Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Stanovení aminů pomocí HPLC s fluorescenční detekcí

A simple and sensitive method for the determination of free aliphatic and aromatic amines using derivatives agents (dansyl chloride, 9-fluorenylmethyl chloroformate and 4-Chloro-7-nitrobenzofurazan) as a labelling reagent by high-performance liq-uid chromatography with fluorescence detection (HPLC-FLD) has been developed. Derivatization conditions including reagent concentration, buffer pH, reaction time and temperature were optimized. A fluorescence derivatization - high-performance liquid chromatography (HPLC) method, which enables the femtomole-level detection of analytes, is a powerful tool for the analysis with high sensitivity and selectivity. In recent decades, improvised explosive devices (IEDs) have become an increasing topic of public concern, with high-profile incidents such as the Bali (2002), London transport (2005), Boston Marathon (2013) and Brussels (2016) bombings garnering mass international attention.[1] Although the majority of media coverage has fo-cused on large-scale incidents, there has also been a rise in explosive incidents in-volving smaller devices such as pipe bombs. This is particularly the case in the Unit-ed States, where pipe bombs are considered to make up the vast majority of IED en-counter. These devices can be easily constructed from everyday materials.[2] The mixture nitromethane with amines is applicable for this. Determination of resi-dues after an explosion is important. This method (HPLC-FLD) could be useful for their determination. The proposed method is sensitive and reproducible for the de-termination of aliphatic and aromatic amines.V práci je popsán vývoj metody pro stanovení alifatických aminů pomocí kapalinové chromatografie s využitím citlivé fluorescenční detekce. Je zde popsán způsob derivatizece. Nalezené podmínky byly testovány na reálných vzorcích, které byly získány po odpálení namíchaných směsí

Lipidomické profily plazmy pacientů s karcinomem ledvin, prsu a prostaty se liší od zdravých kontrol

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1, and SM 41:1 These seven lipids represent a potential biomarker panel for kidney, breast, and prostate cancer screening, but a further verification step in a prospective study has to be performed to verify clinical utility.Včasná detekce rakoviny je jednou z nenaplněných potřeb klinické medicíny. Periferní analýza krve je preferovanou metodou pro efektivní populační screening, protože odběr krve je dobře zakotven v klinické praxi a je minimálně invazivní pro pacienty. Lipidy jsou důležité biomolekuly a odchylky v koncentracích lipidů mohou odrážet patologické poruchy. Lipidomická profilace lidské plazmy spojením ultra-vysokoúčinné superkritické kapalinové chromatografie a hmotnostní spektrometrie je zkoumána s cílem odlišit pacienty s karcinomem prsu, ledvin a prostaty od zdravých kontrol. Průměrná citlivost, specifičnost a přesnost při profilování lipidů byla 85 %, 95 % a 92 % u rakoviny ledvin; 91 %, 97 %, a 94 % pro rakovinu prsu; a 87 %, 95 % a 92 % pro rakovinu prostaty. Není pozorována žádná souvislost statistických modelů se stádiem nádoru. Statisticky nejvýznamnějšími druhy lipidů pro diferenciaci zkoumaných typů nádorů jsou CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1 a SM 41:1. Těchto sedm lipidů představuje potenciální biomarkerový panel pro screening rakoviny ledvin, prsu a prostaty, ale k ověření klinické užitečnosti musí být proveden další ověřovací krok v prospektivní studii

Výzkum a vývoj systémů využívajících obnovitelné zdroje energie a potenciál úspor energie pro bytové a rodinné domy:Vývoj stavebnictví a využívání OZE ve výstavbě

Rekapitulace řešení projektu v roce 2001 seznam autorů, kteří se na řešení projektu v roce 2001 podíleli. I. Část. Vývoj stavebnictví a využívání OZE ve výstavbě: Tepelně-technické vlastnosti obytných budov. Možnosti porovnání různých opatření k racionálnímu zacházení s energií v budově. Vývoj a trendy v bytové výstavbě. Popis projektu, cíle, plány a hlavní směry řešení úkolu

Preliminary design of the COMPASS upgrade tokamak

COMPASS Upgrade is a new medium size, high magnetic field tokamak (R = 0.9 m, Bt = 5 T, Ip = 2 MA) currently under design in the Czech Republic. It will provide unique capabilities for addressing some of the key challenges in plasma exhaust physics, advanced confinement modes and advanced plasma configurations as well as testing new plasma facing materials and liquid metal divertor concepts. This paper contains an overview of the preliminary engineering design of the main systems of the COMPASS Upgrade tokamak (vacuum vessel, central solenoid and poloidal field coils, toroidal field coils, support structure, cryostat, cryogenic system, power supply system and machine monitoring and protection system). The description of foreseen auxiliary plasma heating systems and plasma diagnostics is also provided as well as a summary of expected plasma performance and available plasma configurations

Overview of the COMPASS results

International audienc