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Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied.To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19.Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C).Aspirin use within the first day of hospitalization.The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups.Among the 2 446 650 COVID-19-positive patients who were screened, 189 287 were hospitalized and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were White, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85; 95% CI, 0.79-0.92; P .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal hemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral hemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of hemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P .001;80 years: OR, 0.79; 95% CI, 0.69-0.91; P .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P .001;3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P .001).In this cohort study of US adults hospitalized with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomized clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin's efficacy in patients with high-risk conditions.

Free-standing, composite hydrogels containing the visible-light responsive metal-free semiconductor graphitic carbon nitride (g-C3N4) as an integral component have been fabricated by direct casting...

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3–5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8–10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.

Rationale The contractile dysfunction that underlies heart failure involves perturbations in multiple biological processes ranging from metabolism to electrophysiology. Yet the epigenetic mechanisms that are altered in this disease state have not been elucidated. SWI/SNF chromatin-remodeling complexes are plausible candidates based on mouse knockout studies demonstrating a combined requirement for the BRG1 and BRM catalytic subunits in adult cardiomyocytes. Brg1 / Brm double mutants exhibit metabolic and mitochondrial defects and are not viable although their cause of death has not been ascertained. Objective To determine the cause of death of Brg1 / Brm double-mutant mice, to test the hypothesis that BRG1 and BRM are required for cardiac contractility, and to identify relevant downstream target genes. Methods and results A tamoxifen-inducible gene-targeting strategy utilizing αMHC-Cre-ERT was implemented to delete both SWI/SNF catalytic subunits in adult cardiomyocytes. Brg1 / Brm double-mutant mice were monitored by echocardiography and electrocardiography, and they underwent rapidly progressive ventricular dysfunction including conduction defects and arrhythmias that culminated in heart failure and death within 3 weeks. Mechanistically, BRG1/BRM repressed c - Myc expression, and enforced expression of a DOX-inducible c - MYC trangene in mouse cardiomyocytes phenocopied the ventricular conduction defects observed in Brg1 / Brm double mutants. BRG1/BRM and c-MYC had opposite effects on the expression of cardiac conduction genes, and the directionality was consistent with their respective loss- and gain-of-function phenotypes. To support the clinical relevance of this mechanism, BRG1/BRM occupancy was diminished at the same target genes in human heart failure cases compared to controls, and this correlated with increased c - MYC expression and decreased CX43 and SCN5A expression. Conclusion BRG1/BRM and c-MYC have an antagonistic relationship regulating the expression of cardiac conduction genes that maintain contractility, which is reminiscent of their antagonistic roles as a tumor suppressor and oncogene in cancer.

Objectives: To determine the presence of post-needling induced pain in subjects who had suffered a stroke and received trigger point (TrP) dry needling (DN), and to investigate the effects of including TrP-DN into a rehabilitation program for shoulder pain in this population. Methods: A randomized clinical trial was conducted. Sixteen patients who had suffered a stroke and presented with shoulder pain were randomly assigned to receive rehabilitation alone or rehabilitation combined with DN. Both groups received a neurorehabilitation session including modulatory interventions targeting the central nervous system. Patients in the DN group also received a single session of DN over active TrPs in the shoulder musculature. A numerical pain rating scale (NPRS, 0–10) was used to asses post-needling induced pain at 1 min, 24 h, and 72 h after needling. Shoulder pain (NPRS, 0–10) was assessed at baseline, and 3 and 7 days after DN in both groups. Results: Five (62%) patients receiving TrP-DN reported post-needling induced pain. Post hoc analysis found that post-needling induced pain decreased significantly at 24 and 72 h (both p Conclusion: This trial found that 50% of stroke patients receiving DN experienced post-needling induced pain, a side effect that almost disappeared 72 h after the intervention without any additional therapeutic action. In addition, the inclusion of TrP-DN into a rehabilitation session was effective at decreasing shoulder pain in these patients.

Desert mule deer (Odocoileus hemionus eremicus) densities in central Arizona are below historic levels, likely due to neonatal mortality influencing desert mule deer population dynamics. However, no direct assessments have been made into causes and timing of neonatal mortalities in central Arizona. The objectives of our study were to determine the causes and timing of mortalities of desert mule deer fawns, estimate the annual survival rate of adult females and fawns, and quantify predator effects on fawn survival. In 2007 and 2008 we captured 52 adult female desert mule deer and equipped pregnant females with vaginal implant transmitters to aid in capturing fawns. We performed survival analyses using Program MARK and compared competing models with Akaike's information criterion. We captured 44 desert mule deer fawns; summer survival was 0.432 (95% CI = 0.292–0.584) and annual fawn survival was 0.071 (95% CI = 0.013–0.303). Predation accounted for 64% of fawn mortality. Probability of fawn surviva...

Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI-0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI induced by left-anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI-0100: inhalation of nebulized peptide. When given within 30 min of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI-0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after 2 weeks by Massons trichrome staining, suggesting that MMI-0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI-0100 can protect the myocardium from ischemic damage.

Neonatal survival and juvenile recruitment are crucial to maintaining viable elk (Cervus elaphus) populations. Neonate survival is known to be influenced by many factors, including bed-site selection. Although neonates select the actual bed-site location, they must do so within the larger calf-rearing area selected by the mother. As calves age, habitat selection should change to meet the changing needs of the growing calf. Our main objectives were to characterize habitat selection at 2 spatial scales and in areas with different predator assemblages in New Mexico. We evaluated bed-site selection by calves and calf-rearing area selection by adult females. We captured 108 elk calves by hand and fitted them with ear tag transmitters in two areas in New Mexico: the Valle Vidal and Blue Range Wolf Recovery Area. In both study areas, we found that concealing cover structure and distance to that cover influenced bed-site selection of young calves (i.e.

ENUSA mines an ore-body in the ‘Schisto-greywacke complex’ near Ciudad Rodrigo, close to the Portuguesc border. The uranium ore (pitchblende) is associated with sulphide minerals (pyrite, chalcopyrite). The whole Spanish yellow cake production (250 t U∼Os/year) is obtained from this mine (MINA FE) by bioleaching, although at the beginning, in 1973. it was an acid heap-leaching operation.

addition of PKA inhibitors before IEC-6 infection with CS prevents CS-induced apoptosis (p

Summary The taxonomic position of two soil isolates, strains A288 T and A290 T [provisionally assigned to the genus Actinomadura ] was clarified in a polyphasic study. The organisms showed a combination of chemotaxonomic and morphological properties typical of actinomadurae. They also formed distinct phyletic lines in the 16S rRNA Actinomadura gene tree; strain A288 T was associated with A. nitritigenes whereas strain A290 T was closely related to a group that consisted of A. citrea , A. coerulea , A. glauciflava , A. luteofluorescens and A. verrucosospora . Strains A288 T and A290 T showed key phenotypic features which readily distinguish them from one another and from representatives of related validly described species of Actinomadura . It is proposed that the two organisms be classified as new species of the genus Actinomadura . The names proposed for the new taxa are Actinomadura mexicana (A290 T = DSM 44485 T = NRRL B-24203 T ), and Actinomadura meyerii (A288 T = DSM 44485 T = NRRL B-24203 T ).

We studied Greater Scaup (Aythya marilla) nest site selection on Grassy Island, New Brunswick, during 1995 and 1996 by describing site selection in relation to habitat characteristics and association with larids using univariate comparisons. We pooled nesting data from both years and found that nesting sites were significantly closer to larid colonies and the edge of the patch of vegetation in which the nests were situated, had less forb canopy cover, more sedge cover, greater overhead concealment and lateral cover at 0–0.25 m, and less ground moisture than random sites. We evaluated Greater Scaup nests delimited as close to or far from larid colonies at 30 m and documented that nests closer to larid colonies were found in shorter vegetation that was closer to the edge of the patch of vegetation with less lateral cover at 0.25–0.5 m, but had greater overhead concealment than nests farther away. Advancements in the ecological understanding of the species, including habitat use patterns and species associations, will increase the likelihood of conservation successes.

Background The pathogenesis of diabetic cardiomyopathy (DCM) involves the enhanced activation of peroxisome proliferator activating receptor (PPAR) transcription factors, including the most prominent isoform in the heart, PPARα. In cancer cells and adipocytes, post-translational modification of PPARs have been identified, including ligand-dependent degradation of PPARs by specific ubiquitin ligases. However, the regulation of PPARs in cardiomyocytes and heart have not previously been identified. We recently identified that muscle ring finger-1 (MuRF1) and MuRF2 differentially inhibit PPAR activities by mono-ubiquitination, leading to the hypothesis that MuRF3 may regulate PPAR activity in vivo to regulate DCM. Methods MuRF3−/− mice were challenged with 26 weeks 60 % high fat diet to induce insulin resistance and DCM. Conscious echocardiography, blood glucose, tissue triglyceride, glycogen levels, immunoblot analysis of intracellular signaling, heart and skeletal muscle morphometrics, and PPARα, PPARβ, and PPARγ1 activities were assayed. Results MuRF3−/− mice exhibited a premature systolic heart failure by 6 weeks high fat diet (vs. 12 weeks in MuRF3+/+). MuRF3−/− mice weighed significantly less than sibling-matched wildtype mice after 26 weeks HFD. These differences may be largely due to resistance to fat accumulation, as MRI analysis revealed MuRF3−/− mice had significantly less fat mass, but not lean body mass. In vitro ubiquitination assays identified MuRF3 mono-ubiquitinated PPARα and PPARγ1, but not PPARβ. Conclusions These findings suggest that MuRF3 helps stabilize cardiac PPARα and PPARγ1 in vivo to support resistance to the development of DCM. MuRF3 also plays an unexpected role in regulating fat storage despite being found only in striated muscle. Electronic supplementary material The online version of this article (doi:10.1186/s12902-015-0028-z) contains supplementary material, which is available to authorized users.