Webblynch9534

The American College of Cardiology and American Heart Association recently published guidelines narrowing the indications for low-dose aspirin use. The suitability of the electronic health record (EHR) to identify patients for low-dose aspirin deprescribing is unknown. To apply the 3 low-dose aspirin guidelines to EHR data, the guidelines were deconstructed into components from their narrative text and assigned computer-interpretable definitions based on electronic data interchange standards. These definitions were used to search EHR data to identify patients for aspirin deprescribing. To verify EHR records for low-dose aspirin, we then compared the records with a survey of patients' self-reported use of low-dose aspirin. Of the 3 aspirin guidelines, only 1 had a definition suitable for EHR implementation. The other 2 contained difficult-to-implement phrases (e.g., "higher ASCVD risk", "increased bleeding risk"). An EHR search with the single implementable guideline identified 86,555 people for possible aspirin deprescribing (2% of 5,598,604). Only 676 of 1,135 (60%) patients who self-reported taking low-dose aspirin had an active EHR record for low-dose aspirin at that time. Limitations exist when using EHR data to identify patients for possible low-dose aspirin deprescribing such as incomplete EHR capture of and the interpretation of non-specific terminology when translating guidelines into an electronic equivalent. In conclusion, data show many people unnecessarily take low-dose aspirin.We performed this investigation to determine the effects on mortality of thrombolytic therapy in low-risk patients with pulmonary embolism (PE). This was a retrospective cohort study based on administrative data from the Nationwide Inpatient Sample, 2016 and 2017. Patients with a primary (first-listed) diagnosis of acute PE who were not in shock and not on a ventilator who did not have acute cor pulmonale were defined as low-risk. Patients were identified by International Classification of Diseases-10-Clinical Modification Codes. Mortality was assessed according to treatment with catheter-directed thrombolysis, intravenous thrombolytic therapy, or anticoagulants alone. Mortality with inferior vena cava (IVC) filters was also assessed. Mortality was lowest in low-risk patients treated with anticoagulants alone, 6,765 of 331,430 (2.0%). Mortality was somewhat higher with catheter-directed thrombolysis, 195 of 6915 (2.8%; p less then 0.0001), and highest with intravenous thrombolysis 510 of 5,200 (9.8%; p less then 0.0001). Matched patients showed similar results. CA-074 methyl ester IVC filters did not reduce mortality in patients treated with anticoagulants alone. Mortality was only 0.5% higher in patients treated with anticoagulants who had saddle PE than in patients with nonsaddle PE, 450 of 17,935 (2.5%) versus 6,315 of 313,495 (2.0%; p less then 0.0001). However, a larger proportion of low-risk patients with saddle PE received catheter-directed thrombolysis than patients who had nonsaddle PE, 2,330 of 21,760 (11%) versus 4,585 of 321,785 (1.4%; p less then 0.0001). Similarly, a larger proportion of patients with saddle PE received intravenous thrombolytic therapy than patients with nonsaddle PE, 1,495 of 21,760 (6.9%) versus 3,705 of 321,785 (1.2%; p less then 0.0001). In conclusion, low-risk patients with PE did not have lower mortality with catheter-directed thrombolysis or intravenous thrombolytic therapy than with anticoagulants alone, and IVC filters did not reduce mortality with anticoagulants alone.Fucoxanthin chlorophyll-binding proteins (FCPs) are the major light-harvesting complexes of diatoms. In this work, FCPs isolated from Cyclotella meneghiniana have been studied by means of optically detected magnetic resonance (ODMR) and time-resolved electron paramagnetic resonance (TR-EPR), with the aim to characterize the photoprotective mechanism based on triplet-triplet energy transfer (TTET). The spectroscopic properties of the chromophores carrying the triplet state have been interpreted on the basis of a delved analysis of the recently solved crystallographic structures of FCP. The results point toward a photoprotective role for two fucoxanthin molecules exposed to the exterior of the FCP monomers. This shows that FCP has adopted a structural strategy different from that of related light-harvesting complexes from plants and other microalgae, in which the photoprotective role is carried out by two highly conserved carotenoids in the interior of the complex.Dihydroorotatequinone oxidoreductases (DHOQOs) are membrane bound enzymes responsible for oxidizing dihydroorotate (DHO) to orotate with concomitant reduction of quinone to quinol. They have FMN as prosthetic group and are part of the monotopic quinone reductase superfamily. These enzymes are also members of the dihydroorotate dehydrogenases (DHODHs) family, which besides membrane bound DHOQOs, class 2, includes soluble enzymes which reduce either NAD+ or fumarate, class 1. As key enzymes in both the de novo pyrimidine biosynthetic pathway as well as in the energetic metabolism, inhibitors of DHOQOs have been investigated as leads for therapeutics in cancer, immunological disorders and bacterial/viral infections. This work is a thorough bioinformatic approach on the structural conservation and taxonomic distribution of DHOQOs. We explored previously established structural/functional hallmarks of these enzymes, while searching for uncharacterized common elements. We also discuss the cellular role of DHOQOs and organize the identified protein sequences within six sub-classes 2A to 2F, according to their taxonomic origin and sequence traits. We concluded that DHOQOs are present in Archaea, Eukarya and Bacteria, including the first recognition in Gram-positive organisms. DHOQOs can be the single dihydroorotate dehydrogenase encoded in the genome of a species, or they can coexist with other DHODHs, as the NAD+ or fumarate reducing enzymes. Furthermore, we show that the type of catalytic base present in the active site is not an absolute criterium to distinguish between class 1 and class 2 enzymes. We propose the existence of a quinone binding motif ("ExAH") adjacent to a hydrophobic cavity present in the membrane interacting N-terminal domain.Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.Analysis of the specificity and kinetics of neutralizing antibodies (nAbs) elicited by SARS-CoV-2 infection is crucial for understanding immune protection and identifying targets for vaccine design. In a cohort of 647 SARS-CoV-2-infected subjects, we found that both the magnitude of Ab responses to SARS-CoV-2 spike (S) and nucleoprotein and nAb titers correlate with clinical scores. The receptor-binding domain (RBD) is immunodominant and the target of 90% of the neutralizing activity present in SARS-CoV-2 immune sera. Whereas overall RBD-specific serum IgG titers waned with a half-life of 49 days, nAb titers and avidity increased over time for some individuals, consistent with affinity maturation. We structurally defined an RBD antigenic map and serologically quantified serum Abs specific for distinct RBD epitopes leading to the identification of two major receptor-binding motif antigenic sites. Our results explain the immunodominance of the receptor-binding motif and will guide the design of COVID-19 vaccines and therapeutics.Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide, reaching near fixation in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate. Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts an interprotomer contact and that the conformation is shifted toward an ACE2 binding-competent state, which is modeled to be on pathway for virion membrane fusion with target cells. Consistent with this more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated.A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.

Compared to conventional full sternotomy (FS) approaches, minimally invasive mitral valve surgery (MIMVS) offers improved cosmesis, decreased pain and bleeding, and faster recovery, without compromising repair or survival rates. However, little is known about outcomes in patients with pulmonary hypertension (PH), an independent risk factor for morbidity and mortality.

Retrospective review was performed between 2002 and 2019 for all adult patients undergoing isolated mitral valve (MV) surgery. Patients with PH (mean pulmonary artery pressure ≥ 25 mmHg) were stratified by FS or MIMVS and nearest-neighbor propensity score matching was performed to adjust for differences in baseline characteristics.

Overall, 591 surgeries (317 MIMVS, 274 FS) met inclusion criteria during the study period. Nearest neighbor propensity matching generated 112 well-matched pairs. Cardiopulmonary bypass (137 vs 89.5 min, P < 0.001), cross clamp (102 vs 63 min, P < 0.001), and total operative times (241 vs. 178.5 min, p < 0.