnym poziomie wypełnienia substancją magazynowaną (zbiornik pusty, częściowo wypełniony oraz zbiornik całkowicie wypełniony). Wyniki badań wskazują, iż zwiększanie poziomu wypełnienia powoduje gwałtowny spadek częstotliwości drgań własnych, co może mieć istotne znaczenie dla odporności dynamicznej zbiorników poddanych wstrząsom górniczym lub wymuszeniom sejsmicznym