Pseudouridine (Ψ) is the most common noncanonical nucleotide present in naturally occurring RNA and serves a variety of roles in the cell, typically appearing where structural stability is crucial to function. Ψ residues are isomerized from native uridine residues by a class of highly conserved enzymes known as pseudouridine synthases. In order to quantify the thermodynamic impact of pseudouridylation on U-A base pairs, 24 oligoribonucleotides, 16 internal and eight terminal Ψ-A oligoribonucleotides, were thermodynamically characterized via optical melting experiments. The thermodynamic parameters derived from two-state fits were used to generate linearly independent parameters for use in secondary structure prediction algorithms using the nearestneighbor model. On average, internally pseudouridylated duplexes were 1.7 kcal/mol more stable than their U-A counterparts, and terminally pseudouridylated duplexes were 1.0 kcal/mol more stable than their U-A equivalents. Due to the fact that Ψ-A pairs maintain the same Watson-Crick hydrogen bonding capabilities as the parent U-A pair in A-form RNA, the difference in stability due to pseudouridylation was attributed to two possible sources: the novel hydrogen bonding capabilities of the newly relocated imino group as well as the novel stacking interactions afforded by the electronic configuration of the Ψ residue. The newly derived nearest-neighbor parameters for Ψ-A base pairs may be used in conjunction with other nearest-neighbor parameters for accurately predicting the most likely secondary structure of A-form RNA containing Ψ-A base pairs.

Hydrogen-bonding, intra-strand base-stacking, and inter-strand base-stacking energies were calculated for RNA and DNA dimers at the MP2(full)/6-311G** level of theory. Standard A-form RNA and B-form DNA geometries from average fiber diffraction data were employed for all base monomer and dimer geometries, and all dimer binding energies were obtained via single-point calculations. The effects of water solvation were considered using the PCM model. The resulting dimer binding energies were used to calculate the 10 unique RNA and 10 unique DNA computational nearest-neighbor energies, and the ranking of these computational nearest neighbor energies are in excellent agreement with the ranking of the experimental nearest neighbor free energies. These results dispel the notion that average fiber diffraction geometries are insufficient for calculating RNA and DNA stacking energies.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected patients commonly have elevated troponin and D-dimer levels, but limited imaging exists to support most likely etiologies in efforts to avoid staff exposure. The purpose of this study was to report transthoracic echocardiographic (TTE) findings in SARS-CoV-2 patients with correlating troponin and D-dimer levels. Methods: We identified 66 SARS-CoV-2 patients (mean age 60 ± 15.7 years) admitted within a large, eight-hospital healthcare system over a 6-week period with a TTE performed. TTE readers were blinded to laboratory data with intra-observer and inter-observer analysis assessed. Results: Sixty-six of 1780 SARS-CoV-2 patients were included and represented a high-risk population as 38 (57.6%) were ICU-admitted, 47 (71.2%) had elevated D-dimer, 41 (62.1%) had elevated troponin, and 25 (37.9%) died. Right ventricular (RV) dilation was present in 49 (74.2%) patients. The incidence and average D-dimer elevation was similar between moderate/severe vs. mild/no RV dilation (69.6% vs 67.6%, P = 1.0; 3736 ± 2986 vs 4141 ± 3351 ng/mL, P = .679). Increased left ventricular (LV) wall thickness was present in 46 (69.7%) with similar incidence of elevated troponin and average troponin levels compared to normal wall thickness (66.7% vs 52.4%, P = .231; 0.88 ± 1.9 vs 1.36 ± 2.4 ng/mL, P = .772). LV dilation was rare (n = 6, 9.1%), as was newly reduced LV ejection fraction (n = 2, 3.0%). Conclusion: TTE in SARS-CoV-2 patients is scarce, technically difficult, and reserved for high-risk patients. RV dilation is common in SARS-CoV-2 but does not correlate with elevated D-dimer levels. Increased LV wall thickness is common, while newly reduced LV ejection fraction is rare, and neither correlates with troponin levels.

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Coronavirus disease 2019 is a global pandemic affecting >3 million people in >170 countries, resulting in >200 000 deaths; 35% to 40% of patients and deaths are in the United States. The coronavirus disease 2019 crisis is placing an enormous burden on health care in the United States, including residency and fellowship training programs. The balance between mitigation, training and education, and patient care is the ultimate determinant of the role of cardiology fellows in training during the coronavirus disease 2019 crisis. On March 24, 2020, the Accreditation Council for Graduate Medical Education issued a formal response to the pandemic crisis and described a framework for operation of graduate medical education programs. Guidance for deployment of cardiology fellows in training during the coronavirus disease 2019 crisis is based on the principles of a medical mission, and adherence to preparation, protection, and support of our fellows in training. The purpose of this review is to describe our departmental strategic deployment of cardiology fellows in training using the Accreditation Council for Graduate Medical Education framework for pandemic preparedness.

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Metaanalyses of trials comparing medical treatment versus surgical closure of patent foramen ovale (PFO) have shown that percutaneous closure is more effective for preventing recurrent thromboembolic events [1]. Common complications of any occluder device include device thrombus formation, transient ischemic attack, pericardial tamponade, device dislocation, arrhythmias, and endocarditis [1]. In this article, we take a closer look at endocarditis post-device implant. It is established that up to 6 months post-implant, there is a high likelihood of device infection because endothelialization is incomplete [2]. Late-onset (>6 months) endocarditis of any occluder device is exceptionally rare. There have been scattered reports of late endocarditis with the popular AMPLATZER (St. Jude Medical, St. Paul, MN, USA) device [2][3][4]. There has been one reported case of late endocarditis with the HELEX septal occluder (W.L. Gore & Associates, Newark, DE, USA)where the patient was treated with open-heart surgery [5]. Here, we present a case of delayed-onset right-and left-sided bacterial endocarditis of the HELEX devicemade even more remarkable by the resounding success of non-surgical management. Case reportA 50-year-old African American man presented to our medical center with weakness, fever, lethargy, and chills. His medical history was significant for a 4 mm PFO that was repaired in 2010 (five years prior to current admission, repair reason unknown), paroxysmal atrial fibrillation, type 2 diabetes mellitus with resultant foot ulcer, hypertension, chronic hepatitis B, chronic