Gross Motor Coordination: We Have a Problem! A Study With the Körperkoordinations Test für Kinder in Youth (6–13 Years)

The main goal of our cross-sectional research was to determine the current values of gross motor coordination (GMC) of Italian boys and girls between 6 and 13 years of age. Secondary goals were to study gender differences, and the four subtests trend with ages. Results were compared with the references proposed by KTK authors and with similar searches. Anthropometric measurements and KTK data from 2,206 schoolchildren (girls: n = 1,050; boys: n = 1,156) were collected. The KTK raw score (RS) increased with the age of the subjects (r = 0.678; p < 0.001). In 11–13-year-old subjects, the increase in results is less than in younger subjects. RS showed differences by gender (F = 5.899; p = 0.015) and age (F = 269.193; p < 0.001) without interaction gender × age. Motor quotient (MQ) tended to decrease with age (r = −0.148; p < 0.001); it showed differences by gender (F = 79.228; p < 0.001), age (F = 14.217; p < 0.001), and an interaction gender × age (F = 2.249; p < 0.05). Boys showed better performance than did girls in the raw scores of three of four subtests (JS: F = 24.529; MS: F = 9.052; HH: F = 11.105). Girls show better performances than did boys in the WB (F = 14.52). Differences between genders make us believe it appropriate to maintain a differentiated standardization. RS increased with age, and it seems reasonable, therefore, to maintain a GMC age-based normalization. On the contrary, MQ tended to decrease. All this makes us speculate that today's young people accumulate less significant motor experiences over the years compared to those achieved by their peers in the 1970s. Italian data were lower than German references and Belgian results but slightly higher than the Brazilian ones. The comparison among these four searches confirmed a worrying downward trend in GMC and its characterization by geographical and sociocultural areas. Updated parameters of the KTK can provide helpful references to improve policies to support physical activity, sport, and physical education in youth.

Investigating the analgesic properties of Kurkinorin, a novel mu-opioid receptor analogue of Salvinorin A

<p>Background: The mu-opioid receptor (MOPr) activating drugs such as morphine, fentanyl, etorphine and methadone are used to treat moderate to severe pain. However, their long-term use produces serious adverse effects such as respiratory depression, sedation, tolerance, nausea, dependence, and constipation and this signifies the search for an alternate pain therapeutic agent. Here we report the investigation of antinociceptive and side effect profiles of a structurally unique MOPr-activating drug, kurkinorin from Salvinorin A (Sal A) that was compared with morphine and herkinorin. Methods: Adult male B6-SJL mice (22-29 g) were used to investigate the antinociceptive effects of kurkinorin, herkinorin and morphine utilising the 50° C warm-water tail-withdrawal assay. The 2% intra-dermal formalin assay was used to evaluate acute nociceptive and inflammatory pain and paw oedema. The side effect profiles were evaluated by measuring core-body temperature and utilising behavioural tests of motor co-ordination (accelerating rotarod test). Kurkinorin’s rewarding properties were assessed using the conditioned place preference (CPP) assay in male Sprague-Dawley rats (240-350 g). Results: Kurkinorin produced significant antinociceptive effects in the tail-withdrawal assay at both 5 (p<0.01, 10 min, p<0.001, 15-60 min) and 10 mg/kg (p<0.001, 5-90 min, p<0.01, 120 min) and attenuated both nociceptive and inflammatory pain in the 2% intra-dermal formalin model in mice. The analgesic effects of kurkinorin at 10 mg/kg were similar to the analgesic effects of morphine at the same dose. The decrease in pain score in the intra-dermal formalin assay with kurkinorin and morphine produced a corresponding reduction of paw oedema. In comparison, herkinorin had reduced analgesic effects in the tail-withdrawal assay (10 mg/kg, p<0.05, 30 min) and attenuated inflammatory pain in the intra-dermal formalin assay (10 mg/kg, p<0.001) with reduced paw oedema (10 mg/kg, p<0.05). Morphine produced significant motor incoordination effects from 15-60 min post injection whereas kurkinorin produced no significant motor impairment. Kurkinorin and herkinorin (5 mg/kg, i.p) did not produce rewarding effects, whereas morphine produced a significant, rewarding effect in the CPP assay. Kurkinorin produced no change in the core body temperature while morphine significantly reduced the body temperature. Conclusions: Kurkinorin is central acting and is as potent as morphine in attenuating acute nociceptive and inflammatory pain. It produced no significant sedative and rewarding effects. Therefore, kurkinorin has been identified as a structurally new class of mu-opioid analgesic, displaying improvements compared to morphine.</p>

Investigating the analgesic properties of Kurkinorin, a novel mu-opioid receptor analogue of Salvinorin A

<p>Background: The mu-opioid receptor (MOPr) activating drugs such as morphine, fentanyl, etorphine and methadone are used to treat moderate to severe pain. However, their long-term use produces serious adverse effects such as respiratory depression, sedation, tolerance, nausea, dependence, and constipation and this signifies the search for an alternate pain therapeutic agent. Here we report the investigation of antinociceptive and side effect profiles of a structurally unique MOPr-activating drug, kurkinorin from Salvinorin A (Sal A) that was compared with morphine and herkinorin. Methods: Adult male B6-SJL mice (22-29 g) were used to investigate the antinociceptive effects of kurkinorin, herkinorin and morphine utilising the 50° C warm-water tail-withdrawal assay. The 2% intra-dermal formalin assay was used to evaluate acute nociceptive and inflammatory pain and paw oedema. The side effect profiles were evaluated by measuring core-body temperature and utilising behavioural tests of motor co-ordination (accelerating rotarod test). Kurkinorin’s rewarding properties were assessed using the conditioned place preference (CPP) assay in male Sprague-Dawley rats (240-350 g). Results: Kurkinorin produced significant antinociceptive effects in the tail-withdrawal assay at both 5 (p<0.01, 10 min, p<0.001, 15-60 min) and 10 mg/kg (p<0.001, 5-90 min, p<0.01, 120 min) and attenuated both nociceptive and inflammatory pain in the 2% intra-dermal formalin model in mice. The analgesic effects of kurkinorin at 10 mg/kg were similar to the analgesic effects of morphine at the same dose. The decrease in pain score in the intra-dermal formalin assay with kurkinorin and morphine produced a corresponding reduction of paw oedema. In comparison, herkinorin had reduced analgesic effects in the tail-withdrawal assay (10 mg/kg, p<0.05, 30 min) and attenuated inflammatory pain in the intra-dermal formalin assay (10 mg/kg, p<0.001) with reduced paw oedema (10 mg/kg, p<0.05). Morphine produced significant motor incoordination effects from 15-60 min post injection whereas kurkinorin produced no significant motor impairment. Kurkinorin and herkinorin (5 mg/kg, i.p) did not produce rewarding effects, whereas morphine produced a significant, rewarding effect in the CPP assay. Kurkinorin produced no change in the core body temperature while morphine significantly reduced the body temperature. Conclusions: Kurkinorin is central acting and is as potent as morphine in attenuating acute nociceptive and inflammatory pain. It produced no significant sedative and rewarding effects. Therefore, kurkinorin has been identified as a structurally new class of mu-opioid analgesic, displaying improvements compared to morphine.</p>

Clinical Outcome in Cerebral Vasospasm Patients Treated with and without Intra-Arterial Nimodipine Infusion

Background Cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage (aSAH) is still a problem. Hypertension, hypervolemia, and hemodilution (triple-H) therapy and oral nimodipine only a modest effect on patients. Intra-arterial treatment, including nimodipine, has been studied, but only as retrospective and single-arm prospective studies. We compared the outcomes between CV patients who received an adjunct intra-arterial nimodipine infusion (IANI) and those who received the standard medical treatment alone in a prospective randomized controlled trial. Methods In this study, patients between the age of 18 and 80 years, who underwent angiography within 14 days after aneurysm obliteration, were recruited and randomized to receive adjunct IANI or not, if they were identified with angiographic vasospasm. All the angiographic and neurologic data were recorded and analyzed during their admission, at the discharge date, and during the 6-month follow-up period. Results From June 2016 to December 2018, we enrolled 68 patients who were randomized into two groups, 36 in the intervention group and 32 in the control group. The patients' characteristics, aneurysm data, and modalities of treatment were similar between the two groups. Within 24 hours after IANI, Glasgow Coma Scale (GCS) score and motor strength revealed a significant improvement of 33.33 and 38.89%, respectively, in the intervention group versus 12.5 and 9.38%, respectively, in the control group. At discharge, the intervention group still had significant motor improvement (58.33 vs. 21.88%; p = 0.002). Conclusion IANI could be considered an effective treatment for CV without significant complications. This is the first RCT demonstrating statistically significant motor strength improvement within 24 hours and at discharge.

Effects of Force Modulation on Large Muscles during Human Cycling

Voluntary force modulation is defined as the ability to tune the application of force during motion. However, the mechanisms behind this modulation are not yet fully understood. In this study, we examine muscle activity under various resistance levels at a fixed cycling speed. The main goal of this research is to identify significant changes in muscle activation related to the real-time tuning of muscle force. This work revealed significant motor adaptations of the main muscles utilized in cycling as well as positive associations between the force level and the temporal and spatial inter-cycle stability in the distribution of sEMG activity. From these results, relevant biomarkers of motor adaptation could be extracted for application in clinical rehabilitation to increase the efficacy of physical therapy.

Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities

BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. METHODS: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. RESULTS: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. CONCLUSION: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.

Immunization with neural-derived peptides as a neuroprotective therapy for spinal cord injury

Spinal cord injury (SCI) induces several destructive events that develop immediately after the primary insult. These phenomena increase tissue damage; that is why, numerous therapeutic approaches are studied in order to neutralize these destructive mechanisms. In line with this, several studies indicate that after injury, neural tissue could be protected by an adaptive immune response directed against self-antigens. Immunization with neural-derived peptides (INDP) reduces secondary degeneration of neurons after spinal cord insult and promotes a significant motor recovery. The combination of antioxidants or other immunomodulatory peptides after SCI can improve the protective effect induced by INDP. INDP in acute SCI is a promising strategy, so further studies should be addressed to be able to formulate the best strategy.

Predicting Clinically Significant Improvement After Robot-Assisted Upper Limb Rehabilitation in Subacute and Chronic Stroke

Prior studies examining predictors of favorable clinical outcomes after upper limb robot-assisted therapy (RT) have many shortcomings. Therefore, the aim of this study was to identify meaningful predictors and a prediction model for clinically significant motor improvement in upper limb impairment after RT for each stroke phase. This retrospective, single-center study enrolled patients with stroke who received RT using InMotion2 along with conventional therapy (CT) from January 2015 to September 2019. Demographic characteristics, clinical measures, and robotic kinematic measures were evaluated. The primary outcome measure was the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and we classified patients with improvement more than the minimal clinically important difference as responders for each stroke phase. Univariable and multivariable logistic regression analyses were performed to assess the relationship between potential predictors and RT responders and determine meaningful predictors. Subsequently, meaningful predictors were included in the final prediction model. One hundred forty-four patients were enrolled. The Hand Movement Scale and time since onset were significant predictors of clinically significant improvement in upper limb impairment (P = 0.045 and 0.043, respectively), as represented by the FMA-UE score after RT along with CT, in patients with subacute stroke. These variables were also meaningful predictors with borderline statistical significance in patients with chronic stroke (P = 0.076 and 0.066, respectively). Better hand movement and a shorter time since onset can be used as realistic predictors of clinically significant motor improvement in upper limb impairment after RT with InMotion2 alongside CT in patients with subacute and chronic stroke. This information may help healthcare professionals discern optimal patients for RT and accurately inform patients and caregivers about outcomes of RT.

TDP-43 maximizes nerve conduction velocity by repressing a cryptic exon for paranodal junction assembly in Schwann cells

TDP-43 is extensively studied in neurons in physiological and pathological contexts. However, emerging evidence indicates that glial cells are also reliant on TDP-43 function. We demonstrate that deletion of TDP-43 in Schwann cells results in a dramatic delay in peripheral nerve conduction causing significant motor deficits in mice, which is directly attributed to the absence of paranodal axoglial junctions. By contrast, paranodes in the central nervous system are unaltered in oligodendrocytes lacking TDP-43. Mechanistically, TDP-43 binds directly to Neurofascin mRNA, encoding the cell adhesion molecule essential for paranode assembly and maintenance. Loss of TDP-43 triggers the retention of a previously unidentified cryptic exon, which targets Neurofascin mRNA for nonsense-mediated decay. Thus, TDP-43 is required for neurofascin expression, proper assembly and maintenance of paranodes, and rapid saltatory conduction. Our findings provide a framework and mechanism for how Schwann cell-autonomous dysfunction in nerve conduction is directly caused by TDP-43 loss-of-function.

Progression of Motor and Non-Motor Symptoms in Multiple System Atrophy: A Prospective Study from the Catalan-MSA Registry

Background/Objective: Multiple system atrophy (MSA) is a highly debilitating, rare neurodegenerative disorder with two clinical motor variants (parkinsonian or MSA-P and cerebellar or MSA-C). There is a wide span of motor and non-motor symptoms (NMS) that progress over time. We studied the cohort from the Catalan Multiple System Atrophy Registry (CMSAR) to determine which symptoms are most likely to progress throughout a 2-year follow-up. Methods: We analyzed baseline, 12-month, and 24-month follow-up evaluations from the 80 cases recruited by the CMSAR. Evaluations included the UMSARS assessment, cognitive and neuropsychiatric evaluations, and a non-motor scale (NMSS-PD). Statistical analysis was done using a Generalized Estimated Equations (GEE) model. Results: Both UMSARS I and II sub-scores significantly increased at 12- and 24-month follow-ups (p < 0.001), with a median total score increase of 11 and 12.5 points, respectively. Items on UMSARS I that significantly worsened were mostly motor affecting daily activities. NMS, including urinary and sexual dysfunction, as well as sleep difficulties showed a significant progression on the NMSS-PD; however, other NMS such as postural hypotension, gastrointestinal, and mood dysfunction, although prevalent, did not show a clear progression on clinical scales. Conclusion: Within 24 months and as early as 12 months, MSA cases may experience significant motor worsening, affecting basic daily activities. NMS are prevalent; however, not all clinical scales register a clear progression of symptoms, perhaps suggesting that they are not sensitive enough for non-motor evaluation.