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Esophageal adenocarcinoma continues to bear high morbidity and mortality. Prehabilitation, using exercise, nutrition, and psychosocial strategies to optimize patients prior to surgical resection, is largely underexplored in this malignancy, especially in patients undergoing neoadjuvant chemotherapy. Objectives of this study were (i) to determine feasibility of prehabilitation during treatment in patients with esophageal cancer and (ii) to establish differences between hospital and home-based exercise. Patients were recruited from August 2019 – February 2023 and blindly randomized to either supervised or homebased exercise, receiving identical nutritional and psychosocial support. The main outcome measures were recruitment, retention, and dropout rates. The secondary outcomes included cardiorespiratory fitness, functional capacity, and quality of life. Forty-four subjects were blindly randomized: 23 to supervised exercise and 21 to home-based exercise (72% recruitment rate). Overall compliance for the supervised group was 72%; home-based group was 77%. Baseline to pre-operative, both groups experienced significant increases in sit-to-stand, arm curls, and amount of weekly moderate–vigorous physical activity. The home-based group experienced an additional considerable decrease in up-and-go test times. Both groups maintained cardiorespiratory fitness and saw substantial increases in some quality-of-life scores. Multimodal prehabilitation is feasible for patients with esophageal cancer undergoing neoadjuvant chemotherapy. In both groups, patient fitness, which is relevant for this patient population given the anticipated decline in functional status during this period, was maintained. This study provides a foundation for future prehabilitation interventions in this patient population. [ABSTRACT FROM AUTHOR]

Introduction Vascular smooth muscle cells (VSMC) are highly specialized and retain remarkable plasticity, which allows for a transition from a contractile to synthetic phenotype in response to functional demands and [...], Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation. Key words: atherosclerosis, smooth muscle cell dedifferentiation, mitochondria, OXPHOS, beta oxidation, ROS, phenotype switch. L&apos;atherosclerose est l&apos;une des principales causes de morbidite et de mortalite dans le monde occidental. Meme si les manifestations cliniques de la maladie sont bien documentees, l&apos;etiologie et Revolution en demeurent a preciser. Recemment, on a montre que les mitochondries sont compromises dans d&apos;importants processus cellulaires jouant un role dans Revolution de l&apos;atherosclerose. En depit du lien entre les mitochondries et l&apos;atherosclerose, les modes d&apos;action durant la phase precoce de la maladie demeurent a etre elucides. Ce projet avait pour but d&apos;etudier le role des mitochondries dans la dedifferenciation des cellules musculaires lisses vasculaires (CMLV). Nous avons utilise un modele in vitro de tissu aortique de souris en culture dans un milieu denue de serum. Nous avons mesure la fonction mitochondriale a l&apos;aide de la respirometrie a haute resolution. A l&apos;aide de l&apos;immunobuvardage, nous avons evalue les proteines associees a la capacite des CMLV de passer d&apos;un phenotype a un autre (<>), ainsi que la densite des mitochondries. Les resultats montrent que l&apos;activite du complexe mitochondrial intrinseque I est regulee a la hausse de facon marquee au cours de la dedifferenciation des CMLV. Nous avons aussi observe une diminution du couplage entre la phosphorylation et l&apos;oxydation, ce qui peut correspondre a une augmentation du ratio ADP:ATP. Ces donnees laissent entrevoir une augmentation des fuites dans la chaine de transport des electrons et une atteinte de la fonction mitochondriale, en particulier au niveau du complexe I. Ce projet fournit d&apos;importants renseignements sur role des mitochondries dans le debut du processus atherosclerotique et illustre que des variations detectables de la fonction et de l&apos;expression des mitochondries sont liees a la dedifferenciation des CMLV. [Traduit par la Redaction] Mots-cles: atherosclerose, dedifferenciation des cellules musculaires lisses, mitochondrie, phosphorylation oxydative, beta oxydation, derives reactifs de l&apos;oxygene, capacite de passer d&apos;un phenotype a un autre.

Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[[sup.18]F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow. perfusion; distribution; metabolic vasodilators doi:10.1152/ajpregu.00808.2005

Background: Exercise training is a component of the pre-habilitation program. While in one previous study the training was home-based, in a subsequent investigation it was supervised in hospital. The hypothesis of this secondary analysis of the two studies was to determine whether supervised exercise further accelerates the return to baseline walking ability.Methods: Data from two consecutive randomized control trials (RCT) comparing pre-habilitation to the rehabilitation of cancer patients scheduled for colorectal surgery were pooled for analysis. The interventions were similar and included home-based exercise training, nutritional counseling and protein supplementation, and relaxation techniques administered either before surgery (pre-habilitation) or after surgery (rehabilitation). Patients in the second RCT received additional supervised exercise sessions. Functional capacity was assessed with the 6-minute walk test (6 MWT) at baseline, before surgery, and at 4 and 8 weeks after surgery. Adjusted logistic regression was used to determine the improvement of the 6-minute walk distance (6MWD).Results: Baseline mean 6MWD of 63 patients in the supervised group was 465.1 m (SD, 115), and that of 77 patients in the nonsupervised group was 407.8 m (SD, 109) (P < 0.01). Perioperative supervised exercise training enhanced further functional capacity and muscle strength when compared with the nonsupervised group (P < 0.01). Those receiving exercise supervision had over two times higher chances to return to baseline after surgery. Supervised pre-habilitation was the best combination (4 weeks OR = 7.71, and at 8 weeks OR = 8.62).Conclusion: Supervised exercise training leads to meaningful changes in functional capacity thus accelerating the postoperative return to baseline activities. [ABSTRACT FROM AUTHOR]