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Renato Cannizzaro,1 Stefania Maiero,1 Mara Fornasarig,1 Vincenzo Canzonieri,2 Raffaella Magris,1 Giovanni Guarnieri,1 Martina Urbani,3 Angela Buonadonna,4 Tanja Baresic,5 Paola Spessotto61Oncological Gastroenterology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 2Pathology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 3Oncologic Radiation Therapy and Diagnostic Imaging, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 4Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 5Nuclear Medicine, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; 6Molecular Oncology, Department of Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, ItalyAbstract: The potential role of the probe-based confocal laser endomicroscopy (pCLE) has been analyzed in different pathologic conditions of the gastrointestinal tract. Here, we analyzed a case of extrapulmonary high grade neuroendocrine rectal carcinoma (HGNEC) using, for the first time, the pCLE system. A 72-year old man was diagnosed with an 8 cm diameter rectal HGNEC by standard colonoscopy integrated with the pCLE system. The diagnosis of neuroendocrine carcinoma was confirmed by immunohistochemical analyses. By using the pCLE system, we well defined and resolved vascular structures and mucosal architecture. An altered mucosal pattern and vascular defects, peculiar for HGNEC, were observed at high magnification, allowing the identification of a pattern which was quite different from that observed in poorly differentiated adenocarcinomas (PDA) where tissues appear darker, very irregular, even if glandular structures can still be recognized. This underlines the usefulness of pCLE in discriminating HGNECs from PDAs. In conclusion, pCLE could represent a valid and helpful method for in vivo HGNEC diagnosis, allowing prompt and careful management of the patient.Keywords: probe-based confocal endomicroscopy, neoangiogenesis, extrapulmonary high grade neuroendocrine carcinoma, poorly differentiated adenocarcinoma

Aim: we investigated the effects of a 10 week training program (i.e., minute oscillatory stretching; MOS) on the mechanical responses and walking capability in people with type 2 diabetes (T2D)., Methods: seventeen T2D patients performed maximum voluntary contractions of the plantar flexor muscles during which Achilles tendon stiffness (k T ) and muscle-tendon stiffness (k M ) were evaluated at different percentages of the maximum voluntary force (MVC). In addition, each participant was requested to walk at different walking speeds (i.e. 2, 3, 4, 5, and 6 kmh -1 ) while their net energy cost of walking (C net ), cumulative EMG activity per distance travelled (CMAPD) and kinematic parameters (step length, step frequency, the ankle/knee range of motion) were evaluated., Results: maximum tendon elongation increased after MOS training, and k T significantly decreased (between 0 and 20% of MVC). No differences were observed for muscle elongation or k M after training. C net decreased after training (at the slowest tested speeds) while no changes in CMAPD were observed. Step length and ankle ROM during walking increased after training at the slowest tested speeds, while step frequency decreased; no significant effects were observed for knee ROM., Conclusion: these results indicate the effectiveness of 10 weeks of MOS training in reducing tendon stiffness and the energy cost during walking in people with T2D. This training protocol requires no specific instrumentation, can be easily performed at home, and has a high adherence (92 ± 9%). It could, thus, be useful to mitigate mechanical tendon deterioration and improve physical behaviour in this population., (© 2024. The Author(s).)

Introduction: Parkinson's disease (PD) is a prevalent neurodegenerative condition observed primarily in the elderly population that gives rise to motor and non-motor symptoms, one of which is muscle weakness. The aim of this study was to characterize the vastus lateralis torque-fascicle length (T-L) and the knee extensors torque-angular velocity (T-V) and power-angular velocity (P-V) relationships in PD patients and to investigate the influence of muscle geometry on muscle mechanics., Methods: Participants (11 PD: patients, 9 CR: age matched healthy controls; 10 CY: young healthy controls) performed: (i) isometric contractions (e.g., MVC) to obtain the torque-angle and T-L relationships; (ii) isokinetic (e.g., iso-velocity) contractions to obtain the T-V and P-V relationships. During the experiments, the architecture of vastus lateralis (pennation angle, fascicle length, muscle thickness) was also determined by using an ultrasound apparatus., Results: Significant differences were observed between PD patients and physically matched control groups (CR and CY) in terms of maximum isometric force (calculated as the apex of the T-L curve) and maximum mechanical power (apex of the P-V curve), but not in maximum shortening velocity. Among the mechanical variables investigated, mechanical power was able to identify differences between the less and the more affected side in PD patients, suggesting that this parameter could be useful for clinical evaluation in this population., Conclusions: The observed results cannot be explained by differences in muscle geometry at rest (similar in the three cohorts), but rather by the muscle capacity to change in shape during contraction, that is impaired in PD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Magris, Nardello, Bombieri, Monte and Zamparo.)

Aim: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized, among the others, by muscle weakness. PD patients reach lower values of peak torque during maximal voluntary contractions but also slower rates of torque development (RTD) during explosive contractions. The aim of this study was to better understand how an impairment in structural/mechanical (peripheral) factors could explain the difficulty of PD patients to raise torque rapidly., Methods: Participants (PD patients and healthy matched controls) performed maximum voluntary explosive fixed-end contraction of the knee extensor muscles during which dynamic muscle shape changes (in muscle thickness, pennation angle, and belly gearing: the ratio between muscle belly velocity and fascicle velocity), muscle-tendon unit (MTU) stiffness and EMG activity of the vastus lateralis (VL) were investigated. Both the affected (PDA) and less affected limb (PDNA) were investigated in patients., Results: Control participants reached higher values of peak torque and showed a better capacity to express force rapidly compared to patients (PDA and PDNA). EMG activity was observed to differ between patients (PDA) and controls, but not between controls and PDNA. This suggests a specific neural/nervous effect on the most affected side. On the contrary, MTU stiffness and dynamic muscle shape changes were found to differ between controls and patients, but not between PDA and PDNA. Both sides are thus similarly affected by the pathology., Conclusion: The higher MTU stiffness in PD patients is likely responsible for the impaired muscle capability to change in shape which, in turn, negatively affects the torque rise., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

In this study, we used kinematic, kinetic, metabolic and ultrasound analysis to investigate the role of elastic energy utilization on the mechanical and physiological demands of a movement task (hopping) that primarily involves the plantar-flexor muscles to determine the contribution of tendon work to total mechanical work and its relationship with apparent efficiency (AE) in bouncing gaits. Metabolic power (PMET) and (positive) mechanical power at the whole-body level (PMEC) were measured during hopping at different frequencies (2, 2.5, 3 and 3.5 Hz). The (positive) mechanical power produced during the Achilles tendon recoil phase (PTEN) was obtained by integrating ultrasound data with an inverse dynamic approach. As a function of hopping frequency, PMEC decreased steadily and PMET exhibited a U-shape behaviour, with a minimum at about 3 Hz. AE (PMEC/PMET) showed an opposite trend and was maximal (about 0.50) at the same frequency when PTEN was also highest. Positive correlations were observed: (i) between PTEN and AE (AE=0.22+0.15PTEN, R2=0.67, P<0.001) and the intercept of this relationship indicates the value of AE that should be expected when tendon work is nil; (ii) between AE and tendon gearing (Gt=Δmuscle-tendon unit length/Δmuscle belly length; R2=0.50, P<0.001), where a high Gt indicates that the muscle is contracting more isometrically, thus allowing the movement to be more economical (and efficient); (iii) between Gt and PTEN (R2=0.73, P<0.001), which indicates that Gt could play an important role in the tendon's capability to store and release mechanical power., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Changes in muscle shape could play an important role during contraction allowing to circumvent some limits imposed by the fascicle force-velocity (F-V) and power-velocity (P-V) relationships. Indeed, during low-force high-velocity contractions, muscle belly shortening velocity could exceed muscle fascicles shortening velocity, allowing the muscles to operate at higher F-V and P-V potentials (i.e., at a higher fraction of maximal force/power in accordance to the F-V and P-V relationships). By using an ultrafast ultrasound, we investigated the role of muscle shape changes (vastus lateralis) in determining belly gearing (muscle belly velocity/fascicle velocity) and the explosive torque during explosive dynamic contractions (EDC) at angular accelerations ranging from 1000 to 4000°.s -2 . By means of ultrasound and dynamometric data, the F-V and P-V relationships both for fascicles and for the muscle belly were assessed. During EDC, fascicle velocity, belly velocity, belly gearing, and knee extensors torque data were analysed from 0 to 150 ms after torque onset; the fascicles and belly F-V and P-V potentials were thus calculated for each EDC. Absolute torque decreased as a function of angular acceleration (from 80 to 71 Nm, for EDC at 1000 and 4000°.s -1 , respectively), whereas fascicle velocity and belly velocity increased with angular acceleration ( P < 0.001). Belly gearing increased from 1.11 to 1.23 (or EDC at 1000 and 4000°.s -1 , respectively) and was positively corelated with the changes in muscle thickness and pennation angle (the changes in latter two equally contributing to belly gearing changes). For the same amount of muscle's mechanical output (force or power), the fascicles operated at higher F-V and P-V potential than the muscle belly (e.g., P-V potential from 0.70 to 0.56 for fascicles and from 0.65 to 0.41 for the muscle belly, respectively). The present results experimentally demonstrate that belly gearing could play an important role during explosive contractions, accommodating the largest part of changes in contraction velocity and allowing the fascicle to operate at higher F-V and P-V potentials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Monte, Bertucco, Magris and Zamparo.)

Ensuring stability of the human vertical posture is a complex task requiring both anticipatory and compensatory postural strategies when a standing person performs fast actions and interacts with the environment, which can include other persons. How people adjust their preparatory and compensatory postural adjustments in situations when they interact with an active partner is still poorly understood. In this study we investigated the postural adjustments while two healthy persons played a traditional childhood game. While standing facing each other, they were asked to push with their hands against the hands of the opponent only, and to make the opponent to take a step. We explored strategies when pushing the opponent's hands generated perturbations to the posture of both players and when one of the players withdrew the arms to neutralize the opponent's pushing action. Electromyograms were recorded from the leg and trunk muscles and used to quantify early (EPAs), anticipatory (APAs) and compensatory (CPAs) postural adjustments, as well as the co-activation and reciprocal changes in the activity of agonist-antagonist pairs. Results showed higher indices of muscle co-activation during EPAs during the game compared to the control conditions. We found that postural preparation strategies defined whether a participant kept or lost balance during the game. Our results highlight the importance of muscle co-activation, the role of anticipation, and the difference in strategies while interacting with an active partner as compared to interactions with passive objects., (Copyright © 2021 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC., Methods: Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC-MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients., Results: 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC-MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was "tricarboxylic acid cycle". Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC)., Conclusion: This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.