Facilitation of sensory transmission to motoneurons during cortical or sensory-evoked primary afferent depolarization (PAD) in humans.

Sensory and corticospinal tract (CST) pathways activate spinal GABAergic interneurons that have axoaxonic connections onto proprioceptive (Ia) afferents that cause long-lasting depolarizations (termed primary afferent depolarization, PAD). In rodents, sensory-evoked PAD is produced by GABAA receptors at nodes of Ranvier in Ia afferents, rather than at presynaptic terminals, and facilitates spike propagation to motoneurons by preventing branch-point failures, rather than causing presynaptic inhibition. We examined in 40 human participants whether putative activation of Ia-PAD by sensory or CST pathways can also facilitate Ia afferent activation of motoneurons via the H-reflex. H-reflexes in several leg muscles were facilitated by prior conditioning from low-threshold proprioceptive, cutaneous or CST pathways, with a similar long-lasting time course (∼200 ms) to phasic PAD measured in rodent Ia afferents. Long trains of cutaneous or proprioceptive afferent conditioning produced longer-lasting facilitation of the H-reflex for up to 2 min, consistent with tonic PAD in rodent Ia afferents mediated by nodal α5-GABAA receptors for similar stimulation trains. Facilitation of H-reflexes by this conditioning was likely not mediated by direct facilitation of the motoneurons because isolated stimulation of sensory or CST pathways did not alone facilitate the tonic firing rate of motor units. Furthermore, cutaneous conditioning increased the firing probability of single motor units (motoneurons) during the H-reflex without increasing their firing rate at this time, indicating that the underlying excitatory postsynaptic potential was more probable, but not larger. These results are consistent with sensory and CST pathways activating nodal GABAA receptors that reduce intermittent failure of action potentials propagating into Ia afferent branches. KEY POINTS: Controlled execution of posture and movement requires continually adjusted feedback from peripheral sensory pathways, especially those that carry proprioceptive information about body position, movement and effort. It was previously thought that the flow of proprioceptive feedback from Ia afferents was only reduced by GABAergic neurons in the spinal cord that sent axoaxonic projections to the terminal endings of sensory axons (termed GABAaxo neurons). Based on new findings in rodents, we provide complementary evidence in humans to suggest that sensory and corticospinal pathways known to activate GABAaxo neurons that project to dorsal parts of the Ia afferent also increase the flow of proprioceptive feedback to motoneurons in the spinal cord. These findings support a new role for spinal GABAaxo neurons in facilitating afferent feedback to the spinal cord during voluntary or reflexive movements.

MAFLD considerations as a part of the global hepatitis C elimination effort: an international perspective.

BACKGROUND: The World Health Organization (WHO) set a goal to eliminate hepatitis C (HCV) infection globally by 2030, with specific targets to reduce new viral hepatitis infections by 80% and reduce related deaths by 65%. However, an overlooked aspect that may hinder these efforts is the impact other liver diseases could have by continuing to drive liver disease progression and offset the beneficial impact of DAAs on end-stage liver disease and hepatocellular carcinoma (HCC). In particular, the decrease in HCV prevalence has been countered by a marked increase in the prevalence of metabolic-associated fatty liver disease (MAFLD). AIMS: To review the potential interaction of HCV and MAFLD. METHODS: We have reviewed the literature relating to an arrange of interaction of HCV, metabolic dysfunction and MAFLD. RESULTS: In this viewpoint, international experts suggest a holistic and multidisciplinary approach for the management of the growing number of treated HCV patients who achieved SVR, taking into consideration the overlooked impact of MAFLD for reducing morbidity and mortality in people who have had HCV. CONCLUSIONS: This will strengthen and improve the continuum of care cascade for patients with liver disease(s) and holds the potential to alleviate the cost burden of disease; and increase quality of life for patients following DAAs treatment.

High-density EMG E-textile systems for the control of active prostheses.

Myoelectric control of active prostheses requires electrode systems that are easy to apply for daily repositioning of the electrodes by the user. In this study we propose the use of Smart Fabric and Interactive Textile (SFIT) systems as an alternative solution for recording high-density EMG signals for myoelectric control. A sleeve covering the upper and lower arm, which contains 100 electrodes arranged in four grids of 5 × 5 electrodes, was used to record EMG signals in 3 subjects during the execution of 9 tasks of the wrist and hand. The signals were analyzed by extracting wavelet coefficients which were classified with linear discriminant analysis. The average classification accuracy for the nine tasks was 89.1 ± 1.9 %. These results show that SFIT systems can be used as an effective way for muscle-machine interfacing.