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Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura ® , Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics which were studied longitudinally over three years. Their evaluations assessed postural sway variability, potential for slips and trips, gait metrics, sit-to-stand durations, scores from the sensory organization test (SOT), and gross motor function measure (GMFM) scores. Findings indicated a decline in postural complexity and stability in the medial-lateral (ML) axis, a reduction in toe clearance, and an augmented risk of stumbling for the participants. Over the two-year period of ERT, both siblings exhibited a progressive decline in walking velocity, characterized by reductions in step length and prolonged gait cycle time. The elder sibling demonstrated a notable increase in double support duration, indicative of heightened reliance on proprioceptive input to maintain stability during ambulation. Additionally, sit-to-stand times lengthened for siblings, further reflecting declines in motor function. Despite these challenges, SOT scores showed improvement after two years of ERT, suggesting some preservation of sensory integration. These findings in SOT scores indicate that cerliponase alfa treatment in patients with atypical CLN2 disease may confer benefits in postural stability, lower extremity strength, and ankle stiffness. However, declines in more complex motor functions, including sit-to-stand performance and postural complexity, persist, underscoring the progressive nature of the disease despite ongoing therapeutic intervention., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Persons with multiple sclerosis (PwMS) suffer from sleep disturbances, fatigue and pain, which can be due, at least in part, to decreased levels of endogenous melatonin. These alterations could exacerbate postural instability, gait disorders and fall risk. Acute effects of exogenous melatonin on physical disorders have been studied in PwMS but its long-term effects on these parameters have not been explored yet in this population. This study aimed to determine the impact of chronic melatonin intake on dynamic postural stability, walking performance and fall risk in PwMS., Methods: This randomized placebo-controlled study included 27 PwMS who were assigned to either melatonin group (MG, n=15) or placebo group (PG, n=12) (3 mg/night for 12 weeks). Dynamic postural balance (force platform), walking performance (locometer) and fall risk (Four Square Step Test) were evaluated pre (T0)- and post (T1)-intervention. Sleep quality (Pittsburgh Sleep Quality Index (PSQI)), fatigue perception (Fatigue Severity Scale (FSS)), neuropathic pain (Neuropathic Pain Questionnaire 4 (DN4)) and quality of life (International Multiple Sclerosis (MS) Quality of Life Questionnaire) were also assessed at T0 and T1., Results: The center of pressure mean velocity decreased in MG compared with PG in the frontal plane (22.98 %, p=0.028). Stride length and walking speed increased in MG comparatively with PG (18.09 %, p=0.036; 9.65 %, p=0.025, respectively). The PSQI (55.89 %, p<0.001), FSS (32.38 %, p=0.003) and DN4 (32.41 %, p=0.035) scores decreased in MG compared with PG., Conclusion: 12-week melatonin supplementation can be recommended for managing MS-related gait disorders and dynamic postural imbalance. This therapy may also be prescribed for PwMS due to its anti-fatigue and analgesic effects as well as its benefits on sleep quality., Clinical Registration: This study was prospectively recorded in the Pan African Clinical Trial Registry database (PACTR202007465309582) (https://pactr.samrc.ac.za/.)., Competing Interests: Declaration of Competing Interest The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Correct identification of those patients presenting with an acute vestibular syndrome (AVS) or an acute imbalance syndrome (AIS) that have underlying posterior-circulation stroke (PCS) and thus may benefit from revascularization (intravenous thrombolysis (IVT), endovascular therapy (EVT)) is important. Treatment guidelines for AVS/AIS patients are lacking. We reviewed the evidence on acute treatment strategies in AVS/AIS focusing on predictors for IVT/EVT and outcome., Methods: We performed a systematic search (MEDLINE, Embase) to identify studies reporting on acute treatment in PCS presenting as AVS/AIS (PROSPERO-registration = CRD42024537272). Key parameters were extracted. Risk of bias was assessed (Downs-and-Black quality assessment checklist)., Results: We identified 3883 citations and included seven study cohorts (n = 1000 patients including 950 ischemic strokes). Overall, 251/1000 patients (25.1%) received IVT; EVT was performed in 46/368 (12.5%). Acute vertigo/dizziness was reported in 295/1000 (29.5%) patients. AVS criteria were met in 186/407 (45.7%) patients evaluated, and AIS criteria in 82/346 (23.7%). IVT was reported in 71/195 (36.4%) AVS/AIS patients and EVT in 13/77 (16.9%) cases, whereas the door-to-needle time (DNT) was significantly longer for PCS compared to anterior-circulation stroke (90 ± 29min vs. 74 ± 30min, p = 0.003) in one study. DNT was similar in those patients presenting with AVS/AIS compared to all PCS presentations in another study (70 ± 39min (AVS/AIS) vs. 63 ± 35min (all)). An mRS ≤ 2 after 90 days was noted in 68.4-69.6% of PCS. No outcome data were identified for AVS/AIS patients., Conclusions: Insufficient data exist to drive any firm recommendation about treating otherwise eligible patients with AVS/AIS with IVT/EVT and judgments must be made on a case-by-case basis. Further research on this specific patient group is needed., Competing Interests: Declarations. Conflicts of interest: Jonathan A. Edlow reviews medico-legal cases for both plaintiff and defense law firms. Some cases involve patients with dizziness. Alexander A. Tarnutzer has received consultant and / or speaker fees from Mitsubishi Tanabe Pharma, AstraZeneca, Teva Pharma and Schwabe Pharma. Ethical approval and informed consent: Being a systematic review of the literature, no ethical approval or consent was necessary., (© 2024. The Author(s).)

Vestibular rehabilitation (VR) is a therapeutic approach that minimizes the impacts of balance alterations by enhancing the central vestibular compensation mechanism. The present study investigates the effect of repeated balance exercises on the central vestibular compensation mechanism in a reserpine-induced progressive model of parkinsonism in aged rats. Male Wistar rats were assigned to three cohort experiments: Exp 1: repeated balance exercises (narrow beam test) - performed every 48 h during 20 days; Exp 2: balance exercises performed on the 0 th and 8 th days; Exp 3: balance exercises performed only on the 0 th and 20 th days. For each experiment, the animals were divided into two groups (n = 7 per group): CTL (vehicle) and RES (reserpine 0.1 mg/kg). The animals received 4 (exp. 2) or 10 (exp 1 and 3) s.c. injections (0.1 mg/kg), one every 48 h. The cohorts were evaluated using catalepsy and open field tests (0 th , 8 th and 20 th days). After completion of behavioral tests, the brains were analyzed for immunohistochemistry for tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT). The RES group presented motor deficits in the catalepsy and open field tests on day 20, but not on day 8. There was no decrease in the number of TH neurons and terminals in the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and dorsal striatum (DS) for animals from Exp. 2. However, a decrease was observed in the SNpc, VTA and striatum of animals from Exp 1 and Exp 3. In the balance beam test, the animals in the RES group showed a longer crossing time from day 8 to day 14 (Exp 1), on the 8 th day (Exp 2) and on the 20 th day (Exp. 3). This finding was correlated with a decrease in the number of ChAT immunoreactive cells in the pedunculopontine tegmental nucleus (PPN) for the animals that performed the dynamic balance test only once (Exp. 2 and 3), but no reduction was observed in the animals that performed the test repeatedly (Epx. 1). Thus, it was possible to verify that repeated exposure of the animals to balance assessment tasks potentiated the performance of the central vestibular compensation mechanism in the animal model of parkinsonism., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The efficacy of subthalamic stimulation on axial signs of Parkinson's disease (PD) is debated in the literature. This study delves into the dynamic interplay of gait and posture, specifically probing their nuanced response to subthalamic stimulation and levodopa., Methods: We used wearable sensor technology to examine alterations in the spatiotemporal parameters of gait and posture in individuals with PD before and 6 months after subthalamic deep brain stimulation (STN-DBS) surgery. Thirty-three subjects with PD were evaluated in two pre-operative and four post-operative conditions comprising OFF/ON medication and stimulation states. Standardized response mean (SRM) values were calculated to assess treatment responsiveness., Results: Significant improvements in spatiotemporal gait parameters, including speed, stride length, cadence, and turning, were observed following STN-DBS surgery. Quantitatively, stimulation outperformed levodopa in enhancing gait speed, stride length, and turning, as indicated by SRM. Levodopa moderately improved stride time variability and asymmetry, while stimulation alone demonstrated limited efficacy. Postural parameters exhibited minimal change following STN-DBS, although stimulation showed a slight benefit in certain postural aspects., Conclusion: Our findings suggest positive effects of stimulation and levodopa on gait and postural parameters, with STN-DBS demonstrating superior efficacy in enhancing gait speed, stride length, and turning. However, gait variability remains unaddressed by current therapies, highlighting the need for novel treatments targeting regions beyond the basal ganglia., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

While levodopa is the most effective drug for symptom treatment of Parkinson's Disease (PD), its long-term use often leads to side effects such as uncontrolled involuntary movements known as levodopa-induced dyskinesia (LID). LID has been shown to increase postural sway, but the extent to which these hyperkinetic movements alter postural sway strategies has not been explored. We recruited 25 people with idiopathic PD, of which 13 exhibit clinical signs of LID, and 10 healthy older adults. Participants performed thirty-second standing trials with no added task (single-task) and with performing a cognitive dual-task, known to provoke dyskinesia. Participants with PD were tested in their practical OFF and ON states. The root-means-square (RMS) accelerations were obtained from inertial sensors attached to the lumbar, trunk, and head. Sway ratios (superior-to-inferior segment) were calculated to determine the effect of LID on postural sway strategies. Participants with LID showed greater RMS head sway, compared to those without LID and older adults. The head-to-trunk sway ratio was greater in participants with LID during the ON state or when dual-tasking. In addition, the head-to-lumbar sway ratio was greater in participants with LID in the ON state during both single- and dual-tasking. Our results reveal an altered postural control strategy in PD with LID, presenting increased sway in superior segments of the kinematic chain, leading to head instability. Unlike PD without LID and older adults, PD with LID exhibit multi-link sway in the ON state, which has important implications for measuring postural sway in the presence of dyskinesias., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to explore the effect of 8-week oral supplementation on postural control in young women with iron deficiency anemia (IDA)., Methods: This study involved 15 women with IDA who received 160 mg of elemental iron daily in the form of dried ferrous sulfate capsules (80 mg twice daily) taken in two divided doses for 8 weeks. The mean velocity of oscillations of the center of pressure (CoPv) was recorded to evaluate postural control pre- and post-supplementation. In addition, simple reaction time (SRT) and weight discrimination tests were performed to assess attentional capacity and proprioceptive acuity, respectively., Results: This study revealed significant increases (P < 0.001, mean difference = 1.83, 95% CI: -17.25; -9.42) in proprioceptive acuity values, as well as decreases in CoPv [firm (EO (P < 0.01, mean difference = 0.52, 95% CI: 0.69; 2.92), EC (P < 0.05, mean difference = 0.75, 95% CI: 0.24; 3.45)) and foam (EO (P < 0.001, mean difference = 0.64, 95% CI: 1.71; 4.44) ; EC (P < 0.001, mean difference = 1.04, 95% CI: 3.51; 7.97))] and SRT (P < 0.001, mean difference = 59.31, 95% CI: 103.02; 168.71) values post-supplementation compared to pre-supplementation., Conclusion: This study showed significant improvements in postural control in young women with IDA after 8 weeks of oral iron supplementation. These improvements were probably related to the enhanced bioavailability of iron, which may have influenced neural processes inducing improvements in attention capacity and proprioceptive acuity., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The study followed ethical guidelines from the Helsinki Declarations and was approved by the local ethics committee (CPP SUD N° 0213/2020). Additionally, the study has been registered in the Pan-African Clinical Trials Registry (pactr.samrc.ac.za) under the registration number PACTR202310737053661., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Caffeine consumption can elicit improvements in aspects of physical function in older adults but also, negatively modify standing balance, potentially increasing fall risk. However, balance alterations and changes in physical function induced by commonly consumed caffeine vehicles such as coffee have not been investigated. Therefore, this study investigated coffee ingestion providing 3 mg·kg BW -1 caffeine on balance performance and physical function, in a group of older adults. In a randomised, crossover design, 22 older adults (Male n = 10, Age: 68 ± 6 years) completed bipedal standing balance and physical function assessments (Senior Fitness Test) under one of the following conditions: caffeinated coffee (COF), decaffeinated coffee (DEC), placebo (PLA) or a control (CON) (no fluid ingestion). Centre of pressure (COP) root mean square and power frequency were calculated to characterise postural performance and strategy, respectively. The complexity (i.e., regularity) of the COP signal was also determined by calculating sample entropy. Caffeinated coffee had limited effects on COP outcomes. Frequency of the COP in the anteroposterior direction was greater following COF compared to DEC (P = 0.047;g = 0.29) but there were no statistical differences between COF and PLA or CON (P > 0.05). Furthermore, there were no significant performance differences between any conditions in all tests of physical function (P > 0.05). This suggests that coffee has limited effects on balance performance or physical function but may influence both balance complexity and the strategy utilised to maintain upright stance. Overall, a strong cup of coffee does not significantly influence balance and measures of functional performance in healthy older adults., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Older adults are at risk of adverse effects during chemotherapy including nausea and fatigue, but many also suffer from dizziness and peripheral neuropathy. This may lead to balance and walking impairments and increased risk of falls and affect health-related quality of life. Moreover, these symptoms are often underreported with inadequate awareness among health professionals leading to deficient focus on the need for targeted assessment and rehabilitation. We aimed to examine the prevalence of dizziness, impaired walking balance, and neuropathy and falls in older adults ≥65 years with gastrointestinal cancer receiving chemotherapy and the associations between these symptoms. Further, we aimed to examine the quantity of patients reporting these symptoms to the oncologist., Materials and Methods: This is a cross-sectional study among patients ≥65 years with gastrointestinal cancers who have completed three or more series of chemotherapy. The prevalence of dizziness, impaired walking balance, neuropathy, and reporting of these adverse effects was examined through structured questionnaires., Results: Of two hundred patients (57 % male, mean age 74.4 years) the prevalence of dizziness was 54 % and the prevalence of patients experiencing impaired walking balance was 48 %. Symptoms of neuropathy was present in 32 % of patients and 11 % experienced falls during chemotherapy. Symptoms of neuropathy was associated with experiencing dizziness: odds ratio (OR) 1.98 (95 % confidence interval [CI]: 1.06; 3.71) and impaired balance: OR 3.61 (95 % CI: 1.87; 6.96). Less than half the patients (48 %) told the oncologist about these symptoms., Discussion: Dizziness and impaired walking balance during chemotherapy are underreported yet profound symptoms among older patients with cancer. Dizziness and impaired balance should be systematically assessed during chemotherapy among older patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

The current study aimed to explore the effect of daily caffeine supplementation (100 mg/day) and 12-week of Zumba training on functional performances in middle-aged women. Eighty-five middle-aged women were randomized into 4 groups including control, Zumba training (ZT), caffeine supplementation (Ca) or caffeine-Zumba training (Ca + ZT) groups. Functional performances were assessed using 10 m Walk, Timed Up and Go, Functional Reach, and 30-Second Chair Stand tests. As results, ZT, Ca and Ca + ZT intervention programs showed a significant (p < 0.05) functional performances improvement. However, Ca + ZT group showed significant (p < 0.001) better scores in terms of mobility (95%CI [0.71, 1.43]), gait speed (95%CI [0.52, 1.71]) and lower body endurance strength (95%CI [-6.93, -1.92]), except for dynamic balance (95%CI [-9.41, -3.44]). In conclusion, 12-week of Zumba training improves functional performances in middle-aged women, and daily caffeine intake is an effective alternative for improving such performances. Supplementing caffeine (100 mg/day) to Zumba training was effective in boosting Zumba benefits on these functional performances., (© 2024. The Author(s).)

Purpose: To explore the reliability and validity of clinically-relevant outcome measures for balance (i.e., The Short Physical Performance Battery [SPPB] - Balance Subscale) and sensation (i.e., monofilament threshold testing) for use in clinical trials of chemotherapy-induced peripheral neuropathy (CIPN)., Methods: Adult, post-treatment cancer survivors (N = 142) who had reported ≥ 4/10 CIPN symptom severity following neurotoxic chemotherapy were recruited from six National Cancer Institute Community Oncology Research Program (NCORP) sites associated with the University of Rochester Cancer Center NCORP Research Base. Participants completed the monofilament threshold test at the screening and baseline time points (i.e., one week apart), while the Quality of Life Questionnaire-CIPN20, Treatment-Induced Neuropathy Assessment Scale, and SPPB - Balance Subscale were completed at baseline. Test-retest reliability of the monofilament threshold testing scores was assessed using the Intraclass Correlation Coefficient (ICC). The convergent validity among monofilament threshold testing, SPPB - Balance Subscale, and CIPN patient-reported outcome (PRO) scores at baseline was assessed using Spearman's correlation., Results: Ceiling effects were observed for SPPB-Balance Subscale scores as 113 (79.6%) respondents reported the highest score. Agreement between the screening and baseline monofilament threshold testing scores was moderate (ICC = 0.65). Monofilament threshold testing (r s Range: 0.14 - 0.21) and SPPB Balance Subscale scores (r s Range: -0.36 - -0.22) showed largely low correlations with all PRO measures., Conclusions: Monofilament threshold testing demonstrated moderate test-retest reliability, but low convergent validity with CIPN PROs, while the SPPB - Balance Subscale demonstrated low convergent validity with CIPN PROs and ceiling effects (i.e., highest possible score) among post-treatment cancer survivors with CIPN. Future research is needed to identify promising measures of balance and sensation loss for use in clinical trials that complement CIPN PROs to aid in the identification of clinically relevant treatments for CIPN., Trial Registration: NCT04367490 [April 29, 2020]., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

While the hazardous effects of microplastics (MPs) are increasingly reported, it remains uncertain if MPs induce inner ear dysfunction. Nonetheless, prevalence of inner ear dysfunction was observed across all age groups. In this study, we investigated whether MP polyethylene affect inner ear function in a murine model. To detect hearing loss and balance defect after polyethylene (PE) exposure, we evaluated hearing threshold levels, assessed cerebral glucose metabolism, conducted transcriptome analysis, and performed behavioral studies. C57BL/6 J mice (5-week-old) were grouped into control (n = 10) and PE-fed groups (n = 10). Mice were orally administered 100 ppm/100 μL (equivalent to 10 μg) of PE every day for 4 months. We identified the accumulation of PE in the cochlea and vestibular region. The fragmented PE in inner ear was 3.00 ± 0.38 µm in size; the administered PE concentration was 1.14 ± 1.06 mg/g. Fourier transform infrared spectrometry confirmed that the properties of the MP were identical with those of PE fed to the mice. Transcriptomic analysis showed up-regulation of PER1, NR4A3 and CEBPB at the PE exposed inner ear tissue and it was confirmed using qRT-PCR, western blotting, and immunofluorescence staining. We observed abnormalities in balance related behavior assessment in the PE group. Exposure to PE increased the hearing thresholds and decreased glucose metabolism in the bilateral lateral entorhinal cortex, right primary auditory cortex, and right secondary auditory cortex. We can conclude that PE exposure induced inner ear dysfunction such as hearing loss and balance disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Dynamic balance assessments such as walking adaptability may yield a more realistic prediction of drug-induced falls compared with postural stability measurements, as falls often result from limited gait adjustments when walking. The Interactive Walkway (IWW) measures walking adaptability but sensitivity to medication effects is unknown. If proven sensitive and specific, IWW could serve as a biomarker for targeted fall-risk assessments in early clinical drug development. In this three-way crossover study, 18 healthy elderly (age: 65-80 years) subjects received 5 mg zolpidem, 10 mg suvorexant, or placebo in the morning. Assessments were performed pre-dose and approximately hourly until 9 h post-dose. IWW assessments included an 8-meter walking test, goal-directed stepping, obstacle-avoidance, and tandem-walking. Other pharmacodynamic measurements were the Timed-Up-and-Go (TUG) test at a comfortable and fast pace, adaptive tracking, and body sway. A decline in performance was observed for zolpidem compared with placebo for 3 h post-dose in IWW walking adaptability outcome measures, TUG, adaptive tracking, and body sway. For the IWW tasks, a decrease in walking speed (among others) was observed. IWW parameters were not affected by suvorexant compared with placebo at any timepoint. However, an increase of 9.8% (95%CI: 1.8%, 18.5%) in body sway was observed for suvorexant compared with placebo up to 3 h post-dose. The IWW successfully quantified drug effects of two hypnotic drugs and distinguished between zolpidem and suvorexant regarding their effects on walking. As a biomarker, the IWW demonstrated sensitivity in assessing dynamic balance and potential fall risk in early phase clinical drug development., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Ageing, sex and polypharmacy affect physical function., Objectives: This mouse study investigates how ageing, sex and polypharmacy interact and affect grip strength, balance beam and wire hang, correlating and comparing the different test results between and within subgroups., Methods: Young (2.5 months) and old (21.5 months) C57BL/6 J male and female mice (n = 10-6/group) were assessed for physical function at baseline on grip strength, balance beam and wire hang with three trials of 60 s (WH60s) and one trial of 300 s (WH300s). Mice were randomised to control or diet containing a high Drug Burden Index (DBI, total anticholinergic and sedative drug exposure) polypharmacy regimen (metoprolol, simvastatin, citalopram, oxycodone and oxybutynin at therapeutic oral doses). Following 6-8 weeks of treatment, mice were reassessed., Results: High DBI polypharmacy and control mice both showed age group differences on all tests (p < 0.05). Only control mice showed sex differences, with females outperforming males on the WH60s and balance beam for old mice, WH300s for young mice (p < 0.05). Polypharmacy reduced grip strength in all subgroups (p < 0.05) and only in old females reduced wire hang time and cumulative behaviour and balance beam time and %walked (p < 0.05). Physical function assessments were all correlated with each other, with differences between subgroups (p < 0.05), and mice within subgroups showed interindividual variability in performance., Conclusion: Age, sex and polypharmacy have variable effects on different tests, and behavioural measures are useful adjuvants to assessing performance. There was considerable within-group variability in change in measures over time. These findings can inform design and sample size of future studies., (© 2024 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Introduction: Women with breast cancer who underwent taxane-based chemotherapy demonstrate diminished postural stability. However, the data concerning dynamic postural stability among women with breast cancer during taxane-based chemotherapy remains insufficient., Purpose: To investigate postural stability among women with breast cancer during taxane-based chemotherapy., Methods: Fifteen women with breast cancer participated in this study. Postural stabilities were assessed at five intervals during the course of chemotherapy treatment. Static postural stability was measured during single leg with eyes open (SEO) and eyes closed (SEC) conditions, while dynamic postural stability was measured during performance of the limit of stability test (LOS). Postural stability was described using 95% confidence ellipse area (EA), center of pressure (COP) path length (PL), and COP average velocity (AV)., Results: For static postural stability assessment, SEO condition was found to have significant increases in EA, PL, and AV (p = .001, p < .001, and p = .02, respectively). For dynamic postural stability assessment, a significant difference in EA was observed in the forward, backward, right, and left directions (p = .02, p = .02, p < .001, and p = .01, respectively). In addition, a significant difference in PL was found while performing in a backward direction (p = .02)., Conclusions: The findings showed that women with breast cancer may have experienced decreased static and dynamic postural stability.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls., Methods: Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures., Results: PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers., Conclusion: Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.

Caffeine (CAF) has been shown to be an effective ergogenic aid in enhancing sports performance, including vertical jump (VJ), sprint, balance, agility, and freestyle swimming performance (FSP). However, whether acute CAF supplementation improves FSP in moderately trained female swimmers has not been well documented. Therefore, this study aimed to investigate the effects of CAF intake on vertical jump, balance, auditory reaction time (ART), and swimming performance in female swimmers. In a double-blind, cross-over design, eight moderately trained female swimmers (age: 21.3 ± 1.4 years, height: 161.2 ± 7.1 cm, body mass: 56.3 ± 6.7 kg, body mass index (BMI): 21.9 ± 1.3 kg/m 2 , and habitual CAF intake: 246.4 ± 111.4 mg/day) ingested caffeine (CAF) (6 mg/kg) or a placebo (PLA) 60 min before completing VJ, balance, ART, and 25/50 m FSP. CAF supplementation resulted in a significantly lower time both in 25m ( p = 0.032) and 50m ( p = 0.033) FSP. However, CAF resulted in no significant difference in VJ, ART, and RPE ( p > 0.05). Balance test results showed a non-significant moderate main effect (d = 0.58). In conclusion, CAF seems to reduce time in short-distance swimming performances, which could be the determinant of success considering the total time of the race. Thus, we recommend coaches and practitioners incorporate CAF into swimmers' nutrition plans before competitions, which may meet the high performance demands.

Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. Although mounting studies have been conducted, no effective therapy is available to halt its progression. Indole-3-carbinol (I3C) is a naturally occurring compound obtained by β-thioglucosidase-mediated autolysis of glucobrassicin in cruciferous vegetables. Besides its powerful antioxidant activity, I3C has shown neuroprotection against depression and chemically induced neurotoxicity via its anti-inflammatory and antiapoptotic effects. This study aimed to investigate the neuroprotective effects of I3C against rotenone (ROT)-induced PD in male albino rats. The possible protective mechanisms were also explored. PD was induced by subcutaneous administration of ROT (2 mg/kg) for 28 days. The effects of I3C (25, 50, and 100 mg/kg/day) were assessed by catalepsy test (bar test), spontaneous locomotor activity, rotarod test, weight change, tyrosine hydroxylase (TH) expression, α-synuclein (α-Syn) expression, striatal dopamine (DA) content, and histological examination. The highest dose of I3C (100 mg/kg) was the most effective to prevent ROT-mediated motor dysfunctions and amend striatal DA decrease, weight loss, neurodegeneration, TH expression reduction, and α-Syn expression increase in both the midbrain and striatum. Further mechanistic investigations revealed that the neuroprotective effects of I3C are partially attributed to its anti-inflammatory and antiapoptotic effects and the activation of the sirtuin 1/AMP-activated protein kinase pathway. Altogether, these results suggested that I3C could attenuate biochemical, molecular, and functional changes in a rat PD model with following repeated rotenone exposures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Our understanding of how balance control responds to levodopa over the course of a single day in people with Parkinson's disease (PD) is limited with the majority of studies focused on isolated comparisons of ON vs. OFF levodopa medication., Objective: To evaluate the temporal dynamics of postural control following the first levodopa dose of the day during a challenging standing task in a group of people with PD., Methods: Changes in postural control were evaluated by monitoring cortical activity (covering frontal, motor, parietal and occipital areas), body sway parameters (force platform), and lower limb muscle activity (tibialis anterior and gastrocnemius medialis) in 15 individuals with PD during a semi-tandem standing task. Participants were assessed during two 60 second trials every 30 minutes (ON-30 ON-60 etc.) for 3 hours after the first matinal dose (ON-180)., Results: Compared to when tested OFF-medication, cortical activity was increased across all four regions from ON-60 to ON-120 with early increases in alpha and beta band activity observed at ON-30. Levodopa was associated with increased gastrocnemius medialis activity (ON-30 to ON-120) and ankle co-contraction (ON-60 to ON-120). Changes in body sway outcomes (particularly in the anterior-posterior direction) were evident from ON-60 to ON-120., Conclusions: Our results reveal a 60-minute window within which postural control outcomes may be obtained that are different compared to OFF-state and remain stable (from 60-minutes to 120-minutes after levodopa intake). Identifying a window of opportunity for measurement when individuals are optimally medicated is important for observations in a clinical and research setting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite the high incidence of traumatic brain injury (TBI), there is no universal treatment to safely treat patients. Blunt brain injuries destroy primary neural tissue that results in impaired perfusion, excessive release of glutamate, inflammation, excitotoxicity, and progressive secondary neuronal cell death. We hypothesized that administration of cannabidiol (CBD) directly to a brain contusion site, will optimize delivery to the injured tissue which will reduce local neural excitation and inflammation to spare neural tissue and improve neurological outcome following TBI. CBD was infused into a gelfoam matrix forming an implant (CBDi), then applied over the dura at the contusion site as well as delivered systemically by injection (CBD.IP). Post-injury administration of CBDi+IP greatly reduced defecation scores, lesion volume, the loss of neurons in the ipsilateral hippocampus, the number of injured neurons of the contralateral hippocampus, and reversed TBI-induced glial fibrillary acidic protein (GFAP) upregulation which was superior to either CBD.IP or CBDi treatment alone. Vestibulomotor performance on the beam-balance test was restored by 12 days post-TBI and sustained through 28 days. CBDi+IP treated rats exhibited preinjury levels of spontaneous alternation on the spontaneous alternation T-maze. In the object recognition test, they had greater mobility and exploration of novel objects compared to contusion or implant alone consistent with reduced anxiety and restored cognitive function. These results suggest that dual therapy by targeting the site of injury internally with a CBD-infused medical carrier followed by systemic supplementation may offer a more effective countermeasure than systemic or implant treatment alone for the deleterious effects of penetrating head wounds., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Caffeine ingestion may influence balance control via numerous mechanisms. Although previously investigated using various study designs and methods, here we aimed to create the first evidence-based consensus regarding the effects of caffeine on the control of upright stance via systematic review (PROSPERO registration CRD42021226939). Embase, PubMed/MEDLINE, SPORTDiscus and Web of Science databases were searched on 27 January 2021 to identify placebo-controlled trials investigating caffeine-induced changes in human standing balance. Reference lists of eligible studies were also searched. Overall, nine studies involving a total of 290 participants were included. All studies were moderate to strong in quality according to the QualSyst tool. Balance-related outcome measures were collected across a range of different participant ages, stances and sensory conditions. The results show that younger participants' balance was generally unaffected by caffeine ingestion. However, a significant balance impairment was observed following caffeine ingestion in all studies involving older participants (average age >65 years). Our results therefore suggest an age-dependent effect of caffeine ingestion on human standing. Further research into this effect is warranted as only one study has directly compared younger and older adults. Nonetheless, an important implication of our findings is that caffeine ingestion may increase fall risk in older adults. Furthermore, based on our findings, caffeine ingestion should be considered as a potential confounding factor when assessing human standing balance, particularly in older adults.

Objective: Early postural instability (PI) is a red flag for the diagnosis of Parkinson's disease (PD). Several patients, however, fall within the first three years of disease, particularly when turning. We investigated whether PD patients, without clinically overt PI, manifest abnormal reactive postural responses to ecological perturbations resembling turning., Methods: Fifteen healthy subjects and 20 patients without clinically overt PI, under and not under L-Dopa, underwent dynamic posturography during axial rotations around the longitudinal axis, provided by a robotic mechatronic platform. We measured reactive postural responses, including body displacement and reciprocal movements of the head, trunk, and pelvis, by using a network of three wearable inertial sensors., Results: Patients showed higher body displacement of the head, trunk and pelvis, and lower joint movements at the lumbo-sacral junction than controls. Conversely, movements at the cranio-cervical junction were normal in PD. L-Dopa left reactive postural responses unchanged., Conclusions: Patients with PD without clinically overt PI manifest abnormal reactive postural responses to axial rotations, unresponsive to L-Dopa. The biomechanical model resulting from our experimental approach supports novel pathophysiological hypotheses of abnormal axial rotations in PD., Significance: PD patients without clinically overt PI present subclinical balance impairment during axial rotations, unresponsive to L-Dopa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

A therapeutic approach for promoting neuroprotection and brain functional regeneration after strokes is still lacking. Histone deacetylase 1 (HDAC1), which belongs to the histone deacetylase family, is involved in the transcriptional repression of cell-cycle-modulated genes and DNA damage repair during neurodegeneration. Our previous data showed that the protein level and enzymatic activity of HDAC1 are deregulated in stroke pathogenesis. A novel compound named 5104434 exhibits efficacy to selectively activate HDAC1 enzymatic function in neurodegeneration, but its potential in stroke therapy is still unknown. In this study, we adopted an induced rat model with cerebral ischemia using the vessel dilator endothelin-1 to evaluate the potential of compound 5104434. Our results indicated compound 5104434 selectively restored HDAC1 enzymatic activity after oxygen and glucose deprivation, preserved neurite morphology, and protected neurons from ischemic damage in vitro. In addition, compound 5104434 attenuated the infarct volume, neuronal loss, apoptosis, DNA damage, and DNA breaks in cerebral ischemia rats. It further ameliorated the behavioral outcomes of neuromuscular response, balance, forepaw strength, and functional recovery. Collectively, our data support the efficacy of compound 5104434 in stroke therapy and contend that it can be considered for clinical trial evaluation.

Background: The risk of fall seriously affects the health and quality of life of the middle-aged and elderly people, especially the injury and disability caused by fall of the middle-aged and elderly people, which imposes a huge burden on family and social medical care. Baduanjin exercise may be an effective intervention to enhance the muscle strength and stability of lower limbs, improve the balance ability and gait of middle-aged and elderly people, reduce the incidence of falls, improve the quality of life, and promote the health of middle-aged and elderly people. The aim of this study is to summarize evidence and systematically review the efficacy and safety of Baduanjin on the fall and balance function in middle-aged and elderly people., Methods: We conducted a systematic search of English and Chinese RCTs in the following 8 electronic databases: PubMed, EMBASE, Web of Science, The Cochrane Library, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, from their respective dates of inception to July 2021. Other resources will be searched if necessary. The primary outcome is the fall rate in middle-aged and elderly people and the secondary outcomes include the Single-Leg Standing (SLS) Test, Berg Balance Scale (BBS), Timed Up and Go (TUG) Test. The study selection, data extraction, risk of bias, data synthesis and analysis, reporting biases, and the quality of evidence will be independently conducted by 2 reviewers who use the EndNote X9 software, Cochrane handbook assessment tool, RevMan 5.3 software, a funnel plot and GRADE system., Results: This study will evaluate the effect of Baduanjin on falls and balance function of middle-aged and elderly people from multiple outcome evaluation indicators such as fall rate, and provide high-quality evidence., Conclusion: This study will provide evidence for whether Baduanjin has an effect on falls and balance function in middle-aged and elderly people., Ethics and Dissemination: Ethics approval is not required for systematic review, since it does not infringe on personal interests. The results will be submitted to peer-review journals or disseminated at scientific conferences., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The aim of the present study was to explore the effect of caffeine consumption (CC) on cognitive motor interference while walking and maintaining balance in middle-aged women. Twenty middle-aged women (52 ± 2.0 years; height 158 ± 2.0 cm; body mass 77 ± 14.9 kg; body mass index ±3.4 kg/m 2 , mean ± SD) participated in this study. Participants completed measures of a single task (ST) cognitive, a ST motor and a dual task (DT) cognitive-motor tests before and after either caffeine (100 mg) or placebo ingestion. Results showed that before CC, both motor (P < 0.0005) and cognitive (P < 0.05) performances decreased in the DT condition compared to the ST one. After CC, no significant difference in the motor performances between ST and DT conditions was observed. In fact, both standing and walking DT performances were improved as indicated by a significant (P < 0.05) decrease in the dual task cost (DTC) of motor performances. In conclusion, middle-aged women showed difficulties to manage DT situations in which a cognitive and a motor task must be performed concurrently. Caffeine is an effective ergogenic aid to improve both cognitive and motor performances during DT conditions and could be an alternative to nullify the deteriorating effect of DT when maintaining balance and walking in middle-aged women. These enhancements could offer great potential for everyday functioning., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss., Methods: We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron's membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions' recovery were assessed with appropriate qualitative and quantitative evaluations., Results: We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome's intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment., Conclusions: We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients., (© 2021. The Author(s).)

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P < 0.001) reduction in the muscle rigidity and catalepsy along with a significant (P < 0.001) increase in body weight, rearing behaviour, locomotion and muscle activity as compared to the rotenone-treated group in the dose dependent manner, showing maximum effect at the 50 mg/kg. It also showed reversal of levels of oxidative stress parameters thus, reducing the neuronal oxidative stress. The level of DA was also estimated which showed an increase in the level of DA in the VA plus standard drug treated animals as compared to rotenone treated group. Histopathological evaluation showed a high number of eosinophilic lesions in the rotenone group which were found to be very less in the VA co-treated group. The study thus proved that co-treatment of VA and levodopa-carbidopa, significantly protected the brain from neuronal damage due to oxidative stress and attenuated the motor defects indicating the possible therapeutic potential of VA as a neuroprotective in PD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: Attentional deficits following degeneration of brain cholinergic systems contribute to gait-balance deficits in Parkinson disease (PD). As a step toward assessing whether α4β2* nicotinic acetylcholine receptor (nAChR) stimulation improves gait-balance function, we assessed target engagement of the α4β2* nAChR partial agonist varenicline., Methods: Nondemented PD participants with cholinergic deficits were identified with [ 18 F]fluoroethoxybenzovesamicol positron emission tomography (PET). α4β2* nAChR occupancy after subacute oral varenicline treatment was measured with [ 18 F]flubatine PET. With a dose selected from the nAChR occupancy experiment, varenicline effects on gait, balance, and cognition were assessed in a double-masked placebo-controlled crossover study. Primary endpoints were normal pace gait speed and a measure of postural stability., Results: Varenicline doses (0.25mg per day, 0.25mg twice daily [b.i.d.], 0.5mg b.i.d., and 1.0mg b.i.d.) produced 60 to 70% receptor occupancy. We selected 0.5mg orally b.i.d for the crossover study. Thirty-three participants completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved sustained attention test performance. We obtained identical conclusions in 28 participants with treatment compliance confirmed by plasma varenicline measurements., Interpretation: Varenicline occupied α4β2* nicotinic acetylcholine receptors, was tolerated well, enhanced attention, and altered gait performance. These results are consistent with target engagement. α4β2* agonists may be worth further evaluation for mitigation of gait and balance disorders in PD. ANN NEUROL 2021;90:130-142., (© 2021 American Neurological Association.)

Purpose/background: This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report., Methods/procedures: This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose., Findings/results: At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours., Implications/conclusions: These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine changes in clinical features and striatal dopamine reuptake transporter (DAT) density after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH)., Methods: Participants with probable iNPH were assessed at baseline by means of clinical rating scales, brain MRI, and SPECT with [ 123 I]-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT). Levodopa responsiveness was also evaluated. Patients who did or did not undergo lumboperitoneal shunt were clinically followed up and repeated SPECT after 2 years., Results: We enrolled 115 patients with iNPH. Of 102 patients without significant levodopa response and no signs of atypical parkinsonism, 92 underwent FP-CIT SPECT (58 also at follow-up) and 59 underwent surgery. We identified a disequilibrium subtype (phenotype 1) and a locomotor subtype (phenotype 2) of higher-level gait disorder. Gait impairment correlated with caudate DAT density in both phenotypes, whereas parkinsonian signs correlated with putamen and caudate DAT binding in patients with phenotype 2, who showed more severe symptoms and lower striatal DAT density. Gait and caudate DAT binding improved in both phenotypes after surgery ( p < 0.01). Parkinsonism and putamen DAT density improved in shunted patients with phenotype 2 ( p < 0.001). Conversely, gait, parkinsonian signs, and striatal DAT binding worsened in patients who declined surgery ( p < 0.01)., Conclusions: This prospective interventional study highlights the pathophysiologic relevance of striatal dopaminergic dysfunction in the motor phenotypic expression of iNPH. Absence of levodopa responsiveness, shunt-responsive parkinsonism, and postsurgery improvement of striatal DAT density are findings that corroborate the notion of a reversible striatal dysfunction in a subset of patients with iNPH., (© 2021 American Academy of Neurology.)

Dihydromyricetin (DMY) is highly effective in counteracting acute alcohol intoxication. However, its poor aqueous solubility and permeability lead to the low oral bioavailability and limit its clinic application. The aim of this work is to use Solutol®HS15 (HS 15) as surfactant to develop novel micelle to enhance the oral bioavailability of DMY by improving its solubility and permeability. The DMY-loaded Solutol®HS15 micelles (DMY-Ms) were prepared by the thin-film hydration method. The particle size of DMY-Ms was 13.97 ± 0.82 nm with an acceptable polydispersity index of 0.197 ± 0.015. Upon entrapped in micelles, the solubility of DMY in water was increased more than 25-fold. The DMY-Ms had better sustained release property than that of pure DMY. In single-pass intestinal perfusion models, the absorption rate constant (Ka) and permeability coefficient (Papp) of DMY-Ms were 5.5-fold and 3.0-fold than that of pure DMY, respectively. The relative bioavailability of the DMY-Ms (AUC 0-∞ ) was 205% compared with that of pure DMY (AUC 0-∞ ), indicating potential for clinical application. After administering DMY-Ms, there was much lower blood alcohol level and shorter duration of the loss of righting relax (LORR) in drunk animals compared with that treated by pure DMY. In addition, the oral administration of DMY-Ms greatly reduced oxidative stress, and significantly defended liver and gastric mucosa from alcoholic damages in mice with alcohol-induced tissue injury. Taken together, HS 15-based micelle system greatly improves the bioavailability of DMY and represents a promising strategy for the management of acute alcoholism. Graphical abstract.

Parkinson's disease (PD) is characterized by motor impairment, affecting quality of life and increasing fall risk, due to ineffective postural control. To this day, the diagnosis remains based on clinical approach. Similarly, motor evaluation is based on heterogeneous, operator-dependent observational criteria. A synthetic, replicable index to quantify motor impairment is still lacking. Hence, we have designed a new measure of postural stability which assesses the trunk displacement in relation to the center of mass, that we named trunk displacement index (TDI). Twenty-three PD patients and twenty-three healthy controls underwent motor examination through a stereophotogrammetric system. A correlation analysis was performed to assess the relationship of TDI with gait parameters and clinical motor scale (UPDRS-III). The TDI sensitivity was estimated, comparing pre- and post- L-DOPA subclinical dose intake. The TDI showed significant correlations with many gait parameters and with the UPDRS-III. Furthermore, the TDI resulted capable in discriminating between off and on state in PD, whereas gait parameters failed two show any difference between those two conditions. Our results suggest that the TDI may be considered a highly sensitive biomechanical index, reflecting the overall motor condition in PD, and provided of clinical relevance due to the correlation with the clinical evaluation.

Background: The human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (huMOG-EAE) model, generates B-cell driven demyelination in mice, making it a suitable multiple sclerosis model to study B cell depletion., Objectives: We investigated the effect of subcutaneous anti-CD20 antibody treatment on huMOG-EAE gray matter (GM) pathology., Methods: C57Bl/6, 8-week old mice were immunized with 200 huMOG 1-125 and treated with 50 μg/mouse of anti-CD20 antibody (n = 16) or isotype control (n = 16). Serial brain volumetric 9.4 T MRI scans was performed at baseline, 1 and 5 wkPI. Disease severity was measured by clinical disability score (CDS) and performance on rotarod test., Results: Anti-CD20 antibody significantly reduced brain volume loss compared with the isotype control across all timepoints longitudinally in the basal ganglia (p = 0.01), isocortex (p = 0.025) and thalamus (p = 0.023). The CDS was reduced significantly with anti-CD20 antibody vs. the isotype control at 3 (p = 0.003) and 4 (p = 0.03) wkPI, while a trend was observed at 5 (p = 0.057) and 6 (p = 0.086) wkPI. Performance on rotarod was also improved significantly at 3 (p = 0.007) and 5 (p = 0.01) wkPI compared with the isotype control. At cellular level, anti-CD20 therapy suppressed the percentage of proliferative nuclear antigen positive microglia in huMOG-EAE isocortex (p = 0.016). Flow cytometry confirmed that anti-CD20 antibody strongly depleted the CD19-expressing B cell fraction in peripheral blood mononuclear cells, reducing it from 39.7% measured in isotype control to 1.59% in anti-CD20 treated mice (p < 0.001)., Conclusions: Anti-CD20 antibody treatment delayed brain tissue neurodegeneration in GM, and showed clinical benefit on measures of disease severity in huMOG-EAE mice., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Oxidative stress has been identified as one of the major causes of nigrostriatal degeneration in PD. Ascorbic acid plays a role as an efficient antioxidant to protect cells from free radical damage, but it is easily oxidized and loses its antioxidant activity. To overcome this limitation, we have recently developed NXP031, a single-stranded DNA aptamer that binds to ascorbic acid with excellent specificity, reducing its oxidation and increasing its efficacy. This study investigated the neuroprotective effects of NXP031 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Acute degeneration of nigral dopaminergic neurons was induced by four consecutive treatments of MPTP (20 mg/kg) in male C57BL/6 J mice. NXP031 (Vitamin C/Aptamin C 200 mg/4 mg/kg) was administered intraperitoneally for 5 days following MPTP. We observed that the administration of NXP031 ameliorated MPTP-induced loss of dopaminergic neurons in the SN and exhibited improvement of MPTP-mediated motor impairment. We further found that NXP031 increased plasma ascorbic acid levels and inhibited microglia activation-induced neuroinflammation in the SN, which might contribute to the protective effects of NXP031 on nigrostriatal degeneration. Our findings suggest that NXP031 could be a potential therapeutic intervention in PD., (Copyright © 2020. Published by Elsevier B.V.)

Lipid peroxidation is a key to a portfolio of neurodegenerative diseases and plays a central role in α-synuclein (α-syn) toxicity, mitochondrial dysfunction and neuronal death, all key processes in the pathogenesis of Parkinson's disease (PD). Polyunsaturated fatty acids (PUFAs) are important constituents of the synaptic and mitochondrial membranes and are often the first molecular targets attacked by reactive oxygen species (ROS). The rate-limiting step of the chain reaction of ROS-initiated PUFAs autoxidation involves hydrogen abstraction at bis-allylic sites, which can be slowed down if hydrogens are replaced with deuteriums. In this study, we show that targeted overexpression of human A53T α-syn using an AAV vector unilaterally in the rat substantia nigra reproduces some of pathological features seen in PD patients. Chronic dietary supplementation with deuterated PUFAs (D-PUFAs), specifically 0.8% D-linoleic and 0.3% H-linolenic, produced significant disease-modifying beneficial effects against α-syn-induced motor deficits, synaptic pathology, oxidative damage, mitochondrial dysfunction, disrupted trafficking along axons, inflammation and DA neuronal loss. These findings support the clinical evaluation of D-PUFAs as a neuroprotective therapy for PD.

Alzheimer's disease (AD) is a progressive, chronic and age-related neurodegenerative disorder that affects millions of people across the world. In pursuit of new anti-AD remedies, 2-[Hydroxy-(4-nitrophenyl)methyl]-cyclopentanone (NMC), a β hydroxyl ketone derivative was studied to explore its neuroprotective potentials against AD. The in-vitro AChE and BuChE enzymes inhibition were evaluated by Ellman protocol and antioxidant potentials of NMC by DPPH free radical scavenging assay. In-vivo behavioral studies were performed in the transgenic 5xFAD mice model of AD using shallow water maze (SWM), Paddling Y-Maze (PYM), elevated plus maze (EPM) and balance beam (BB) tests. Also, the ex-vivo cholinesterase inhibitory effects of NMC and histopathological analysis of amyloid-β plaques were determined in the frontal cortex and hippocampal regions of the mice brain. NMC exhibited significant in vitro anti-cholinesterase enzyme potentials with an IC 50 value of 67 μg/ml against AChE and 96 μg/ml against BuChE respectively. Interestingly, the activities of AChE and BuChE enzymes were also significantly lower in the cortex and hippocampus of NMC-treated groups. Also, in the DPPH assessment, NMC displayed substantial antioxidant properties with an IC 50 value observed as 171 μg/ml. Moreover, histopathological analysis via thioflavin-s staining displayed significantly lower plaques depositions in the cortex and hippocampus region of NMC-treated mice groups. Furthermore, SWM, PYM, EPM, and BB behavioral analysis indicated that NMC enhanced spatial learning, memory consolidation and improved balance performance. Altogether, to the best of our knowledge, we believe that NMC may serve as a potential and promising anti-cholinesterase, antioxidant and neuroprotective agent against AD.

The present work aimed to evaluate the effect of 3 mg·kg -1 caffeine consumption on the standing and dynamic balance performance of older adults and sought to establish if caffeine ingestion can modulate the influence of a cognitive dual task on balance performance. Twelve apparently healthy participants (8 females) aged >65 years (72 ± 3.7 years) completed the study. Bipedal postural sway, four square step test, timed up and go, Y-balance (anterior reach only) and force-time characteristics of sit-to-stand performance were used to assess standing and dynamic balance. Attention and working memory were assessed using a serial 3s and 7s subtraction task during seated rest and completion of the bipedal standing assessment and Y-balance test. This battery of assessments was completed on two separate occasions, once following the consumption of a non-ergogenic placebo and again following the consumption of 3 mg·kg -1 caffeine. The administration of treatments was randomised, counterbalanced and double-blind. Caffeine reduced performance in the bipedal standing balance assessments, evidenced by an increase in COP ML , COP Path , COP Velocity . Performance during the dynamic balance tests was unaffected, other than rate of force development during the sit-to-stand, which was improved following caffeine ingestion. The introduction of a cognitive dual task had either limited effects, or improved facets of bipedal standing balance, whilst performance during the dynamic balance task was significantly reduced. In both balance assessments, there was evidence for a reduction in the performance of the cognitive task when both the balance and cognitive tests were performed simultaneously, with this effect not modulated by caffeine consumption. These findings refute the idea that caffeine ingestion may have positive effects on balance performance. However, despite a caffeine-induced reduction in bipedal standing balance, it is unlikely that caffeine ingestion would exacerbate fall risk given the limited effects in the dynamic balance tests. Future work should establish if these effects are generalisable to older frail participants and if caffeine can modulate the detrimental effects of an acute exercise bout on balance performance.

Introduction: Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis., Materials and Methods: A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 μg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated., Results: The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups., Conclusions: These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.

Introduction: Postural balance is the result of a complex interaction of sensory input which keeps us upright. Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Our objective was to analyse postural stability and its relationship with the risk of falls in haemodialysis patients using a force platform., Material and Methods: This was a prospective cross-sectional study. Postural balance was recorded using a force platform in prevalent haemodialysis patients. We collected epidemiological, dialysis, analytical and treatment data. The incidence of falls was recorded over the 6 months following the tests. The postural stability analysis was performed with a portable strain gauge platform (AMTI AccuGait®) and a specific software unit for stabilometry (Balance Trainer® program). We measured 31 balance parameters; the balance variables used were: Area95; AreaEffect; VyMax; Xrange and Yrange. The stabilometry studies were performed in 3 situations: with eyes open; with eyes closed; and with the patient performing a simultaneous task. We performed one study at the start of the dialysis session, and a second study at the end. Stabilometry was measured in a control group under similar conditions., Results: We studied 32 patients with a mean age of 68 years old; of this group, 20 subjects were male and 12 were female. Their mean weight was 74kg, with a mean BMI of 27.6kg/m 2 . In the controls, there were no significant differences in the stabilometry between the 3 situations studied. Both pre- and post-haemodialysis, patients with closed eyes showed greater imbalance, and there were significant differences with the other situations and controls. We found a significant increase in instability after the haemodialysis session, and greater instability in the 13 patients with diabetes (P<.05). The 4 patients with hyponatraemia (Na<136mmol/l) had worse balance in the simultaneous task situation (P=.038). Various drugs, such as insulin (P=.022), antiplatelet agents (P=.036) and beta-blockers (P=.029), were associated with imbalance. The 10 patients who suffered falls had greater imbalance, Yrange, Xrange, Area95 and AreaEffect, both pre- and post-haemodialysis (P<.05) than those without falls., Conclusions: Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Prevention programmes which include specific exercises to improve balance could be beneficial in reducing the risk of falls in this population., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Autophagy dysfunctions are involved in the pathogenesis of Parkinson's disease (PD). In the present study, we aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) in the inhibitory effect of insulin-like growth factor-1 (IGF-1) against excessive autophagy in PD animal and cellular models. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment significantly induced mouse movement disorder and decreased the protein level of tyrosine hydroxylase (TH) in the substantia nigra (SN) and dopamine (DA) content in striatum. Along with the dopamine neuron injury, we observed significant upregulations of microtubule-associated light chain-3 II (LC3-II) and α-synuclein as well as a downregulation of P62 in MPTP-treated mice. These changes could be restored by IGF-1 pretreatment. Cotreatment with IGF-1R antagonist JB-1 or GPER antagonist G15 could block the neuroprotective effects of IGF-1. 1-Methy-4-phenylpyridinium (MPP + ) treatment could also excessively activate autophagy along with the reduction of cell viability in SH-SY5Y cells. IGF-1 could inhibit the neurotoxicity through promoting the phosphorylation of Akt and mammalian target of rapamycin (mTOR), which could also be antagonized by JB-1 or G15. These data suggest that IGF-1 inhibits MPTP/MPP + -induced autophagy on dopaminergic neurons through the IGF-1R/PI3K-Akt-mTOR pathway and GPER.

Aims: The aim of the current study was to investigate the association of type 2 diabetes (T2D) and insulin treatment with changes in muscle mass, muscle strength, and physical performance in older adults., Methods: In 731 participants of the population-based KORA-Age study aged 74.6 ± 6.2 years (T2D: n = 118; insulin treatment: n = 20), skeletal muscle index (SMI [kg/m 2 ]), hand grip strength (GS [kg]), and a timed up and go test (TUG [s]) were performed at baseline and after a follow-up time of 3 years. The association of T2D and insulin therapy with changes in muscle parameters was analyzed using linear regression models., Results: After adjustment for sex, age, BMI, physical activity, smoking, and multimorbidity, T2D was associated with the change in SMI during follow-up (β - 0.1 (95% CI - 0.3 to - 0.02) kg/m 2 ; p = 0.02), but not with a change in GS (β - 0.9 (95% CI - 1.9 to 0.04) kg) or TUG (β - 0.1 (95% CI - 0.7 to 0.5) s). Insulin therapy was positively associated with change in SMI (β 0.6 (95% CI 0.3-0.9) kg/m 2 ; p = 0.001), but not in GS (β - 1.6 (95% CI - 4.1 to 0.8) kg) or TUG (β 1.6 (95% CI - 0.2-3.4) s) in comparison with treatment with oral anti-diabetic medication alone., Conclusions: Participants with T2D showed an accelerated decline in muscle mass compared to non-diabetic participants. Insulin therapy was associated with preserved muscle mass, but not muscle function parameters, indicating a discrepancy between muscle mass and function in this high-risk population.

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1-16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected. In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected. The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech. Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research., Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis., Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes., Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary., Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance., Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) μg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) μg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed., Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

Cyclic nucleotide-gated (CNG) channels, which are directly activated by cAMP and cGMP, have long been known to play a key role in retinal and olfactory signal transduction. Emerging evidence indicates that CNG channels are also involved in signaling pathways important for pain processing. Here, we found that the expression of the channel subunits CNGA2, CNGA3, CNGA4 and CNGB1 in dorsal root ganglia, and of CNGA2 in the spinal cord, is transiently altered after peripheral nerve injury in mice. Specifically, we show using in situ hybridization and quantitative real-time RT-PCR that CNG channels containing the CNGB1b subunit are localized to populations of sensory neurons and predominantly excitatory interneurons in the spinal dorsal horn. In CNGB1 knockout (CNGB1 -/- ) mice, neuropathic pain behavior is considerably attenuated whereas inflammatory pain behavior is normal. Finally, we provide evidence to support CNGB1 as a downstream mediator of cAMP signaling in pain pathways. Altogether, our data suggest that CNGB1-positive CNG channels specifically contribute to neuropathic pain processing after peripheral nerve injury., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Anti-epileptic drug (AED) prophylaxis in the first-seven days post-traumatic brain injury (TBI) is known to reduce seizure frequency acutely. AED efficacy is equivalent; therefore, choice of AED may rest with their side-effects. We hypothesise that AEDs that impair balance will prolong recovery, shown by a longer hospital stay. We compared length of hospital stay (and reported dizziness) in TBI patients receiving the commonest AEDs used in our TBI patients, Phenytoin (which may cause imbalance), and Levetiracetam (which does not affect balance)., Method: A retrospective observational study was performed on TBI patients admitted to a Major Trauma Unit between October 2013 and June 2018. 100 of 278 patients treated with phenytoin or levetiracetam monotherapy for seizure prophylaxis were included. The inclusion criteria of admission Glasgow Coma Score of 14 or more and length of stay less than 3 weeks minimised confounding variables such as non-ambulant patients. Length of hospital stay and incidence of dizziness were assessed., Results: The length of hospital stay was longer for patients on Phenytoin versus Levetiracetam, i.e., 10.74 vs. 7.58 days (p = 0.015; unpaired, two-sided t test). Dizziness reported by patients on phenytoin was 24% and levetiracetam was 8% (p = 0.018; Chi-squared test)., Conclusion: In this cohort, using Phenytoin for acute TBI, seizure prophylaxis was associated with longer length of stay and more dizziness compared to Levetiracetam. Given their equivalent AED efficacy in acute TBI seizure prophylaxis, our data suggest that Levetiracetam is preferable to Phenytoin for early seizure prophylaxis in TBI. This requires evaluation in larger, prospective studies.

In male handball, limited knowledge exists about the body posture and postural control in correlation to their injury occurrence and their impact on physical constitution. 91 male handball players participated and were asked about playing position and years, NSAIDs intake, sustained injuries and therapy duration. A three-dimensional back scanner and a pressure measuring plate were used. Shoulder injuries cause a differing scapular height and increase the vertebrae rotation in correlation to playing years. Lower limb injuries lead to a decrease on the Centre of Pressure (CoP) with growing game experience. Wing players show the lowest injury risk. Lower limb and shoulder girdle are mostly affected regarding the incidence of injuries. Pivot players suffer most injuries in the lower limb area (59%), whereas wing players mostly have shoulder injuries (19%). Being injured, 21% of the players continue playing, 79% pause for a minimum of six months (25%). No correlation can be determined between level of profession, use of NSAIDs and body posture or postural control. Playing position, employment situation or NSAIDs have no influence on type of injury, body posture or postural control. While shoulder injuries can be recognized in the vertebrae area, lower limb injuries can affect the CoP., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose of Review: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of numerous chemotherapy drugs. CIPN negatively impacts function and quality of life during and after treatment. We will provide a review of the data describing the physical consequences of CIPN and discuss the possible long term impact on emotional well-being and quality of life., Recent Findings: CIPN negatively affects physical function and many aspects of quality of life. Exercise interventions are likely to reduce the risk of falls associated with CIPN. There remains a need for evidence-based interventions focused on improving symptoms, function, and quality of life in persons with CIPN.