Rate versus rhythm control and outcomes in patients with atrial fibrillation and chronic kidney disease: Data from the GUSTO-III Trial

Background: Atrial fi brillation (AF) and chronic kidney disease (CKD) have both beenshown to portend worse outcomes after acute myocardial infarction (MI); however, the benefi tof a rhythm control strategy in patients with CKD post-MI is unclear.Methods: We prospectively studied 985 patients with new-onset AF post-MI in theGUSTO-III trial, of whom 413 (42%) had CKD (creatinine clearance < 60 mL/min).A rhythm control strategy, defi ned as the use of an antiarrhythmic medication and/orelectrical cardioversion, was used in 346 (35%) of patients.Results: A rhythm control strategy was used in 34% of patients with CKD and 36% of patientswith no CKD. At hospital discharge, sinus rhythm was present in 487 (76%) of patients treatedwith a rate control strategy, vs. 276 (80%) in those treated with rhythm control (p = 0.20). CKDwas associated with a lower odds of sinus rhythm at discharge (unadjusted OR 0.56, 95% CI0.38–0.84, p < 0.001). However, in multivariable analyses, treatment with a rhythm controlstrategy was not associated with discharge rhythm (HR 1.068, 95% CI 0.69–1.66, p = 0.77),30-day mortality (HR 0.78, 95% CI 0.54–1.12, p = 0.18) or mortality from day 30 to 1 year(HR 1.00, 95% CI 0.59–1.69, p = 0.99). CKD status did not signifi cantly impact the relationshipbetween rhythm control and outcomes.Conclusions: Treatment with a rhythm or rate control strategy does not signifi cantly impactshort-term or long-term mortality in patients with post-MI AF, regardless of kidney disease status.Future studies to investigate the optimal management of AF in CKD patients are needed

The Non-Canonical CTD of RNAP-II Is Essential for Productive RNA Synthesis in Trypanosoma brucei

The carboxy-terminal domain (CTD) of the largest subunit (RPB1) of RNA polymerase II (RNAP-II) is essential for gene expression in metazoa and yeast. The canonical CTD is characterized by heptapeptide repeats. Differential phosphorylation of canonical CTD orchestrates transcriptional and co-transcriptional maturation of mRNA and snRNA. Many organisms, including trypanosomes, lack a canonical CTD. In these organisms, the CTD is called a non-canonical CTD or pseudo-CTD (ΨCTD. In the African trypanosome, Trypanosoma brucei, the ΨCTD is ∼285 amino acids long, rich in serines and prolines, and phosphorylated. We report that T. brucei RNAP-II lacking the entire ΨCTD or containing only a 95-amino-acid-long ΨCTD failed to support cell viability. In contrast, RNAP-II with a 186-amino-acid-long ΨCTD maintained cellular growth. RNAP-II with ΨCTD truncations resulted in abortive initiation of transcription. These data establish that non-canonical CTDs play an important role in gene expression

The Primarily Undergraduate Nanomaterials Cooperative: A New Model for Supporting Collaborative Research at Small Institutions on a National Scale

The Primarily Undergraduate Nanomaterials Cooperative (PUNC) is an organization for research-active faculty studying nanomaterials at Primarily Undergraduate Institutions (PUIs), where undergraduate teaching and research go hand-in-hand. In this perspective, we outline the differences in maintaining an active research group at a PUI compared to an R1 institution. We also discuss the work of PUNC, which focuses on community building, instrument sharing, and facilitating new collaborations. Currently consisting of 37 members from across the United States, PUNC has created an online community consisting of its Web site (nanocooperative.org), a weekly online summer group meeting program for faculty and students, and a Discord server for informal conversations. Additionally, in-person symposia at ACS conferences and PUNC-specific conferences are planned for the future. It is our hope that in the years to come PUNC will be seen as a model organization for community building and research support at primarily undergraduate institutions

The structure of the bacterial oxidoreductase enzyme DsbA in complex with a peptide reveals a basis for substrate specificity in the catalytic cycle of DsbA enzymes

Oxidative protein folding in Gram-negative bacteria results in the formation of disulfide bonds between pairs of cysteine residues. This is a multistep process in which the dithiol-disulfide oxidoreductase enzyme, DsbA, plays a central role. The structure of DsbA comprises an all helical domain of unknown function and a thioredoxin domain, where active site cysteines shuttle between an oxidized, substrate-bound, reduced form and a DsbB-bound form, where DsbB is a membrane protein that reoxidizes DsbA. Most DsbA enzymes interact with a wide variety of reduced substrates and show little specificity. However, a number of DsbA enzymes have now been identified that have narrow substrate repertoires and appear to interact specifically with a smaller number of substrates. The transient nature of the DsbA-substrate complex has hampered our understanding of the factors that govern the interaction of DsbA enzymes with their substrates. Here we report the crystal structure of a complex between Escherichia coli DsbA and a peptide with a sequence derived from a substrate. The binding site identified in the DsbA-peptide complex was distinct from that observed for DsbB in the DsbA-DsbB complex. The structure revealed details of the DsbA-peptide interaction and suggested a mechanism by which DsbA can simultaneously show broad specificity for substrates yet exhibit specificity for DsbB. This mode of binding was supported by solution nuclear magnetic resonance data as well as functional data, which demonstrated that the substrate specificity of DsbA could be modified via changes at the binding interface identified in the structure of the comple

Soluble ST2 in Ambulatory Patients With Heart Failure: Association With Functional Capacity and Long-Term Outcomes

ST2 is involved in cardioprotective signaling in the myocardium and has been identified as a potentially promising biomarker in HF. We evaluated ST2 levels and their association with functional capacity and long-term clinical outcomes in a cohort of ambulatory heart failure (HF) patients enrolled in the HF-ACTION study—a multicenter, randomized study of exercise training in HF

A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis

We previously reported association of co-occurrence of HLA-DRB1 shared epitope (SE) and RANKL SNPs with younger age of RA onset in 182 rheumatoid factor positive (RF) European American (EA) early RA patients. Here, we fine-mapped the 48 kb RANKL region in the extended 210 EA RF-positive early RA cohort, sought replication of RA-associated SNPs in additional 501 EA and 298 African-Americans (AA) RA cohorts, and explored functional consequences of RA-associated SNPs