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Abstract Emotions have the potential to modulate human voluntary movement by modifying muscle afferent discharge which in turn may affect kinesthetic acuity. We examined if heart rate (HR)-related physiological changes induced by music-elicited emotions would underlie alterations in healthy young adults’ ankle joint target-matching strategy quantified by joint position sense (JPS). Participants (n = 40, 19 females, age = 25.9 ± 2.9 years) performed ipsilateral-, and contralateral ankle target-matching tasks with their dominant and non-dominant foot using a custom-made foot platform while listening to classical music pieces deemed to evoke happy, sad, or neutral emotions (each n = 10). Participants in the 4th group received no music during the task. Absolute (ABS), constant (CONST), and variable (VAR) target-matching errors and HR-related data were analyzed. Participants performed the contralateral target-matching task with smaller JPS errors when listening to sad vs. happy music (ABS: p 0.05). Overall, our results suggest that music-induced emotions have the potential to affect target-matching strategy and HR-related metrics but the changes in HR-metrics do not underlie the alteration of ankle joint target-matching strategy in response to classical music-elicited emotions.

Background The similarity between movement patterns and force-vector specificity of training exercises and the target movement will likely result in the greatest transfer of the practiced skills and physical abilities to the intended sports skill performance. Therefore, this review aimed to investigate whether specific adaptations in athletic performance would be observed following direction specific exercise training. Methodology The literature search was performed in PubMed, Web of Science, and MEDLINE. Studies comparing acute (post-activation potentiation enhancement) and short-term (>2 weeks) effects of horizontally vs. vertically oriented resistance and plyometric training on athletic performance of recreationally active participants of either sex were included. The effect sizes were determined using a robust variance estimation random-effects model and were reported as Hedge’s g. Results Twenty-two studies were included. For acute studies (n = 4), a small non-significant effect favoring horizontal training (HT) for sprint performance improvements (g = −0.19, p = 0.17) was evident. For short-term studies (n = 18), the results showed non-significant, small to large differences between HT and vertical training (VT) in pooled vertical and horizontal jump improvements (g = 0.06, p = 0.67), vertical (g = 0.21, p = 0.17) and horizontal jump (g = −0.15, p = 0.40), pooled vertical and horizontal maximal strength (g = 0.27, p = 0.42), horizontal (g = −0.83, p = 0.16) and vertical maximal strength (g = 0.78, p = 0.28), pooled short and medium distance sprint (g = −0.23, p = 0.16), short (g = −0.33 [−0.85, 0.19], p = 0.19) and medium (g = −0.12 [−0.37, 0.13], p = 0.28) distance sprint, and COD speed and maneuverability (g = −0.45, p = 0.26). Conclusions HT and VT were both equally effective in improving vertically and horizontally athletic performance, potentially refuting the theory of directional specificity of training on athletic performance outcomes.

Abstract Background Beam walking is a new test to estimate dynamic balance. We characterized dynamic balance measured by the distance walked on beams of different widths in five age groups of healthy adults (20, 30, 40, 50, 60 years) and individuals with neurological conditions (i.e., Parkinson, multiple sclerosis, stroke, age: 66.9 years) and determined if beam walking distance predicted prospective falls over 12 months. Methods Individuals with (n = 97) and without neurological conditions (n = 99, healthy adults, age 20–60) participated in this prospective longitudinal study. Falls analyses over 12 months were conducted. The summed distance walked under single (walking only) and dual-task conditions (walking and serial subtraction by 7 between 300 to 900) on three beams (4, 8, and 12-cm wide) was used in the analyses. Additional functional tests comprised grip strength and the Short Physical Performance Battery. Results Beam walking distance was unaffected on the 12-cm-wide beam in the healthy adult groups. The distance walked on the 8-cm-wide beam decreased by 0.34 m in the 20-year-old group. This reduction was ~ 3 × greater, 1.1 m, in the 60-year-old group. In patients, beam walking distances decreased sharply by 0.8 m on the 8 versus 12 cm beam and by additional 1.6 m on the 4 versus 8 cm beam. Beam walking distance under single and dual-task conditions was linearly but weakly associated with age (R2 = 0.21 for single task, R2 = 0.27 for dual-task). Age, disease, and beam width affected distance walked on the beam. Beam walking distance predicted future falls in the combined population of healthy adults and patients with neurological conditions. Based on receiver operating characteristic curve analyses using data from the entire study population, walking ~ 8.0 of the 12 m maximum on low-lying beams predicted future fallers with reasonable accuracy. Conclusion Balance beam walking is a new but worthwhile measure of dynamic balance to predict falls in the combined population of healthy adults and patients with neurological conditions. Future studies are needed to evaluate the predictive capability of beam walking separately in more homogenous populations. Clinical Trial Registration Number NCT03532984.

Abstract Background Various physical fitness qualities such as muscle strength, speed and endurance are related to soccer performance. Accordingly, the combination of strength and endurance training (i.e., concurrent training [CT]) is an often-encountered training regimen in soccer. Less is known about the effects of CT sequencing on performance in young soccer players. The aim of this study was to assess the sequencing effects of strength and intermittent endurance training applied within the same training session (intrasession) on measures of physical fitness and soccer performance in young soccer players. Methods Fifty male adolescent soccer players volunteered to participate in this study which was conducted in the Netherlands in 2019. Players were randomly assigned to a strength-endurance (SE) or an endurance-strength (ES) group in matched pairs based on their countermovement jump (CMJ) performance at baseline. Both groups completed a 12-weeks in-season training program with two weekly CT sessions. Training sessions consisted of 15 min plyometric exercises and 15 min soccer-specific intermittent endurance training. Both groups performed the same training volumes and the only difference between the groups was the CT intrasession sequencing scheme (SE vs. ES). Pre and post intervention, proxies of muscle power (CMJ, squat jump [SJ]), linear sprint speed (30-m sprint test), agility (Illinois test with / without ball), and soccer performance (ball kicking velocity) were tested. Results Data from 38 players aged 14.8 ± 1.0 years (body height 172.9 ± 8.1 cm, body mass: 57.0 ± 7.2 kg, soccer experience: 8.8 ± 2.8 years, age from peak-height-velocity [PHV]: +1.2 ± 1.0 years) were included. Significant main time effects were found for CMJ (p = 0.002, d = 0.55), SJ (p = 0.004, d = 0.51), the Illinois agility test with ball (p = 0.016, d = 0.51), and ball kicking velocity (p = 0.016, d = 0.51). Significant group-by-time interactions were observed for 30-m linear sprint speed (p

Biomechanics (ISSN 2673-7078) is an international, peer-reviewed, open access journal covering all aspects of biomechanics, which can be described as the application of principles and methods of mechanics to the quantitative study of biological systems [...]

Abstract Background Despite the increasing number of research studies examining the effects of age on the control of posture, the number of annual fall-related injuries and deaths continues to increase. A better understanding of how old age affects the neural mechanisms of postural control and how countermeasures such as balance training could improve the neural control of posture to reduce falls in older individuals is therefore necessary. The aim of this review is to determine the effects of age on the neural correlates of balance skill learning measured during static (standing) and dynamic (walking) balance tasks in healthy individuals. Methods We determined the effects of acute (1–3 sessions) and chronic (> 3 sessions) balance skill training on balance in the trained and in untrained, transfer balance tasks through a systematic review and quantified these effects by robust variance estimation meta-analysis in combination with meta-regression. We systematically searched PubMed, Web of Science, and Cochrane databases. Balance performance and neural plasticity outcomes were extracted and included in the systematic synthesis and meta-analysis. Results Forty-two studies (n = 622 young, n = 699 older individuals) were included in the systematic synthesis. Seventeen studies with 508 in-analysis participants were eligible for a meta-analysis. The overall analysis revealed that acute and chronic balance training had a large effect on the neural correlates of balance skill learning in the two age groups combined (g = 0.79, p

Abstract Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed’s IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.

Background: Astrocytoma, an IDH-mutant is a common primary brain tumor. Total surgical resection is not feasible due to peritumoral infiltration mediated by extracellular matrix (ECM) molecules. Methods: This study aimed at determining the expression pattern of ECM molecules in different prognostic groups of WHO grade 2 and grade 3 patients and identifying the effect of onco-radiotherapy on tumor cell invasion of grade 3 patients. Gene and protein expression of ECM molecules was determined by qRT-PCR and immunohistochemistry, respectively. Results: In the different prognostic groups of grade 2 tumors HMMR, IDH-1, MKI-67, PDGF-A and versican, in grade 3 tumors integrin α-3, and in both groups integrin α-3 and IDH-1 mRNA expression was significantly different. Regarding protein expression, only integrin αV expression changed significantly in the prognostic groups of grade 2 tumors. Conclusions: Based on the invasion spectrum determined by this joint gene and protein expression analysis, there was a sensitivity of 87.5% and a negative predictive value of 88.9% regarding the different prognostic groups of grade 2 astrocytoma. For grade 3 tumors, the applied standard oncotherapeutic modalities apparently lacked significant anti-invasive effects.

Abstract Background The quantity and quality of skeletal muscle are important determinants of daily function and metabolic health. Various forms of physical exercise can improve muscle function, but this effect can be inconsistent and has not been systematically examined across the health-neurological disease continuum. The purpose of this systematic scoping review with meta-analyses was to determine the effects and potential moderators of exercise training on morphological and neuromuscular muscle quality (MMQ, NMQ) in healthy older individuals. In addition and in the form of a scoping review, we examined the effects of exercise training on NMQ and MMQ in individuals with neurological conditions. Methods A systematic literature search was performed in the electronic databases Medline, Embase, and Web of Science. Randomized controlled trials were included that examined the effects of exercise training on muscle quality (MQ) in older individuals with and without neurological conditions. Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling–Zhang test. Results Thirty studies (n = 1494, 34% females) in healthy older individuals and no studies in individuals with neurological conditions were eligible for inclusion. Exercise training had small effects on MMQ (g = 0.21, 95% confidence interval [CI]: 0.03–0.40, p = 0.029). Heterogeneity was low (median I 2 = 16%). Training and demographic variables did not moderate the effects of exercise on MMQ. There was no association between changes in MMQ and changes in functional outcomes. Exercise training improved NMQ (g = 0.68, 95% CI 0.35–1.01, p

Abstract Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including KCa1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to KCa1.1 in GBM are largely unknown we used electrophysiology combined with pharmacology and gene silencing to address the functional expression of KCa1.1/β subunits complexes in both primary tumor cells and in the glioblastoma cell line U-87 MG. The pattern of the sensitivity (activation/inhibition) of the whole-cell currents to paxilline, lithocholic acid, arachidonic acid, and iberiotoxin; the presence of inactivation of the whole-cell current along with the loss of the outward rectification upon exposure to the reducing agent DTT collectively argue that KCa1.1/β3 complex is expressed in U-87 MG. Similar results were found using human primary glioblastoma cells isolated from patient samples. Silencing the β3 subunit expression inhibited carbachol-induced Ca2+ transients in U-87 MG thereby indicating the role of the KCa1.1/β3 in the Ca2+ signaling of glioblastoma cells. Functional expression of the KCa1.1/β3 complex, on the other hand, lacks cell cycle dependence. We suggest that the KCa1.1/β3 complex may have diagnostic and therapeutic potential in glioblastoma in the future.

Abstract Patients undergoing unilateral orthopedic or neurological rehabilitation have different levels of impairments in the right- or left-dominant hand. However, how handedness and the complexity of the motor task affect motor skill acquisition and its interlimb transfer remains unknown. In the present study, participants performed finger key presses on a numeric keypad at 4 levels of sequence complexities with each hand in a randomized order. Furthermore, they also performed motor sequence practice with the dominant hand to determine its effect on accuracy, reaction time, and movement time. The NASA-TLX at the end of each block of both testing and practice was used to confirm participants’ mental workload related to sequence complexity. Both right- and left-handed participants performed the motor sequence task with faster RT when using their right hand. Although participants had increasing RT with increasing sequence complexity, this association was unrelated to handedness. Motor sequence practice produced motor skill acquisition and interlimb transfer indicated by a decreased RT, however, these changes were independent of handedness. Higher sequence complexity was still associated with longer RT after the practice, moreover, both right- and left-handed participants’ RT increased with the same magnitude with the increase in sequence complexity. Similar behavioral pattern was observed in MT as in RT. Overall, our RT results may indicate left-hemisphere specialization for motor sequencing tasks, however, neuroimaging studies are needed to support these findings. On the other hand, handedness did not affect motor skill acquisition by the dominant hand or interlimb transfer to the non-dominant hand regardless of task complexity level.

Abstract Detection of changes in dynamic balance could help identify older adults at fall risk. Walking on a narrow beam with its width, cognitive load, and arm position manipulated could be an alternative to current tests. Therefore, we examined additive and interactive effects of beam width, cognitive task (CT), and arm position on dynamic balance during beam walking in older adults. Twenty older adults (69 ± 4y) walked on 6, 8, and 10-cm wide beams (2-cm high, 4-m-long), with and without CT, with three arm positions (free, crossed, akimbo). We determined cognitive errors, distance walked, step speed, root mean square (RMS) of center of mass (COM) displacement and trunk acceleration in the frontal plane. Beam width decrease progressively reduced distance walked and increased trunk acceleration RMS. Step speed decreased on the narrowest beam and with CT. Arm crossing decreased distance walked and step speed. COM displacement RMS and cognitive errors were not affected by any manipulation. In conclusion, distance walked indicated that beam width and arm position, but less so CT, affected dynamic balance, implying that beam walking has the potential to become a test of fall risk. Stability measurements suggested effective trunk adjustments to control COM position and keep dynamic balance during the task.

Changes in old age that contribute to the complex issue of an increased metabolic cost of walking (mass-specific energy cost per unit distance traveled) in older adults appear to center at least in part on changes in gait biomechanics. However, age-related changes in energy metabolism, neuromuscular function and connective tissue properties also likely contribute to this problem, of which the consequences are poor mobility and increased risk of inactivity-related disease and disability. The U.S. National Institute on Aging convened a workshop in September 2021 with an interdisciplinary group of scientists to address the gaps in research related to the mechanisms and consequences of changes in mobility in old age. The goal of the workshop was to identify promising ways to move the field forward toward improving gait performance, decreasing energy cost, and enhancing mobility for older adults. This report summarizes the workshop and brings multidisciplinary insight into the known and potential causes and consequences of age-related changes in gait biomechanics. We highlight how gait mechanics and energy cost change with aging, the potential neuromuscular mechanisms and role of connective tissue in these changes, and cutting-edge interventions and technologies that may be used to measure and improve gait and mobility in older adults. Key gaps in the literature that warrant targeted research in the future are identified and discussed.

Abstract Background Age-related changes in muscle properties affect daily functioning, therefore a reliable assessment of such properties is required. We examined the effects of age on reliability, muscle quality and interrelation among muscle architecture (MA) parameters of the gastrocnemius medialis (GM), tibialis anterior (TA), and vastus lateralis (VL) muscles. Methods Three raters scored ultrasound (US) scans of 12 healthy younger and older adults, on fascicle length (FL), pennation angle (PA) and muscle thickness (MT). Intra- and inter-rater reliability of MA measures in rest and contraction was assessed by intraclass correlation coefficients (ICC) and standard error of measurements (SEM, SEM%). The relationship between MA parameters was examined using Pearson correlation coefficients. Muscle quality (MQ) was examined using mean pixel intensity. Results Reliability was moderate to excellent for TA in both groups (ICCs: 0.64–0.99, SEM% = 1.6–14.8%), and for VL in the younger group (ICCs: 0.67–0.98, SEM% = 2.0–18.3%). VL reliability was poor to excellent in older adults (ICCs: 0.22–0.99, SEM% = 2.7–36.0%). For GM, ICCs were good to excellent (ICCs: 0.76–0.99) in both groups, but GM SEM% were higher in older adults (SEM%Younger = 1.5–10.7%, SEM%Older = 1.6–28.1%). Muscle quality was on average 19.0% lower in older vs. younger adults. In both groups, moderate to strong correlations were found for VL FL and MT (r ≥ 0.54), and TA PA and MT (r ≥ 0.72), while TA FL correlated with MT (r ≥ 0.67) in younger adults only. Conclusions In conclusion, age- and muscle-specificities were present in the relationships between MT and PA, and MT and FL at rest. Furthermore, the reliability of MA parameters assessed with 2D panoramic US is acceptable. However, the level of reliability varies with age, muscle and MA measure. In older adults notably, the lowest reliability was observed in the VL muscle. Among the MA parameters, MT appears to be the simplest and most easily reproducible parameter in all muscles and age groups.

We examined the effects of side-dominance on the laterality of standing stability using ground reaction force, motion capture (MoCap), and EMG data in healthy young adults. We recruited participants with strong right (n = 15) and left (n = 9) hand and leg dominance (side-dominance). They stood on one or two legs on a pair of synchronized force platforms for 50 s with 60 s rest between three randomized stance trials. In addition to 23 CoP-related variables, we also computed six MoCap variables representing each lower-limb joint motion time series. Moreover, 39 time- and frequency-domain features of EMG data from five muscles in three muscle groups were analyzed. Data from the multitude of biosignals converged and revealed concordant patterns: no differences occurred between left- and right-side dominant participants in kinetic, kinematic, or EMG outcomes during bipedal stance. Regarding single leg stance, larger knee but lower ankle joint kinematic values appeared in left vs right-sided participants during non-dominant stance. Left-vs right-sided participants also had lower medial gastrocnemius EMG activation during non-dominant stance. While right-side dominant participants always produced larger values for kinematic data of ankle joint and medial gastrocnemius EMG activation during non-dominant vs dominant unilateral stance, this pattern was the opposite for left-sided participants, showing larger values when standing on their dominant vs non-dominant leg, i.e., participants had a more stable balance when standing on their right leg. Our results suggest that side-dominance affects biomechanical and neuromuscular control strategies during unilateral standing.

Physical fatigue (PF) negatively affects postural control, resulting in impaired balance performance in young and older adults. Similar effects on postural control can be observed for mental fatigue (MF) mainly in older adults. Controversial results exist for young adults. There is a void in the literature on the effects of fatigue on balance and cortical activity. Therefore, this study aimed to examine the acute effects of PF and MF on postural sway and cortical activity. Fifteen healthy young adults aged 28 ± 3 years participated in this study. MF and PF protocols comprising of an all-out repeated sit-to-stand task and a computer-based attention network test, respectively, were applied in random order. Pre and post fatigue, cortical activity and postural sway (i.e., center of pressure displacements [CoPd], velocity [CoPv], and CoP variability [CV CoPd, CV CoPv]) were tested during a challenging bipedal balance board task. Absolute spectral power was calculated for theta (4–7.5 Hz), alpha-2 (10.5–12.5 Hz), beta-1 (13–18 Hz), and beta-2 (18.5–25 Hz) in frontal, central, and parietal regions of interest (ROI) and baseline-normalized. Inference statistics revealed a significant time-by-fatigue interaction for CoPd (p = 0.009, d = 0.39, Δ 9.2%) and CoPv (p = 0.009, d = 0.36, Δ 9.2%), and a significant main effect of time for CoP variability (CV CoPd: p = 0.001, d = 0.84; CV CoPv: p = 0.05, d = 0.62). Post hoc analyses showed a significant increase in CoPd (p = 0.002, d = 1.03) and CoPv (p = 0.003, d = 1.03) following PF but not MF. For cortical activity, a significant time-by-fatigue interaction was found for relative alpha-2 power in parietal (p < 0.001, d = 0.06) areas. Post hoc tests indicated larger alpha-2 power increases after PF (p < 0.001, d = 1.69, Δ 3.9%) compared to MF (p = 0.001, d = 1.03, Δ 2.5%). In addition, changes in parietal alpha-2 power and measures of postural sway did not correlate significantly, irrespective of the applied fatigue protocol. No significant changes were found for the other frequency bands, irrespective of the fatigue protocol and ROI under investigation. Thus, the applied PF protocol resulted in increased postural sway (CoPd and CoPv) and CoP variability accompanied by enhanced alpha-2 power in the parietal ROI while MF led to increased CoP variability and alpha-2 power in our sample of young adults. Potential underlying cortical mechanisms responsible for the greater increase in parietal alpha-2 power after PF were discussed but could not be clearly identified as cause. Therefore, further future research is needed to decipher alternative interpretations.

Cognitive resources contribute to balance control. There is evidence that mental fatigue reduces cognitive resources and impairs balance performance, particularly in older adults and when balance tasks are complex, for example when trying to walk or stand while concurrently performing a secondary cognitive task.We conducted a systematic literature search in PubMed (MEDLINE), Web of Science and Google Scholar to identify eligible studies and performed a random effects meta-analysis to quantify the effects of experimentally induced mental fatigue on balance performance in healthy adults. Subgroup analyses were computed for age (healthy young vs. healthy older adults) and balance task complexity (balance tasks with high complexity vs. balance tasks with low complexity) to examine the moderating effects of these factors on fatigue-mediated balance performance.We identified 7 eligible studies with 9 study groups and 206 participants. Analysis revealed that performing a prolonged cognitive task had a small but significant effect (SMDwm = −0.38) on subsequent balance performance in healthy young and older adults. However, age- and task-related differences in balance responses to fatigue could not be confirmed statistically.Overall, aggregation of the available literature indicates that mental fatigue generally reduces balance in healthy adults. However, interactions between cognitive resource reduction, aging and balance task complexity remain elusive.

Random practice is a form of differential learning and its favorable acute effects on motor performance are well described when visual tasks are practiced. However, no study to date has investigated the acute effects of differential learning using variable proprioceptive stimuli instead of the visual cues. The aim of the present study was to compare the acute effects of randomized versus blocked lower-extremity proprioceptive training stimuli on balance and postural adjustments. In two conditions, healthy young males (n = 15, age = 23 years) performed 16 one-legged landings on a board tilted in four directions: 1) tilt direction unknown and randomized and 2) tilt direction known with order of presentation blocked. Multi-segmental angular sway while balancing on an unstable surface and postural responses to perturbation stimulus by surface tilts were measured before and 4 min after training. Overall frontal-plane postural sway on the unstable surface decreased (p < 0.05, η2 = 0.022) in both conditions, while sagittal-plane postural sway remained unchanged. When the surface was toes-up tilted in the perturbation test, the sagittal-plane shank-thigh-pelvis alignment improved in both conditions (p < 0.05, η2 = 0.017), but the direction of the segmental positioning was non-uniform across participants. We conclude that randomization vs. blocking of units of lower-extremity proprioceptive training did not affect balance and postural control in our cohort of healthy young adults but the improvements were test-specific.

Introduction: There are scant data to demonstrate that the long-term non-pharmaceutical interventions can slow the progression of motor and non-motor symptoms and lower drug dose in Parkinson's disease (PD).Methods: After randomization, the Exercise-only (E, n = 19) group completed an initial 3-week-long, 15-session supervised, high-intensity sensorimotor agility exercise program designed to improve the postural stability. The Exercise + Maintenance (E + M, n = 22) group completed the 3-week program and continued the same program three times per week for 6 years. The no exercise and no maintenance control (C, n = 26) group continued habitual living. In each patient, 11 outcomes were measured before and after the 3-week initial exercise program and then, at 3, 6, 12, 18, 24, 36, 48, 60, and 72 months.Results: The longitudinal linear mixed effects modeling of each variable was fitted with maximum likelihood estimation and adjusted for baseline and covariates. The exercise program strongly improved the primary outcome, Motor Experiences of Daily Living, by ~7 points and all secondary outcomes [body mass index (BMI), disease and no disease-specific quality of life, depression, mobility, and standing balance]. In E group, the detraining effects lasted up to 12 months. E+M group further improved the initial exercise-induced gains up to 3 months and the gains were sustained until year 6. In C group, the symptoms worsened steadily. By year 6, levodopa (L-dopa) equivalents increased in all the groups but least in E + M group.Conclusion: A short-term, high-intensity sensorimotor agility exercise program improved the PD symptoms up to a year during detraining but the subsequent 6-year maintenance program was needed to further increase or sustain the initial improvements in the symptoms, quality of life, and drug dose.

Alzheimer’s disease (AD) is a neurodegenerative disorder and the most common cause of dementia worldwide. In AD, neurodegeneration spreads throughout different areas of the central nervous system (CNS) in a gradual and predictable pattern, causing progressive memory decline and cognitive impairment. Deposition of neurofibrillary tangles (NFTs) in specific CNS regions correlates with the severity of AD and constitutes the basis for disease classification into different Braak stages (I-VI). Early clinical symptoms are typically associated with stages III-IV (i.e., limbic stages) when the involvement of the hippocampus begins. Histopathological changes in AD have been linked to brain proteome alterations, including aberrant posttranslational modifications (PTMs) such as the hyperphosphorylation of Tau. Most proteomic studies to date have focused on AD progression across different stages of the disease, by targeting one specific brain area at a time. However, in AD vulnerable regions, stage-specific proteomic alterations, including changes in PTM status occur in parallel and remain poorly characterized. Here, we conducted proteomic, phosphoproteomic, and acetylomic analyses of human postmortem tissue samples from AD (Braak stage III-IV, n=11) and control brains (n=12), covering all anatomical areas affected during the limbic stage of the disease (total hippocampus, CA1, entorhinal and perirhinal cortices). Overall, ~6000 proteins, ~9000 unique phosphopeptides and 221 acetylated peptides were accurately quantified across all tissues. Our results reveal significant proteome changes in AD brains compared to controls. Among others, we have observed the dysregulation of pathways related to the adaptive and innate immune responses, including several altered antimicrobial peptides (AMPs). Notably, some of these changes were restricted to specific anatomical areas, while others altered according to disease progression across the regions studied. Our data highlights the molecular heterogeneity of AD and the relevance of neuroinflammation as a major player in AD pathology. Data are available via ProteomeXchange with identifier PXD027173.

Background: Repetitive sit-to-stand (rSTS) is a fatigue perturbation model to examine the age-effects on adaptability in posture and gait, yet the age-effects on muscle activation during rSTS per se are unclear. We examined the effects of age and exhaustive rSTS on muscle activation magnitude, onset, and duration during ascent and descent phases of the STS task.Methods: Healthy older (n = 12) and younger (n = 11) adults performed rSTS, at a controlled frequency dictated by a metronome (2 s for cycle), to failure or for 30 min. We assessed muscle activation magnitude, onset, and duration of plantar flexors, dorsiflexors, knee flexors, knee extensors, and hip stabilizers during the initial and late stages of rSTS. Before and after rSTS, we measured maximal voluntary isometric knee extension force, and rate of perceived exertion, which was also recorded during rSTS task.Results: Older vs. younger adults generated 35% lower maximum voluntary isometric knee extension force. During the initial stage of rSTS, older vs. younger adults activated the dorsiflexor 60% higher, all 5 muscle groups 37% longer, and the hip stabilizers 80% earlier. Older vs. younger adults completed 467 fewer STS trials and, at failure, their rate of perceived exertion was ~17 of 20 on the Borg scale. At the end of the rSTS, maximum voluntary isometric knee extension force decreased 16% similarly in older and younger, as well as the similar age groups decline in activation of the dorsiflexor and knee extensor muscles (all p < 0.05).Conclusion: By performing 467 fewer STS trials, older adults minimized the potential effects of fatigability on muscle activation, voluntary force, and motor function. Such a sparing effect may explain the minimal changes in gait after rSTS reported in previous studies, suggesting a limited scope of this perturbation model to probe age-effects on muscle adaptation in functional tasks.

PurposeThe aim of this study was to compare the effects of moderate intensity, low volume (MILV) vs. low intensity, high volume (LIHV) strength training on sport-specific performance, measures of muscular fitness, and skeletal muscle mass in young kayakers and canoeists.MethodsSemi-elite young kayakers and canoeists (N = 40, 13 ± 0.8 years, 11 girls) performed either MILV (70–80% 1-RM, 6–12 repetitions per set) or LIHV (30–40% 1-RM, 60–120 repetitions per set) strength training for one season. Linear mixed-effects models were used to compare effects of training condition on changes over time in 250 and 2,000 m time trials, handgrip strength, underhand shot throw, average bench pull power over 2 min, and skeletal muscle mass. Both between- and within-subject designs were used for analysis. An alpha of 0.05 was used to determine statistical significance.ResultsBetween- and within-subject analyses showed that monthly changes were greater in LIHV vs. MILV for the 2,000 m time trial (between: 9.16 s, SE = 2.70, p < 0.01; within: 2,000 m: 13.90 s, SE = 5.02, p = 0.01) and bench pull average power (between: 0.021 W⋅kg–1, SE = 0.008, p = 0.02; within: 0.010 W⋅kg–1, SE = 0.009, p > 0.05). Training conditions did not affect other outcomes.ConclusionYoung sprint kayakers and canoeists benefit from LIHV more than MILV strength training in terms of 2,000 m performance and muscular endurance (i.e., 2 min bench pull power).

Although a general age-related decline in neural plasticity is evident, the effects of age on neural plasticity after motor practice are inconclusive. Inconsistencies in the literature may be related to between-study differences in task difficulty. Therefore, we aimed to determine the effects of age and task difficulty on motor learning and associated brain activity. We used task-related electroencephalography (EEG) power in the alpha (8–12 Hz) and beta (13–30 Hz) frequency bands to assess neural plasticity before, immediately after, and 24-h after practice of a mirror star tracing task at one of three difficulty levels in healthy younger (19–24 yr) and older (65–86 yr) adults. Results showed an age-related deterioration in motor performance that was more pronounced with increasing task difficulty and was accompanied by a more bilateral activity pattern for older vs. younger adults. Task difficulty affected motor skill retention and neural plasticity specifically in older adults. Older adults that practiced at the low or medium, but not the high, difficulty levels were able to maintain improvements in accuracy at retention and showed modulation of alpha TR-Power after practice. Together, these data indicate that both age and task difficulty affect motor learning, as well as the associated neural plasticity.

Abstract Alzheimer’s disease (AD) is pathologically characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tangles and widespread neuronal loss in the brain. In recent years, blood biomarkers have emerged as a realistic prospect to highlight accumulating pathology for secondary prevention trials. Neurofilament light chain (NfL), a marker of axonal degeneration, is robustly elevated in the blood of many neurological and neurodegenerative conditions, including AD. A strong relationship with cerebrospinal fluid (CSF) NfL suggests that these biomarker modalities reflect the same pathological process. Yet, the connection between blood NfL and brain tissue pathology has not been directly compared. In this study, longitudinal plasma NfL from cognitively healthy controls (n = 12) and AD participants (n = 57) were quantified by the Simoa platform. On reaching post-mortem, neuropathological assessment was performed on all participants, with additional frozen and paraffin-embedded tissue acquired from 26 participants for further biochemical (Aβ1–42, Aβ1–40, tau) and histological (NfL) evaluation. Plasma NfL concentrations were significantly increased in AD and correlated with cognitive decline, independent of age. Retrospective stratification based on Braak staging revealed that baseline plasma NfL concentrations were associated with higher neurofibrillary tangle pathology at post-mortem. Longitudinal increases in plasma NfL were observed in all Braak groupings; a significant negative association, however, was found between plasma NfL at time point 1 and both its rate of change and annual percentage increase. Immunohistochemical evaluation of NfL in the medial temporal gyrus (MTG) demonstrated an inverse relationship between Braak stages and NfL staining. Importantly, a significant negative correlation was found between the plasma NfL measurement closest to death and the level of NfL staining in the MTG at post-mortem. For the first time, we demonstrate that plasma NfL associates with the severity of neurofibrillary tangle pathology and neurodegeneration in the post-mortem brain.

Background/Aims: Reliable and valid neuropsychological tests for patients with dementia are scarce. To improve the assessment of attention and inhibitory control in dementia, we determined the feasibility, test-retest reliability, and validity of a Flanker task. Methods: Participants with all-cause diagnosed dementia (n = 22, mean age 84 years; mean Mini-Mental State Examination [MMSE] score = 19.4) performed a computerized Flanker task twice within 7 days. The Flanker task required participants to indicate the direction of target arrows flanked by congruent or incongruent arrows. Number of completed trials, accuracy, and reaction times (RTs) were recorded, and interference scores were calculated from basic scores. We examined the psychometric properties of the Flanker task and its relationship with the MMSE and Stroop test. Results: The Flanker task was feasible. Test-retest reliability was good for number of correct answers and RTs, and fair to poor for accuracy and the interference scores. The correlation of the Flanker task with Stroop and MMSE performance was fair to poor. Conclusion: The Flanker task appears to be feasible, and a reliable and valid measure of selective attention. Although the test-retest reliability for the Flanker RT interference measure was fair, future studies need to confirm its validity to measure inhibitory control in patients with dementia.

Abstract Neurodegenerative disorders are frequent, incurable diseases characterised by abnormal protein accumulation and progressive neuronal loss. Despite their growing prevalence, the underlying pathomechanism remains unclear. Lemur tyrosine kinase 2 (LMTK2) is a member of a transmembrane serine/threonine-protein kinase family. Although it was described more than a decade ago, our knowledge on LMTK2’s biological functions is still insufficient. Recent evidence has suggested that LMTK2 is implicated in neurodegeneration. After reviewing the literature, we identified three LMTK2-mediated mechanisms which may contribute to neurodegenerative processes: disrupted axonal transport, tau hyperphosphorylation and enhanced apoptosis. Moreover, LMTK2 gene expression is decreased in an Alzheimer’s disease mouse model. According to these features, LMTK2 might be a promising therapeutic target in near future. However, further investigations are required to clarify the exact biological functions of this unique protein.

Semi-quantitative scoring is a method that is widely used to estimate the quantity of proteins on chromogen-labelled immunohistochemical (IHC) tissue sections. However, it suffers from several disadvantages, including its lack of objectivity and the fact that it is a time-consuming process. Our aim was to test a recently established artificial intelligence (AI)-aided digital image analysis platform, Pathronus, and to compare it to conventional scoring by five observers on chromogenic IHC-stained slides belonging to three experimental groups. Because Pathronus operates on grayscale 0-255 values, we transformed the data to a seven-point scale for use by pathologists and scientists. The accuracy of these methods was evaluated by comparing statistical significance among groups with quantitative fluorescent IHC reference data on subsequent tissue sections. The pairwise inter-rater reliability of the scoring and converted Pathronus data varied from poor to moderate with Cohen’s kappa, and overall agreement was poor within every experimental group using Fleiss’ kappa. Only the original and converted that were obtained from Pathronus original were able to reproduce the statistical significance among the groups that were determined by the reference method. In this study, we present an AI-aided software that can identify cells of interest, differentiate among organelles, protein specific chromogenic labelling, and nuclear counterstaining after an initial training period, providing a feasible and more accurate alternative to semi-quantitative scoring.

Abstract Background A detailed gait analysis (e.g., measures related to speed, self-affinity, stability, and variability) can help to unravel the underlying causes of gait dysfunction, and identify cognitive impairment. However, because geriatric patients present with multiple conditions that also affect gait, results from healthy old adults cannot easily be extrapolated to geriatric patients. Hence, we (1) quantified gait outcomes based on dynamical systems theory, and (2) determined their discriminative power in three groups: healthy old adults, geriatric patients with- and geriatric patients without cognitive impairment. Methods For the present cross-sectional study, 25 healthy old adults recruited from community (65 ± 5.5 years), and 70 geriatric patients with (n = 39) and without (n = 31) cognitive impairment from the geriatric dayclinic of the MC Slotervaart hospital in Amsterdam (80 ± 6.6 years) were included. Participants walked for 3 min during single- and dual-tasking at self-selected speed while 3D trunk accelerations were registered with an IPod touch G4. We quantified 23 gait outcomes that reflect multiple gait aspects. A multivariate model was built using Partial Least Square- Discriminant Analysis (PLS-DA) that best modelled participant group from gait outcomes. Results For single-task walking, the PLS-DA model consisted of 4 Latent Variables that explained 63 and 41% of the variance in gait outcomes and group, respectively. Outcomes related to speed, regularity, predictability, and stability of trunk accelerations revealed with the highest discriminative power (VIP > 1). A high proportion of healthy old adults (96 and 93% for single- and dual-task, respectively) was correctly classified based on the gait outcomes. The discrimination of geriatric patients with and without cognitive impairment was poor, with 57% (single-task) and 64% (dual-task) of the patients misclassified. Conclusions While geriatric patients vs. healthy old adults walked slower, and less regular, predictable, and stable, we found no differences in gait between geriatric patients with and without cognitive impairment. The effects of multiple comorbidities on geriatric patients’ gait possibly causes a ‘floor-effect’, with no room for further deterioration when patients develop cognitive impairment. An accurate identification of cognitive status thus necessitates a multifactorial approach.

Dementia is one of the major burdens of our aging society. According to certain predictions, the number of patients will double every 20 years. Although Alzheimer’s disease (AD), as the most frequent neurodegenerative dementia, has been extensively analysed, less is known about dementia with Lewy bodies (DLB). Neuropathological hallmarks of DLB are the deposition of intracellular Lewy bodies (LB) and Lewy neurites (LN). DLB belongs to the α-synucleinopathies, as the major component of these inclusions is pathologically aggregated α-synuclein. Depending on the localization of LBs and LNs in the central nervous system cognitive and motor symptoms can occur. In our work, we will systematically review the possible etiology and epidemiology, pathological (both macroscopic and microscopic) features, structural and functional imaging findings, with a special emphasis on the clinico-pathological correlations. Finally, we summarize the latest clinical symptoms-based diagnostic criteria and the novel therapeutic approaches. Since DLB is frequently accompanied with AD pathology, highlighting possible differential diagnostic approaches is an integral part of our paper. Although our present knowledge is insufficient, the rapid development of diagnostic and research methods provide hope for better diagnosis and more efficient treatment, contributing to a better quality of life.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder. Depositions of amyloid β peptide (Aβ) and tau protein are among the major pathological hallmarks of AD. Aβ and tau burden follows predictable spatial patterns during the progression of AD. Nevertheless, it remains obscure why certain brain regions are more vulnerable than others; to investigate this and dysregulated pathways during AD progression, a mass spectrometry-based proteomics study was performed. Methods: In total 103 tissue samples from regions early (entorhinal and parahippocampal cortices - medial temporal lobe (MTL)) and late affected (temporal and frontal cortices - neocortex) by tau pathology were subjected to label-free quantitative proteomics analysis. Results: Considering dysregulated proteins during AD progression, the majority (625 out of 737 proteins) was region specific, while some proteins were shared between regions (101 proteins altered in two areas and 11 proteins altered in three areas). Analogously, many dysregulated pathways during disease progression were exclusive to certain regions, but a few pathways altered in two or more areas. Changes in protein expression indicate that synapse loss occurred in all analyzed regions, while translation dysregulation was preponderant in entorhinal, parahippocampal and frontal cortices. Oxidative phosphorylation impairment was prominent in MTL. Differential proteomic analysis of brain areas in health state (controls) showed higher metabolism and increased expression of AD-related proteins in the MTL compared to the neocortex. In addition, several proteins that differentiate brain regions in control tissue were dysregulated in AD. Conclusions: This work provides the comparison of proteomic changes in brain regions affected by tau pathology at different stages of AD. Although we identified commonly regulated proteins and pathways during disease advancement, we found that the dysregulated processes are predominantly region specific. In addition, a distinct proteomic signature was found between MTL and neocortex in healthy subjects that might be related to AD vulnerability. These findings highlight the need for investigating AD's cascade of events throughout the whole brain and studies spanning more brain areas are required to better understand AD etiology and region vulnerability to disease.

TAR DNA-binding protein 43 (TDP-43) is the major component of the ubiquitin-positive protein aggregates seen in the majority of frontotemporal lobar degeneration and amyotrophic lateral sclerosis cases. TDP-43 belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family that is involved in the regulation of RNA transcription, splicing, transport and translation. There are a great many hnRNPs, which often have overlapping functions and act cooperatively in RNA processing. Here we demonstrate that another hnRNP family member, hnRNP E2, shows a striking accumulation within dystrophic neurites and cytoplasmic inclusions in the frontal cortex and hippocampus of a subset of FTLD-TDP cases belonging to pathological subtypes A and C, where hnRNP E2 was found to co-localize with 87% of TDP-43 immunopositive inclusions. hnRNP E2-positive inclusions were not seen in FTLD-TDP cases with the C9orf72 expansion or in any other neurodegenerative disorders examined. This interaction with TDP-43 in specific FTLD subtypes suggests different underlying neurodegenerative pathways.

Osteopontin (OPN), a multifunctional phosphoglycoprotein also presents in saliva, plays a crucial role in tumour progression, inflammation and mucosal protection. Mucosal barrier injury due to high-dose conditioning regimen administered during autologous and allogeneic peripheral stem cell transplantation (APSCT) has neither efficient therapy nor established biomarkers. Our aim was to assess the biomarker role of OPN during APSCT, with primary focus on oral mucositis (OM). Serum and salivary OPN levels were determined by ELISA in 10 patients during APSCT at four stages of transplantation (day −3/−7, 0, +7, +14), and in 23 respective healthy controls. Results: There was a negative correlation between both salivary and serum OPN levels and grade of OM severity during APSCT (r = −0.791, p = 0.019; r = −0.973, p = 0.001). Salivary OPN increased at days +7 (p = 0.011) and +14 (p = 0.034) compared to controls. Among patients, it was higher at day +14 compared to the time of admission (day −3/−7) (p = 0.039) and transplantation (day 0) (p = 0.011). Serum OPN remained elevated at all four stages of transplantation compared to controls (p = 0.013, p = 0.02, p = 0.011, p = 0.028). During APSCT elevated salivary OPN is a potential non-invasive biomarker of oral mucositis whereas the importance of high serum OPN warrants further studies.

Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years’ interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H&E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely resected tumours.

Falls are the leading cause of mortality, morbidity and poor quality of life in older adults with or without neurological conditions. Applying machine learning (ML) models to gait analysis outcomes offers the opportunity to identify individuals at risk of future falls. The aim of this study was to determine the effect of different data pre-processing methods on the performance of ML models to classify neurological patients who have fallen from those who have not for future fall risk assessment. Gait was assessed using wearables in clinic while walking 20 m at a self-selected comfortable pace in 349 (159 fallers, 190 non-fallers) neurological patients. Six different ML models were trained on data pre-processed with three techniques such as standardisation, principal component analysis (PCA) and path signature method. Fallers walked more slowly, with shorter strides and longer stride duration compared to non-fallers. Overall, model accuracy ranged between 48% and 98% with 43–99% sensitivity and 48–98% specificity. A random forest (RF) classifier trained on data pre-processed with the path signature method gave optimal classification accuracy of 98% with 99% sensitivity and 98% specificity. Data pre-processing directly influences the accuracy of ML models for the accurate classification of fallers. Using gait analysis with trained ML models can act as a tool for the proactive assessment of fall risk and support clinical decision-making.

Neurological patients can have severe gait impairments that contribute to fall risks. Predicting falls from gait abnormalities could aid clinicians and patients mitigate fall risk. The aim of this study was to predict fall status from spatial-temporal gait characteristics measured by a wearable device in a heterogeneous population of neurological patients. Participants (n = 384, age 49–80 s) were recruited from a neurology ward of a University hospital. They walked 20 m at a comfortable speed (single task: ST) and while performing a dual task with a motor component (DT1) and a dual task with a cognitive component (DT2). Twenty-seven spatial-temporal gait variables were measured with wearable sensors placed at the lower back and both ankles. Partial least square discriminant analysis (PLS-DA) was then applied to classify fallers and non-fallers. The PLS-DA classification model performed well for all three gait tasks (ST, DT1, and DT2) with an evaluation of classification performance Area under the receiver operating characteristic Curve (AUC) of 0.7, 0.6 and 0.7, respectively. Fallers differed from non-fallers in their specific gait patterns. Results from this study improve our understanding of how falls risk-related gait impairments in neurological patients could aid the design of tailored fall-prevention interventions.

This systematic review and meta-analysis examined the dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairments. We included single-modality randomized controlled aerobic, anaerobic, multicomponent or psychomotor exercise trials that quantified training frequency, session and program duration and specified intensity quantitatively or qualitatively. We defined total exercise duration in minutes as the product of program duration, session duration, and frequency. For each study, we grouped test-specific Hedges' d (n = 163) and Cohen's d (n = 23) effect sizes in the domains Global cognition, Executive function and Memory. We used multilevel mixed-effects models to investigate dose-related predictors of exercise effects. In healthy older adults (n = 23 studies), there was a small positive effect of exercise on executive function (d = 0.27) and memory (d = 0.24), but dose-parameters did not predict the magnitude of effect sizes. In older adults with cognitive impairments (n = 13 studies), exercise had a moderate positive effect on global cognition (d = 0.37). For older adults with cognitive impairments, we found evidence for exercise programs with a short session duration and high frequency to predict higher effect sizes (d = 0.43-0.50). In healthy older adults, dose-parameters did not predict the magnitude of exercise effects on cognition. For older adults with cognitive impairments, exercise programs with shorter session duration and higher frequency may generate the best cognitive results. Studies are needed in which different exercise doses are directly compared among randomized subjects or conditions.

INTRODUCTION:While fatigue is ubiquitous in old age and visibly interferes with mobility, studies have not yet examined the effects of self-reported fatigue on healthy older adults' gait. As a model that simulates this daily phenomenon, we systematically reviewed eleven studies that compared the effects of experimentally induced muscle and mental performance fatigability on gait kinematics, variability, kinetics, and muscle activity in healthy older adults. METHODS:We searched for studies in databases (PubMed and Web of Science) using Fatigue, Gait, and Clinical conditions as the main terms and extracted the data only from studies that experimentally induced fatigue by sustained muscle or mental activities in healthy older adults. RESULTS:Eleven studies were included. After muscle performance fatigability, six of nine studies observed increases in stride length, width, gait velocity (Effect Size [ES] range: 0.30 to 1.22), inter-stride trunk acceleration variability (ES: 2.06), and ankle muscle coactivation during gait (ES: 0.59, n = 1 study). After sustained mental activity, the coefficient of variation of stride outcomes increased (ES: 0.59 to 0.67, n = 1 study) during dual-task but not single-task walking. CONCLUSION:Muscle performance fatigability affects spatial and temporal features of gait and, mainly, inter-stride trunk acceleration variability. In contrast, sustained mental activity tends only to affect step variability during dual tasking. A critical and immediate step for future studies is to determine the effects of self-reported fatigue on gait biomechanics and variability in healthy older adults to verify the viability of experimentally induced fatigue as a model for the study of gait adaptability in old age.

Background: Age-related changes in the sensorimotor system and cognition affect gait adaptation, especially when locomotion is combined with a cognitive task. Performing a dual-task can shift the focus of attention and thus require task prioritization, especially in older adults. To gain a better understanding of the age-related changes in the sensorimotor system, we examined how age and dual-tasking affect adaptive gait and task prioritization while walking on a split-belt treadmill.Methods: Young (21.5 ± 1.0 years, n = 10) and older adults (67.8 ± 5.8 years, n = 12) walked on a split-belt treadmill with a 2:1 belt speed ratio, with and without a cognitive Auditory Stroop task. Symmetry in step length, limb excursion, and double support time, and strategy variables swing time and swing speed were compared between the tied-belt baseline (BL), early (EA) and late split-belt adaptation (LA), and early tied-belt post-adaptation (EP).Results: Both age groups adapted to split-belt walking by re-establishing symmetry in step length and double support time. However, young and older adults differed on adaptation strategy. Older vs. young adults increased swing speed of the fast leg more during EA and LA (0.10–0.13 m/s), while young vs. older adults increased swing time of the fast leg more (2%). Dual-tasking affected limb excursion symmetry during EP. Cognitive task performance was 5–6% lower during EA compared to BL and LA in both age groups. Older vs. young adults had a lower cognitive task performance (max. 11% during EA).Conclusion: Healthy older adults retain the ability to adapt to split-belt perturbations, but interestingly age affects adaptation strategy during split-belt walking. This age-related change in adaptation strategy possibly reflects a need to increase gait stability to prevent falling. The decline in cognitive task performance during early adaptation suggests task prioritization, especially in older adults. Thus, a challenging motor task, like split-belt adaptation, requires prioritization between the motor and cognitive task to prevent adverse outcomes. This suggests that task prioritization and adaptation strategy should be a focus in fall prevention interventions.

Squamous cell papilloma (SCP) is generally a human papillomavirus (HPV) induced exophytic or endophytic proliferation on the surface of the skin, oral cavity, larynx, esophagus, cervix, vagina, and anal canal. The endophytic type SCP can cause differential diagnostic difficulties with keratoacanthoma, inverted follicular keratosis, and squamous cell carcinoma; however, these lesions are not associated with HPV infection. The authors present a female patient who noticed an extremely rapidly growing tumor destructing the left lower eyelid. The histological analysis of the biopsy sample revealed a virus-induced squamoproliferative lesion. The eyelid affected was completely removed, and the histological examination resulted in a HPV induced endophytic squamous cell papilloma. The tarsus and the conjunctiva were replaced by a chondromucosal graft harvested from the nasal septum, while the skin defect could be closed directly. Restoration of the eyelid function has been achieved with satisfying functional and cosmetic results.

Two clinically distinct diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), have recently been classified as two extremes of the FTD/ALS spectrum. The neuropathological correlate of FTD is frontotemporal lobar degeneration (FTLD), characterized by tau-, TDP-43-, and FUS-immunoreactive neuronal inclusions. An earlier discovery that a hexanucleotide repeat expansion mutation in chromosome 9 open reading frame 72 (C9orf72) gene causes ALS and FTD established a special subtype of ALS and FTLD with TDP-43 pathology (C9FTD/ALS). Normal individuals carry 2–10 hexanucleotide GGGGCC repeats in the C9orf72 gene, while more than a few hundred repeats represent a risk for ALS and FTD. The proposed molecular mechanisms by which C9orf72 repeat expansions induce neurodegenerative changes are C9orf72 loss-of-function through haploinsufficiency, RNA toxic gain-of-function, and gain-of-function through the accumulation of toxic dipeptide repeat proteins. However, many more cellular processes are affected by pathological processes in C9FTD/ALS, including nucleocytoplasmic transport, RNA processing, normal function of nucleolus, formation of membraneless organelles, translation, ubiquitin proteasome system, Notch signalling pathway, granule transport, and normal function of TAR DNA-binding protein 43 (TDP-43). Although the exact molecular mechanisms through which C9orf72 repeat expansions account for neurodegeneration have not been elucidated, some potential therapeutics, such as antisense oligonucleotides targeting hexanucleotide GGGGCC repeats in mRNA, were successful in preclinical trials and are awaiting phase 1 clinical trials. In this review, we critically discuss each proposed mechanism and provide insight into the most recent studies aiming to elucidate the molecular underpinnings of C9FTD/ALS.

Combining training of muscle strength and cardiorespiratory fitness within a training cycle could increase athletic performance more than single-mode training. However, the physiological effects produced by each training modality could also interfere with each other, improving athletic performance less than single-mode training. Because anthropometric, physiological, and biomechanical differences between young and adult athletes can affect the responses to exercise training, young athletes might respond differently to concurrent training (CT) compared with adults. Thus, the aim of the present systematic review with meta-analysis was to determine the effects of concurrent strength and endurance training on selected physical fitness components and athletic performance in youth. A systematic literature search of PubMed and Web of Science identified 886 records. The studies included in the analyses examined children (girls age 6–11 years, boys age 6–13 years) or adolescents (girls age 12–18 years, boys age 14–18 years), compared CT with single-mode endurance (ET) or strength training (ST), and reported at least one strength/power—(e.g., jump height), endurance—(e.g., peak V°O2, exercise economy), or performance-related (e.g., time trial) outcome. We calculated weighted standardized mean differences (SMDs). CT compared to ET produced small effects in favor of CT on athletic performance (n = 11 studies, SMD = 0.41, p = 0.04) and trivial effects on cardiorespiratory endurance (n = 4 studies, SMD = 0.04, p = 0.86) and exercise economy (n = 5 studies, SMD = 0.16, p = 0.49) in young athletes. A sub-analysis of chronological age revealed a trend toward larger effects of CT vs. ET on athletic performance in adolescents (SMD = 0.52) compared with children (SMD = 0.17). CT compared with ST had small effects in favor of CT on muscle power (n = 4 studies, SMD = 0.23, p = 0.04). In conclusion, CT is more effective than single-mode ET or ST in improving selected measures of physical fitness and athletic performance in youth. Specifically, CT compared with ET improved athletic performance in children and particularly adolescents. Finally, CT was more effective than ST in improving muscle power in youth.

Reductions in the base of support (BOS) make standing difficult and require adjustments in the neural control of sway. In healthy young adults, we determined the effects of reductions in mediolateral (ML) BOS on peroneus longus (PL) motor evoked potential (MEP), intracortical facilitation (ICF), short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI) using transcranial magnetic stimulation (TMS). We also examined whether participant-specific neural excitability influences the responses to increasing standing difficulty. Repeated measures ANOVA revealed that with increasing standing difficulty MEP size increased, SICI decreased (both p < 0.05) and ICF trended to decrease (p = 0.07). LICI decreased only in a sub-set of participants, demonstrating atypical facilitation. Spearman’s Rank Correlation showed a relationship of ρ = 0.50 (p = 0.001) between MEP size and ML center of pressure (COP) velocity. Measures of M1 excitability did not correlate with COP velocity. LICI and ICF measured in the control task correlated with changes in LICI and ICF, i.e., the magnitude of response to increasing standing difficulty. Therefore, corticospinal excitability as measured by MEP size contributes to ML sway control while cortical facilitation and inhibition are likely involved in other aspects of sway control while standing. Additionally, neural excitability in standing is determined by an interaction between task difficulty and participant-specific neural excitability.

Age and sex affect the neuromuscular system including performance fatigability. Data on performance fatigability and underlying mechanisms in hand muscles are scarce. Therefore, we determined the effects of age and sex on force decline, and the mechanisms contributing to force decline, during a sustained isometric maximal voluntary contraction (MVC) with the index finger abductor (first dorsal interosseous, FDI). Subjects (n = 51, age range: 19–77 years, 25 females) performed brief and a 2-min sustained MVC with the right FDI. Abduction force and root mean squared electromyographic activity (rms-EMG) were recorded in both hands. Double-pulse stimulation was applied to the ulnar nerve during (superimposed twitch) and after (doublet-force) the brief and sustained MVCs. Compared to females, males were stronger (134%, p < 0.001) and exhibited a greater decline in voluntary (difference: 8%, p = 0.010) and evoked (doublet) force (difference: 12%, p = 0.010) during and after the sustained MVC. Age did not affect MVC, force decline and superimposed twitch. The ratio between the doublet- and MVC-force was greater in females (0.33, p = 0.007) and in older (0.38, p = 0.06) individuals than in males (0.30) and younger (0.30) individuals; after the sustained MVC this ratio increased with age and the increase was larger for females compared to males (p = 0.04). The inadvertent contralateral, left force and rms-EMG activity increased over time (2.7–13.6% MVC and 5.4–17.7% MVC, respectively). Males had higher contralateral forces than females (p = 0.012) and contralateral force was higher at the start of the contralateral contraction in older compared with young subjects (difference: 29%, p = 0.008). In conclusion, our results suggest that the observed sex-differences in performance fatigability were mainly due to differences in peripheral muscle properties. Yet the reduced amount of contralateral activity and the larger difference in evoked versus voluntary force in female subjects indicate that sex-differences in voluntary activation should not be overlooked. These data obtained in neurological healthy adults provides a framework and help the interpretation and referencing of neurophysiological measures in patients suffering from neuromuscular diseases, who often present with symptoms of performance fatigability.

Alzheimer’s disease (AD) is the most common neurodegenerative dementia. Mapping the pathomechanism and providing novel therapeutic options have paramount significance. Recent studies have proposed the role of LMTK2 in AD. However, its expression pattern and association with the pathognomonic neurofibrillary tangles (NFTs) in different brain regions and neuropathological stages of AD is not clear. We performed chromogenic (CHR) LMTK2 and fluorescent phospho-tau/LMTK2 double-labelling (FDL) immunohistochemistry (IHC) on 10−10 postmortem middle frontal gyrus (MFG) and anterior hippocampus (aHPC) samples with early and late neuropathological Braak tau stages of AD. MFG in early stage was our ‘endogenous control’ region as it is not affected by NFTs. Semiquantitative CHR-IHC intensity scoring revealed significantly higher (p < 0.001) LMTK2 values in this group compared to NFT-affected regions. FDL-IHC demonstrated LMTK2 predominance in the endogenous control region, while phospho-tau overburden and decreased LMTK2 immunolabelling were detected in NFT-affected groups (aHPC in early and both regions in late stage). Spearman’s correlation coefficient showed strong negative correlation between phospho-tau/LMTK2 signals within each group. According to our results, LMTK2 expression is inversely proportionate to the extent of NFT pathology, and decreased LMTK2 level is not a general feature in AD brain, rather it is characteristic of the NFT-affected regions.

We accomplish activities of daily living through a combination of or isolated isometric, shortening (concentric), lengthening (eccentric) contractions regarded as fundamental patterns of muscle activation. It has been widely recognized that a unique neural strategy may control lengthening contractions but it is still unclear if this neural strategy is uniform across muscles. Here we review evidence for task-specific differences in neural control of muscle lengthening and shortening as indexed by surface electromyographic activity, corticospinal excitability, anatomical properties, and motor unit behavior. The emerging hypothesis is that the neural control of task-specificity associated with muscle lengthening and shortening may not be uniform across all healthy human muscles.

Fall prediction in geriatric patients remains challenging because the increased fall risk involves multiple, interrelated factors caused by natural aging and/or pathology. Therefore, we used a multi-factorial statistical approach to model categories of modifiable fall risk factors among geriatric patients to identify fallers with highest sensitivity and specificity with a focus on gait performance. Patients (n = 61, age = 79; 41% fallers) underwent extensive screening in three categories: (1) patient characteristics (e.g., handgrip strength, medication use, osteoporosis-related factors) (2) cognitive function (global cognition, memory, executive function), and (3) gait performance (speed-related and dynamic outcomes assessed by tri-axial trunk accelerometry). Falls were registered prospectively (mean follow-up 8.6 months) and one year retrospectively. Principal Component Analysis (PCA) on 11 gait variables was performed to determine underlying gait properties. Three fall-classification models were then built using Partial Least Squares-Discriminant Analysis (PLS-DA), with separate and combined analyses of the fall risk factors. PCA identified 'pace', 'variability', and 'coordination' as key properties of gait. The best PLS-DA model produced a fall classification accuracy of AUC = 0.93. The specificity of the model using patient characteristics was 60% but reached 80% when cognitive and gait outcomes were added. The inclusion of cognition and gait dynamics in fall classification models reduced misclassification. We therefore recommend assessing geriatric patients' fall risk using a multi-factorial approach that incorporates patient characteristics, cognition, and gait dynamics.

When two tasks are performed simultaneously, performance often declines in one or both tasks. These so-called dual-task costs are more pronounced in old than in young adults. One proposed neurological mechanism of the dual-task costs is that old compared with young adults tend to execute single-tasks with higher brain activation. In the brain regions that are needed for both tasks, the reduced residual capacity may interfere with performance of the dual-task. This competition for shared brain regions has been called structural interference. The purpose of the study was to determine whether structural interference indeed plays a role in the age-related decrease in dual-task performance. Functional magnetic resonance imaging (fMRI) was used to investigate 23 young adults (20-29 years) and 32 old adults (66-89 years) performing a calculation (serial subtraction by seven) and balance-simulation (plantar flexion force control) task separately or simultaneously. Behavioral performance decreased during the dual-task compared with the single-tasks in both age groups, with greater dual-task costs in old compared with young adults. Brain activation was significantly higher in old than young adults during all conditions. Region of interest analyses were performed on brain regions that were active in both tasks. Structural interference was apparent in the right insula, as quantified by an age-related reduction in upregulation of brain activity from single- to dual-task. However, the magnitude of upregulation did not correlate with dual-task costs. Therefore, we conclude that the greater dual-task costs in old adults were probably not due to increased structural interference.