Project description:BackgroundDyspnoea is rarely mentioned in the clinical description of adult-onset isolated dystonia. In this study, we present the clinical features of 13 patients with Meige syndrome (cranio-cervical dystonia) with breathing difficulties.MethodsA retrospective case note review was performed of patients presenting with Meige syndrome and shortness of breath, to a neuro-laryngology MDT clinic.ResultsSome patients were severely limited by their breathlessness, but others did not volunteer these symptoms. The majority of patients were referred with the assumption that the larynx was the cause of the problem; however half the patients did not have evidence of laryngeal involvement. Of the patients who had laryngeal involvement, injecting the larynx alone did not always relieve the dyspnoea. The majority of our patients responded to injection of the suprahyoid muscles, including genioglossus, digastric and mylohyoid.ConclusionWe recommend routinely establishing if the patient with Meige syndrome has signs or symptoms of breathlessness, and establishing the level of the problem, as this can be treated successfully.
Project description:The inherent compliance of soft fluidic actuators makes them attractive for use in wearable devices and soft robotics. Their flexible nature permits them to be used without traditional rotational or prismatic joints. Without these joints, however, measuring the motion of the actuators is challenging. Actuator-level sensors could improve the performance of continuum robots and robots with compliant or multi-degree-of-freedom joints. We make the reinforcing braid of a pneumatic artificial muscle (PAM or McKibben muscle) "smart" by weaving it from conductive, insulated wires. These wires form a solenoid-like circuit with an inductance that more than doubles over the PAM contraction. The reinforcing and sensing fibers can be used to measure the contraction of a PAM actuator with a simple, linear function of the measured inductance. Whereas other proposed self-sensing techniques rely on the addition of special elastomers or transducers, the technique presented in this work can be implemented without modifications of this kind. We present and experimentally validate two models for Smart Braid sensors based on the long solenoid approximation and the Neumann formula, respectively. We test a McKibben muscle made from a Smart Braid in quasistatic conditions with various end-loads and in dynamic conditions. We also test the performance of the Smart Braid sensor alongside steel.
Project description:Excess of histamine in gut lumen generates a pronounced gastrointestinal discomfort, which may include diarrhea and peristalsis dysfunctions. Deleterious effects of histamine can be alleviated with antihistamine drugs targeting histamine receptors. However, many antihistamine agents come with various undesirable side effects. Vegetal diamine oxidase (vDAO) might be a relevant alternative owing to its histaminase activity. Mammalian intestinal mucosa contains an endogenous DAO, yet possessing lower activity compared to that of vDAO preparation. Moreover, in several pathological conditions such as inflammatory bowel disease and irritable bowel syndrome, this endogenous DAO enzyme can be lost or inactivated. Here, we tested the therapeutic potential of vDAO by focusing on the well-known effect of histamine on gut motility. Using ex vivo and in vitro assays, we found that vDAO is more potent than commercial anti-histamine drugs at inhibiting histamine-induced contraction of murine distal colon muscles. We also identified pyridoxal 5'-phosphate (the biologically active form of vitamin B6) as an effective enhancer of vDAO antispasmodic activity. Furthermore, we discovered that rectally administered vDAO can be retained on gut mucosa and remain active. These observations make administration of vDAO in the gut lumen a valid alternative treatment for histamine-induced intestinal dysfunctions.
Project description:A highly porous metal-organic framework DUT-48, isoreticular to DUT-49, is reported with a high surface area of 4560 m2·g-1 and methane storage capacity up to 0.27 g·g-1 (164 cm3·cm-3) at 6.5 MPa and 298 K. The flexibility of DUT-48 and DUT-49 under external and internal (adsorption-induced) pressure is analyzed and rationalized using a combination of advanced experimental and computational techniques. While both networks undergo a contraction by mechanical pressure, only DUT-49 shows adsorption-induced structural transitions and negative gas adsorption of n-butane and nitrogen. This adsorption behavior was analyzed by microcalorimetry measurements and molecular simulations to provide an explanation for the lack of adsorption-induced breathing in DUT-48. It was revealed that for DUT-48, a significantly lower adsorption enthalpy difference and a higher framework stiffness prevent adsorption-induced structural transitions and negative gas adsorption. The mechanical behavior of both DUT-48 and DUT-49 was further analyzed by mercury porosimetry experiments and molecular simulations. Both materials exhibit large volume changes under hydrostatic compression, demonstrating noteworthy potential as shock absorbers with unprecedented high work energies.
Project description:Stac3 regulates excitation-contraction coupling (EC coupling) in vertebrate skeletal muscles by regulating the L-type voltage-gated calcium channel (Cav channel). Recently a stac-like gene, Dstac, was identified in Drosophila and found to be expressed by both a subset of neurons and muscles. Here, we show that Dstac and Dmca1D, the Drosophila L-type Cav channel, are necessary for normal locomotion by larvae. Immunolabeling with specific antibodies against Dstac and Dmca1D found that Dstac and Dmca1D are expressed by larval body-wall muscles. Furthermore, Ca2+ imaging of muscles of Dstac and Dmca1D deficient larvae found that Dstac and Dmca1D are required for excitation-contraction coupling. Finally, Dstac appears to be required for normal expression levels of Dmca1D in body-wall muscles. These results suggest that Dstac regulates Dmca1D during EC coupling and thus muscle contraction.
Project description:Duchenne Muscular Dystrophy is a genetic disease caused by the lack of the protein dystrophin. Dystrophic muscles are highly susceptible to contraction-induced injury, and following contractile activity, have disrupted plasma membranes that allow leakage of calcium ions into muscle fibers. Because of the direct relationship between increased intracellular calcium concentration and muscle dysfunction, therapeutic outcomes may be achieved through the identification and restriction of calcium influx pathways. Our purpose was to determine the contribution of sarcolemmal lesions to the force deficits caused by contraction-induced injury in dystrophic skeletal muscles. Using isolated lumbrical muscles from dystrophic (mdx) mice, we demonstrate for the first time that poloxamer 188 (P188), a membrane-sealing poloxamer, is effective in reducing the force deficit in a whole mdx skeletal muscle. A reduction in force deficit was also observed in mdx muscles that were exposed to a calcium-free environment. These results, coupled with previous observations of calcium entry into mdx muscle fibers during a similar contraction protocol, support the interpretation that extracellular calcium enters through sarcolemmal lesions and contributes to the force deficit observed in mdx muscles. The results provide a basis for potential therapeutic strategies directed at membrane stabilization of dystrophin-deficient skeletal muscle fibers.
Project description:Myeloid cells play a critical role in regulating muscle degeneration and regeneration. Thus, alterations with aging in the myeloid cell response to muscle damage may affect the progression of the injury in old animals. We hypothesized that neutrophil levels remain elevated and that macrophage accumulation is reduced or delayed in injured muscles of old compared with young animals. Muscles of young and old mice were injured with lengthening contractions and analyzed 2 or 5 days later. Regardless of age, neutrophil (Gr-1+) and macrophage (CD68+) content increased dramatically by Day 2. Between 2 and 5 days, macrophages increased further, whereas neutrophils declined to a level that in old muscles was not different from uninjured controls. M2 macrophages (CD163+) also increased between 2 and 5 days, reaching higher levels in muscles of old mice than in young mice. Although no evidence of persisting neutrophils or reduced M2 accumulation in old muscle was found, total macrophage accumulation was lower in old mice. Furthermore, messenger RNA levels showed age-related changes in macrophage-associated genes that may indicate alterations in myeloid cell function. Overall, differences between muscles of old and young mice in the inflammatory response through the early stages of injury may contribute to defects in muscle regeneration.
Project description:Background:This study aimed to identify which maximum voluntary isometric contraction (MVIC) and sub-MVIC tests produce the highest activation of the erector spinae muscles and the greatest reduction in inter-individual variability, to put them forward as reference normalization maneuvers for future studies. Methods:Erector spinae EMG activity was recorded in 38 healthy women during five submaximal and three maximal exercises. Results:None of the three MVIC tests generated the maximal activation level in all the participants. The maximal activation level was achieved in 68.4% of cases with the test performed on the roman chair in the horizontal position (96.3 ± 7.3; p < 0.01). Of the five submaximal maneuvers, the one in the horizontal position on the roman chair produced the highest percentage of activation (61.1 ± 16.7; p < 0.01), and one of the lowest inter-individual variability values in the normalized signal of a trunk flexion-extension task. Conclusions:A modified Sorensen MVIC test in a horizontal position on a roman chair and against resistance produced the highest erector spinae activation, but not in 100% of participants, so the execution of several normalization maneuvers with the trunk at different inclinations should be considered to normalize the erector spinae EMG signal. A modified Sorensen test in a horizontal position without resistance is the submaximal maneuver that produces the highest muscle activation and the greatest reduction in inter-individual variability, and could be considered a good reference test for normalization.
Project description:ObjectiveInvoluntary isolated body movements are prominent in pre-term and full-term infants. Proprioceptive and tactile afferent feedback following limb muscle contractions is associated with somatotopic EEG responses. Involuntary contractions of respiratory muscles, primarily the diaphragm - hiccups - are also frequent throughout the human perinatal period during active behavioural states. Here we tested whether diaphragm contraction provides afferent input to the developing brain, as following limb muscle contraction.MethodsIn 13 infants on the neonatal ward (30-42 weeks corrected gestational age), we analysed EEG activity (18-electrode recordings in six subjects; 17-electrode recordings in five subjects; 16-electrode recordings in two subjects), time-locked to diaphragm contractions (n = 1316) recorded with a movement transducer affixed to the trunk.ResultsAll bouts of hiccups occurred during wakefulness or active sleep. Each diaphragm contraction evoked two initial event-related potentials with negativity predominantly across the central region, and a third event-related potential with positivity maximal across the central region.ConclusionsInvoluntary contraction of the diaphragm can be encoded by the brain from as early as ten weeks prior to the average time of birth.SignificanceHiccups - frequently observed in neonates - can provide afferent input to developing sensory cortices in pre-term and full-term infants.
Project description:Numerous studies have suggested that the myofascial trigger points are responsible for most of the myofascial pain syndrome, so it seems reasonable that its destruction is a good therapeutic solution. The effectiveness of dry needling (DN) has been confirmed in muscles with myofascial trigger points, hypertonicity, and spasticity. The objective of this study is to analyze the need of repetitive punctures on muscles in different situations. The levator auris longus (LAL) muscle and gastrocnemius muscle from adult male Swiss mice were dissected and maintained alive, while being submerged in an oxygenated Ringer's solution. DN was evaluated under four animal models, mimicking the human condition: normal healthy muscles, muscle fibers with contraction knots, muscles submerged in a depolarizing Ringer solution (KCl-CaCl2), and muscles submerged in Ringer solution with formalin. Thereafter, samples were evaluated with optical microscopy (LAL) and scanning electron microscopy (gastrocnemius). Healthy muscles allowed the penetration of needles between fibers with minimal injuries. In muscles with contraction knots, the needle separated many muscle fibers, and several others were injured, while blood vessels and intramuscular nerves were mostly not injured. Muscles submerged in a depolarizing solution inducing sustained contraction showed more injured muscular fibers and several muscle fibers separated by the needle. Finally, the muscles submerged in Ringer solution with formalin showed a few number of injured muscular fibers and abundant muscle fibers separated by the needle. Scanning electron microscopy images confirm the optical analyses. In summary, dry needling is a technique that causes mild injury irrespective of the muscle tone.