Short all-out isokinetic cycling exercises of 90 and 15 s unlock exercise-induced hypoalgesia.

BACKGROUND: Acute physical activity leads to exercise-induced hypoalgesia (EIH). However, to what degree it can be induced by very short but highly intensive exercise is largely unknown. This study aims to investigate the effects of two different short all-out isokinetic exercise sessions on EIH. METHODS: Twenty young male participants underwent three different interventions (90, 15 s all-out isokinetic cycling, respectively, and control) after an individualized low-intensity warm-up in a randomized-controlled-crossover design. Before (pre), after warm-up (post 1) as well as immediately post-intervention (post 2) pain sensitivity was measured employing pressure pain thresholds (PPT; in N) at the elbow, knee and ankle joints as well as the sternum and forehead. Performance parameters (e.g. lactate, perceived exertion, heart rate) were documented. RESULTS: A 'time' × 'intervention' × 'body site' interaction effect (p < 0.001, η2 partial = 0.110) was observed for PPT. Both isokinetic interventions resulted in EIH at all body sites, even after ruling out any warm-up effects, while effects were larger for 90 s (maximum increase of 25.7 ± 11.7 N) compared to 15 s (maximum increase of 19.3 ± 18.9 N), and control (maximum increase of 8.0 ± 6.1 N). Compared to control, 15 s also resulted in hypoalgesic effects and differences were not observed at all sites. In this study, 90 s resulted in higher lactate, subjective exhaustion and heart rate levels compared to 15 s and control (p < 0.001), while higher values were also observed for 15 s compared to control. CONCLUSION: Global EIH assessed immediately after exercise can be induced by short highly intensive exercises. The effects are greater when the subjective and the objective exertion are higher as induced by the 90 s intervention. SIGNIFICANCE STATEMENT: This study investigates the potential for brief, highly intensive exercise sessions to induce exercise-induced hypoalgesia (EIH). The research demonstrates that EIH can indeed be triggered by such short workouts, with greater effects observed during a 90 s session compared to a 15 s one, most likely due to higher subjective and objective exertion. These findings offer insights into the potential for extremely brief but intense exercises to alleviate pain, impacting exercise recommendations and pain management strategies.

Calculation of Oxygen Uptake during Ambulatory Cardiac Rehabilitation.

Background: Cardiopulmonary exercise testing is not used routinely. The goal of this study was to determine whether accurate estimates of VO2 values can be made at the beginning and at the end of a rehabilitation program. Methods: A total of 91 cardiac rehabilitation patients were included. Each participant had to complete cardiopulmonary exercise testing at the beginning and at the end of a rehabilitation program. Measured VO2 values were compared with estimates based on three different equations. Results: Analyses of the means of the differences in the peak values showed very good agreement between the results obtained with the FRIEND equation or those obtained with a combination of rules of thumb and the results of the measurements. This agreement was confirmed with the ICCs and with the standard errors of the measurements. The ACSM equation performed worse. The same tendency was seen when considering the VO2 values at percentage-derived work rates. Conclusions: The FRIEND equation and the more easily applicable combination of rules of thumb are suitable for estimating the peak VO2 and the VO2 at a percentage-derived work rate in cardiac patients both at the beginning and at the end of a cardiac rehabilitation program.

64Cu tumor labeling with hexadentate picolinic acid-based bispidine immunoconjugates.

Discussed are two picolinate appended bispidine ligands (3,7-diazabicyclo[3.3.1]nonane derivatives) in comparison with an earlier described bis-pyridine derivative, which are all known to strongly bind CuII. The radiopharmacological characterization of the two isomeric bispidine complexes includes quantitative labeling with 64CuII at ambient conditions with high radiochemical purities and yields (molar activities >200 MBq/nmol). Challenge experiments in presence of EDTA, cyclam, human serum and SOD demonstrate high stability and inertness of the 64Cu-bispidine complexes. Biodistribution studies performed in Wistar rats indicate a rapid renal elimination for both 64Cu-labeled chelates. The bispidine ligand with the picolinate group in N7 position was selected for further biological experiments, and its backbone was therefore substituted with a benzyl-NCS group at C9. Two tumor target modules (TMs), targeting prostate stem cell antigen (PSCA), overexpressed in prostate cancer, and the fibroblast activation protein (FAP) in fibrosarcoma, were selected for thiourea coupling with the NCS-functionalized ligand and lysine residues of TMs. Small animal PET experiments on tumor-bearing mice showed specific accumulation of the 64Cu-labeled TMs in PSCA- and FAP-overexpressing tumors (standardized uptake value (SUV) for PC3: 2.7±0.6 and HT1080: 7.2±1.25) with almost no uptake in wild type tumors.

Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment.

BACKGROUND: Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression. Aiming to modulate the TME with increased clinical safety and effectiveness, we developed novel small and size-extended immunotheranostic UniCAR target modules (TMs) targeting FAP. METHODS: The specific binding and functionality of the αFAP-scFv TM and the size-extended αFAP-IgG4 TM were assessed using 2D and 3D in vitro models as well as in vivo. Their specific tumor accumulation and diagnostic potential were evaluated using PET studies after functionalization with a chelator and suitable radionuclide. RESULTS: The αFAP-scFv and -IgG4 TMs effectively and specifically redirected UniCAR T-cells using 2D, 3D, and in vivo models. Moreover, a remarkably high and specific accumulation of radiolabeled FAP-targeting TMs at the tumor site of xenograft mouse models was observed. CONCLUSIONS: These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients.