Should we increase betablocker after cardiac resynchronization therapy: the results of the caribe-hf study (cardiac resynchronization in combination with betablocker treatment in advanced chronic heart failure)

Cardiac resynchronization therapy (CRT), combined with optimal medical therapy (OMT), is an established treatment for patients with advanced chronic heart failure (ACHF). In ACHF, carvedilol at the dose used in clinical trials reduces morbidity and mortality. However, patients often cannot tolerate the drug at the targeted dosage. Aim of the CARIBE-HF prospective observational study was to investigate the role of CRT in the implementation of carvedilol therapy in patients with ACHF. Methods: One hundred and 6 patients (aged 65±12 [mean±sd] years) with ACHF were enrolled and treated with OMT, in which carvedilol was titrated up to the maximal dose (phase 1). Subsequently, patients with left ventricular (LV) ejection fraction < 35%, NYHA class III-IV and QRS interval ≥ 120 msec were assigned to CRT. Both CRT and NO-CRT patients underwent long-term follow-up till 7 years (1193,98±924 days), while efforts to up-titrate the carvedilol dose were continued during the second phase (471±310 days). Phase 1 was completed by 84 patients (79%), and 15 (18%) underwent CRT. The mean carvedilol dose in the CRT group was 19.0±17.8 mg, against 32.7±19.1 mg in the remaining 69 patients (p=0.018). At the end of phase 2, CRT patients presented a significantly greater variation of increasing in the carvedilol dose than NO-CRT patients ( 20.0±19.8 mg vs –0.3±20.5 mg; p=0.015), a greater NYHA class reduction (-0.8±0.6 vs -0.2±0.7; p=0.011), and a greater increase in LV ejection fraction ( 10.8±9 vs 3.1±6.1; p=0.018). In conclusion, the data from the CARIBE study suggest that, in ACHF, CRT may be effective in enabling the target dose of carvedilol to be reached. The significant improvement seen in LV function was probably due to a synergistic effect of CRT and carvedilol. During the extended follow-up (mean 1193,98±924 days) the mean dosage of carvedilol in CRT group was significantly higher (

Extracellular Superoxide Dismutase Expression in Papillary Thyroid Cancer Mesenchymal Stem/Stromal Cells Modulates Cancer Cell Growth and Migration

Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid. We report mutually exclusive desmoplasia and inflammation in papillary and follicular thyroid cancers and the presence of multipotent mesenchymal stem/stromal cells (MSCs) in non-carcinogenic thyroids and papillary thyroid cancer (PTC). The phenotypic and differentiation characteristics of Thyroid MSCs and PTC MSCs were comparable with bone marrow MSCs. A molecular level analysis showed increased FIBROBLAST ACTIVATING PROTEIN, COLLAGEN 1 TYPE A1, TENASCIN, and SOD3 expression in PTC MSCs compared to Thyroid MSCs, suggesting the presence of MSCs with a fibrotic fingerprint in papillary thyroid cancer tumors and the autocrine-paracrine conversion of SOD3 expression, which was enhanced by cancer cells. Stromal SOD3 had a stimulatory effect on cancer cell growth and an inhibitory effect on cancer cell migration, thus indicating that SOD3 might be a novel player in thyroid tumor stroma

Aqueous Nile blue: a simple, versatile and safe reagent for the detection of latent fingermarks

Nile blue A in aqueous solution undergoes spontaneous hydrolysis to the photoluminescent compound Nile red. This reagent provides a simple and safe approach to the detection of latent fingermarks on porous and non-porous surfaces

Reconsidering figures of merit for performance and stability of perovskite photovoltaics

The development of hybrid organic-inorganic halide perovskite solar cells (PSCs) that combine high performance and operational stability is vital for implementing this technology. Recently, reversible improvement and degradation of PSC efficiency have been reported under illumination-darkness cycling. Quantifying the performance and stability of cells exhibiting significant diurnal performance variations is challenging. We report the outdoor stability measurements of two types of devices showing either reversible photo-degradation or reversible efficiency improvement under sunlight. Instead of the initial (or stabilized) efficiency and T as the figures of merit for the performance and stability of such devices, we propose using the value of the energy output generated during the first day of exposure and the time needed to reach its 20% drop, respectively. The latter accounts for both the long-term irreversible degradation and the reversible diurnal efficiency variation and does not depend on the type of process prevailing in a given perovskite cell

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : an analysis of data from the Global Burden of Disease Study 2019

Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2.5 originating from ambient and household air pollution.Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2.5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure-response curve from the extracted relative risk estimates using the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2.5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2.5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2.5 exposure, with an estimated 3.78 (95% uncertainty interval 2.68-4.83) deaths per 100 000 population and 167 (117-223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13.4% (9.49-17.5) of deaths and 13.6% (9.73-17.9) of DALYs due to type 2 diabetes were contributed by ambient PM2.5, and 6.50% (4.22-9.53) of deaths and 5.92% (3.81-8.64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2.5.Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2.5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : An analysis of data from the Global Burden of Disease Study 2019

Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2·5 originating from ambient and household air pollution. Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2·5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure–response curve from the extracted relative risk estimates using the MR-BRT (meta-regression—Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2·5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2·5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals. Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2·5 exposure, with an estimated 3·78 (95% uncertainty interval 2·68–4·83) deaths per 100 000 population and 167 (117–223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13·4% (9·49–17·5) of deaths and 13·6% (9·73–17·9) of DALYs due to type 2 diabetes were contributed by ambient PM2·5, and 6·50% (4·22–9·53) of deaths and 5·92% (3·81–8·64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2·5. Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2·5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes

Multi-messenger searches via IceCube’s high-energy neutrinos and gravitational-wave detections of LIGO/Virgo

We summarize initial results for high-energy neutrino counterpart searches coinciding with gravitational-wave events in LIGO/Virgo\u27s GWTC-2 catalog using IceCube\u27s neutrino triggers. We did not find any statistically significant high-energy neutrino counterpart and derived upper limits on the time-integrated neutrino emission on Earth as well as the isotropic equivalent energy emitted in high-energy neutrinos for each event