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4%; SD, 5.6) or higher intake of low-quality carbohydrate (mean, 47.0%; SD, 13.0). Moreover, there was an inverse association between the plant-based low-carbohydrate scores for low-quality carbohydrate and new-onset hypertension. However, there was a U-shaped association between the animal-based low-carbohydrate scores for low-quality carbohydrate and new-onset hypertension (P for nonlinearity less then 0.001). In summary, both high and low percentages of carbohydrate diets were associated with increased risk of new-onset hypertension, with minimal risk at 50% to 55% carbohydrate intake. Our findings support the intake of high-quality carbohydrate, and the substitution of plant-based products for low-quality carbohydrate for prevention of hypertension.[Figure see text].[Figure see text].

Percutaneous needle electrolysis (PNE) consists of a galvanic current combined with the insertion of a solid needle into the tissues of the musculoskeletal system. The application of a galvanic current through a needle can alter the morphology and composition during treatment application. This procedure may also provoke a localized temperature increase.

The aim was to evaluate the safety of the PNE procedure by analyzing possible alterations of the needles employed.

Physio Invasiva

and AguPunt EPI

brand needles, commonly used for the application of this technique, were analyzed in response to three different treatment protocols. Temperature changes were evaluated with the needles immersed in a test tube containing Ringer's solution, and electrical resistance was evaluated with a multimeter. The morphology of the needles, pre- and post-treatment, was examined with a scanning electron microscope (FEI Quanta 600), and the composition of the needles was evaluated using RX diffusion with Oxford Instruments software.

Ringer's solution contained in the test tubes examined did not present temperature changes. No changes were observed in the needles under investigation with respect to electrical resistance, morphology, or composition with a protocol applying 3-mA intensity for 3 s and three applications. However, important morphological alterations were observed that affected needle composition after 50 applications (at 3 mA for 3 s).

PNE, applied according to conventional protocols, appeared to be safe and athermal, and did not provoke a loss of metal particles or modify the morphology of the needles used when studied in vitro.

PNE, applied according to conventional protocols, appeared to be safe and athermal, and did not provoke a loss of metal particles or modify the morphology of the needles used when studied in vitro.[Figure see text].

Cardiac macrophages (cMPs) are increasingly recognized as important regulators of myocardial homeostasis and disease, yet the role of noncoding RNA in these cells is largely unknown. Small RNA sequencing of the entire miRNomes of the major cardiac cell fractions revealed microRNA-21 (miR-21) as the single highest expressed microRNA in cMPs, both in health and disease (25% and 43% of all microRNA reads, respectively). MiR-21 has been previously reported as a key microRNA driving tissue fibrosis. Here, we aimed to determine the function of macrophage miR-21 on myocardial homeostasis and disease-associated remodeling.

Macrophage-specific ablation of miR-21 in mice driven by Cx3cr1-Cre was used to determine the function of miR-21 in this cell type. As a disease model, mice were subjected to pressure overload for 6 and 28 days. Cardiac function was assessed in vivo by echocardiography, followed by histological analyses and single-cell sequencing. Cocultures of macrophages and cardiac fibroblasts were used to sy molecule for the profibrotic role of cMPs.

Our data indicate a critical role of cMPs in pressure overload-induced cardiac fibrosis and dysfunction and reveal macrophage miR-21 as a key molecule for the profibrotic role of cMPs.Background Coronavirus disease 2019 (COVID-19) is a respiratory disease associated with thrombotic outcomes with coagulation and endothelial disorders. Based on that, several anticoagulation guidelines have been proposed. We aimed to determine whether anticoagulation therapy modifies the risk of developing severe COVID-19. Methods and Results Patients with COVID-19 initially admitted in medical wards of 24 French hospitals were included prospectively from February 26 to April 20, 2020. We used a Poisson regression model, Cox proportional hazard model, and matched propensity score to assess the effect of anticoagulation on outcomes (intensive care unit admission or in-hospital mortality). The study enrolled 2878 patients with COVID-19, among whom 382 (13.2%) were treated with oral anticoagulation therapy before hospitalization. After adjustment, anticoagulation therapy before hospitalization was associated with a better prognosis with an adjusted hazard ratio of 0.70 (95% CI, 0.55-0.88). Analyses performed using propensity score matching confirmed that anticoagulation therapy before hospitalization was associated with a better prognosis, with an adjusted hazard ratio of 0.43 (95% CI, 0.29-0.63) for intensive care unit admission and adjusted hazard ratio of 0.76 (95% CI, 0.61-0.98) for composite criteria intensive care unit admission or death. In contrast, therapeutic or prophylactic low- or high-dose anticoagulation started during hospitalization were not associated with any of the outcomes. Conclusions Anticoagulation therapy used before hospitalization in medical wards was associated with a better prognosis in contrast with anticoagulation initiated during hospitalization. Anticoagulation therapy introduced in early disease could better prevent COVID-19-associated coagulopathy and endotheliopathy, and lead to a better prognosis.

Sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors) prevent heart failure (HF) hospitalizations in patients with type 2 diabetes and improve outcomes in those with HF and reduced ejection fraction, regardless of type 2 diabetes. Mechanisms of HF benefits remain unclear, and the effects of SGLT2 inhibitor on hemodynamics (filling pressures) are not known. The EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) was designed to address this knowledge gap.

EMBRACE-HF is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of ejection fraction, with or without type 2 diabetes) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. see more The primary end point was change in PA diastolic pressure (PADP) from baseline to end of treaeatment groups were observed in Kansas City Cardiomyopathy Questionnaire scores, natriuretic peptide levels, and 6-min walking distance.

In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT03030222.

In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT03030222.Background Restless legs syndrome (RLS) is associated with higher cardiovascular disease (CVD) risk. However, it remains unknown whether treatment of RLS lowers the cardiovascular risk associated with RLS. Methods and Results All data were collected retrospectively, but subjects were prospectively followed forward in time to determine outcomes of interest. We used the Truven Health MarketScan Commercial Claims and Encounters database from January 1, 2006, through December 31, 2014. Participants were 169 393 individuals, which included 24 199 nonpregnant participants with an RLS diagnosis (16 694 receiving treatments for RLS and 7505 without treatment) during 2006 to 2008 and 145 194 age- and sex-matched participants without RLS. All participants were free of CVD before January 1, 2009 (analysis baseline). Incident CVD cases (myocardial infarction, angina, stroke, atrial fibrillation, and heart failure) were identified. We adjusted for potential confounders, such as presence of chronic conditions and medication use. We identified 16 574 incident CVD cases during 2009 to 2014. Relative to the non-RLS group, the adjusted hazard ratio (HR) for future CVD was 1.26 (95% CI, 1.20-1.32) (P less then 0.001) for the RLS with treatment group, and 1.53 (95% CI, 1.42-1.65) (P less then 0.001) for the RLS without treatment group. Significant lower CVD risk was observed for all different RLS treatments, including dopaminergics, anticonvulsants, benzodiazepines, and opiates (adjusted HRs range, 0.71-0.84; P less then 0.001 for all), except for ergot-dopamine use. Conclusions RLS was associated with higher future CVD risk. However, RLS was associated with statistically significantly less future cardiovascular risk in RLS patients with treatment than in those without treatment.[Figure see text].[Figure see text].Are all protein interactions fully optimized? Do suboptimal interactions compromise specificity? What is the functional impact of frustration? Why does evolution not optimize some contacts? Proteins and their complexes are best described as ensembles of states populating an energy landscape. These ensembles vary in breadth from narrow ensembles clustered around a single average X-ray structure to broader ensembles encompassing a few different functional "taxonomic" states on to near continua of rapidly interconverting conformations, which are called "fuzzy" or even "intrinsically disordered". Here we aim to provide a comprehensive framework for confronting the structural and dynamical continuum of protein assemblies by combining the concepts of energetic frustration and interaction fuzziness. The diversity of the protein structural ensemble arises from the frustrated conflicts between the interactions that create the energy landscape. When frustration is minimal after folding, it results in a narrow ensemble,ire by providing a multiplicity of biological activities. In accord, we show that non-native interactions in folding or interaction landscapes can cooperate to generate diverse functional states, which are essential to facilitate adaptation to different cellular conditions. Thus, we propose that not fully optimized structures may actually be beneficial for biological activities of proteins via an alternative set of suboptimal interactions. The importance of such variability has not been recognized across different areas of biology.This account provides a modern view on folding, function, and assembly across the protein universe. The physical framework presented here is applicable to the structure and dynamics continuum of proteins and opens up new perspectives for drug design involving not fully structured, highly dynamic protein assemblies.Finding highly efficient and reusable catalysts for advanced oxidation processes is a crucial endeavor to resolve the severe water pollution problems. Although numerous nanocatalysts have been developed in the past few decades, their recyclability along with sustainably high catalytic efficiency still remain challenging. Here, we propose a new strategy for designing efficient and reusable catalysts, that is, introducing Cu as a reductant into a metallic glass-based catalyst and constructing three-dimensional hierarchical porous architectures via a laser 3D printing technique. The as-printed 3D porous MG/Cu catalysts exhibit exceptional catalytic efficiency in degrading RhB with a normalized rate constant approximately 620 times higher than commercial nano zero-valent iron, outperforming most reported Fenton-type catalysts so far. Strikingly, the catalysts exhibit an excellent reusability and can be used more than 100 times (the highest record so far) without apparent efficiency decay. It is revealed that Cu-doping could improve the surface reducibility and promote the electronic transfer, rendering the 3D-printed MG/Cu catalysts with a sustainably active Fe(II)-rich surface and, therefore, unprecedented reusability.