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A reversible photoinduced intramolecular crankshaft-type rearrangement in a glycoconjugate proceeds simultaneously at both the –N–N and CH–C– bonds.

High-resolution NMR experiments revealed that differently substituted quinazolinone-based Schiff bases undergo anti to syn isomerisation on exposure to ultraviolet light in DMSO solution.

The aim of this study was to compare 5-year cardiovascular, renal, and bioprosthetic valve durability outcomes in patients with severe aortic stenosis (AS) and chronic kidney disease (CKD) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).Patients with severe AS and CKD undergoing TAVR or SAVR are a challenging, understudied clinical subset.Intermediate-risk patients with moderate to severe CKD (estimated glomerular filtration rate 60 mL/min/mThe study population included 1,045 TAVR patients (512 SAPIEN XT, 533 SAPIEN 3) and 479 SAVR patients. At 5 years, SAVR was better than SAPIEN XT TAVR (52.8% vs 68.0%; P = 0.04) but similar to SAPIEN 3 TAVR (52.8% vs 58.7%; P = 0.89). Perioperative AKI was more common after SAVR than TAVR (26.3% vs 10.3%; P 0.001) and was independently associated with long-term outcomes. Compared with SAVR, bioprosthetic valve failure and stage 2 or 3 structural valve deterioration were significantly greater for SAPIEN XT TAVR (P 0.05) but not for SAPIEN 3 TAVR.In intermediate-risk patients with AS and CKD, SAPIEN 3 TAVR and SAVR were associated with a similar risk for the primary endpoint at 5 years. AKI was more common after SAVR than TAVR, and SAPIEN 3 valve durability was comparable with that of surgical bioprostheses.

A new approach to assessing the effect of the transmission of spin-polarization by π-orbitals (π-TSP) is presented. In order to switch off the π-TSP effect, we artificially average the α- and β-densities of the valence π-orbitals when calculating the exchange-correlation contribution to the Fock matrix in the unrestricted Kohn-Sham framework. The π-TSP effect is then evaluated as the difference between the results obtained with switched-on and switched-off options. This approach is applied to estimate the π-TSP effect on the Fermi-contact contribution to spin-spin couplings and EPR hyperfine structure coupling constants. The π-TSP effect on the distribution of spin-density, spin-spin coupling pathways and pathways of EPR hyperfine couplings is demonstrated for benzene, naphthalene, 1,3,5,7,9-decapentaene and the 1,3,5,7,9-decapentaen-1-yl radical. The sign alternation of the spin-polarization transmitted by π-orbitals is explained in a theoretical framework based on perturbation theory. However, the delocalized nature of the π-system can interfere with the sign alternation in certain cases, two of which - the cyclobutadiene dication and the cyclooctatetraene dication - are examined, and an explanation for which is provided.

ObjectiveImmediate facial nerve reconstruction is the standard of care following radical parotidectomy; however, quality of life comparisons with those undergoing limited superficial parotidectomy without facial nerve sacrifice is lacking.MethodPatients who underwent parotidectomy were contacted to determine quality of life using the University of Washington Quality of Life and Parotidectomy Specific Quality of Life questionnaires. A total of 29 patients (15 in the radical parotidectomy and 14 in the limited superficial parotidectomy groups) completed and returned questionnaires.ResultsUsing the University of Washington Quality of Life Questionnaire, similar quality of life was noted in both groups, with the radical parotidectomy group having significantly worse speech and taste scores. Using the Parotidectomy Specific Quality of Life Questionnaire, the radical parotidectomy group reported significantly worse speech, eye symptoms and eating issues.ConclusionThose undergoing radical parotidectomy with reconstruction had comparable overall quality of life with the limited superficial parotidectomy group. The Parotidectomy Specific Quality of Life Questionnaire better identified subtle quality of life complaints. Eye and oral symptoms remain problematic, necessitating better rehabilitation and more focused reconstructive efforts.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated.We analyzed Optum® claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations.A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR]=0.82, 95% confidence interval [CI] 0.74-0.91, p=0.0003) and statins (HR=0.85, 95% CI 0.77-0.94, p=0.0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins.In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where these medications were initiated preoperatively.

Introduction: The development of adeno-associated virus (AAV) vectors as safe vehicles for in vivo delivery of therapeutic genes has been a major milestone in the advancement of gene therapy, enabl...

Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance olaparib in patients with platinum-sensitive relapsed ovarian cancer (PSROC) and BRCA mutation significantly improved progression-free survival (PFS) and prolonged overall survival (OS). Following disease progression on olaparib, efficacy of subsequent chemotherapy remains unknown. Patients and methods: We conducted a post-hoc hypothesis-generating analysis of SOLO2 data to determine the efficacy of different chemotherapy regimens following RECIST disease progression in patients who received olaparib or placebo. We evaluated time to second progression (TTSP) calculated from the date of RECIST progression to the next progression/death. Results: The study population comprised 147 patients who received chemotherapy as their first subsequent treatment after RECIST progression. Of these, 69 (47%) and 78 (53%) were originally randomized to placebo and olaparib arms, respectively. In the placebo-treated cohort, 27/69 and 42/69 received non-platinum and platinum-based chemotherapy, respectively, compared with 24/78 and 54/78, respectively, in the olaparib-treated cohort. Among patients treated with chemotherapy (N = 147), TTSP was significantly longer in the placebo than in the olaparib arm: 12.1 versus 6.9 months [hazard ratio (HR) 2.17, 95% confidence interval (CI) 1.47-3.19]. Similar result was obtained on multivariable analysis adjusting for prognostic factors at RECIST progression (HR 2.13, 95% CI 1.41-3.22). Among patients treated with platinum-based chemotherapy (n = 96), TTSP was significantly longer in the placebo arm: 14.3 versus 7.0 months (HR 2.89, 95% CI 1.73-4.82). Conversely, among patients treated with non-platinum-based chemotherapy (n = 51), the TTSP was comparable in the placebo and olaparib arms: 8.3 versus 6.0 months (HR 1.58, 95% CI 0.86-2.90). Conclusions: Following progression from maintenance olaparib in the recurrent setting, the efficacy of platinum-based subsequent chemotherapy seems to be reduced in BRCA1/2-mutated patients with PSROC compared to patients not previously receiving poly (ADP-ribose) polymerase inhibitors (PARPi). The optimal strategy for patients who relapse after PARPi is an area of ongoing research.

Background: Clinical presentations of coronavirus disease 2019 (COVID-19) among children with asthma have rarely been investigated. This study aimed to assess clinical manifestations and outcome of COVID-19 among children with asthma, and whether the use of asthma medications was associated with outcomes of interest. Methods: The Global Asthma Network (GAN) conducted a global survey among GAN centers. Data collection was between November 2020 and April 2021. Results: Fourteen GAN centers from 10 countries provided data on 169 children with asthma infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was asymptomatic in 58 (34.3%), mild in 93 (55.0%), moderate in 14 (8.3%), and severe/critical in 4 (2.4%). Thirty-eight (22.5%) patients had exacerbation of asthma and 21 (12.4%) were hospitalized for a median of 7 days (interquartile range 3–16). Those who had moderate or more severe COVID-19 were significantly more likely to have exacerbation of asthma as compared to those who were asymptomatic or had mild COVID-19 (adjusted odds ratio (adjOR) 3.97, 95% CI 1.23–12.84). Those who used inhaled bronchodilators were significantly more likely to have a change of asthma medications (adjOR 2.39, 95% CI 1.02–5.63) compared to those who did not. Children who used inhaled corticosteroids (ICS) did not differ from those who did not use ICS with regard to being symptomatic, severity of COVID-19, asthma exacerbation, and hospitalization. Conclusions: Over dependence on inhaled bronchodilator may be inappropriate. Use of ICS may be safe and should be continued in children with asthma during the pandemic of COVID-19. © 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

EPR and NMR experiments on a quinazolinone-based Schiff's base in DMSO solution showed that irradiation with UV light (365 nm) leads to photochemically-induced isomerization from the anti- to the higher-energy syn-form around the –N–N linkage. The anti- to syn-isomerization was relatively fast, and the maximum amount of conversion detected (25%) was reached within 10 min; thermodynamic equilibrium re-established itself in about 15 min. DFT calculations were performed on the investigated compound and small model systems, and reproduced the experimental fact of the anti-conformer being lower in energy than the syn. Theoretical analysis of excited states, including visualisation of natural transition orbitals, identified possible pathways for syn–anti isomerisation, although the details vary with π-system size, making the use of small models of limited utility. The investigated compound probably isomerises through the third singlet excited state (S3), a π–π* excitation, relaxing through S2, also a π–π* state.

Left atrial appendage occlusion has become a safe and effective alternative for stroke-risk reduction among patients with non-valvular atrial fibrillation (AF). Although complete closure is ideal, residual peri-device leaks (PDL) are not uncommon and have been associated with an increased residual risk of stroke. PDL closure has been proposed as an alternate strategy to allow for the safe discontinuation of oral anticoagulation. We describe the safety and feasibility of successful PDL closure using a non-fenestrated Cardioform (Gore Medical, Flagstaff, Arizona) septal occluder after initial Watchman (Boston Scientific, Marlborough, Massachusetts) implantation.

OBJECTIVES Functional mitral regurgitation (MR) is observed with ischaemic heart disease or aortic valve disease. Assessing the value of mitral valve repair or replacement (MVR/P) is complicated by frequent discordance between preoperative transthoracic echocardiographic (pTTE) and intraoperative transoesophageal echocardiographic (iTOE) assessment of MR severity. We examined the association of pTTE and iTOE with postoperative mortality in patients with or without MR, at the time of coronary artery bypass grafting (CABG) and/or aortic valve replacement without MVR/P. METHODS Medical records of 6629 patients undergoing CABG and/or aortic valve replacement surgery with or without functional MR and who did not undergo MVR/P were reviewed. MR severity assessed by pTTE and iTOE were examined for association with postoperative mortality using proportional hazards regression while accounting for patient and operative characteristics. RESULTS In 72% of 709 patients with clinically significant (moderate or greater) functional MR detected by pTTE, iTOE performed after induction of anaesthesia demonstrated a reduction in MR severity, while 2% of patients had increased severity of MR by iTOE. iTOE assessment of MR was better associated with long-term postoperative mortality than pTTE in patients with moderate MR [hazard ratio (HR) 1.31 (1.11–1.55) vs 1.02 (0.89–1.17), P-value for comparison of HR 0.025] but was not different for more than moderate MR [1.43 (0.96–2.14) vs 1.27 (0.80–2.02)]. CONCLUSIONS In patients undergoing CABG and/or aortic valve replacement without MVR/P, these findings support intraoperative reassessment of MR severity by iTOE as an adjunct to pTTE in the prediction of mortality. Alone, these findings do not yet provide evidence for an operative strategy.

OBJECTIVE This study aimed to examine the cumulative experience of peri-device leak (PDL) closure following left atrial appendage (LAA) closure. BACKGROUND The management of PDL following LAA closure remains controversial. While PDL closure has been proposed, procedural features and clinical outcomes have not been well established. METHODS A systematic review of all published cases of PDL closure with available anatomical, procedural, and clinical outcomes was performed. RESULTS We identified 18 indexed publications and 110 cases between April 2013 and March 2020. 71 patients (mean age 72 ± 8 yrs), met study criteria and were included. PDL closure was most common in males, bilobar LAA morphology, and after Watchman procedures. The mean PDL size was 7.6 ± 5.8 mm (range 2-26 mm). Leaks were classified according to size: small (

Background The effect of transcatheter aortic valve replacement (TAVR) on kidney function stage in patients with aortic stenosis remains poorly understood. We hypothesized that in some patients, TAVR results in improved kidney function by alleviating cardiorenal syndrome. Objectives The purpose of this study was to assess change in chronic kidney disease (CKD) stage following TAVR, identify variables associated with pre- and post-TAVR estimated glomerular filtration rate (eGFR), and assess association of post-TAVR eGFR with mortality. Methods Patients (n = 5,190) receiving TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2, and PARTNER 2 S3 trials between April 2007 and October 2014 were included. Pre-TAVR and procedural variables associated with post-TAVR eGFR, change in CKD stage at ≤7 days post-TAVR, and association of post-TAVR eGFR on intermediate-term mortality were assessed. Results At baseline, CKD stage ≥2 was present in 91% of patients. CKD stage either improved or was unchanged following TAVR in the majority of patients (77% stage 1, 90% stage 2, 89% stage 3A, 94% stage 3B, and 99% stage 4). Progression to CKD stage 5 occurred in 1 (0.035%) of 2,892 patients within 7 days post-TAVR. Of 3,546 patients in whom data were available, 70 (2.0%) underwent post-TAVR dialysis. Higher pre-TAVR eGFR and transfemoral approach were strongly associated with higher post-TAVR eGFR. Lower baseline and longitudinal post-TAVR eGFR were associated with lower intermediate-term survival. Conclusions In patients with severe aortic stenosis undergoing TAVR, even with baseline impaired eGFR, CKD stage is more likely to stay the same or improve than worsen. Aortic stenosis may contribute to cardiorenal syndrome that improves with TAVR.

Unroofed coronary sinus (CS) defects are rare anomalies that result from embryologic developmental abnormalities, leading to partial or complete absence of the common wall between the CS and the left atrium. They account for less than 1% of atrial septal defects, having a strong association with a

In order to better understand why some children retaliate when they feel provoked and others do not, the present study identified "pacifistically-oriented" children who made negative interpretations in response to unambiguous provocations, yet did not endorse revenge goals, and compared them to "revenge-seeking" children who also made negative interpretations but did endorse revenge goals. Groups were identified based on seventh graders' (N = 367; 54.77% male; 22.89% racial/ethnic minority) responses to hypothetical situations in which a peer excluded and insulted them. Comparing these groups revealed that Pacifists endorsed relationship-maintaining goals and emotion regulation goals more highly than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs about negative reciprocity and aggression being legitimate more highly than Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were Pacifists, based on a measure of vigilance for signs of disrespect and expectations that others would disrespect them. Together these findings point to social-cognitive and emotion-related processes that may inhibit revenge-seeking in unambiguous provocation situations, even when children interpret the peer's behavior quite negatively.

Highlights • The coumadin ridge is a very unusual location for a cardiac PFE. • Although benign, large, mobile cardiac PFEs can pose a significant embolic risk. • Multimodality CV imaging can differentiate cardiac PFE from other cardiac tumors., Graphical abstract

Graphical abstract, Highlights • A pulmonary artery intimal sarcoma can grow significantly within the mediastinum. • This case is an interesting example of an anterior wall myocardial infarction. • Multimodality cardiac imaging is important in assessing a large extracardiac mass.

Self-assessment is a critical skill for health care professionals. Because these professionals must be lifelong, self-directed learners and self-regulating practitioners, the ability to self-assess is essential for them. The aims of this study were to measure how dental students self-assessed and peer-assessed their performance in preclinical operative procedures and to evaluate any relationship between their assessment ability and preclinical skills or academic performance. The study was conducted from 2015 to 2016. Third-year students at Harvard School of Dental Medicine self-assessed their work on four preclinical practical exams: Class II amalgam preparation, Class II amalgam restoration, Class III composite preparation, and Class III composite restoration. Three faculty members graded the same preparations and restorations. The difference between the students' self-assessment and the mean faculty assessment was calculated as the student-faculty (S-F) gap. An absolute S-F gap was also calculated with absolute values of differences. A total of 71 students completed these practical exams: 36 in the Class of 2016 and 35 in the Class of 2017. All 71 self-assessments for each of the four practical exams were collected for a response rate of 100%. The results showed that the mean S-F gap ranged from 2% to 8%, and the absolute S-F gap ranged from 7% to 12%. Preclinical performance was correlated with self-assessment accuracy. Low-performing students significantly overestimated their self-assessments compared to the rest of the class. High-performing students had more accurate self-assessments and tended to underestimate themselves. Overall, these results showed that the students had room for improving the accuracy of their self-assessments.

Graphical abstract, Highlights • Malignant mesothelioma of the pericardium presents with progressive constrictive pathophysiology. • Multimodality imaging provides advanced tissue characterization of unknown pericardial collections. • Pericardial tumors can mimic constrictive pericarditis.

Nonsteroidal anti-inflammatory drugs and colchicine remain the standard of care as the initial treatment of acute pericarditis. Corticosteroids and traditional immunosuppressive medications are often added if patients develop recurrent symptoms and remain medically refractory. There has been growing interest in the use of interleukin-1 receptor antagonists (IL-1RAs) in managing pericarditis, especially, in medically refractory cases. Anakinra-Treatment for Recurrent Idiopathic Pericarditis is a recent pilot trial showing a benefit of using the IL-1RA, anakinra, in recurrent pericarditis. Publications remain limited and more outcomes trials are needed. This review focuses on the mechanism of action, clinical utility, current, and future studies that investigate the role of IL-1RAs in the management of recurrent pericarditis.

ObjectiveCongenital pericardial defect (CPD) is a rare entity with an estimated frequency of 0.01%–0.04%. The recognition of this anomaly is important since it can be associated with serious complications. The aim of this study and review was to describe clinical and imaging features that help in establishing the diagnosis of this condition.MethodsWe retrospectively reviewed all adult patients at the Cleveland Clinic Health System with the diagnosis of CPD between the years 2000 and 2015. Baseline clinical characteristics, clinical manifestations, ECG, transthoracic echocardiography (TTE), cardiac CT and cardiac magnetic resonance (CMR) images were reviewed.ResultsEight patients were included in the study. Sixty-three percent of patients were males with mean age at diagnosis of 48 years, 63% had a partial pericardial defect on the left side and right ventricular (RV) dilation on TTE. Three patients had CMR. Levocardia was present in all CMRs. One patient had greater than 60° clockwise rotation and none of the CMRs showed ballooning of the left ventricular apex. One patient required surgical pericardioplasty. The remaining seven patients had a median follow-up of 17.3 months (5–144.9 months) and all remained asymptomatic.ConclusionCPDs are more likely to be partial on the left side and patients often have RV dilation on the TTE and levocardia on CMR. Most patients remain stable and do not require surgical intervention. TTE and CMR play an important role in making the diagnosis of this anomaly.