Contemporary outcomes of mitral valve repair for degenerative disease in the era of increased penetrance of percutaneous mitral valve technology.

Objective: The study objective was to evaluate the surgical outcomes of mitral valve repair in the era of percutaneous technology. Methods: We retrospectively reviewed 452 patients who underwent mitral valve repair for degenerative disease between 2010 and 2021. Survival, mitral valve reoperation, and mitral regurgitation recurrence were assessed using Cox regression, dichotomized for those aged more than or less than 60 years. Results: Median age in years (interquartile range) was 52 (47-57) in the younger cohort and 67 (63-73) in the older cohort (P < .0001). Preoperative comorbidities and leaflet pathology were comparable between groups. After adjustment for sex, prior sternotomy, diabetes, atrial fibrillation, and type of leaflet repair, age 60 years or more was not associated with increased mortality (hazard ratio, 6.96, 95% confidence interval, 0.85-56.8, P = .07). Considering death as a competing outcome, cumulative incidence of mitral valve reoperation at 1, 3, and 5 years was 0.9%, 1.4%, and 1.8% in the younger cohort, respectively, and 2.7%, 4.0%, and 5.1% in the older cohort, respectively (subhazard ratio, 2.95, 95% confidence interval, 0.84-10.4, P = .09). Cumulative incidence of mitral regurgitation recurrence with moderate-severe or greater mitral regurgitation at 1, 3, and 5 years was 1.4%, 3.6%, and 5.1%, and 2.7%, 3.5%, and 4.7% in the younger and older cohorts, respectively (subhazard ratio, 0.85, 95% confidence interval, 0.29-2.50, P = .76). Subgroup analysis focusing on isolated mitral valve repairs (n = 388) showed equivalent results with respect to mortality (hazard ratio, 5.31, 95% confidence interval, 0.64-44.0, P = .12), mitral valve reoperation (subhazard ratio, 4.04, 95% confidence interval, 0.89-18.4, P = .07), and mitral regurgitation recurrence (subhazard ratio, 0.98, 95% confidence interval, 0.30-3.15, P = .97). Conclusions: Mitral valve repair outcomes continue to be excellent, even in low-risk patients aged more than 60 years.

Ocular and systemic determinants of perifoveal and macular vessel parameters in healthy African Americans.

PURPOSE: To determine the relationship of various systemic and ocular characteristics with perifoveal and macular vessel density in healthy African American eyes. DESIGN: A population-based cross-sectional study of prospectively recruited African Americans ≥40 years of age. Participants underwent 3×3 mm and 6×6 mm macula scans using spectral-domain optical coherence tomography angiography (OCTA), clinical examinations and clinical questionnaires. Participants with glaucoma, severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy and macular oedema were excluded. Custom MATLAB based software quantified vessel area density (VAD) and vessel skeleton density (VSD) in the superficial retinal layer of the macula. Multivariable regression analysis, controlling for inter-eye correlation, was performed to determine systemic and ocular determinants of macular vessel metrics using stepwise selection. Candidate variables included: age, gender, body mass index, history of smoking, history of diabetes, diabetes duration, history of stroke or brain haemorrhage, systolic blood pressure, diastolic blood pressure (DBP), pulse pressure, mean arterial pressure, central subfield thickness (CSFT), visual field mean deviation, intraocular pressure, axial length (AL), mean ocular perfusion pressure and signal strength (SS). RESULTS: A total of 2221 OCTA imaged eyes from 1472 participants were included in this study. Reduced perifoveal and macular VAD and VSD were independently associated with longer AL, reduced SS, reduced CSFT and older age. Male gender and lower DBP were also associated with reduced perifoveal and macular VSD. CONCLUSIONS: When interpreting OCTA images in a clinical setting, it is important to consider the effects ocular and systemic characteristics may have on the macular microcirculation.

Intrasession Repeatability and Intersession Reproducibility of Macular Vessel Parameters on Optical Coherence Tomography Angiography in Glaucomatous and Non-Glaucomatous Eyes.

PURPOSE: Using optical coherence tomography angiography (OCTA), this study compared intrasession repeatability versus intersession reproducibility of macular vessel parameters in glaucoma and non-glaucoma subjects. METHODS: 6 × 6 mm2 macular OCTA scans (Cirrus HD-OCT 5000) were acquired from glaucomatous and non-glaucomatous subjects as part of an observational, longitudinal study. Vessel area density (VAD) and vessel skeleton density (VSD) were calculated using research-based quantification software while perfusion density (PDZ) and vessel density (VDZ) were calculated using commercially developed software (Cirrus 11.0, Carl Zeiss Meditec). Intrasession repeatability and intersession reproducibility were determined using within-eye standard deviation (SW), within-eye coefficient of repeatability (CRW), within-eye coefficient of variation (CVW), and intraclass correlation coefficients (ICC). RESULTS: The intrasession repeatability and intersession reproducibility for macular OCTA parameters were similar to one another for both non-glaucomatous and glaucomatous eyes. Intrasession CVW from the non-glaucoma group (n = 73) was 1.097% for VAD, 1.007% for VSD, 2.980% for PDZ, and 2.714% for VDZ. Intersession CVW from the non-glaucoma group (n = 55) was 1.389% for VAD, 1.279% for VSD, 2.935% for PDZ, and 2.695% for VDZ. Intrasession CVW from the glaucoma group (n = 59) was 1.189% for VAD, 0.970% for VSD, 3.827% for PDZ, and 3.542% for VDZ. Intersession CVW from the glaucoma group (n = 45) was 1.412% for VAD, 1.132% for VSD, 3.915% for PDZ, and 3.654% for VDZ. Non-glaucomatous intrasession ICC ranged from 0.711 to 0.824, non-glaucomatous intersession ICC ranged from 0.649 to 0.762, glaucomatous intrasession ICC ranged from 0.710 to 0.853, and glaucomatous intersession ICC ranged from 0.661 to 0.827. CONCLUSIONS: Macular OCTA scans can be a useful tool in monitoring the longitudinal progression of glaucoma due to their high repeatability and reproducibility.

Evaluating the Catalytic Potential of a General RNA-Cleaving FANA Enzyme.

The discovery of synthetic genetic polymers (XNAs) with catalytic activity demonstrates that natural genetic polymers are not unique in their ability to function as enzymes. However, all known examples of in vitro selected XNA enzymes function with lower activity than their natural counterparts, suggesting that XNAs might be limited in their ability to fold into structures with high catalytic activity. To explore this problem, we evaluated the catalytic potential of FANAzyme 12-7, an RNA-cleaving catalyst composed entirely of 2'-fluoroarabino nucleic acid (FANA) that was evolved to cleave RNA at a specific phosphodiester bond located between an unpaired guanine and a paired uracil in the substrate recognition arm. Here, we show that this activity extends to chimeric DNA substrates that contain a central riboguanosine (riboG) residue at the cleavage site. Surprisingly, FANAzyme 12-7 rivals known DNAzymes that were previously evolved to cleave chimeric DNA substrates under physiological conditions. These data provide convincing evidence that FANAzyme 12-7 maintains the catalytic potential of equivalent DNAzymes, which has important implications for the evolution of XNA catalysts and their contributions to future applications in synthetic biology.

Specific behavioral and cellular adaptations induced by chronic morphine are reduced by dietary omega-3 polyunsaturated fatty acids.

Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellular and behavioral levels. As omega-3 polyunsaturated fatty acids (n-3 PUFAs) play a ubiquitous role in behavioral and cellular processes, we proposed that supplemental n-3 PUFAs, enriched in docosahexanoic acid (DHA), could offset these adaptations following chronic opioid exposure. We used an 8 week regimen of n-3 PUFA supplementation followed by 8 days of morphine in the presence of this diet. We first assessed the effect of morphine in different behavioral measures and found that morphine increased anxiety and reduced wheel-running behavior. These effects were reduced by dietary n-3 PUFAs without affecting morphine-induced analgesia or hyperlocomotion, known effects of this opiate acting at mu opioid receptors. At the cellular level we found that morphine reduced striatal DHA content and that this was reversed by supplemental n-3 PUFAs. Chronic morphine also increased glutamatergic plasticity and the proportion of Grin2B-NMDARs in striatal projection neurons. This effect was similarly reversed by supplemental n-3 PUFAs. Gene analysis showed that supplemental PUFAs offset the effect of morphine on genes found in neurons of the dopamine receptor 2 (D2)-enriched indirect pathway but not of genes found in dopamine receptor 1(D1)-enriched direct-pathway neurons. Analysis of the D2 striatal connectome by a retrogradely transported pseudorabies virus showed that n-3 PUFA supplementation reversed the effect of chronic morphine on the innervation of D2 neurons by the dorsomedial prefontal and piriform cortices. Together these changes outline specific behavioral and cellular effects of morphine that can be reduced or reversed by dietary n-3 PUFAs.