Effects of Cistanche tubulosa Wight Extract on Locomotive Syndrome: A Placebo-Controlled, Randomized, Double-Blind Study.

In an aging society, preventing dysfunction and restoring function of the locomotive organs are necessary for long-term quality of life. Few interventional studies have investigated supplementation for locomotive syndrome. Additionally, very few interventional clinical studies on locomotive syndrome have been performed as placebo-controlled, randomized, double-blind studies. We previously found that the administration of 30% ethanolic extract of Cistanche tubulosa improved walking ability in a cast-immobilized skeletal muscle atrophy mouse model. Therefore, we conducted a clinical study to evaluate the effects of C. tubulosa (CT) extract on the locomotive syndrome. Twenty-six subjects with pre-symptomatic or mild locomotive syndrome completed all tests and were analyzed in the study. Analyses of muscle mass and physical activity were performed based on the full analysis set. Intake of CT extract for 12 weeks increased step width (two-step test) and gait speed (5 m walking test) in patients over 60 years old compared with those in a placebo control (p = 0.046). In contrast, the skeletal muscle mass of the body trunk and limbs was unchanged following administration of CT extract. Adverse effects were evaluated by blood tests; no obvious adverse events were observed following the intake of CT extract. In conclusion, this placebo-controlled, randomized, double-blind study demonstrated that treatment with CT extract significantly prevented a decline in walking ability without any notable adverse effects in patients with locomotive syndrome.

Olfactory ensheathing cells seeded decellularized scaffold promotes axonal regeneration in spinal cord injury rats.

Spinal cord decellularized (DC) scaffolds can promote axonal regeneration and restore hindlimb motor function of spinal cord defect rats. However, scarring caused by damage to the astrocytes at the margin of injury can hinder axon regeneration. Olfactory ensheathing cells (OECs) integrate and migrate with astrocytes at the site of spinal cord injury, providing a bridge for axons to penetrate the scars and grow into lesion cores. The purpose of this study was to evaluate whether DC scaffolds carrying OECs could better promote axon growth. For these studies, DC scaffolds were cocultured with primary extracted and purified OECs. Immunofluorescence and electron microscopy were used for verification of cells adhere and growth on the scaffold. Scaffolds with OECs were transplanted into rat spinal cord defects to evaluate axon regeneration and functional recovery of hind limbs. Basso, Beattie, and Bresnahan (BBB) scoring was used to assess motor function recovery, and glial fibrillary acidic protein (GFAP) and NF200-stained tissue sections were used to evaluate axonal regeneration and astrological scar distribution. Our results indicated that spinal cord DC scaffolds have good histocompatibility and spatial structure, and can promote the proliferation of adherent OECs. In animal experiments, scaffolds carrying OECs have better axon regeneration promoting protein expression than the SCI model, and improve the proliferation and distribution of astrocytes at the site of injury. These results proved that the spinal cord DC scaffold with OECs can promote axon regeneration at the site of injury, providing a new basis for clinical application.

LL-00066471, a novel positive allosteric modulator of α7 nicotinic acetylcholine receptor ameliorates cognitive and sensorimotor gating deficits in animal models: Discovery and preclinical characterization.

α7 nicotinic acetylcholine receptor (α7 nAChR) is an extensively validated target for several neurological and psychiatric conditions namely, dementia and schizophrenia, owing to its vital roles in cognition and sensorimotor gating. Positive allosteric modulation (PAM) of α7 nAChR represents an innovative approach to amplify endogenous cholinergic signaling in a temporally restricted manner in learning and memory centers of brain. α7 nAChR PAMs are anticipated to side-step burgeoning issues observed with several clinical-stage orthosteric α7 nAChR agonists, related to selectivity, tolerance/tachyphylaxis, thus providing a novel dimension in therapeutic strategy and pharmacology of α7 nAChR ion-channel. Here we describe a novel α7 nAChR PAM, LL-00066471, which potently amplified agonist-induced Ca2+ fluxes in neuronal IMR-32 neuroblastoma cells in a α-bungarotoxin (α-BTX) sensitive manner. LL-00066471 showed excellent oral bioavailability across species (mouse, rat and dog), low clearance and good brain penetration (B/P ratio > 1). In vivo, LL-00066471 robustly attenuated cognitive deficits in both procognitive and antiamnesic paradigms of short-term episodic and recognition memory in novel object recognition task (NORT) and social recognition task (SRT), respectively. Additionally, LL-00066471 mitigated apomorphine-induced sensorimotor gating deficits in acoustic startle reflex (ASR) and enhanced antipsychotic efficacy of olanzapine in conditioned avoidance response (CAR) task. Further, LL-00066471 corrected redox-imbalances and reduced cortico-striatal infarcts in stroke model. These finding together suggest that LL-00066471 has potential to symptomatically alleviate cognitive deficits associated with dementias, attenuate sensorimotor gating deficits in schizophrenia and correct redox-imbalances in cerebrovascular disorders. Therefore, LL-00066471 presents potential for management of cognitive impairments associated with neurological and psychiatric conditions.

Transcranial magnetic stimulation and gait disturbances in Parkinson's disease: A systematic review.

Transcranial magnetic stimulation (TMS) may offer a reliable means of characterizing important pathophysiologic aspects of motor impairments in Parkinson's disease (PD). Moreover, high-frequency repetitive TMS (rTMS), especially if delivered bilaterally over motor cortical regions, can have beneficial effects on parkinsonian motor symptoms. However, only a few studies have investigated the effects of rTMS on freezing of gait (FOG) and other gait disturbances in PD. We aimed at investigating in this narrative review the usefulness of TMS for exploring the pathophysiology of gait impairment and at evaluating the therapeutic effects of rTMS in this context. The combination of rTMS and treadmill training was found to enhance the effect of physical therapy. Use of an H-coil enables stimulation of deep regions of the brain (for example medial prefrontal cortex) and may be used as a target for add-on therapy in the future. In contrast, theta burst stimulation has proven to be ineffective in treating gait disturbances in PD patients. Dual-mode NIBS, in particular preconditioning motor cortex rTMS by transcranial direct current stimulation, might also represent a novel therapeutic approach for patients with gait disturbances. Recent studies suggest that the supplementary motor area could be an appropriate target for brain stimulation when treating PD patients with FOG. Further large sample and well-designed clinical studies are required to evaluate how the possible positive effects of rTMS can be sustained over time and to determine the optimal stimulation protocols including target, stimulation intensity/duration and number of sessions.

Patient selected goals and satisfaction after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.

Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation.

Spinal cord injury (SCI) is the destruction of spinal cord motor and sensory resulted from an attack on the spinal cord, which can cause significant physiological damage. The inflammasome is a multiprotein oligomer resulting in inflammation; the NLRP3 inflammasome composed of NLRP3, apoptosis-associated speck-like protein (ASC), procaspase-1, and cleavage of procaspase-1 into caspase-1 initiates the inflammatory response. Subventricular Zone (SVZ) is the origin of neural stem/progenitor cells (NS/PCs) in the adult brain. Extracellular vesicles (EVs) are tiny lipid membrane bilayer vesicles secreted by different types of cells playing an important role in cell-cell communications. The aim of this study was to investigate the effect of intrathecal transplantation of EVs on the NLRP3 inflammasome formation in SCI rats. Male wistar rats were divided into three groups as following: laminectotomy group, SCI group, and EVs group. EVs was isolated from SVZ, and characterized by western blot and DLS, and then injected into the SCI rats. Real-time PCR and western blot were carried out for gene expression and protein level of NLRP3, ASC, and Caspase-1. H&E and cresyl violet staining were performed for histological analyses, as well as BBB test for motor function. The results indicated high level in mRNA and protein level in SCI group in comparison with laminectomy (p < 0.001), and injection of EVs showed a significant reduction in the mRNA and protein levels in EVs group compared to SCI (p < 0.001). H&E and cresyl violet staining showed recovery in neural cells of spinal cord tissue in EVs group in comparison with SCI group. BBB test showed the promotion of motor function in EVs group compared to SCI in 14 days (p < 0.05). We concluded that the injection of EVs could recover the motor function in rats with SCI and rescue the neural cells of spinal cord tissue by suppressing the formation of the NLRP3 inflammasome complex.

Kinematic comparison of the use of walking sticks versus a rolling walker during gait in adult degenerative scoliosis patients.

STUDY DESIGN: A repeated-measurement, single-center, prospective study. OBJECTIVE: To compare the spatiotemporal and kinematic data using gait analysis in adult degenerative scoliosis (ADS) patients using walking sticks (WS) versus rolling walkers (RW). ADS patients undergo compensatory changes that can result in an altered gait pattern. RW are frequently prescribed, but result in a forward flexed kyphotic posture during ambulation. Gait using WS allows for more upright alignment in ADS patients. METHODS: Fifty-three ADS patients with symptomatic degenerative scoliosis performed over-ground walking at self-selected speed with WS and with a RW. Trunk and lower extremity angles along with spatiotemporal parameters were measured and compared. RESULTS: When using WS, patients exhibited less flexion at the head (WS: - 4.8° vs. RW: 11.0°, p = 0.001), and lumbar spine (WS: - 0.9° vs. RW: 4.2°, p = 0.001); while there was significantly more extension, of the cervical spine (WS: - 1.6° vs. RW: - 7.4°, p = 0.002) when using the RW. At the initial contact phase of gait, patients using WS showed decreased flexion at the ankle (WS 0.7° vs. RW: 3.8°, p = 0.018), knee (WS: 0.3° vs. RW: 4.8°, p = 0.001), hip (WS: 22.6° vs. RW: 27.3°, p = 0.001), and pelvis (WS: 10.2° vs. RW: 14.8°, p = 0.001). In contrast, the use of WS resulted in slower ambulation (WS: 0.6 m/s vs. RW: 0.7 m/s, p = 0.001). CONCLUSIONS: In ADS patients who have not undergone surgical correction, the use of WS resulted in a more upright posture, which may be more beneficial to the compensatory changes that lead to gait disturbance in ADS patients. Ambulation using WS resulted in slower gait versus a RW, due to the momentum induced by the forward flexed posture when using a RW. We recommend the use of WS for patients with ADS as it improves gait kinematics and may be a safer option.

Neuroprotective role of taurine on MK-801-induced memory impairment and hyperlocomotion in zebrafish.

Schizophrenia is a neuropsychiatric condition that reaches around 1% of people worldwide. Because taurine exerts a neuroprotective role in the brain, this molecule is a promising candidate to reduce schizophrenia-like symptoms. Here, we investigated a possible neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion in zebrafish using the inhibitory avoidance task and the novel tank diving test, respectively. First, we assessed the influence of different MK-801 doses (0.1, 0.3, 0.5, 1 and 2 mg/kg, i.p.) on memory consolidation. Although all MK-801 doses tend to reduce the retention index, only 2 mg/kg MK-801 showed robust amnesic effects. Then, we evaluated whether taurine pretreatments (42, 150 and 400 mg/L for 60 min) prevent MK-801-induced cognitive impairment. Immediately after the training, animals were exposed to non-chlorinated water or taurine and subsequently challenged with 2 mg/kg MK-801, i.p. The test session was performed 24 h after training. Although taurine alone did not change memory retention when compared with control, taurine pretreatments prevented MK-801-induced memory deficit. Importantly, no locomotor changes were observed 24 h after the training session. In the novel tank diving test, MK-801 induced hyperlocomotion and disrupted vertical activity, while 400 mg/L taurine pretreatment prevented these effects. Overall, our novel findings indicate a neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion, reinforcing the growing utility of zebrafish models to investigate the beneficial effects of different compounds against glutamate excitotoxicity.

A botanical drug composed of three herbal materials attenuates the sensorimotor gating deficit and cognitive impairment induced by MK-801 in mice.

OBJECTIVES: A botanical drug derived from the ethanolic extract composed of Clematis chinensis Osbeck (Ranunculaceae), Trichosanthes kirilowii Maximowicz (Cucurbitaceae) and Prunella vulgaris Linné (Lamiaceae) has been used to ameliorate rheumatoid arthritis as an ethical drug in Korea. In our study, we investigated the effect of this herbal complex extract (HCE) on schizophrenia-like behaviours induced by MK-801. METHODS: HCE (30, 100 or 300 mg/kg, p.o) was orally administered to male ICR mice to a schizophrenia-like animal model induced by MK-801. We conducted an acoustic startle response task, an open-field task, a novel object recognition task and a social novelty preference task. KEY FINDINGS: We found that a single administration of HCE (100 or 300 mg/kg) ameliorated MK-801-induced abnormal behaviours including sensorimotor gating deficits and social or object recognition memory deficits. In addition, MK-801-induced increases in phosphorylated Akt and GSK-3ß expression levels in the prefrontal cortex were reversed by HCE (30, 100 or 300 mg/kg). CONCLUSIONS: These results imply that HCE ameliorates MK-801-induced dysfunctions in prepulse inhibition, social interactions and cognitive function, partly by regulating the Akt and GSK-3ß signalling pathways.

Danhong injection facilitates recovery of post-stroke motion deficit via Parkin-enhanced mitochondrial function.

BACKGROUND: A cerebral ischemic stroke involves mitochondrial dysfunction, motor deficits, and paralysis; and Danhong injection (DHI) might possess mitochondrial protection and functional recovery in a stroke subject through promoting expression of parkin, a ubiquitin ligase playing a key role in the regulation of proteins and mitochondria quality control. OBJECTIVE: To investigate the therapeutic effects of DHI on the histological, cellular, and functional recovery of Wistar rats after middle cerebral artery occlusion/reperfusion (MCAO/R). METHODS: One hundred and twenty healthy male Wistar rats (250-300 g), were randomly assigned to six groups (twenty rats/group). Rats were subjected to 1 h MCAO/R and subsequently administered the intravenous doses of DHI (0.75, 1.5, and 3 mL/kg) to the respective groups (twice a day for 14 days). Unlike the other groups, the sham group received surgery without vessel occlusion. All the animals were tested for gait behavior using the CatWalk system. The body weight/survival rates were recorded daily for 14 days. The parkin protein expression of the brain tissue was quantified by immunohistochemistry analysis. Additionally, cultured cortical neurons were incubation with DHI or minocycline (MC) and then deprived of oxygen and glucose for 2 h (to resemble ischemic/reperfusion), followed by 4 h reoxygenation. Cellular and mitochondrial phenotypes were assayed by high content analysis. RESULTS: Neurological integrity and paw parameters of the animals were altered in the model group but significantly ameliorated by DHI administration. Also, the infarct volume and survival rate were significantly improved in DHI groups. DHI enhanced the expression of parkin protein in the brain and improved the relative mitochondrial reductase activity of the cultured neurons. CONCLUSIONS: The overall result shows that daily intervention with DHI provides neuroprotection and survival to improve gait motion in Wistar rats.

Blocking CCN2 Reduces Progression of Sensorimotor Declines and Fibrosis in a Rat Model of Chronic Repetitive Overuse.

Fibrosis may be a key factor in sensorimotor dysfunction in patients with chronic overuse-induced musculoskeletal disorders. Using a clinically relevant rodent model, in which performance of a high demand handle-pulling task induces tissue fibrosis and sensorimotor declines, we pharmacologically blocked cellular communication network factor 2 (CCN2; connective tissue growth factor) with the goal of reducing the progression of these changes. Young adult, female Sprague-Dawley rats were shaped to learn to pull at high force levels (10 min/day, 5 weeks), before performing a high repetition high force (HRHF) task for 3 weeks (2 h/day, 3 days/week). HRHF rats were untreated, or treated in task weeks 2 and 3 with a monoclonal antibody that blocks CCN2 (FG-3019), or a control immunoglobulin G (IgG). Control rats were untreated or received FG-3019, IgG, or vehicle (saline) injections. Mean task reach rate and grasp force were higher in 3-week HRHF + FG-3019 rats, compared with untreated HRHF rats. Grip strength declined while forepaw mechanical sensitivity increased in untreated HRHF rats, compared with controls; changes improved by FG-3019 treatment. The HRHF task increased collagen in multiple tissues (flexor digitorum muscles, nerves, and forepaw dermis), which was reduced with FG-3019 treatment. FG-3019 treatment also reduced HRHF-induced increases in CCN2 and transforming growth factor ß in muscles. In tendons, FG-3019 reduced HRHF-induced increases in CCN2, epitendon thickening, and cell proliferation. Our findings indicate that CCN2 is critical to the progression of chronic overuse-induced multi-tissue fibrosis and functional declines. FG-3019 treatment may be a novel therapeutic strategy for overuse-induced musculoskeletal disorders. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2004-2018, 2019.

Shorter pulse width reduces gait disturbances following deep brain stimulation for essential tremor.

OBJECTIVE: Gait disturbances are frequent side effects occurring during chronic thalamic deep brain stimulation (DBS) in patients with essential tremor (ET). Adapting stimulation settings to shorter pulse widths has been shown to reduce side effects of subthalamic DBS. Here, we assess how a reduction of pulse width changes gait performance of affected patients. METHODS: Sensor-based gait assessment was performed to record spatiotemporal gait parameters in 10 healthy subjects (HS) and 7 patients with ET with gait disturbances following thalamic DBS. Patients were tested during standard DBS, after 72 hours of stimulation withdrawal and at least 30 days after adjusting DBS settings to a shorter pulse width of 40 µs (DBS40PW). RESULTS: Patients with ET on standard DBS showed significantly higher variability of several spatiotemporal gait parameters compared with HS. Variability of stride length and range of motion of the shanks significantly decreased OFF DBS as compared with standard DBS. This improvement was maintained over 30 days with DBS40PW while providing effective tremor suppression in six out of seven patients. CONCLUSION: Shorter pulse widths may reduce gait disturbances in patients with ET that are induced by DBS while preserving a level of tremor suppression equal to standard stimulation settings.

Manual therapy prevents onset of nociceptor activity, sensorimotor dysfunction, and neural fibrosis induced by a volitional repetitive task.

Painful and disabling musculoskeletal disorders remain prevalent. In rats trained to perform repetitive tasks leading to signs and dysfunction similar to those in humans, we tested whether manual therapy would prevent the development of the pathologies and symptoms. We collected behavioral, electrophysiological, and histological data from control rats, rats that trained for 5 weeks before performing a high-repetition high-force (HRHF) task for 3 weeks untreated, and trained rats that performed the task for 3 weeks while being treated 3x/week using modeled manual therapy (MMT) to the forearm (HRHF + MMT). The MMT included bilateral mobilization, skin rolling, and long axis stretching of the entire upper limb. High-repetition high-force rats showed decreased performance of the operant HRHF task and increased discomfort-related behaviors, starting after training. HRHF + MMT rats showed improved task performance and decreased discomfort-related behaviors compared with untreated HRHF rats. Subsets of rats were assayed for presence or absence of ongoing activity in C neurons and slow Aδ neurons in their median nerves. Neurons from HRHF rats had a heightened proportion of ongoing activity and altered conduction velocities compared with control and MMT-treated rats. Median nerve branches in HRHF rats contained increased numbers of CD68 macrophages and degraded myelin basic protein, and showed increased extraneural collagen deposition, compared with the other groups. We conclude that the performance of the task for 3 weeks leads to increased ongoing activity in nociceptors, in parallel with behavioral and histological signs of neuritis and nerve injury, and that these pathophysiologies are largely prevented by MMT.

AAV9 intracerebroventricular gene therapy improves lifespan, locomotor function and pathology in a mouse model of Niemann-Pick type C1 disease.

Niemann-Pick type C disease (NP-C) is a fatal neurodegenerative lysosomal storage disorder. It is caused in 95% of cases by a mutation in the NPC1 gene that encodes NPC1, an integral transmembrane protein localized to the limiting membrane of the lysosome. There is no cure for NP-C but there is a disease-modifying drug (miglustat) that slows disease progression but with associated side effects. Here, we demonstrate in a well-characterized mouse model of NP-C that a single administration of AAV-mediated gene therapy to the brain can significantly extend lifespan, improve quality of life, prevent or ameliorate neurodegeneration, reduce biochemical pathology and normalize or improve various indices of motor function. Over-expression of human NPC1 does not cause adverse effects in the brain and correctly localizes to late endosomal/lysosomal compartments. Furthermore, we directly compare gene therapy to licensed miglustat. Even at a low dose, gene therapy has all the benefits of miglustat but without adverse effects. On the basis of these findings and on-going ascendency of the field, we propose intracerebroventricular gene therapy as a potential therapeutic option for clinical use in NP-C.

Combination Therapy with Low-Dose IVIG and a C1-esterase Inhibitor Ameliorates Brain Damage and Functional Deficits in Experimental Ischemic Stroke.

Acute ischemic stroke causes a high rate of deaths and permanent neurological deficits in survivors. Current interventional treatment, in the form of enzymatic thrombolysis, benefits only a small percentage of patients. Brain ischemia triggers mobilization of innate immunity, specifically the complement system and Toll-like receptors (TLRs), ultimately leading to an exaggerated inflammatory response. Here we demonstrate that intravenous immunoglobulin (IVIG), a scavenger of potentially harmful complement fragments, and C1-esterase inhibitor (C1-INH), an inhibitor of complement activation, exert a beneficial effect on the outcome of experimental brain ischemia (I) and reperfusion (R) injury induced by transient occlusion of middle cerebral artery in mice. Both IVIG and C1-INH significantly and in a dose-responsive manner reduced brain infarction size, neurological deficit and mortality when administered to male mice 30 min before ischemia or up to 6 h after the onset of reperfusion. When combined, suboptimal doses of IVIG and C1-INH potentiated each other's neuroprotective therapeutic effects. Complement C3 and TLR2 signals were colocalized and significantly greater in brain cells adjacent to infracted brain lesions when compared to the corresponding regions of the contralateral hemisphere and to control (sham) mice. Treatment with IVIG and C1-INH effectively reduced deposition of C3b and downregulated excessive TLR2 and p-JNK1 expression at the site of I/R injury. Taken together, these results provide a rationale for potential use of IVIG and C1-INH, alone or in combination with ischemic stroke and other neurological conditions that involve inappropriately activated components of the innate immune system.

Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial.

PURPOSE: As populations shift to include a larger proportion of older adults, the necessity of research targeting older populations is becoming increasingly apparent. Dietary interventions with blueberry have been associated with positive outcomes in cell and rodent models of aging. We hypothesized that dietary blueberry would improve mobility and cognition among older adults. METHODS: In this study, 13 men and 24 women, between the ages of 60 and 75 years, were recruited into a randomized, double-blind, placebo-controlled trial in which they consumed either freeze-dried blueberry (24 g/day, equivalent to 1 cup of fresh blueberries) or a blueberry placebo for 90 days. Participants completed a battery of balance, gait, and cognitive tests at baseline and again at 45 and 90 days of intervention. RESULTS: Significant supplement group by study visit interactions were observed on tests of executive function. Participants in the blueberry group showed significantly fewer repetition errors in the California Verbal Learning test (p = 0.031, ηp2 = 0.126) and reduced switch cost on a task-switching test (p = 0.033, ηp2 = 0.09) across study visits, relative to controls. However, no improvement in gait or balance was observed. CONCLUSIONS: These findings show that the addition of easily achievable quantities of blueberry to the diets of older adults can improve some aspects of cognition.

Magnesium Sulfate Prevents Neurochemical and Long-Term Behavioral Consequences of Neonatal Excitotoxic Lesions: Comparison Between Male and Female Mice.

Magnesium sulfate (MgSO4) administration to mothers at risk of preterm delivery is proposed as a neuroprotective strategy against neurological alterations such as cerebral palsy in newborns. However, long-term beneficial or adverse effects of MgSO4 and sex-specific sensitivity remain to be investigated. We conducted behavioral and neurochemical studies of MgSO4 effects in males and females, from the perinatal period to adolescence in a mouse model of cerebral neonatal lesion. The lesion was produced in 5-day-old (P5) pups by ibotenate intracortical injection. MgSO4 (600 mg/kg, i.p.) prior to ibotenate prevented lesion-induced sensorimotor alterations in both sexes at P6 and P7. The lesion increased glutamate level at P10 in the prefrontal cortex, which was prevented by MgSO4 in males. In neonatally lesioned adolescent mice, males exhibited more sequelae than females in motor and cognitive functions. In the perirhinal cortex of adolescent mice, the neonatal lesion induced an increase in vesicular glutamate transporter 1 density in males only, which was negatively correlated with cognitive scores. Long-term sequelae were prevented by neonatal MgSO4 administration. MgSO4 never induced short- or long-term deleterious effect on its own. These results also strongly suggest that sex-specific neuroprotection should be foreseen in preterm infants.

"Long-term stability of stimulating spiral nerve cuff electrodes on human peripheral nerves".

BACKGROUND: Electrical stimulation of the peripheral nerves has been shown to be effective in restoring sensory and motor functions in the lower and upper extremities. This neural stimulation can be applied via non-penetrating spiral nerve cuff electrodes, though minimal information has been published regarding their long-term performance for multiple years after implantation. METHODS: Since 2005, 14 human volunteers with cervical or thoracic spinal cord injuries, or upper limb amputation, were chronically implanted with a total of 50 spiral nerve cuff electrodes on 10 different nerves (mean time post-implant 6.7 ± 3.1 years). The primary outcome measures utilized in this study were muscle recruitment curves, charge thresholds, and percent overlap of recruited motor unit populations. RESULTS: In the eight recipients still actively involved in research studies, 44/45 of the spiral contacts were still functional. In four participants regularly studied over the course of 1 month to 10.4 years, the charge thresholds of the majority of individual contacts remained stable over time. The four participants with spiral cuffs on their femoral nerves were all able to generate sufficient moment to keep the knees locked during standing after 2-4.5 years. The dorsiflexion moment produced by all four fibular nerve cuffs in the active participants exceeded the value required to prevent foot drop, but no tibial nerve cuffs were able to meet the plantarflexion moment that occurs during push-off at a normal walking speed. The selectivity of two multi-contact spiral cuffs was examined and both were still highly selective for different motor unit populations for up to 6.3 years after implantation. CONCLUSIONS: The spiral nerve cuffs examined remain functional in motor and sensory neuroprostheses for 2-11 years after implantation. They exhibit stable charge thresholds, clinically relevant recruitment properties, and functional muscle selectivity. Non-penetrating spiral nerve cuff electrodes appear to be a suitable option for long-term clinical use on human peripheral nerves in implanted neuroprostheses.

¿Mides la velocidad de la marcha en tu práctica diaria? Una revisión / Do you measure gait speed in your daily clinical practice? A review

La velocidad de la marcha (VM) a paso habitual es una medida fácil, rápida, económica, fiable e informativa. Con un cronómetro, como los que actualmente se encuentran en todos los móviles, dos marcas en el suelo y una mínima estandarización, un profesional sanitario obtiene una medida más objetiva y rápida respecto a muchas de las escalas habituales de valoración de las actividades de la vida diaria, por ejemplo. La VM es uno de los pilares del fenotipo de fragilidad y está fuertemente relacionada con la sarcopenia. Es un potente marcador de caídas, discapacidad incidente y de muerte, útil sobre todo como cribado en el ámbito comunitario o de atención primaria. Paralelamente, en los últimos años empieza a tener evidencia también en el pronóstico de procesos médicos agudos o en el paciente posquirúrgico, y se está estudiando la utilidad de esta herramienta en los pacientes con demencia, a la luz de su relación con las alteraciones cognitivas. La VM cumple los requerimientos fundamentales para una buena herramienta de cribado. Sin embargo, no se utiliza en la práctica clínica. ¿Por qué? Esta revisión, que no pretende ser sistemática ni exhaustiva, tiene diferentes objetivos: 1)revisar la relación entre VM y fragilidad; 2)revisar las principales técnicas de mediciön; 3)aportar evidencia en diferentes perfiles clínicos (personas mayores aparentemente sanas, con deterioro cognitivo, con cáncer, con otras patologías o problemas de salud) y en diferentes ámbitos (comunitario, hospitalización, rehabilitación), y 4)reflexionar de manera crítica sobre por qué todavía no se utiliza de manera rutinaria y qué faltaría para potenciar esta utilización (AU)

Gait speed (GS), measured at usual pace, is an easy, quick, reliable, non-expensive and informative measurement. With a standard chronometer, like those that currently found in mobile phones, and with two marks on the floor, trained health professionals obtain a more objective and quick measurement compared with many geriatric scales used in daily practice. GS is one of the pillars of the frailty phenotype, and is closely related to sarcopenia. It is a powerful marker of falls incidence, disability and death, mostly useful in the screening of older adults that live in the community. In recent years, the evidence is reinforcing the usefulness of GS in acute care and post-surgical patients. Its use in patients with cognitive impairment is suggested, due to the strong link between cognitive and physical function. Although GS meets the criteria for a good geriatric screening tool, it is not much used in clinical practice. Why? This review has different aims: (I) disentangling the relationship between GS and frailty; (II) reviewing the protocols to measure GS and the reference values; (III) reviewing the evidence in different clinical groups (older adults with frailty, with cognitive impairment, with cancer or other pathologies), and in different settings (community, acute care, rehabilitation), and (IV) speculating about the reasons for its poor use in clinical practice and about the gaps to be filled (AU)

Review of Drop Hallux: Assessment and Surgical Repair.

Peroneal nerve palsy is common. The hallmark clinical manifestation of peroneal nerve palsy is drop foot. In the drop foot condition, the ankle cannot flex, and the foot does not clear the ground during the swing phase of gait. Spontaneous nerve repair can yield complete or incomplete resolution of drop foot. Some patients with incomplete resolution are left with a drop hallux condition, in which the ankle can dorsiflex, but the hallux remains unable to dorsiflex. This has not been thoroughly discussed in the past, regarding surgical repair. In the present report, we have reviewed the drop hallux condition and an effective surgical repair option (extensor hallucis longus to tibialis anterior tendon anastomosis). Our case report presents a healthy 27-year-old male who had persistent drop hallux after drop foot resolution, 3 years after external fixation of a closed, proximal tibia-fibula fracture.