The influence of accelerated electrons on neuronal structures is scarcely explored compared to gamma and X-rays. This study aims to investigate the effects of accelerated electron radiation on some pivotal neurotransmitter circuits (cholinergic and serotonergic) of rats\' myenteric plexus. Male Wistar rats were irradiated with an electron beam (9 MeV, 5 Gy) generated by a multimodality linear accelerator. The contractile activity of isolated smooth muscle samples from the gastric corpus was measured. Furthermore, an electrical stimulation (200 μs, 20 Hz, 50 s, 60 V) was performed on the samples and an assessment of the cholinergic and serotonergic circuits was made. Five days after irradiation, the recorded mechanical responses were biphasic-contraction/relaxation in controls and contraction/contraction in irradiated samples. The nature of the contractile phase of control samples was cholinergic with serotonin involvement. The relaxation phase involved ACh-induced nitric oxide release from gastric neurons. There was a significant increase in serotonergic involvement during the first and second contractile phases of the irradiated samples, along with a diminished role of acetylcholine in the first phase. This study demonstrates an increased involvement of serotonergic neurotransmitter circuits in the gastric myenteric plexus caused by radiation with accelerated electrons.

Heart failure with preserved ejection fraction (HFpEF) is characterized by biomechanically dysfunctional cardiomyocytes. Underlying cellular changes include perturbed myocardial titin expression and titin hypophosphorylation leading to titin filament stiffening. Beside these well-studied alterations at the cardiomyocyte level, exercise intolerance is another hallmark of HFpEF caused by molecular alterations in skeletal muscle (SKM). Currently, there is a lack of data regarding titin modulation in the SKM of HFpEF. Therefore, the aim of the present study was to analyze molecular alterations in limb SKM (tibialis anterior (TA)) and in the diaphragm (Dia), as a more central SKM, with a focus on titin, titin phosphorylation, and contraction-regulating proteins. This study was performed with muscle tissue, obtained from 32-week old female ZSF-1 rats, an established a HFpEF rat model. Our results showed a hyperphosphorylation of titin in limb SKM, based on enhanced phosphorylation at the PEVK region, which is known to lead to titin filament stiffening. This hyperphosphorylation could be reversed by high-intensity interval training (HIIT). Additionally, a negative correlation occurring between the phosphorylation state of titin and the muscle force in the limb SKM was evident. For the Dia, no alterations in the phosphorylation state of titin could be detected. Supported by data of previous studies, this suggests an exercise effect of the Dia in HFpEF. Regarding the expression of contraction regulating proteins, significant differences between Dia and limb SKM could be detected, supporting muscle atrophy and dysfunction in limb SKM, but not in the Dia. Altogether, these data suggest a correlation between titin stiffening and the appearance of exercise intolerance in HFpEF, as well as a differential regulation between different SKM groups.

Volumetric muscle loss (VML) injury causes irreversible deficits in muscle mass and function, often resulting in permanent disability. The current standard of care is physical therapy, but it is limited in mitigating functional deficits. We have previously optimized a rehabilitation technique using electrically stimulated eccentric contraction training (EST) that improved muscle mass, strength, and size in VML-injured rats. A biosponge scaffold composed of extracellular matrix proteins has previously enhanced muscle function postVML. This study aimed to determine whether combining a regenerative therapy (i.e., biosponge) with a novel rehabilitation technique (i.e., EST) could enhance recovery in a rat model of VML. A VML defect was created by removing ~20% of muscle mass from the tibialis anterior muscle in adult male Lewis rats. Experimental groups included VML-injured rats treated with biosponge with EST or biosponge alone (n = 6/group). EST was implemented 2 weeks postinjury at 150 Hz and was continued for 4 weeks. A linear increase in eccentric torque over 4 weeks showed the adaptability of the VML-injured muscle to EST. Combining biosponge with EST improved peak isometric torque by ~52% compared with biosponge treatment alone at 6 weeks postinjury. Application of EST increased MyoD gene expression and the percentage of large (>2000 μm2) type 2B myofibers but reduced fibrotic tissue deposition in VML-injured muscles. Together, these changes may provide the basis for improved torque production. This study demonstrates the potential for combined regenerative and rehabilitative therapy to improve muscle recovery following VML.

Filamins are mechanosensitive actin crosslinking proteins that organize the actin cytoskeleton in a variety of shapes and tissues. In muscles, filamin crosslinks actin filaments from opposing sarcomeres, the smallest contractile units of muscles. This happens at the Z-disc, the actin-organizing center of sarcomeres. In flies and vertebrates, filamin mutations lead to fragile muscles that appear ruptured, suggesting filamin helps counteract muscle rupturing during muscle contractions by providing elastic support and/or through signaling. An elastic region at the C-terminus of filamin is called the mechanosensitive region and has been proposed to sense and counteract contractile damage. Here we use molecularly defined mutants and microscopy analysis of the Drosophila indirect flight muscles to investigate the molecular details by which filamin provides cohesion to the Z-disc. We made novel filamin mutations affecting the C-terminal region to interrogate the mechanosensitive region and detected three Z-disc phenotypes: dissociation of actin filaments, Z-disc rupture, and Z-disc enlargement. We tested a constitutively closed filamin mutant, which prevents the elastic changes in the mechanosensitive region and results in ruptured Z-discs, and a constitutively open mutant which has the opposite elastic effect on the mechanosensitive region and gives rise to enlarged Z-discs. Finally, we show that muscle contraction is required for Z-disc rupture. We propose that filamin senses myofibril damage by elastic changes in its mechanosensory region, stabilizes the Z-disc, and counteracts contractile damage at the Z-disc.

The paramount importance of mechanical forces in morphogenesis and embryogenesis is widely recognized, but understanding the mechanism at the cellular and molecular level remains challenging. Because of its simple internal organization, Caenorhabditis elegans is a rewarding system of study. As demonstrated experimentally, after an initial period of steady elongation driven by the actomyosin network, muscle contractions operate a quasi-periodic sequence of bending, rotation, and torsion, that leads to the final fourfold size of the embryos before hatching. How actomyosin and muscles contribute to embryonic elongation is investigated here theoretically. A filamentary elastic model that converts stimuli generated by biochemical signals in the tissue into driving forces, explains embryonic deformation under actin bundles and muscle activity, and dictates mechanisms of late elongation based on the effects of energy conversion and dissipation. We quantify this dynamic transformation by stretches applied to a cylindrical structure that mimics the body shape in finite elasticity, obtaining good agreement and understanding of both wild-type and mutant embryos at all stages.

We sought to determine the physiological relevance of pannexin/purinergic-dependent signaling in mediating conducted vasodilation elicited by capillary stimulation through skeletal muscle contraction. Using hamster cremaster muscle and intravital microscopy we stimulated capillaries through local muscle contraction while observing the associated upstream arteriole. Capillaries were stimulated with muscle contraction at low and high contraction (6 and 60CPM) and stimulus frequencies (4 and 40 Hz) in the absence and presence of pannexin blocker mefloquine (MEF; 10-5 M), purinergic receptor antagonist suramin (SUR 10-5 M) and gap-junction uncoupler halothane (HALO, 0.07%) applied between the capillary stimulation site and the upstream arteriolar observation site. Conducted vasodilations elicited at 6CPM were inhibited by HALO while vasodilations at 60CPM were inhibited by MEF and SUR. The conducted response elicited at 4 Hz was inhibited by MEF while the vasodilation at 40 Hz was unaffected by any blocker. Therefore, upstream vasodilations resulting from capillary stimulation via muscle contraction are dependent upon a pannexin/purinergic-dependent pathway that appears to be stimulation parameter-dependent. Our data highlight a physiological importance of the pannexin/purinergic pathway in facilitating communication between capillaries and upstream arteriolar microvasculature and, consequently, indicating that this pathway may play a crucial role in regulating blood flow in response to skeletal muscle contraction.

We assessed the feasibility of implementing a virtually guided Neuromuscular Electrical Stimulation (NMES) protocol over the tibialis anterior (TA) muscle while collecting heart rate (HR), Numeric Pain Rating Scale (NPRS), and quality of contraction (QoC) data. We investigated if HR, NPRS, and QoC differ ON and OFF the TA motor point and explored potential relationships between heart rate variability (HRV) and the NPRS. Twelve healthy adults participated in this cross-sectional study. Three NMES trials were delivered ON and OFF the TA motor point. HR, QoC, and NPRS data were collected. There was no significant difference in HRV ON and OFF the motor point (p > 0.05). The NPRS was significantly greater OFF the motor point (p < 0.05). The QoC was significantly different between motor point configurations (p < 0.05). There was no correlation between the NPRS and HRV (p > 0.05, r = -0.129). We recommend non-electrical methods of measuring muscle activity for future studies. The NPRS and QoC can be administered virtually. Time-domain HRV measures could increase the validity of the protocol. The variables should be explored further virtually to enhance the protocol before eventual ICU studies.

Levosimendan\'s calcium sensitizing effects in heart muscle cells are well established; yet, its potential impact on skeletal muscle cells has not been evidently determined. Despite controversial results, levosimendan is still expected to interact with skeletal muscle through off-target sites (further than troponin C). Adding to this debate, we investigated levosimendan\'s acute impact on fast-twitch skeletal muscle biomechanics in a length-dependent activation study by submersing single muscle fibres in a levosimendan-supplemented solution. We employed our MyoRobot technology to investigate the calcium sensitivity of skinned single muscle fibres alongside their stress-strain response in the presence or absence of levosimendan (100 µM). While control data are in agreement with the theory of length-dependent activation, levosimendan appears to shift the onset of the \'descending limb\' of active force generation to longer sarcomere lengths without notably improving myofibrillar calcium sensitivity. Passive stretches in the presence of levosimendan yielded over twice the amount of enlarged restoration stress and Young\'s modulus in comparison to control single fibres. Both effects have not been described before and may point towards potential off-target sites of levosimendan.

BACKGROUND: Minimizing muscle strain and reducing the risk of musculoskeletal disorders associated with intraoral scanner (IOS) usage require ergonomic awareness, device selection, and workplace adjustments in dental practice. This preliminary clinical study aimed to simulate intraoral scanning tasks using wired and wireless IOSs and assess muscle activation and fatigue for both types.
METHODS: Fourteen participants performed intraoral scanning tasks using wired and wireless IOSs (i700; MEDIT), with weights of 280 g and 328 g, respectively. The same computer system and software conditions were maintained for both groups (N = 14 per IOS group). Electrodes were placed on arm, neck, and shoulder muscles, and maximal voluntary contraction (MVC) was measured. Surface electromyography (EMG) was performed during the simulation, and EMG values were normalized using MVC. The root mean square EMG (%MVC) and muscle fatigue (%) values were calculated. Statistical comparisons were performed using the Mann-Whitney U and Friedman tests, with the Bonferroni adjustment for multiple comparisons (α = 0.05).
RESULTS: Arm (flexor digitorum superficialis) and neck muscles (left sternocleidomastoid and left splenius capitis) showed significantly higher EMG values with wireless IOS (P < 0.05). The neck (left sternocleidomastoid and right levator scapulae) and shoulder muscles (right trapezius descendens) demonstrated significantly higher muscle fatigue with wireless IOS (P < 0.05).
CONCLUSIONS: The consecutive use of heavier wireless IOS may increase the risk of muscle activation and fatigue in certain muscles, which may have clinical implications for dentists in terms of ergonomics and musculoskeletal health.

BACKGROUND: Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG).
METHODS: Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test.
RESULTS: Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction.
CONCLUSIONS: These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity.
BACKGROUND: ChiCTR2000032245.