Search Results (125)

Peripheral and autonomic neuropathy are common in type 2 diabetes; they are associated with oxidative stress and inflammation. Cocoa, rich in polyphenols, may offer neuroprotective benefits. This study evaluated the effect of cocoa supplementation on the biochemical, clinical, and somatosensory profile of neuropathy in individuals with type 2 diabetes. A 12-week, double-blind controlled trial involved 39 subjects randomized to receive cocoa capsules (50 mg polyphenols) or placebo (methylcellulose). Evaluations included glycemic and lipid profiles, neutrophil/lymphocyte ratio, blood pressure, standardized questionnaires, anthropometric measurements, and the rate-dependent depression of the H-reflex. In the cocoa group, the Toronto score decreased by 2.63 points and the BEST score decreased by 1.45 points. In the placebo group, these reductions were 1.84 and 2.21 points, respectively. Neither difference was statistically significant between groups (p > 0.05). Quality-of-Life questionnaire score decreased by 9.2 points in the cocoa group, but without significant difference to the placebo group (p = 0.501). Fasting glucose and HbA1c levels decreased in the placebo group by 38 mg/dL (0.28%) but were not significantly different from the cocoa group (p > 0.05). No other intra- or inter-group differences were significant (p > 0.05). Cocoa supplementation did not show significant improvements over the placebo in the measured outcomes. Both groups showed persistent abnormalities in spinal somatosensory processing, with an RDD of the H-reflex ≥ 0.5. Full article

Since the monotonicity of the best approximant is crucial to establish partial ordering methods, in this paper, we, respectively, characterize the best approximants in Banach function spaces and Lorentz spaces ${\mathrm{\Gamma }}_{p,w}$, in which we especially focus on the monotonicity characterizations. We first study monotonicity characterizations of the metric projection operator onto sublattices in general Banach function spaces by the property $H_g$. The sufficient and necessary conditions for monotonicity of the metric projection onto cones and sublattices are then, respectively, established in ${\mathrm{\Gamma }}_{p,w}$. The Lorentz spaces ${\mathrm{\Gamma }}_{p,w}$ are also shown to be reflexive under the condition $R{B}_p$, which is the basis for the existence of the best approximant. As applications, by establishing the partial ordering methods based on the obtained monotonicity characterizations, the solvability and approximation theorems for best proximity points are deduced without imposing any contractive and compact conditions in ${\mathrm{\Gamma }}_{p,w}$. Our results extend and improve many previous results in the field of the approximation and partial ordering theory. Full article

Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. Results: All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the IGHMBP2 gene, consistent with CMT2S. Other variants were identified in the NEFH (CMT2CC), DYNC1H1 (CMT2O), and MPV17 (CMT2EE) genes. Notably, a previously unreported co-occurrence of MPV17 mutation and congenital heart disease was observed in one case. Conclusions: This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel IGHMBP2 variant and unique phenotypic associations provides new insights for future genotype–phenotype correlation studies. Full article

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article

The carotid body (CB) senses arterial PO₂, PCO₂, and pH levels, eliciting reflex responses to maintain cardiorespiratory homeostasis. Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea, elicits autonomic and cardiorespiratory alterations that are attributed to an enhanced CB chemosensory responsiveness to hypoxia, which in turn activates neurons and glial cells in the nucleus of the tractus solitarius (NTS). Although the CB contribution to the CIH-induced pathological alterations is well-known, the underlying mechanisms are not fully understood. A growing body of new evidence suggests a crucial role for ROS in acute CB oxygen sensing, as well as in the potentiation of chemosensory discharge and the activation of the central chemoreflex pathway in CIH. Indeed, it has been proposed that acute hypoxia disrupts mitochondrial electron transport, increasing ROS and NADH in the chemoreceptor cells, which inhibit voltage-gated K⁺ channels, producing cell depolarization, Ca²⁺ entry, and release of excitatory transmitters. In addition, new evidence supports that the enhanced CB afferent discharge contributes to persistent CIH-induced cardiorespiratory alterations, likely triggering neuroinflammation in the NTS. Thus, in this review, we will examine the experimental evidence that supports the involvement of ROS in the acute O₂ sensing process, and their role in the enhanced CB chemosensory discharges, the glial-related inflammation in the NTS, and the cardiorespiratory alterations induced by CIH. Full article

We have previously shown that neuromodulatory actions on astrocytes can elicit metabotropic glutamate- and N-methyl-D-aspartate receptor-dependent tonic changes in excitability in the mesopontine region. Although in vitro experiments explored robust effects, the in vivo significance of our findings remained unknown. In this project, chronic chemogenetic activation of mesopontine astrocytes and its actions on movement, circadian activity, acoustic startle and spatial memory were tested. The control group of young adult male mice where mesopontine astrocytes expressed only the mCherry fluorescent tag was compared to the group expressing the hM3D(Gq) chemogenetic actuator. Chronic chemogenetic astrocyte activation reduced the amplitude of the acoustic startle reflex and increased the locomotion speed in the resting period. Gait alterations were also demonstrated but no change in the spatial memory was explored. As a potential background of these findings, chronic astrocytic activation decreased the cholinergic neuronal number to 54% and reduced the non-cholinergic neuronal number to 76% of the control. In conclusion, chronic astrocytic activation and the consequential decrease in the neuronal number led to disturbances in movement and circadian activity resembling brainstem-related symptoms of progressive supranuclear palsy, raising the possibility that astrocytic overactivation is involved in the pathogenesis of this disease. Full article

Background/Objectives: After spinal cord injury (SCI), poor dorsiflexor control and involuntary plantar-flexor contraction impair walking. As whole-body vibration (WBV) improves voluntary muscle activation and modulates reflex excitability, it may improve ankle control. In this study, the dosage effects of WBV on walking speed, dorsiflexion, and spinal reflex excitability were examined. Methods: Sixteen people with chronic motor-incomplete SCI participated in this randomized sham-control wash-in study. Two weeks of sham stimulation (wash-in phase) were followed by either 2 weeks of eight repetitions (short bout) or sixteen repetitions of WBV (long bout; intervention phase) per session. Walking speed, ankle angle at mid-swing, and low-frequency depression of the soleus H-reflex were measured before and after the wash-in phase and before and after the intervention phase. Results: A significant dosage effect of WBV was not observed on any of the measures of interest. There were no between-phase or within-phase differences in ankle angle during the swing phase or in low-frequency depression. When dosage groups were pooled together, there was a significant change in walking speed during the intervention phase (mean = 0.04 m/s, standard deviation = 0.06, p = 0.02). There was not a significant correlation between overall change in walking speed and dorsiflexion angle or low-frequency depression during the study. Conclusions: Whole-body vibration did not have a dosage-dependent effect on dorsiflexion during the swing phase or on spinal reflex excitability. Future studies assessing the role of corticospinal tract (CST) descending drive on increased dorsiflexor ability and walking speed are warranted. Full article

Background/Objectives: Sepsis has been shown to depress arterial baroreceptor function, and this effect is counterbalanced by the cholinergic anti-inflammatory pathway. Considering the importance of central adenosine receptors in baroreceptor function, this study tested whether central adenosine A3 receptors (A3ARs) modulate the cholinergic-baroreflex interaction in sepsis and whether this interaction is modulated by mitogen-activated protein kinases (MAPKs) and related proinflammatory cytokines. Methods: Sepsis was induced by cecal ligation and puncture (CLP) and rats were instrumented with femoral and intracisternal (i.c.) catheters. Baroreflex sensitivity (BRS) was measured 24 h later in conscious animals using the vasoactive method, which correlates changes in blood pressure caused by i.v. phenylephrine (PE) and sodium nitroprusside (SNP) to concomitant reciprocal changes in heart rate. Results: The reduction in reflex bradycardic (BRS-PE), but not tachycardic (BRS-SNP), responses elicited by CLP was reversed by i.v. nicotine in a dose-related manner. The BRS-PE effect of nicotine was blunted following intracisternal administration of IB-MECA (A3AR agonist, 4 µg/rat). The depressant action of IB-MECA on the BRS facilitatory action of nicotine was abrogated following central inhibition of MAPK-JNK (SP 600125), PI3K (wortmannin), and TNFα (infliximab), but not MAPK-ERK (PD 98059). Additionally, the nicotine suppression of sepsis-induced upregulation of NFκB and NOX2 expression in the nucleus tractus solitarius (NTS) was negated by A3AR activation. The molecular effect of IB-MECA on NFκB expression disappeared in the presence of SP 600125, wortmannin, or infliximab. Conclusions: The central PI3K/MAPK-JNK/TNFα pathway contributes to the restraining action of A3ARs on cholinergic amelioration of sepsis-induced central neuroinflammatory responses and impairment of the baroreceptor-mediated negative chronotropism. Full article

Introduction: Implanted spinal cord epidural stimulation (SCES) is an emerging neuromodulation approach that increases the excitability of the central pattern generator [CPG] and enhances tonic and rhythmic motor patterns after spinal cord injury (SCI). We determine the effects of exoskeleton-assisted walking [EAW] + epidural stimulation [ES] + resistance training [RT] on volitional motor control as a primary outcome, as well as autonomic cardiovascular profile, body composition, and bladder function compared to EAW + delayed ES + noRT in persons with motor-complete SCI AIS A and B. Methods and Analysis: Twenty male and female participants [age 18–60 years] with traumatic motor-complete SCI [2 years or more post injury], and level of injury below C5 were randomized into either EAW + ES + RT or EAW + delayed-ES + no-RT groups for more than 12 months. Baseline, post-interventions 1 and 2 were conducted six months apart. Measurements included body composition assessment using anthropometry, dual x-ray absorptiometry, and magnetic resonance imaging prior to implantation to evaluate the extent of spinal cord damage, neurophysiologic assessments to record H-reflexes, overground ambulation and peak torque for both groups, and the Walking Index for Spinal Cord Injury Scale [WISCI 2]. Metabolic profile measurements included the resting metabolic rate, fasting biomarkers of HbA1c, lipid panels, total testosterone CRP, IL-6, TNF-α, plasma IGF-I, IGFBP-3, and then a glucose tolerance test. Finally, urodynamic testing was conducted to assess functional bladder improvement due to ES. Results: The restoration of locomotion with ES and EAW may result in a reduction in psychosocial, cardiovascular, and metabolic bladder parameters and socioeconomic burden. The addition of the resistance training paradigm may further augment the outcomes of ES on motor function in persons with SCI. Conclusions: Percutaneous SCES appears to be a feasible and safe rehabilitation approach for the restoration of motor function in persons with SCI. The procedure may be successfully implemented with other task-specific training similar to EAW and resistance training. Full article

Background: Ophioglossum vulgatum Linn. is a medical herb widely distributed in Southwest China. It has been used for the treatment of various diseases, including wounds or dermatitis, since ancient times, but little is known about its pharmacological and pharmaceutical chemistry. Methods: The ethyl acetate fraction of O. vulgatum (OpvE) was prepared with the reflex extraction and fractional extraction method. Its components were detected and identified with the UPLC-Q/TOF-MS system and the SCIEX OS database. The related biological activities and the underlying mechanisms were predicted by computational analysis. HaCaT cells were treated with gradient concentrations of OpvE, and a CCK-8 assay was performed to determine the cell viability. The OpvE-pretreated HaCaT cells were exposed to H₂O₂ or LPS for antioxidative and anti-inflammatory assessment. DPPH, GSH, SOD, and MDA kits were used to evaluate oxidative stress. A serially diluted microbiota assay and a disc diffusion assay were used to evaluate anti-Staphylococcus aureus activities. The transcription of genes was semi-quantitatively studied by reversed real-time PCR. Protein levels were determined with western blotting. Results: The extract ratio of OpvE was 2.00 ± 0.12% (g/g). A total of 21 ingredients were identified. The computational analysis found that the PI3K/Akt signaling pathway might be a crucial target of OpvE. OpvE (7.5~125 μg/mL) stimulated HaCaT cell proliferation and migration by stimulating the over-expressed collagen type I alpha 1 Chain (COL1A1) and fibronectin 1 (FN1) and upregulating PI3K/AKT/GSK3-β signaling pathway. In the antioxidative assay test, 250 μg/mL OpvE scavenged obvious 97.28% DPPH-released free radicals. Pretreatment of OpvE inhibited H₂O₂-induced oxidative stress and protected against LPS-induced inflammatory injury by respectively regulating the Nrf2/HO-1/COX2 and TLR4/MYD88 signaling pathways. OpvE also showed anti-S. aureus properties with a MIC of 1.2 mg/mL, and with this concentration, OpvE produced an 8.3 ± 0.16 mm inhibition zone on a bacterial plate. Conclusions: This work highlighted the phytochemical character and some bioactivities, as well as the underline mechanism, which would support the further studies and application of O. vulgatum Linn. Full article

Background: Reciprocal inhibition (RI) is a spinal reflex that controls posture and movement. The modulation of spinal RI represented by the H-reflex has been studied, before and after voluntary contraction and electrical nerve stimulation but not during voluntary, electrically induced muscle contraction or a combination of voluntary and electrically induced muscle contractions. This study investigates the effects of the ongoing voluntary isometric contraction, the electrically induced isometric contraction, and the combination of voluntary with electrically induced isometric contraction of the Tibialis Anterior (TA) muscle on spinal RI represented by Soleus H-reflex. Methods: Eighteen healthy adults participated. Soleus H-reflex and M-response were measured during four different conditions as follows: (1) at rest, (2) electrically induced isometric contraction of the TA, (3) voluntary isometric contraction of the TA with a 1 kg force, and (4) combined voluntary and electrically induced isometric contraction of the TA with a 1 kg force. Results: The ANOVA clearly demonstrated significant differences in Soleus H-reflex amplitude across the four recording conditions (F3,16, 17.28, p < 0.001). The amplitude at rest was significantly higher than during electrically induced isometric contraction, voluntary isometric contraction, and the combined contraction conditions (p < 0.05). Furthermore, the amplitude recorded during the electrically induced isometric contraction condition significantly surpassed that of voluntary isometric contraction and the combined contraction conditions (p < 0.05). Moreover, there was no significant difference between Soleus H-reflex amplitude recorded during voluntary isometric contraction and the combined voluntary isometric contraction and electrically induced isometric contraction (p < 0.87). The combined voluntary isometric contraction and electrically induced isometric contraction condition had a higher inhibitory effect on the Soleus H-reflex with no significant differences from voluntary isometric contraction. Moreover, both were significantly better than electrically induced isometric contraction (p = 0.05). In terms of Soleus H-reflex latency, there was no significant difference among all four conditions (p > 0.05), meaning Soleus H-reflex latency was not influenced by the conditions. Conclusions: RI can be best modulated by combining voluntary with electrically induced isometric muscle contractions. Full article

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions. Full article

Background/Objectives: Chronic fatigue syndrome and post-COVID-19 syndrome are associated with dysfunction of the autonomic nervous system, which may manifest as syncope and orthostatic intolerance. This study aimed to compare autonomic nervous system function in patients with chronic fatigue syndrome of unknown etiology and those with chronic fatigue syndrome secondary to post-COVID-19 syndrome using multiple diagnostic modalities, and to assess the prevalence and characteristics of syncope in these populations. Methods: This cross-sectional study included 440 patients examined at the Neurocardiological Laboratory of the Institute for Cardiovascular Diseases “Dedinje”. Patients were divided into three groups: chronic fatigue syndrome of unknown etiology (Group 1, n = 210), chronic fatigue syndrome secondary to post-COVID-19 syndrome (Group 2, n = 137), and healthy controls (Group 3, n = 91). Diagnostic modalities included cardiovascular reflex tests, the head-up tilt test, beat-to-beat analysis, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses were performed using analysis of variance, Tukey’s honestly significant difference test, and the Mann–Whitney U test. Results: Both chronic fatigue syndrome groups demonstrated significant autonomic nervous system dysfunction compared to healthy controls (p < 0.05), including reduced baroreceptor sensitivity and impaired heart rate variability parameters. Syncope prevalence was high in both chronic fatigue syndrome groups, with extreme blood pressure variability observed in 45–47% of patients during the head-up tilt test. Patients with post-COVID-19 chronic fatigue syndrome exhibited greater blood pressure increases during the head-up tilt test than those with chronic fatigue syndrome of unknown etiology (p < 0.05). Conclusions: Patients with chronic fatigue syndrome, irrespective of etiology, exhibit significant autonomic nervous system dysfunction and a high prevalence of syncope. Post-COVID-19 chronic fatigue syndrome demonstrates distinct hemodynamic patterns, suggesting unique pathophysiological mechanisms that warrant further investigation. Full article

Background: The vestibular postural control system affects standing stability on an unstable surface. However, it is unclear whether maintaining a standing position on different surfaces alters lateral vestibulospinal tract (LVST) excitability and body control responses following vestibular stimulation. This study aimed to investigate the relationship between the soleus H-reflex following galvanic vestibular stimulation (GVSH), a measure of LVST, and post-stimulus body movement responses while standing with eyes closed on different surfaces. Methods: Twelve healthy volunteers (mean age 20.4 ± 0.5 years, 7 females) performed eyes-closed standing GVSH on firm and foam surfaces. Body control responses in each condition were evaluated using an inertial measurement unit to monitor neck and pelvic movements, along with surface electromyography to assess muscle activity in the tibialis anterior and soleus muscles. Body responses to the GVS were averaged over up to a second after tibial nerve stimulation. Results: We observed a significant negative correlation between the H-wave amplitude of the GVSH on the firm surface and the tibialis anterior muscle activity following stimulation (r = −0.666, p = 0.018). No significant differences were observed during the eyes-closed standing GVSH on either firm or foam surfaces (p = 0.568). Conclusions: Postural maintenance in response to vestibular stimulation may contribute to body stability by regulating tibialis anterior muscle contraction via the LVST. Our findings may help elucidate the neural activity of vestibular function-related standing postural control responses. Full article

Background/Objectives: Acute lateral ankle sprain (ALAS) affects balance, often assessed by changes in traditional center of pressure (COP) parameters. Spatiotemporal measures of COP and time-to-boundary (TTB) analysis may offer improved sensitivity in detecting postural deviations associated with ALAS. However, the neurophysiological mechanism underlying these changes remains unknown. This study aimed to explore the effects of ALAS on spinal reflex excitability in the fibularis longus (FL) during single-leg balance and TTB parameters following ALAS. Methods: Fourteen participants with and without ALAS were recruited within 14 days from the onset of the injury. We assessed FL spinal reflex excitability and postural control during a single-leg stance. The primary outcomes included the H/M ratio, H-latency, and TTB parameters. For H-reflex testing, the peripheral electrical stimulation was delivered at the sciatic nerve before bifurcating into the tibial and common fibular nerve while participants maintained a single-leg balance position with the involved side of the limb. The TTB parameters of the medial–lateral (ML) and anterior–posterior (AP) directions of the mean, SD, and minimum were assessed, which indicate postural correction and strategies. Results: Patients with ALAS had a significantly lower AP-TTB minimum compared with healthy uninjured controls, with a moderate effect size (p = 0.039; d = −0.83). However, there was no significant difference in the H/M ratio (ALAS: 0.29 ± 0.16 vs. CON: 0.24 ± 0.10; p = 0.258) and H-reflex latency (ALAS: 34.6 ± 1.92 vs. CON: 33.8 ± 1.75 ms; p = 0.277); Conclusions: These results indicate that reflex control at the spinal level may have a minimal role in response to balance deficits following ALAS. Full article