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Background: It is still a matter of debate if neuromuscular alterations reflect a primary event in diverticular disease (DD)., Aims: This study aimed to assess colonic wall layers from both stenotic and non-stenotic complicated DD, bio-phenotypic alterations, inflammatory and oxidative status., Methods: A systematic analysis of colonic specimens obtained from stenotic and non-stenotic DD specimens was conducted and compared with controls. Biological activity and qPCR analysis were performed on longitudinal and circular muscles. Western blot analysis was performed throughout colonic wall layers to quantify oxidative and inflammatory markers., Results: A homogenous increase in oxidative stress was observed through all the layers, which were more sharpened in the longitudinal muscle for a loss in antioxidant defenses. In both stenotic and non-stenotic colon, the longitudinal muscle presented an impaired relaxation and a cellular phenotypic switch driven by transforming growth factor-β with an increase in mRNA expression of collagen Iα and a decrease in myosin heavy chain. The circular muscle, as the mucosa, was less affected by molecular alterations. No peculiar increase in inflammatory markers was observed., Conclusion: A longitudinal colonic myopathy is present in DD, independently from the disease stage associated with an oxidative imbalance that could suggest new therapeutic strategies., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The performance of Abbott/St. Jude Medical (Sylmar CA) Tendril pacing leads has not been well characterized., Objective: We sought to assess the performance of Tendril leads as compared with that of different pacing leads., Methods: We retrospectively identified patients implanted with the following leads: Tendril leads 1888 TC, 2088 TC, and 1688 TC, Medtronic (Fridely, MN) 4076 CapSureFix Novus, and Boston Scientific (Natick, MA) FINELINE II Sterox Pacing EZ leads (models 4469, 4470, and 4471). The primary end point was the incidence of lead malfunction assessed by Kaplan-Meier analysis., Results: During the study period, 9782 leads were implanted, including 8512 Tendril leads, 731 Medtronic 4076 CapSureFix Novus leads, and 539 FINELINE II leads. A total of 540 leads (5.5%) malfunctioned during a mean follow-up of 3.6 ± 2.9 years. Lead malfunction manifested predominantly as noise and/or low impedance (95%). Lead malfunction rates were significantly higher at 5 years for Tendril vs non-Tendril leads (7.0% vs 2.1%; P < .001). The highest rate of failure at 5 years was seen in the Tendril 1888 TC leads (9.9%), followed by Tendril 1688 (5.7%) and Tendril 2088 (5.2%) leads. In contrast, malfunction rates were significantly lower for the Medtronic 4076 (2.6%) and FINELINE II (1.7%) leads. During follow-up to 10 years, the incidence of lead malfunction for Optim-insulated Tendril leads (models 1888 TC and 2088 TC) was significantly higher than that for the non-Optim-insulated Tendril 1688 TC lead (24.5% vs 7.1%) (P = .008)., Conclusion: Tendril leads appear to have a higher rate of malfunction than do comparator leads. Optim insulation may partly explain the higher failure rate., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity., Aim: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo., Methods: Antral muscle strips and cells were isolated from surgical gastric samples from obese and normal weight subjects. Muscle contraction and relaxation, myogenic oxidative stress and inflammatory status were analyzed in vitro. Distal antral motility was evaluated in vivo by magnetic resonance imaging., Results: Obese antral muscle cells showed an oxidative-inflammatory imbalance with overexpression of NLRP3 inflammasome, increased IL-1β secretion and caspase1-activation, and reduced antioxidant capacity associated with a myogenic motor impairment of VIP-induced relaxation. The intracellular alterations were characterized by a decreased activation of the cAMP-signaling pathway and a decreased expression of eNOS. These in vitro alterations coincided with the hindering of antral motor activity observed in vivo. Apocynin treatment, counteracting oxidative stress, reverted alterations observed in obese antral muscle., Conclusion: Antral myogenic activity of obese subjects can be impaired by alterations of signaling pathways induced by oxidative stress., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Trypsin immobilized on collagen membranes has been used to digest chromatin polynucleosomes. With this method, the use of protease inhibitor is avoided and the digestion time easily controlled simply by taking the membrane out of the chromatin solution. Its most fundamental advantage is however to allow the mild removing of the most accessible histone fragments without addition of salt then without perturbation of their ionic environment. Degradation of histone fractions were correlated with conformational changes using circular dichroism and electric birefringence measurements. On digestion, the sign of birefringence reversed, becoming negative, and an increase of molar ellipticity was observed. These changes reflecting the unfolding of DNA correspond to the digestion of Hl and also of fragments of H3. This would indicate that H3 and particularly its basic terminal regions, play a fundamental role in the maintenance of chromatin in a compact structure.