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Purpose: To determine the effect of inspiratory muscle training (IMT) on respiratory and peripheral muscle strength, functional exercise capacity, health-related quality of life (HRQoL), fatigue, depression, and cardiac functions in patients with stable angina. Methods: A randomized, controlled, single-blinded study. Twenty patients (59.95 ± 7.35 y, LVEF - 58.77 ± 7.49) with stable angina received IMT at the lowest load (10 cmH2O), and 20 patients (55.85 ± 7.60 y, LVEF - 62.26 ± 7.75) received training at 30% of maximal inspiratory pressure (MIP) seven days/8 weeks. Respiratory muscle strength (MIP; maximal expiratory pressure, MEP), peripheral muscle strength, pulmonary functions, functional exercise capacity (6-min walking test; exercise test), fatigue, HRQoL, depression, and cardiac functions were evaluated before and after. Results: A statistical difference was found between groups in terms of respiratory and peripheral muscle strength, pulmonary functions, functional exercise capacity (p<0.05). The results of fatigue, depression, HRQoL, and cardiac functions were similar between the groups (p>0.05). Conclusions: This study is the first to demonstrate the positive effects of IMT in patients with stable angina. IMT is a safe and effective method and is recommended to be added to cardiopulmonary rehabilitation programs and guidelines, as it results in increased peripheral muscle strength and functional exercise capacity in stable angina patients. [ABSTRACT FROM AUTHOR]

Gamma radiation is widely used to sterilize bone allografts but may impair their strength. While radioprotectant use may reduce radiation damage they may compromise sterility by protecting pathogens. We assessed the radioprotective potential of various agents (L-cysteine, N-acetyl-L-cysteine, L-cysteine-ethyl-ester and L-cysteine-methyl-ester) to identify those which do not protect spores of Bacillus subtilis. We hypothesized charge of these agents will affect their ability to radioprotect spores. We also determined ability of these radioprotectants and a radiosensitizer (nitroimidazole-linked phenanthridinium) to selectively sensitize spores to radiation damage by intercalating into the nucleic acid of spores. Spores were treated either directly in solutions of these agents or treated after being embedded and sealed in bone to assess the ability of these agents to diffuse into bone. L-cysteine and L-cysteine-ethyl-ester did not provide radioprotection. Positively charged L-cysteine-methyl-ester protected the spores, whereas positively charged L-cysteine-ethyl-ester did not, indicating charge does not determine the extent of radioprotection. The spores were sensitized to radiation damage when irradiated in nitroimidazole-linked phenanthridinium solution and sensitization disappeared after rinsing, suggesting nitroimidazole-linked phenanthridinium was unable to intercalate into the nucleic acid of the spores. Some cysteine-derived radioprotectants do not shield bacterial spores against gamma radiation and may be suitable for curbing the radiation damage to bone grafts while achieving sterility. [ABSTRACT FROM AUTHOR]

Both high-cycle fatigue life and fatigue crack propagation resistance of human cortical bone allograft are radiation dose-dependent between 0 and 25 kGy such that higher doses exhibit progressively shorter lifetimes. Recently, we have shown that collagen chain fragmentation and stable crosslink accumulation may contribute to the radiation dose-dependent loss in fatigue crack propagation resistance of human cortical bone. To our knowledge, the influence of these mechanisms on high-cycle fatigue life of cortical bone have not been established. Sequential irradiation has also been shown to mitigate the loss of fatigue life of tendons, however, whether this mitigates losses in fatigue life of cortical bone has not been explored. Our objectives were to evaluate the influence of radiation-induced collagen chain fragmentation and crosslinking on the high-cycle fatigue life of cortical bone in the dose range of 0-15 kGy, and to evaluate the capability of sequential irradiation at 15 kGy to mitigate the loss of high-cycle fatigue life and radiation-induced collagen damage. High-cycle fatigue life specimens from four male donor femoral pairs were divided into 5 treatment groups (0 kGy, 5 kGy, 10 kGy, 15 kGy, and 15 kGy sequentially irradiated) and subjected to high-cycle fatigue life testing with a custom rotating-bending apparatus at a cyclic stress of 35 MPa. Following fatigue testing, collagen was isolated from fatigue specimens, and collagen chain fragmentation and crosslink accumulation were quantified using SDS-PAGE and a fluorometric assay, respectively. Both collagen chain fragmentation (p = 0.006) and non-enzymatic crosslinking (p < 0.001) influenced high-cycle fatigue life, which decreased with increasing radiation dose from 0 to 15 kGy (p = 0.016). Sequential irradiation at 15 kGy did not offer any mitigation in high-cycle fatigue life (p = 0.93), collagen chain fragmentation (p = 0.99), or non-enzymatic crosslinking (p ≥ 0.10) compared to a single radiation dose of 15 kGy. Taken together with our previous findings on the influence of collagen damage on fatigue crack propagation resistance, collagen chain fragmentation and crosslink accumulation both contribute to radiation-induced losses in notched and unnotched fatigue life of cortical bone. To maximize the functional lifetime of radiation sterilized structural cortical bone allografts, pathways other than sequential radiation should be explored to mitigate collagen matrix damage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dylan Crocker reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases. Megan Oest reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases. Clare Rimnac reports financial support was provided by Musculoskeletal Transplant Foundation Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Macrophages are involved in several critical activities associated with tissue repair and regeneration. Current approaches in regenerative medicine are focusing on leveraging the innate immune response to accelerate tissue regeneration and improve long-term healing outcomes. Of particular interest in this regard are the currently known, four main M2 macrophage subtypes: M2 interleukin (IL)-4,IL-13 , M2 IC , M2 IL-10 , M2 non-selective adenosine receptor agonists (NECA) (M2 IL-4,IL-13  → M2 NECA ). In this study, rat bone marrow-derived macrophages (M 0 ) were polarized to each of the four subtypes M2 IL-4,IL-13  → M2 NECA and cultured for 72 h in vitro. Luminex assay results highlighted increased production of tissue inhibitor of metalloproteinases-1 (TIMP-1) for M2 IL-4,IL-13 , higher amounts of transforming growth factor-beta 1 (TGF-β1) for M2 IL-10 , and elevated vascular endothelial growth factor A (VEGF-A) from M2 NECA . Co-culture experiments performed with M2 IL-10 macrophages and L929 fibroblasts highlighted the increased production of soluble collagen within the media as well as higher amounts of collagen in the extracellular matrix. Human umbilical vein endothelial cells (HUVECs) were co-cultured with M2 NECA macrophages, which demonstrated an increase in intercellular adhesion molecule (ICAM) and platelet endothelial cell adhesion molecule (PECAM), as well as increased formation of endothelial tubes. The findings of this study emphasize a critical demand for further characterization and analyses of distinct M 2 subtypes and careful selection of specific macrophage populations for regeneration of specific tissue types. The current, broad classification of "M 2 " may be sufficient in many general tissue engineering applications, but, as conditions are constantly in flux within the microenvironment in vivo, a higher degree of specificity and control over the initial M 2 subtype could result in more consistent long-term outcomes where macrophages are utilized as part of an overall regenerative strategy., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Fatigue crack propagation resistance and high-cycle S-N fatigue life of cortical bone allograft tissue are both negatively impacted in a radiation dose-dependent manner from 0 to 25 kGy. The standard radiation sterilization dose of 25-35 kGy has been shown to induce cleavage of collagen molecules into smaller peptides and accumulation of stable crosslinks within the collagen matrix, suggesting that these mechanisms may influence radiation-induced losses in cyclic fracture resistance. The objective of this study was to determine the radiation dose-dependency of collagen chain fragmentation and crosslink accumulation within the dose range of 0-25 kGy. Previously, cortical bone compact tension specimens from two donor femoral pairs were divided into four treatment groups (0 kGy, 10 kGy, 17.5 kGy, and 25 kGy) and underwent cyclic loading fatigue crack propagation testing. Following fatigue testing, collagen was isolated from one compact tension specimen in each treatment group from both donors. Radiation-induced collagen chain fragmentation was assessed using SDS-PAGE (n = 5), and accumulation of pentosidine, pyridinoline, and non-specific advanced glycation end products were assessed using a fluorometric assay (n = 4). Collagen chain fragmentation increased progressively in a dose-dependent manner (p < 0.001). Crosslink accumulation at all radiation dose levels increased relative to the 0 kGy control but did not demonstrate dose-dependency (p < 0.001). Taken together with our previous findings on fatigue crack propagation behavior, these data suggest that while collagen crosslink accumulation may contribute to reduced notched fatigue behavior with irradiation, dose-dependent losses in fatigue crack propagation resistance are mainly influenced by radiation-induced chain fragmentation., (© 2024. The Author(s).)

Soft-bodied animals, such as worms and snakes, use many muscles in different ways to traverse unstructured environments and inspire tools for accessing confined spaces. They demonstrate versatility of locomotion which is essential for adaptation to changing terrain conditions. However, replicating such versatility in untethered soft-bodied robots with multimodal locomotion capabilities have been challenging due to complex fabrication processes and limitations of soft body structures to accommodate hardware such as actuators, batteries and circuit boards. Here, we present MetaCrawler, a 3D printed metamaterial soft robot designed for multimodal and omnidirectional locomotion. Our design approach facilitated an easy fabrication process through a discrete assembly of a modular nodal honeycomb lattice with soft and hard components. A crucial benefit of the nodal honeycomb architecture is the ability of its hard components, nodes, to accommodate a distributed actuation system, comprising servomotors, control circuits, and batteries. Enabled by this distributed actuation, MetaCrawler achieves five locomotion modes: peristalsis, sidewinding, sideways translation, turn-in-place, and anguilliform. Demonstrations showcase MetaCrawler's adaptability in confined channel navigation, vertical traversing, and maze exploration. This soft robotic system holds the potential to offer easy-to-fabricate and accessible solutions for multimodal locomotion in applications such as search and rescue, pipeline inspection, and space missions., (Creative Commons Attribution license.)

Tracheal stenosis is commonly caused by injury, resulting in inflammation and fibrosis. Inhibiting inflammation and promoting epithelization can reduce recurrence after initial successful treatment of tracheal stenosis. Steroids play an important role in tracheal stenosis management. This study in vitro evaluated effectiveness of a polydopaminated polycaprolactone stent coated with dexamethasone-eluting poly(lactic-co-glycolic) acid microparticles (μPLGA) for tracheal stenosis management. Polydopamination was characterized by Raman spectroscopy and promoted epithelialization while dexamethasone delivery reduced macrophage activity, assessed by individual cell area measurements and immunofluorescent staining for inducible nitric oxide synthase (iNOS). Dexamethasone release was quantified by high-performance liquid chromatography over 30 days. Activation-related increase in cell area and iNOS production by RAW 264.7 were both reduced significantly (p < .05) through dexamethasone release. Epithelial cell spreading was higher on polydopaminated polycaprolactone (PCL) than PCL-alone (p < .05). Force required for stent migration was measured by pullout tests of PCL-μPLGA stents from cadaveric rabbit and porcine tracheas (0.425 ± 0.068 N and 1.082 ± 0.064 N, respectively) were above forces estimated to occur during forced respiration. Biomechanical support provided by stents to prevent airway collapse was assessed by comparing compressive circumferential stiffness, and stiffness of the stent was about 1/10th of the rabbit trachea (0.156 ± 0.023 N/mm vs. 1.420 ± 0.194 N/mm, respectively). A dexamethasone-loaded PCL-μPLGA stent platform can deliver dexamethasone and exhibits sufficient mechanical properties to anchor within the trachea and polydopamination of PCL is conducive to epithelial layer formation. Therefore, a polydopaminated PCL-μPLGA stent is a promising candidate for in vivo evaluation for treatment of tracheal restenosis., (© 2024 Wiley Periodicals LLC.)