Effect of Garcinia binucao Crude Leaf Extract Supplementation on Lifespan of Drosophila melanogaster Chronically Exposed to Alcohol.

Background: Consumption and abuse of alcohol remains a significant cause of concern worldwide. Furthermore, there is evidence of the association between chronic alcohol use and reduced life expectancy. Objectives: To study the effects of Garcinia binucao extract (GBE) supplementation on lifespan of Drosophila melanogaster, in the presence or absence of chronic alcohol exposure. Methods: D. melanogaster was mass cultured and given GBE supplementation in high (1 mg/mL) and low (200 µg/mL) sublethal doses. D. melanogaster flies were divided into groups - with and without chronic alcohol exposure, and their respective lifespans were monitored. Results: In D. melanogaster without alcohol exposure, mean lifespan was highest in the control flies (38.15 days), followed by high-dose GBE (34.42 days), low-dose GBE (33.24 days), and DMSO (22.29 days). In D. melanogaster chronically exposed to alcohol, the longest mean lifespan was observed in flies treated with high-dose GBE (33.80 days), followed by low-dose GBE (33.63 days), the DMSO group (30.30), and the control group (29.65 days), but the differences were not statistically significant. Comparing groups with and without chronic alcohol exposure, the mean lifespan of the control group chronically exposed to alcohol significantly decreased by 9.51 days (p < 0.05). In GBE treatment groups, mean lifespan significantly decreased by 0.82 days in high-dose set-up (p < 0.05), and significantly increased by 0.39 days in the low-dose set-up (p < 0.05) upon chronic alcohol exposure. Conclusion: Garcinia binucao extract supplementation ameliorated the observed reduction in lifespan of Drosophila melanogaster chronically exposed to alcohol.

Machine learning for prediction of ventricular arrhythmia episodes from intracardiac electrograms of automatic implantable cardioverter-defibrillators.

BACKGROUND: Despite effectiveness of the implantable cardioverter-defibrillator (ICD) in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA after ICD implantation is unpredictable. OBJECTIVE: The study aimed to apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs. METHODS: The study included 13,516 patients who received Biotronik ICDs and enrolled in the CERTITUDE registry between January 1, 2010, and December 31, 2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long-range (baseline or first scheduled remote recording), mid-range (scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed. RESULTS: Of 13,516 patients (male, 72%; age, 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained ventricular tachycardia or ventricular fibrillation were observed in 4467 patients (33.0%). Neural networks based on convolutional neural networks using ResNet-like architectures on far-field IEGMs yielded an area under the curve of 0.83 with a 95% confidence interval of 0.79-0.87 in the short term, whereas the long-range and mid-range analyses had minimal predictive value for VA events. CONCLUSION: In this study, applying ML to ICD-acquired IEGMs predicted impending ventricular tachycardia or ventricular fibrillation events seconds before they occurred, whereas midterm to long-term predictions were not successful. This could have important implications for future device therapies.

Safety and efficacy of cerebral embolic protection in transcatheter aortic valve implantation: an updated meta-analysis.

Background: The use of cerebral embolic protection devices during transcatheter aortic valve implantation (TAVI) reveals conflicting data. Aims: This updated meta-analysis aims to evaluate the efficacy and safety of the SENTINEL Cerebral Protection System. Methods: A literature search for relevant studies up to September 2022 was performed. Study outcomes were divided based on time period - overall (up to 30 days) and short (≤7 days). The outcomes studied include stroke (disabling, non-disabling), mortality, neuroimaging findings, transient ischaemic attack, acute kidney injury and major vascular and bleeding complications. Results: A total of 15 studies involving 294,134 patients were included. Regarding overall outcomes, significant reductions were noted for mortality (odds ratio [OR] 0.60, 95% confidence interval [CI]: 0.41-0.88; p=0.008), all stroke (OR 0.64, 95% CI: 0.46-0.88; p=0.006) and disabling stroke (OR 0.42, 95% CI: 0.23-0.74; p=0.003) using the SENTINEL device. No significant differences were noted for other outcomes. There was significant heterogeneity across the studies for mortality (p=0.013) and all stroke (p=0.003). Including only randomised data (n=4), there was only significant reduction in the incidence of disabling stroke (OR 0.39, 95% CI: 0.17-0.89; p=0.026) in the SENTINEL group. In studies reporting ≤7-day outcomes (n=8), use of the SENTINEL device demonstrated significantly lower rates of all stroke (p<0.001), disabling stroke (p<0.001) and major bleeding complications (p=0.02). No differences in neuroimaging outcomes were noted. Conclusions: In this updated meta-analysis, use of the SENTINEL Cerebral Protection System was associated with lower rates of mortality, all stroke and disabling stroke, although significant heterogeneity was noted for mortality and all stroke. Including exclusively randomised data, there was only significant reduction in the incidence of disabling stroke. No significant adverse outcomes with device use were noted.

A Case of Parathyroid Carcinoma in Renal Hyperparathyroidism.

Introduction: Parathyroid carcinoma is a rare malignant endocrine tumor that is usually associated with primary hyperparathyroidism. The coexistence of parathyroid carcinoma and renal hyperparathyroidism is a rare phenomenon. Hence, we present a case of parathyroid carcinoma in a patient with tertiary hyperparathyroidism. Case Presentation: Our patient is a 31-year-old woman with a past medical history of end-stage renal failure (ESRF), on hemodialysis for the past 18 years. She was referred by her nephrologist to the endocrine surgery department for consideration of parathyroidectomy in view of long-standing tertiary hyperparathyroidism complicated by hypercalcemia. Bedside ultrasonography scan (US) of the thyroid revealed three parathyroid glands and a hypoechoic right lower pole thyroid nodule with central calcification. Fine-needle aspiration cytology was performed for the suspected thyroid nodule on the same day, which eventually yielded a follicular lesion of undetermined significance. A right hemithyroidectomy and total parathyroidectomy with deltoid implantation was performed. Intraoperative exploration revealed that the thyroid nodule noted at initial US was found to be the right superior parathyroid gland invading into the right thyroid itself. The right superior parathyroid gland was excised en bloc with the right hemithyroidectomy. Post-operatively, the patient was hypocalcemic but was discharged well on post-operative day 5. Histopathological diagnosis of the right hemithyroidectomy specimen containing the right superior parathyroid gland was consistent with that of parathyroid carcinoma. Conclusion: Parathyroid carcinoma is a rare entity that is difficult to diagnose. In patients with ESRF, the presence of concurrent tertiary hyperparathyroidism makes this even more challenging.

Incidence and Outcomes of New-Onset Right Bundle Branch Block Following Transcatheter Aortic Valve Replacement.

BACKGROUND: The incidence and prognosis of right bundle branch block (RBBB) following transcatheter aortic valve replacement (TAVR) are unknown. Hence, we sought to characterize the incidence of post-TAVR RBBB and determine associated risks of permanent pacemaker (PPM) implantation and mortality. METHODS: All patients 18 years and above without preexisting RBBB or PPM who underwent TAVR at US Mayo Clinic sites and Mayo Clinic Health Systems from June 2010 to May 2021 were evaluated. Post-TAVR RBBB was defined as new-onset RBBB in the postimplantation period. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. The risks of PPM implantation (within 90 days) and mortality following TAVR were compared for patients with and without post-TAVR RBBB using Kaplan-Meier analysis and Cox proportional hazards modeling. RESULTS: Of 1992 patients, 15 (0.75%) experienced new RBBB post-TAVR. There was a higher degree of valve oversizing among patients with new RBBB post-TAVR versus those without (17.9% versus 10.0%; P=0.034). Ten patients (66.7%) with post-TAVR RBBB experienced high-grade atrioventricular block and underwent PPM implantation (median 1 day; Q1, 0.2 and Q3, 4), compared with 268/1977 (13.6%) without RBBB. Following propensity score adjustment for covariates (age, sex, balloon-expandable valve, annulus diameter, and valve oversizing), post-TAVR RBBB was significantly associated with PPM implantation (hazard ratio, 8.36 [95% CI, 4.19-16.7]; P<0.001). No statistically significant increase in mortality was seen with post-TAVR RBBB (hazard ratio, 0.83 [95% CI, 0.33-2.11]; P=0.69), adjusting for age and sex. CONCLUSIONS: Although infrequent, post-TAVR RBBB was associated with elevated PPM implantation risk. The mechanisms for its development and its clinical prognosis require further study.

Anatomy of the Ventricular Outflow Tracts: An Electrophysiology Perspective.

Outflow tract ventricular arrhythmias are the most common type of idiopathic ventricular arrhythmia. A systematic understanding of the outflow tract anatomy improves procedural efficacy and enables electrophysiologists to anticipate and prevent complications. This review emphasizes the three-dimensional spatial relationships between the ventricular outflow tracts using seven anatomical principles. In turn, each principle is elaborated on from a clinical perspective relevant for the practicing electrophysiologist. The developmental anatomy of the outflow tracts is also discussed and reinforced with a clinical case.

OphthoPods: An Analysis of the Educational Content and Changes of Ophthalmology Podcasts.

Objective Podcasts are a novel modality for digitally disseminating ophthalmic knowledge, yet minimal information exists on their offerings. This study sought to describe the growth of ophthalmology podcasts, characterize their features, and analyze clinically pertinent content trends. Materials and Methods Apple Podcasts, Spotify, Google Podcasts, and Google Search were queried for English- language shows relating primarily to ophthalmology. Ninety-six podcasts and 3,594 episodes were analyzed. Results Of the 48 currently active shows, most cover general ophthalmology topics ( n = 25, 52.1%) and are run by multiple hosts ( n = 29, 60.4%) in both academics and private practice. The majority of podcasts released episodes monthly ( n = 21, 21.9%) or less frequently than monthly ( n = 36, 37.5%). Among all episodes, procedural topics ( n = 951 episodes, 26.4%) and clinical education ( n = 1385, 38.5%) were the most prevalent categories. Retina was the most represented subspecialty in podcast production, while oculoplastics and neuro-ophthalmology had the fewest podcasts. Episodes on disease pathophysiology ( p = 0.04) and published research ( p < 0.001) each declined over time. The proportion of episodes released from 2020 to 2022 that discussed digital technologies was 33.3% greater versus 2005 to 2019 ( p = 0.005). Personal retrospective episodes doubled, career guidance and patient perspectives tripled, and wellness and social justice topics increased fivefold (all p < 0.001). Conclusion In summary, the coronavirus disease 2019 pandemic coincided with a rise in ophthalmology podcasts and shifts in content. Podcasts have trended toward practical advice and technologies, reflecting their value in sharing modern, peer-to-peer pearls. Emphases on storytelling and social justice offer unique, clinically relevant perspectives compared with traditional modalities.

Transcriptional Regulators of Plant Adaptation to Heat Stress.

Heat stress (HS) is becoming an increasingly large problem for food security as global warming progresses. As sessile species, plants have evolved different mechanisms to cope with the disruption of cellular homeostasis, which can impede plant growth and development. Here, we summarize the mechanisms underlying transcriptional regulation mediated by transcription factors, epigenetic regulators, and regulatory RNAs in response to HS. Additionally, cellular activities for adaptation to HS are discussed, including maintenance of protein homeostasis through protein quality control machinery, and autophagy, as well as the regulation of ROS homeostasis via a ROS-scavenging system. Plant cells harmoniously regulate their activities to adapt to unfavorable environments. Lastly, we will discuss perspectives on future studies for improving urban agriculture by increasing crop resilience to HS.

Differential responses to ethical vegetarian appeals: Exploring the role of traits, beliefs, and motives.

OBJECTIVE: This research examines differential responses to ethical vegetarian appeals as a fuction of individuals' personalities. BACKGROUND: Ethical vegetarian appeals are persuasive messages promoting the adoption of a plant-based diet on moral grounds. Individuals may vary in their receptivity to such appeals, depending on their morally relevant traits (e.g., agreeableness), beliefs (e.g., speciesism), and motives (e.g., concerns about animal welfare). METHODS: We explored (Study 1, N = 907) and then attempted to confirm (Study 2, N = 980) differential responses to three vegetarian appeals-two highlighting moral concerns (animal welfare, the environment) and a third focusing on individual health (control condition). RESULTS: Both studies revealed several differential effects of our vegetarian appeals on the perceived effectiveness of the appeal and resultant intentions to reduce meat consumption. These mostly consisted of differences in receptivity to appeals focused on animal welfare. However, only one such effect observed in Study 1 was clearly replicated in Study 2: People who more strongly believed that eating meat was "normal" rated the vegetarian appeals focused on animal welfare as less effective. CONCLUSION: Ethical vegetarian appeals may elicit different responses from different people, particularly those focused on animal welfare, depending on how normative one believes meat-eating to be. Such insights can inform behavior change efforts in this area.

Beliefs and counseling practices among dermatologists regarding sexual and other adverse effects of finasteride.

Finasteride may cause low libido and erectile dysfunction and the product label of finasteride also includes post-marketing reactions of sexual dysfunction that continued after discontinuation of treatment, as well as male infertility and depression. The aim of this study was to evaluate the beliefs and counseling practices among dermatologists regarding adverse effects of finasteride. Anonymous paper surveys were personally distributed to 122 attendees at two annual major dermatology meetings. The participation rate was 82% with 47% women and 77% residents of the United States. 51% of respondents believed that finasteride could cause sexual side effects and 18% believed that it could cause persistent sexual side effects. Fewer than a quarter believed that finasteride could cause depression or lower sperm counts. When initiating finasteride, 69% of respondents counseled at least half of their patients about potential sexual side effects with 52% for persistent sexual side effects and 30% for depression. This study identifies the need for greater awareness of the potential adverse effects of finasteride and identifies opportunities for improvement in counseling practices that reflect finasteride's product labeling.

Catheter Ablation of Atrial Fibrillation in Adult Congenital Heart Disease: Procedural Characteristics and Outcomes.

BACKGROUND: The outcomes of catheter ablation for atrial fibrillation in adults with congenital heart disease are not well described. METHODS: In a retrospective study of adult patients with congenital heart disease who underwent catheter ablation for atrial fibrillation between 2000 and 2020 at Mayo Clinic, procedural characteristics and outcomes were collected. The primary outcomes were atrial arrhythmia (AA) recurrence following a 3-month blanking period and repeat ablation. An arrhythmia clinical severity score was assessed pre- and post-ablation based on the duration of arrhythmia episodes, symptoms, cardioversion frequency, and antiarrhythmic drug use. RESULTS: One hundred forty-five patients (age, 57±12 years; 28% female; 63% paroxysmal atrial fibrillation) underwent 198 ablations with a median follow-up of 26 months (interquartile range, 14-69). One hundred ten, 26, and 9 patients had simple, moderate, and complex congenital heart disease, respectively. All patients underwent pulmonary vein isolation, and non-pulmonary vein targets were ablated in 79 (54%). AA recurrence at 12 months was 37% (95% CI, 29%-45%). On univariate analysis, increasing left atrial volume index was associated with higher odds of AA recurrence (odds ratio, 1.03 [1.00-1.06] per 1 mL/m2 increment; P=0.05). Noninducibility of atrial flutter was predictive of decreased odds of AA recurrence (odds ratio, 0.43 [0.21-0.90]; P=0.03). A second ablation was performed in 43 patients after a median of 20 (interquartile range, 8-37) months. Arrhythmia clinical severity scores improved following ablation, reflecting a decrease in symptoms, cardioversions, and antiarrhythmic drugs. CONCLUSIONS: Catheter ablation of atrial fibrillation is feasible and effective in patients with adult congenital heart disease and reduces symptoms. Recurrence of AA frequently requires repeat ablation.

Case report: A case of perinodal atrial tachycardia and review of the relevant clinical anatomy surrounding the retroaortic node.

A 70-year-old female presented with incessant supraventricular tachycardia that was refractory to metoprolol and sotalol. ECG revealed a narrow complex tachycardia with a rate of 163 beats per minute with a short RP relationship. She had salvos of atrial tachycardia which led to a severe reduction in ejection fraction as noted on echocardiography and hemodynamic instability. An electrophysiological study was performed, and findings suggested this to be an atrial tachycardia with earliest activation in the perinodal area. Radiofrequency ablation was carried out along the septum and associated structures to surround this region including the right atrium, non-coronary sinus of Valsalva, and the left atrium (anterior wall outside of the right superior pulmonary vein) to isolate this area and surround the focus with ablation lesions. The patient has done well post-procedure and continues to do well without any recurrence on low-dose flecainide at 8 months.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer.

Background: The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk. Objectives: The authors sought to assess left atrial appendage occlusion (LAAO) as a safe and effective strategy for reducing stroke at no increased bleeding risk in cancer patients with AF. Methods: We reviewed patients with nonvalvular AF who underwent LAAO at Mayo Clinic sites from 2017 to 2020 and identified those who had undergone prior or current treatment for cancer. We compared the incidence of stroke, bleeding, device complications, and death with a control group who underwent LAAO without malignancy. Results: Fifty-five patients were included; 44 (80.0%) were male, and the mean age was 79.0 ± 6.1 years. The median CHA2Ds2-VASc score was 5 (Q1-Q3: 4-6), with 47 (85.5%) having a prior bleeding event. Over the first year, ischemic stroke occurred in 1 (1.4%) patient, bleeding complications in 5 (10.7%) patients, and death in 3 (6.5%) patients. Compared with controls who underwent LAAO without cancer, there was no significant difference in ischemic stroke (HR: 0.44; 95% CI: 0.10-1.97; P = 0.28), bleeding complication (HR: 0.71; 95% CI: 0.28-1.86; P = 0.19), or death (HR: 1.39; 95% CI: 0.73-2.64; P = 0.32). Conclusions: Within our cohort, LAAO in cancer patients was achieved with good procedural success and offered a reduction in stroke at no increased bleeding risk similar to noncancer patients.