Time-restricted feeding improves aortic endothelial relaxation by enhancing mitochondrial function and attenuating oxidative stress in aged mice.

Age-related endothelial dysfunction is a pivotal factor in the development of cardiovascular diseases, stemming, at least in part, from mitochondrial dysfunction and a consequential increase in oxidative stress. These alterations are central to the decline in vascular health seen with aging, underscoring the urgent need for interventions capable of restoring endothelial function for preventing cardiovascular diseases. Dietary interventions, notably time-restricted feeding (TRF), have been identified for their anti-aging effects on mitochondria, offering protection against age-associated declines in skeletal muscle and other organs. Motivated by these findings, our study aimed to investigate whether TRF could similarly exert protective effects on endothelial health in the vasculature, enhancing mitochondrial function and reducing oxidative stress. To explore this, 12-month-old C57BL/6 mice were placed on a TRF diet, with food access limited to a 6-h window daily for 12 months. For comparison, we included groups of young mice and age-matched controls with unrestricted feeding. We evaluated the impact of TRF on endothelial function by measuring acetylcholine-induced vasorelaxation of the aorta. Mitochondrial health was assessed using fluororespirometry, and vascular reactive oxygen species (ROS) production was quantified with the redox-sensitive dye dihydroethidium. We also quantified 4-hydroxynonenal (4-HNE) levels, a stable marker of lipid peroxidation, in the aorta using ELISA. Our findings demonstrated that aged mice on a standard diet exhibited significant impairments in aortic endothelial relaxation and mitochondrial function, associated with elevated vascular oxidative stress. Remarkably, the TRF regimen led to substantial improvements in these parameters, indicating enhanced endothelial vasorelaxation, better mitochondrial function, and reduced oxidative stress in the aortas of aged mice. This investigation establishes a vital foundation, paving the way for subsequent clinical research aimed at exploring the cardiovascular protective benefits of intermittent fasting.

Natural history of the distal aorta following elective root replacement in patients with Marfan syndrome.

OBJECTIVE: It is unclear if the addition of a prophylactic arch operation is beneficial at the time of root replacement in patients with Marfan syndrome (MFS). This project aims to understand the fate of the distal aorta following elective root replacement in patients with MFS. METHODS: Between 2000 and 2019, 124 adult patients with MFS were identified as having undergone elective aortic root replacement with a clamped distal aortic anastomosis during their lifetime. Serial axial imaging was analyzed. The primary outcome was a composite of subsequent type B aortic dissection (TBAD), aneurysmal degeneration (>4 cm), and aortic reintervention. Secondary outcomes included subsequent TBAD and mortality. RESULTS: Mean age at root replacement was 33.3 years. Median follow-up was 11.3 years. Thirty-one patients (25%) experienced the primary outcome, with no survival difference (P = .9). The crossclamp and aortic cannulation sites were stable (growth rate, 0.33 mm/year), and 2 patients (1.6%) required reintervention there. Twenty-three patients (19.8%) experienced subsequent TBAD. Patients with TBAD had a higher rate of distal degeneration (P < .001), but no significant change in survival (P = .2). Preoperative hypertension (odds ratio, 3.96; P < .05) and younger age at root replacement (odds ratio, 1.05; P < .05) increased the risk of TBAD, based on regression analysis. CONCLUSIONS: The distal aorta (including the clamp and cannulation site) overall appears stable in patients with MFS following elective root replacement without prophylactic arch operation. Development of TBAD seems to be the primary driver of distal degeneration. Factors associated with TBAD development included hypertension, underscoring the importance of strict blood pressure control in these patients.

Use of a sutureless aortic valve in reoperative aortic valve replacement.

Objectives: Management of degenerated bioprosthetic aortic valves remains a challenge. Valve-in-valve transcatheter aortic valve replacement (AVR) has limited utility in the presence of small annuli/prosthetic valves. Sutureless valves may offer an advantage over traditional redo AVR by maximizing effective orifice area due to their unique design as well as ease of implant. Methods: Twenty-two patients undergoing redo AVR received a sutureless valve in our institution over the past 5 years. All patients were determined to be poor candidates for valve-in-valve transcatheter AVR due to a combination of small annulus size, low coronary heights, and/or underlying valve characteristics (ie, mechanical valves). Results: Median time from implant to redo AVR was 8 years. One patient died within 30 days. In the 13 patients who had a 21 mm or smaller valve explanted, 5 small, 7 medium, and 1 large Perceval valves were implanted (all with larger internal diameters than the explanted valve). The average postoperative gradient of the cohort valves was 14.8 mm Hg compared with 38.8 mm Hg preoperatively. Conclusions: In addition to their ease of use and rapid deployment, sutureless bioprosthetic aortic valves offer significant physiological advantages in patients with degenerated prosthetic aortic valves and small anatomical annuli. It can also simplify the surgical approach to redo AVR following a Bentall procedure. If long-term durability is confirmed, sutureless valves should be considered in a broader population of patients for both redo and primary aortic valve replacement surgery.

Aortic arch stenting: current strategies, new technologies and future directions.

Operating on the aortic arch is a formidable challenge. Open operations remain the gold standard, but despite improvement in technique and outcomes, they are still associated with significant morbidity and mortality. The last 20 years have seen a remarkable reduction in the operative morbidity associated with treatment of the descending thoracic aorta using thoracic endovascular aneurysm repair (TEVAR). To improve outcomes following arch repair, new TEVAR devices, including both single-branched and multibranched designs, have come to clinical trial. This review discusses the modern state of open and hybrid repairs while introducing the reader to technology for endovascular therapy of the aortic arch. We describe important anatomical and operative considerations for the devices. Given these nuances, we believe the future of the aortic arch to be patient-individualised hybrid repairs, involving both open and endovascular options with a multidisciplinary 'thoracic aorta team' at the helm.

Giant Cell Tumor of Bone Presenting as Left Posteromedial Chest Wall Tumor.

Giant cell tumor is a relatively uncommon bone tumor rarely originating from the chest wall. Given its proximity to vital structures in the thoracic cavity, treatment options may be challenging. We report the case of a patient with a giant cell tumor of the posterolateral chest wall with invasion of the thoracic spine treated with neoadjuvant denosumab, followed by surgical resection.

A germline-limited piggyBac transposase gene is required for precise excision in Tetrahymena genome rearrangement.

Developmentally programmed genome rearrangement accompanies differentiation of the silent germline micronucleus into the transcriptionally active somatic macronucleus in the ciliated protozoan Tetrahymena thermophila. Internal eliminated sequences (IES) are excised, followed by rejoining of MAC-destined sequences, while fragmentation occurs at conserved chromosome breakage sequences, generating macronuclear chromosomes. Some macronuclear chromosomes, referred to as non-maintained chromosomes (NMC), are lost soon after differentiation. Large NMC contain genes implicated in development-specific roles. One such gene encodes the domesticated piggyBac transposase TPB6, required for heterochromatin-dependent precise excision of IES residing within exons of functionally important genes. These conserved exonic IES determine alternative transcription products in the developing macronucleus; some even contain free-standing genes. Examples of precise loss of some exonic IES in the micronucleus and retention of others in the macronucleus of related species suggest an evolutionary analogy to introns. Our results reveal that germline-limited sequences can encode genes with specific expression patterns and development-related functions, which may be a recurring theme in eukaryotic organisms experiencing programmed genome rearrangement during germline to soma differentiation.