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Objective: Age-related differences in neural strategies for motor learning are not fully understood. We determined the effects of age on the relationship between motor network connectivity and motor skill acquisition, consolidation, and interlimb transfer using dynamic imaging of coherent sources.Methods: Healthy younger (n = 24, 18-24 y) and older (n = 24, 65-87 y) adults unilaterally practiced a visuomotor task and resting-state electroencephalographic data was acquired before and after practice as well as at retention.Results: The results showed that right-hand skill acquisition and consolidation did not differ between age groups. However, age affected the ability to transfer the newly acquired motor skill to the non-practiced limb. Moreover, strengthened left- and right-primary motor cortex-related beta conectivity was negatively and positively associated with right-hand skill acquisition and left-hand skill consolidation in older adults, respectively.Conclusion: Age-dependent modulations of bilateral resting-state motor network connectivity indicate age-specific strategies for the acquisition, consolidation, and interlimb transfer of novel motor tasks.Significance: The present results provide insights into the mechanisms underlying motor learning that are important for the development of interventions for patients with unilateral injuries. (C) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

The purpose of this study was to determine the effects of training load (25% vs. 75% of one repetition maximum [1RM]) and fatigue (failure vs. non-failure) during four weeks of unilateral knee extension resistance training (RT) on maximal voluntary force in the trained and the untrained knee extensors. Healthy young adults (n = 42) were randomly assigned to control (CON, n = 9, 24 +/- 4.3 years), low-load RT to failure (LLF, n = 11, 21 +/- 1.3 years, three sets to failure at 25% of 1RM), high-load RT to failure (HLF, n = 11, 21 +/- 1.4 years, three sets to failure at 75% of 1RM), and high-load RT without failure (HLNF, n = 11, 22 +/- 1.5 years, six sets of five repetitions at 75% of 1RM) groups. Before and after the four weeks of training, 1RM, maximal voluntary isometric force, and corticospinal excitability (CSE) were measured. 1RM in the trained (20%, d = 0.70, 15%, d = 0.61) and the untrained knee extensors (5%, d = 0.27, 6%, d = 0.26) increased only in the HLF and HLNF groups, respectively. MVIC force increased only in the trained leg of the HLF (5%, d = 0.35) and HLNF groups (12%, d = 0.67). CSE decreased in the VL of both legs in the HLNF group (-19%, d = 0.44) and no changes occurred in the RF. In conclusion, high- but not low-load RT improves maximal voluntary force in the trained and the untrained knee extensors and fatigue did not further enhance these adaptations. Voluntary force improvements were unrelated to CSE changes in both legs.

Currently, the neuropathological diagnosis of Lewy body disease (LBD) may be stated according to several staging systems, which include the Braak Lewy body stages (Braak), the consensus criteria by McKeith and colleagues (McKeith), the modified McKeith system by Leverenz and colleagues (Leverenz), and the Unified Staging System by Beach and colleagues (Beach). All of these systems use semi-quantitative scoring (4- or 5-tier scales) of Lewy pathology (LP; i.e., Lewy bodies and Lewy neurites) in defined cortical and subcortical areas. While these systems are widely used, some suffer from low inter-rater reliability and/or an inability to unequivocally classify all cases with LP. To address these limitations, we devised a new system, the LP consensus criteria (LPC), which is based on the McKeith system, but applies a dichotomous approach for the scoring of LP (i.e., “absent” vs. “present”) and includes amygdala-predominant and olfactory-only stages. α-Synuclein-stained slides from brainstem, limbic system, neocortex, and olfactory bulb from a total of 34 cases with LP provided by the Newcastle Brain Tissue Resource (NBTR) and the University of Pennsylvania brain bank (UPBB) were scanned and assessed by 16 raters, who provided diagnostic categories for each case according to Braak, McKeith, Leverenz, Beach, and LPC systems. In addition, using LP scores available from neuropathological reports of LP cases from UPBB (n = 202) and NBTR (n = 134), JT (UPBB) and JA (NBTR) assigned categories according to all staging systems to these cases. McKeith, Leverenz, and LPC systems reached good (Krippendorff’s α ≈ 0.6), while both Braak and Beach systems had lower (Krippendorff’s α ≈ 0.4) inter-rater reliability, respectively. Using the LPC system, all cases could be unequivocally classified by the majority of raters, which was also seen for 97.1% when the Beach system was used. However, a considerable proportion of cases could not be classified when using Leverenz (11.8%), McKeith (26.5%), or Braak (29.4%) systems. The category of neocortical LP according to the LPC system was associated with a 5.9 OR (p p = 0.0001) in the 202 UPBB cases. We established that the LPC system has good reproducibility and allows classification of all cases into distinct categories. We expect that it will be reliable and useful in routine diagnostic practice and, therefore, suggest that it should be the standard future approach for the basic post-mortem evaluation of LP.

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&ndash, 99% sensitivity and 48&ndash, 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.

Purpose We examined the possibility that wearing a below-knee compression garment (CG) reduces fatigue-induced strength loss and joint position sense (JPS) errors in healthy adults. Methods Subjects (n = 24, age = 25.5 +/- 4 years) were allocated to either one of the treatment groups that performed 100 maximal isokinetic eccentric contractions at 30 degrees(-1)with the right-dominant knee extensors: (1) with (EXPCG) or (2) without CG (EXP) or to (3) a control group (CONCG:CG, no exercise). Changes in JPS errors, and maximal voluntary isometric contraction (MVIC) torque were measured immediately post-, 24 h post-, and 1 week post-intervention in each leg. All testing was done without the CG. Results CG afforded no protection against JPS errors. Mixed analysis of variance (ANOVA) revealed that absolute JPS errors increased post-intervention in EXPCG and EXP not only in the right-exercised (52%,p = 0.013; 57%,p = 0.007, respectively) but also in the left non-exercised (55%,p = 0.001; 58%,p = 0.040, respectively) leg. Subjects tended to underestimate the target position more in the flexed vs. extended knee positions (75-61 degrees: - 4.6 +/- 3.6 degrees, 60-50 degrees: - 4.2 +/- 4.3 degrees, 50-25 degrees: - 2.9 +/- 4.2 degrees), irrespective of group and time. Moreover, MVIC decreased in EXP but not in EXPCG and CONCG at immediately post-intervention (p = 0.026,d = 0.52) and 24 h post-intervention (p = 0.013,d = 0.45) compared to baseline. Conclusion Altogether, a below-knee CG reduced fatigue-induced strength loss at 80 degrees knee joint position but not JPS errors in healthy younger adults.

Supplemental digital content is available in the text., Introduction The ability to adapt dynamic balance to perturbations during gait deteriorates with age. To prevent age-related decline in adaptive control of dynamic balance, we must first understand how adaptive control of dynamic balance changes across the adult lifespan. We examined how adaptive control of the margin of stability (MoS) changes across the lifespan during perturbed and unperturbed walking on the split-belt treadmill. Methods Seventy-five healthy adults (age range, 18–80 yr) walked on an instrumented split-belt treadmill with and without split-belts. Linear regression analyses were performed for the mediolateral (ML) and anteroposterior (AP) MoS, step length, single support time, step width, double support time, and cadence during unperturbed and perturbed walking (split-belt perturbation), with age as predictor. Results Age did not significantly affect dynamic balance during unperturbed walking. However, during perturbed walking, the ML MoS of the leg on the slow belt increased across the lifespan due to a decrease in bilateral single support time. The AP MoS did not change with aging despite a decrease in step length. Double support time decreased and cadence increased across the lifespan when adapting to split-belt walking. Age did not affect step width. Conclusions Aging affects the adaptive control of dynamic balance during perturbed but not unperturbed treadmill walking with controlled walking speed. The ML MoS increased across the lifespan, whereas bilateral single support times decreased. The lack of aging effects on unperturbed walking suggests that participants’ balance should be challenged to assess aging effects during gait. The decrease in double support time and increase in cadence suggests that older adults use the increased cadence as a balance control strategy during challenging locomotor tasks.

The purpose of this study was to determine whether the increases in corticospinal excitability (CSE) observed after one session of unilateral isometric strength training (ST) are related to changes in intracortical excitability measured by magnetic brain stimulation (TMS) in the trained and the contralateral untrained biceps brachii (BB) and whether such changes scale with training intensity. On three separate days, 15 healthy young men performed one ST session of 12 sets of eight isometric contractions of the right elbow flexors at 0% (control session), 25%, or 75% of the maximal voluntary contraction (MVC) in a random order. Before and after each session separated at least by 1 week, motor evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), contralateral silent period (SP), and intracortical facilitation (ICF) generated by TMS were measured in the trained and the untrained BBs. Compared with baseline, MEPs recorded from the trained BB increased by similar to 47% after training at 75% of MVC (P .05). MEPs in the untrained BB and SICI, SP, and ICF in either BB did not change. Therefore, acute high-intensity but not low-intensity unilateral isometric ST increases CSE in the trained BB without modifications in intracortical inhibition or facilitation. Thus, increases in corticospinal neurons or alpha-alpha-motoneuron excitability could underlie the increases in CSE. Regardless of contraction intensity, acute isometric ST did not modify the excitability of the ipsilateral primary motor cortex measured by TMS.

The aim of this study was to determine the effects of acute resistance training (RT) intensity on motor-evoked potentials (MEPs) generated by transcranial magnetic brain stimulation and on cervicomedullary motor-evoked potentials (CMEPs) produced by electrical stimulation of the corticospinal tract. In four experimental sessions, 14 healthy young men performed 12 sets of eight isometric contractions of the elbow flexors at 0 (Control session), 25, 50, and 75% of the maximal voluntary contraction (MVC). Before and after each session, MEPs, CMEPs, and the associated twitch forces were recorded at rest. MEPs increased by 39% ( P < 0.05 versus 25% in the control condition, Effect size (ES) = 1.04 and 1.76, respectively) after the 50% session and by 70% ( P < 0.05 vs. all other conditions, ES = 0.91–2.49) after the 75% session. In contrast, CMEPs increased similarly after the 25%, 50%, and 75% sessions with an overall increase of 27% ( P < 0.05 vs. control condition, ES = 1.34). The amplitude of maximal compound muscle action potentials (Mmax) was unchanged during the experiment. The MEP- and CMEP-associated twitch forces also increased after RT, but training intensity affected only the increases in MEP twitch forces. The data tentatively suggest that the intensity of muscle contraction used in acute bouts of RT affects cortical excitability. NEW & NOTEWORTHY Resistance training (RT) can acutely increase the efficacy of the corticospinal-motoneuronal synapse, motoneuron excitability and motor cortical excitability. We show that motor-evoked potential generated by transcranial magnetic stimulation but not cervicomedullary electrical stimulation increased in proportion to the intensity of training used during a single session of RT. The data suggest that the intensity of muscle contraction used in acute bouts of RT affects cortical excitability.

BACKGROUND: There is evidence that physical exercise training (PET) conducted at the workplace is effective in improving physical fitness and thus health. However, there is no current systematic review available that provides high-level evidence regarding the effects of PET on physical fitness in the workforce.OBJECTIVES: To quantify sex-, age-, and occupation type-specific effects of PET on physical fitness and to characterize dose-response relationships of PET modalities that could maximize gains in physical fitness in the working population.DATA SOURCES: A computerized systematic literature search was conducted in the databases PubMed and Cochrane Library (2000-2019) to identify articles related to PET in workers.STUDY ELIGIBILITY CRITERIA: Only randomized controlled trials with a passive control group were included if they investigated the effects of PET programs in workers and tested at least one fitness measure.STUDY APPRAISAL AND SYNTHESIS METHODS: Weighted mean standardised mean differences (SMDwm) were calculated using random effects models. A multivariate random effects meta-regression was computed to explain the influence of key training modalities (e.g., training frequency, session duration, intensity) on the effectiveness of PET on measures of physical fitness. Further, subgroup univariate analyses were computed for each training modality. Additionally, methodological quality of the included studies was rated with the help of the Physiotherapy Evidence Database (PEDro) Scale.RESULTS: Overall, 3423 workers aged 30-56 years participated in 17 studies (19 articles) that were eligible for inclusion. Methodological quality of the included studies was moderate with a median PEDro score of 6. Our analyses revealed significant, small-sized effects of PET on cardiorespiratory fitness (CRF), muscular endurance, and muscle power (0.29 ≤ SMDwm ≤ 0.48). Medium effects were found for CRF and muscular endurance in younger workers (≤ 45 years) (SMDwm = 0.71) and white-collar workers (SMDwm = 0.60), respectively. Multivariate random effects meta-regression for CRF revealed that none of the examined training modalities predicted the effects of PET on CRF (R2 = 0). Independently computed subgroup analyses showed significant PET effects on CRF when conducted for 9-12 weeks (SMDwm = 0.31) and for 17-20 weeks (SMDwm = 0.74).CONCLUSIONS: PET effects on physical fitness in healthy workers are moderated by age (CRF) and occupation type (muscular endurance). Further, independently computed subgroup analyses indicated that the training period of the PET programs may play an important role in improving CRF in workers.

Supplemental digital content is available in the text., Introduction Advanced age brings a distal-to-proximal redistribution of positive joint work during walking that is relevant to walking performance and economy. It is unclear whether negative joint work is similarly redistributed in old age. Negative work can affect positive work through elastic energy return in gait. We determined the effects of age, walking speed, and grade on positive and negative joint work in young and older adults. Methods Bilateral ground reaction force and marker data were collected from healthy young (age = 22.5 yr, n = 18) and older (age = 76.0 yr, n = 22) adults walking on a split-belt instrumented treadmill at 1.1, 1.4, and 1.7 m·s−1 at each of three grades (0%, 10%, and −10%). Subjects also performed maximal voluntary eccentric, isometric, and concentric contractions for the knee extensors (120°·s−1, 90°·s−1, and 0°·s−1) and plantarflexors (90°·s−1, 30°·s−1, and 0°·s−1). Results Compared with young adults, older adults exhibited a distal-to-proximal redistribution of positive leg joint work during level (P < 0.001) and uphill (P < 0.001) walking, with larger differences at faster walking speeds. However, the distribution of negative joint work was unaffected by age during level (P = 0.150) and downhill (P = 0.350) walking. Finally, the age-related loss of maximal voluntary knee extensor (P < 0.001) and plantarflexor (P = 0.001) strength was smaller during an eccentric contraction versus concentric contraction for the knee extensors (P < 0.001) but not for the plantarflexors (P = 0.320). Conclusion The distal-to-proximal redistribution of positive joint work during level and uphill walking is absent for negative joint work during level and downhill walking. Exercise prescription should focus on improving ankle muscle function while preserving knee muscle function in older adults trying to maintain their independence.

BACKGROUND Epidemiological studies link serum potassium (K+) to cognitive performance, but whether cognitive prognosis in dementia is related to K+ levels is unknown. OBJECTIVE To determine if K+ levels predict cognitive prognosis in dementia and if this varies according to diagnosis or neuropathological findings. METHODS This longitudinal cohort study recruited 183 patients with mild Alzheimer's disease or Lewy body dementia (LBD). Serum K+ and eGFR were measured at baseline and medications which could affect K+ registered. The Mini-Mental State Examination (MMSE) was measured annually over 5 years, and mortality registered. Association between K+ and √(30 -MMSE) was estimated overall, and according to diagnosis (joint model). Associations between MMSE-decline and K+ were assessed in two subgroups with neuropathological examination (linear regression) or repeated measurements of K+ over 3 years (mixed model). RESULTS Serum K+ at baseline was associated with more errors on MMSE over time (Estimate 0.18, p = 0.003), more so in LBD (p = 0.048). The overall association and LBD interaction were only significant in the 122 patients not using K+ relevant medication. Repeated K+ measures indicated that the association with MMSE errors over time was due to a between-person effect (p

Összefoglaló. Bevezetés: A kórboncolás hozzájárul a súlyos akut légzőszervi szindrómát okozó koronavírus-2 (SARS-CoV-2-) fertőzés klinikopatológiai vonatkozásainak megismeréséhez. Célkitűzés: A SARS-CoV-2-fertőzöttek boncolása során gyűjtött tapasztalatok bemutatása. Módszer: Egymást követően boncolt, védőoltásban nem részesült, SARS-CoV-2-fertőzött elhunytak klinikai adatait, makro- és mikroszkópos észleleteit összegeztük; a tüdőkimetszéseket SARS-CoV-2-nukleokapszid-immunfestéssel vizsgáltuk. Eredmények: A boncolást a halálok megállapítására (n = 14), tumorgyanú (n = 9), illetve törvényi kötelezettség (n = 3) miatt végeztük. A fertőzést a klinikai észlelés vagy a boncolás során (n = 4) végzett SARS-CoV-2-nukleinsav-teszt igazolta. A tünetes betegség átlagos hossza 12,9 nap volt. 21 betegnél (medián életkor 69 év; 18 férfi) állt fenn COVID-19-pneumonia, mely 16 esetben önmagában, 4 esetben bakteriális pneumoniával vagy álhártyás colitisszel szövődve okozott halált; 1 antikoagulált pneumoniás beteg heveny retroperitonealis vérzésben halt meg. 3 betegnél a halált disszeminálódott malignus tumor, 1 betegnél coronariathrombosis, 1 mentálisan retardált betegnél pedig pulmonalis emboliás szövődmény okozta. A COVID-19-pneumoniás tüdők nehezek, tömöttek és vörösen foltozottak voltak. Szövettanilag a betegség időtartamától függően diffúz alveolaris károsodás korai exsudativ vagy későbbi proliferativ fázisa látszott atípusos pneumocytákkal; gyakori volt a microthrombosis (n = 7), a macrothrombosis (n = 5), illetve a pulmonalis embolia (n = 4). A SARS-CoV-2-immunfestés pozitívnak bizonyult az esetek 38,5%-ában, dominálóan az exsudativ fázisban. Minden elhunyt társbetegség(ek)ben szenvedett, így magasvérnyomás-betegségben (n = 17), érelmeszesedésben (n = 14), 2-es típusú diabetesben (n = 8), rosszindulatú daganatban (n = 6), krónikus obstruktív tüdőbetegségben (n = 4), elhízásban (n = 3), vesetranszplantáció utáni immunszuppresszióban (n = 3). Következtetés: Az irodalmi adatokkal összhangban, halálos COVID-19-pneumonia túlnyomóan idős, társbetegség(ek)től sújtott férfiakban alakult ki. A boncolási gyakorlatban a SARS-CoV-2-nukleokapszid-immunfestéstől a diffúz alveolaris károsodás korai fázisában várható pozitivitás. Orv Hetil. 2021; 162(45): 1791-1802.Autopsy is an important tool for the evaluation of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Objectice: The aim of this study was to present our experience with autopsies of patients diagnosed with SARS-CoV-2 infection.Clinical data, macroscopic and microscopic findings of consecutive postmortems of non-vaccinated SARS-CoV-2 patients are summarized. Lung samples were evaluated with SARS-CoV-2 nucleocapsid immunohistochemistry.Autopsies were performed to determine the cause of death (n = 14), suspected tumours (n = 9) or due to legal obligation (n = 3). SARS-CoV-2 infection was verified by ante mortem (n = 22) and post mortem (n = 4) polymerase chain reaction. The mean duration of symptomatic disease was 12.9 days. Of 21 patients with COVID-19 pneumonia, 16 died of respiratory failure, 4 had additional bacterial pneumonia or Clostridioides difficile infection, and 1 developed hemorrhagic complication (n = 1). Other causes of death included disseminated malignancies (n = 3), coronary thrombosis (n = 1) and pulmonary embolism (n = 1). The affected lungs were heavy and had patchy red appearance. Exudative or proliferative phases of diffuse alveolar damage (DAD) were detected with atypical pneumocytes. Microthrombosis (n = 7), macrothrombosis (n = 5) and pulmonary embolism (n = 4) were frequent. The SARS-CoV-2 immunohistochemical reaction was positive in 38.5% of cases. All patients had co-morbidities, namely, hypertension (n = 17), atherosclerosis (n = 14), diabetes (n = 8), malignancies (n = 6), chronic obstructive pulmonary diseases (n = 4), obesity (n = 3) and immunosuppression after kidney transplantation (n = 3).Fatal COVID-19 pneumonia occurred mostly in elderly males with co-morbidities. In the autopsy practice, the SARS-CoV-2 nucleocapsid immunohistochemical reaction may confirm the infectious etiology in the early phase of DAD. Orv Hetil. 2021; 162(45): 1791-1802.

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.

Heindl et al. describe the local proliferation and clustering of T cells in the brain of mice and humans after stroke. This previously unrecognized phenomenon could explain why blocking cerebral leukocyte invasion might fail to improve long-term stroke recovery., Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation—evading the systemic therapy—in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke., Graphical Abstract

Oral mucositis (OM) is a frequent complication of stem cell transplantation-associated toxicity in haematological malignancies, contributing to mortality. Therapy still remains mainly supportive. We assessed risk factors in retrospective analysis of 192 autologous peripheral stem cell transplantation patients with lymphoma and multiple myeloma (MM), respectively. Futhermore, we examined the hormone levels both in serum and saliva during transplantation in 7 postmenopausal female patients with lymphoma compared to healthy controls using electrochemiluminescence immunoassay (ECLIA). Multivariable analysis revealed neutrophil engraftment (p

Made available in DSpace on 2021-06-25T11:04:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) We examined the effects of age on intermuscular beta-band (15–35 Hz) coherence during treadmill walking before and after experimentally induced fatigue. Older (n = 12) and younger (n = 12) adults walked on a treadmill at 1.2 m/s for 3 min before and after repetitive sit-to-stand, rSTS, to induce muscle fatigability. We measured stride outcomes and coherence from 100 steps in the dominant leg for the synergistic (biceps femoris (BF)-semitendinosus, rectus femoris (RF)-vastus lateralis (VL), gastrocnemius lateralis (GL)-Soleus (SL), tibialis anterior (TA)-peroneus longus (PL)) and for the antagonistic (RF-BF and TA-GL) muscle pairs at late swing and early stance. Older vs. younger adults had 43–62% lower GL-SL, RF-VL coherence in swing and TA-PL and RF-VL coherence in stance. After rSTS, RF-BF coherence in late swing decreased by ~ 20% and TA-PL increased by 16% independent of age (p = 0.02). Also, GL-SL coherence decreased by ~ 23% and increased by ~ 23% in younger and older, respectively. Age affects the oscillatory coupling between synergistic muscle pairs, delivered presumably via corticospinal tracts, during treadmill walking. Muscle fatigability elicits age-specific changes in the common fluctuations in muscle activity, which could be interpreted as a compensation for muscle fatigability to maintain gait performance. Department of Human Movement Sciences University Medical Center Groningen University of Groningen Posture and Gait Studies Laboratory (LEPLO) Institute of Biosciences Graduate Program in Movement Sciences São Paulo State University (UNESP) Department of Physical Education Human Movement Research Laboratory (MOVI-LAB) Graduate Program in Movement Sciences São Paulo State University (UNESP) Department of Biomedical Sciences of Cells and Systems University of Groningen University Medical Center Groningen Department of Human Movement Sciences University of Groningen University Medical Center Groningen, A. Deusinglaan 1 Posture and Gait Studies Laboratory (LEPLO) Institute of Biosciences Graduate Program in Movement Sciences São Paulo State University (UNESP) Department of Physical Education Human Movement Research Laboratory (MOVI-LAB) Graduate Program in Movement Sciences São Paulo State University (UNESP) CAPES: 001 CNPq: 309045/2017-7

Healthy aging modifies neuromuscular control of dynamic balance. Challenging tasks could amplify such modifications, providing clinical insights. We examined the effects of age and walking condition difficulty on neuromuscular control of walking balance. We analyzed whole-body kinematics and activity of 13 right leg and trunk muscles in 17 young (11 males and 6 females; age 24 ± 3 years) and 14 older adults (3 males and 11 females; age 69 ± 4 years) while walking on a taped line on the floor and a 6-cm wide beam. Spatiotemporal parameters of gait, margin of stability, motor performance, and muscle synergies were estimated. Regardless of age, maintaining walking balance was more difficult on the beam compared to the taped line as evidenced by a shorter distance walked (17.3%), a reduction in step length (5.8%) and speed (10.3%), as well as a 40.0% smaller margin of stability during beam vs. tape walking. The number of muscle synergies was also higher during beam vs. tape walking. Compared to younger adults, older adults had larger margin of stability during beam walking. Older adults also had higher muscle co-activity within each muscle synergy and greater variance accounted for by the first muscle synergy regardless of condition. Such age-effects may be interpreted as a safer, less efficient, and less complex neuromuscular modular control strategy. In conclusion, beam walking increased the difficulty of maintaining walking balance and induced adaptations in modular control. It seems that healthy older adults reduce the complexity and efficiency of neuromuscular control of walking to preserve walking balance.

Objective: To determine the effects of a high-intensity exercise therapy using sensorimotor and visual stimuli on nondemented Parkinson disease (PD) patients' clinical symptoms, mobility, and standing balance.Design: Randomized clinical intervention, using a before-after trial design.Setting: University hospital setting.Participants: A total of 72 PD patients with Hoehn and Yahr stage of 2-3, of whom 64 were randomized, and 55 completed the study.Intervention: PD patients were randomly assigned to a no physical intervention control (n = 20 of 29 completed, 9 withdrew before baseline testing) or to a high-intensity agility program (15 sessions, 3 weeks, n=35 completed).Main Outcome Measures: Primary outcome was the Movement Disorders Society -Unified Parkinson Disease Rating Scale (MDS-UPDRS) motor experiences of daily living (M-EDL). Secondary outcomes were Beck Depression score, Parkinson Disease Questionnaire-39 (PDQ-39), EuroQoL Five-Dimension (EQ5D) Questionnaire visual analog scale, Schwab and England Activities of Daily Living (SE ADL) Scale, timed Up and Go (TUG) test, and 12 measures of static posturography.Results: The agility program improved MDS-UPDRS M-EDL by 38% compared with the 2% change in control (group by time interaction, P=.001). Only the intervention group improved in PDQ-39 (6.6 points), depression (18%), EQ5D visual analog scale score (15%), the SE ADL Scale score (15%), the TUG test (39%), and in 8 of 12 posturography measures by 42%-55% (all PConclusion: A high -intensity agility program improved nondemented, stage 2-3 PD patients' clinical symptoms, mobility, and standing balance by functionally meaningful margins at short-term follow-up. (C) 2018 by the American Congress of Rehabilitation Medicine

PurposeWe examined the possibility that old adults use flexibility in joint coordination as a compensatory mechanism for the age-related decline in muscle strength when performing the sit-to-stand (STS) task repeatedly under high force and balance demands.MethodYoung (n=14, 22.42.1) and old (n=12, 703.2) healthy adults performed repeated STSs under high and low force and balance demands. The balance demand was manipulated by reducing the base of support and the force demand by increasing body weight with a weight vest. Uncontrolled manifold analysis was used to quantify age differences in motor flexibility.Results p id= Par3 While there were age-typical differences in kinematic STS strategies, flexibility in joint coordination was independent of age and task difficulty during repeated STSs.Discussion p id=Par4That simple manipulations of force and balance demands did not affect flexibility in joint coordination in old and young adults suggests that motor flexibility acts as a compensatory mechanism only at the limits of available muscle strength and balance abilities during STS movements. Intervention studies should identify how changes in specific neuromuscular functions affect flexibility in joint coordination during activities of daily living such as STS.

Objectives: To directly compare the effects of agility exergaming (EXE) and stationary cycling (CYC) exercise training on Parkinson’s disease (PD) patients’ mobility and clinical symptoms. Design: Randomized clinical trial. Setting: Outpatient physiotherapy clinic in a hospital. Participants: Seventy-four stage 2–3, nondemented PD patients were included in this study. Intervention: The groups were as follows: EXE (n = 25), CYC (n = 25), and a wait-listed control group (CON; n = 24). The EXE and CYC groups exercised 5×/week for 5 weeks, matched at 80% of the age-predicted maximal heart rate. Main Outcomes: The primary outcome was the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (UPDRS-II) score. Secondary outcomes were Parkinson’s Disease Quastionnaire-39 (PDQ-39), the Beck Depression Inventory (BDI), the Schwab and England Activities of Daily Living (SE-ADL) scale, Euro-Quality of Life-5 Dimensions (EQ-5D) questionnaire, the Berg Balance Scale (BBS), the Balance Evaluation Systems Test (BESTest), the Tinetti Assessment Tool (TAT), the Dynamic Gait Index, the 6-min walk test (6MWT), and standing posturography. Results: After treatment, UPDRS-II scores improved (mean change: EXE, –4.5 points; CYC, –3.2 points). The results for the other outcomes (EXE and CYC, respectively) were: PDQ, 13 and 17%; BDI, –2.5 and –2.1 points; 6MWT, 129.6 and 141.6 m; and EQ-5D, 12 and 9% (all p < 0.05, but there was no difference between groups). EXE vs. CYC resulted in improved SE-ADL (8.4 and 4.0 points, effect size [ES]: 0.12), BBS (8.8 and 4.2 points, ES: 0.44), and 2 measures of posturography (ES: 0.11 and 0.21) (p < 0.05). BESTtest, TAT, the Dynamic Gait Index, and 4 out of 6 posturography measures did not change (p > 0.05). Conclusion: Two highly different exercise programs resulted in similar improvement of most motor and clinical symptoms in PD patients.

PURPOSE: Limited evidence suggests that cross-education affords clinical benefits in the initial 8 weeks after anterior cruciate ligament (ACL) reconstruction, but it is unknown if such cross-education effects are reproducible and still present in later phases of rehabilitation. We examined whether cross-education, as an adjuvant to standard therapy, would accelerate the rehabilitation up to 26 weeks after ACL reconstruction by attenuating quadriceps weakness.METHODS: ACL-reconstructed patients were randomized into experimental (n = 22) and control groups (n = 21). Both groups received standard care after ACL reconstruction. In addition, the experimental group strength trained the quadriceps of the non-operated leg during weeks 1-12 after surgery (i.e., cross-education). Self-reported knee function was assessed with the Hughston Clinic Knee score as the primary outcome. Secondary outcomes were maximal quadriceps and hamstring strength and single leg hop distance. All outcomes were measured 29 ± 23 days prior to surgery, as a reference, and at 5-week, 12-week, and 26-week post-surgery.RESULTS: Both groups scored 12% worse on self-reported knee function 5-week post-surgery (95% CI 7-17) and showed 15% improvement 26-week post-surgery (95% CI - 20 to - 10). No cross-education effect was found. Interestingly, males scored 8-10% worse than females at each time point post-surgery. None of 33 secondary outcomes showed a cross-education effect. At 26-week post-surgery, both legs improved maximal quadriceps (5-14%) and hamstring strength (7-18%), and the non-injured leg improved 2% in hop distance. The ACL recovery was not affected by limb dominance and age.CONCLUSION: 26 weeks of standard care improved self-reported knee function and maximal leg strength relative to pre-surgery and adding cross-education did not further accelerate ACL recovery.LEVEL OF EVIDENCE: I.CLINICAL TRIAL REGISTRY NAME AND REGISTRATION: This randomized controlled clinical trial is registered at the Dutch trial register ( http://www.trialregister.nl ) under NTR4395.

Introduction Task difficulty affects the amount of interpretable information from a task, which is thought to interfere with motor learning. However, it is unclear whether task difficulty in itself is a stimulus for motor learning because the experimental evidence is mixed in support of the optimal challenge point framework that predicts one specific level of task difficulty to produce the greatest magnitude of motor learning.Purpose We determined the effects of functional task difficulty on motor skill acquisition, retention, and transfer.Methods Healthy young participants (N = 36) learned a mirror star-tracing task at a low, medium, or hard difficulty level defined by the bandwidth of the star. We measured skill acquisition, retention, and transfer to untrained difficulty levels, as well as the perceived mental workload during the task.Results Task difficulty affected motor performance, but did not affect motor learning and transfer. For the groups that practiced the task at the medium and hard but not at the low difficulty level, initial skill level correlated with the magnitude of learning.Conclusions The optimal challenge point framework does not capture the complex relationship between task difficulty and motor learning. Previously reported effects of task difficulty on the magnitude of motor learning are probably mediated by perceived mental workload. Task difficulty did not affect the magnitude of visuomotor skill learning but it affected how learning occurred. The data have implications on how athletes learn new motor skills and patients relearn injury-impaired motor skills during rehabilitation.

Aims Right- and left-side-dominant individuals reveal target-matching asymmetries between joints of the dominant and non-dominant upper limbs. However, it is unclear if such asymmetries are also present in lower limb’s joints. We hypothesized that right-side-dominant participants perform knee joint target-matching tasks more accurately with their non-dominant leg compared to left-side-dominant participants. Methods Participants performed position sense tasks using each leg by moving each limb separately and passively on an isokinetic dynamometer. Results Side-dominance affected (p Conclusions In conclusion, right-side-dominant participants tend to perform a target-matching task more accurately with the non-dominant leg compared to left-side-dominant participants. Our results extend the literature by showing that right-hemisphere specialization under proprioceptive target-matching tasks may be not evident at the lower limb joints.

The interaction between the somatosensory and motor systems is important for normal human motor function and learning. Enhancing somatosensory input using somatosensory electrical stimulation (SES) can increase motor performance, but the neuronal mechanisms underlying these effects are largely unknown. With EEG, we examined whether skill acquisition, consolidation, and interlimb transfer after SES was related to increased activity in sensorimotor regions, as assessed by the N30 somatosensory evoked potential or rather increased connectivity between these regions, as assessed by the phase slope index (PSI). Right- and left-hand motor performance and EEG measures were taken before, immediately after, and 24 h ( day 2) after either SES ( n = 12; 5 men) or Control ( n = 12; 5 men). The results showed skill acquisition and consolidation in the stimulated right hand immediately after SES (6%) and on day 2 (9%) and interlimb transfer to the nonstimulated left hand on day 2 relative to Control (8%, all P < 0.05). Increases in N30 amplitudes correlated with skill acquisition while PSI from electrodes that represent the posterior parietal and primary somatosensory cortex to the electrode representing the primary motor cortex correlated with skill consolidation. In contrast, interlimb transfer did not correlate with the EEG-derived neurophysiological estimates obtained in the present study, which may indicate the involvement of subcortical structures in interlimb transfer after SES. In conclusion, weak peripheral somatosensory inputs in the form of SES improve skill acquisition, consolidation, and interlimb transfer that coincide with different cortical adaptations, including enhanced N30 amplitudes and PSI.NEW & NOTEWORTHY The relationship between adaptations in synaptic plasticity and motor learning following somatosensory electrical stimulation (SES) is incompletely understood. Here, we used for the first time a multifactorial approach that examined skill acquisition, consolidation, and interlimb transfer following 20 min of SES. In addition, we quantified sensorimotor integration and the magnitude and direction of connectivity with EEG. Following artificial electrical stimulation, increases in sensorimotor integration and connectivity were found to correlate with skill acquisition and consolidation, respectively.

Purpose:\ud \ud Cross-education reduces quadriceps weakness 8 weeks after anterior cruciate ligament (ACL) surgery, but the long-term effects are unknown. We investigated whether cross-education, as an adjuvant to the standard rehabilitation, would accelerate recovery of quadriceps strength and neuromuscular function up to 26 weeks post-surgery.\ud \ud Methods:\ud \ud Group allocation was randomized. The experimental (n = 22) and control (n = 21) group received standard rehabilitation. In addition, the experimental group strength trained the quadriceps of the non-injured leg in weeks 1–12 post-surgery (i.e., cross-education). Primary and secondary outcomes were measured in both legs 29 ± 23 days prior to surgery and at 5, 12, and 26 weeks post-surgery.\ud \ud Results:\ud \ud The primary outcome showed time and cross-education effects. Maximal quadriceps strength in the reconstructed leg decreased 35% and 12% at, respectively, 5 and 12 weeks post-surgery and improved 11% at 26 weeks post-surgery, where strength of the non-injured leg showed a gradual increase post-surgery up to 14% (all p ≤ 0.015). Limb symmetry deteriorated 9–10% more for the experimental than control group at 5 and 12 weeks post-surgery (both p ≤ 0.030). One of 34 secondary outcomes revealed a cross-education effect: Voluntary quadriceps activation of the reconstructed leg was 6% reduced for the experimental vs. control group at 12 weeks post-surgery (p = 0.023). Both legs improved force control (22–34%) and dynamic balance (6–7%) at 26 weeks post-surgery (all p ≤ 0.043). Knee joint proprioception and static balance remained unchanged.\ud \ud Conclusion:\ud \ud Standard rehabilitation improved maximal quadriceps strength, force control, and dynamic balance in both legs relative to pre-surgery but adding cross-education did not accelerate recovery following ACL reconstruction.

Mutations in the DMD gene lead to Duchenne and Becker muscular dystrophy (DMD/BMD). Missense mutations are rare cause of DMD/BMD. A six-month-old male patient presented with mild generalized muscle weakness, hypotonia, and delayed motor development. Dystrophinopathy was suspected because of highly elevated serum creatine kinase level (1497 U/L) and tiered DMD gene analysis was performed. Multiplex ligation-dependent probe amplification (MLPA) assay showed deletion of exon 4, which could not be confirmed by another method. Sequencing of exon 4 revealed a novel de novo point mutation (c.227A>T, p.Asn76Ile) in the N-terminal actin-binding domain (N-ABD) of dystrophin protein. The false positive MLPA result was explained by the fact that the affected nucleotide lies directly at the 3' ligation site of the MLPA probe. Sequencing of the whole coding region of DMD gene proved c.227A>T to be the sole variant being potentially pathogenic. According to in silico analyses the mutation was predicted to be highly destabilizing on N-ABD structure possibly leading to protein malfunction. Muscle biopsy was performed and dystrophin immunohistochemistry results were suggestive of BMD. Our results highlight the importance of confirmatory testing of single-exon deletions detected by MLPA and we describe a novel, destabilizing missense mutation in the DMD gene.

Sensory input can modify motor function and magnify interlimb transfer. We examined the effects of low-intensity somatosensory electrical stimulation (SES) on motor practice-induced skill acquisition and intermanual transfer. Participants practiced a visuomotor skill for 25 min and received SES to the practice or the transfer arm. Responses to single- and double-pulse transcranial magnetic stimulation were measured in both extensor carpi radialis. SES did not further increase skill acquisition (motor practice with right hand [RMP]: 30.8% and motor practice with right hand + somatosensory electrical stimulation to the right arm [RMP + RSES]: 27.8%) and intermanual transfer (RMP: 13.6% and RMP + RSES: 9.8%) when delivered to the left arm (motor practice with right hand + somatosensory electrical stimulation to the left arm [RMP + LSES]: 44.8% and 18.6%, respectively). Furthermore, transcranial magnetic stimulation measures revealed no changes in either hand. Future studies should systematically manipulate SES parameters to better understand the mechanisms of how SES affords motor learning benefits documented but not studied in patients.

Background:Walking ability recently emerged as a sub-clinical marker of cognitive decline. Hence, the relationship between baseline gait and future cognitive decline was examined in geriatric patients. Because a “loss of complexity” (LOC) is a key phenomenon of the aging process that exhibits in multiple systems, we propose the idea that age- and cognition-related LOC may also become manifested in gait function. The LOC theory suggests that even healthy aging is associated with a (neuro)physiological breakdown of system elements that causes a decline in variability and an overall LOC. We used coordination dynamics as a conceptual framework and hypothesized that a LOC is reflected in dynamic gait outcomes (e.g. gait regularity, complexity, stability) and that such outcomes could increase the specificity of the gait-cognition link.Methods:19 geriatric patients (age 80.0±5.8) were followed for 14.4±6.6 months. An iPod collected three-dimensional (3D) trunk accelerations while patients walked for 3 minutes. Cognition was evaluated with the Mini-Mental State Examination (MMSE) and the Seven-Minute screen (7MS) test. The Reliable Change Index (RCI) quantified the magnitude of cognitive change. Spearman's Rho coefficients (ρ) indexed correlations between baseline gait and future cognitive change.Results:Seven patients showed reliable cognitive decline (“Cognitive Decline” group), and 12 patients remained cognitively stable (“Cognitive Stable” group) over time. Future cognitive decline was correlated with a more regular (ρ = 0.579*) and predictable (ρ = 0.486*) gait pattern, but not with gait speed.Conclusions:The increase in gait regularity and predictability possibly reflects a LOC due to age- and cognition-related (neuro)physiological decline. Because dynamic versus traditional gait outcomes (i.e. gait speed and (variability of) stride time) were more strongly correlated with future cognitive decline, the use of wearable sensors in predicting and monitoring cognitive and physical health in vulnerable geriatric patients can be considered promising. However, our results are preliminary and do require replication in larger cohorts.

Purpose The Drug Burden Index (DBI) is a tool to quantify the anticholinergic and sedative load of drugs. Establishing functional correlates of the DBI could optimize drug prescribing in patients with dementia. In this cross-sectional study, we determined the relationship between DBI and cognitive and physical functions in a sample of patients with dementia. Methods Using performance-based tests, we measured physical and cognitive functions in 140 nursing home patients aged over 70 with all-cause dementia. We also determined anticholinergic DBI (AChDBI) and sedative DBI (SDBI) separately and in combination as total drug burden (TDB). Results Nearly one half of patients (48%) used at least one DBI-contributing drug. In 33% of the patients, drug burden was moderate (0 0.05). Conclusions A lack of association between drug burden and physical or cognitive function in this sample of patients with dementia could imply that drug prescribing is more optimal for patients with dementia compared with healthy older populations. However, such an interpretation of the data warrants scrutiny as several dementia-related factors may confound the results of the study. Electronic supplementary material The online version of this article (10.1007/s00228-017-2319-y) contains supplementary material, which is available to authorized users.

Background Balance and resistance training can improve healthy older adults' balance and muscle strength. Delivering such exercise programs at home without supervision may facilitate participation for older adults because they do not have to leave their homes. To date, no systematic literature analysis has been conducted to determine if supervision affects the effectiveness of these programs to improve healthy older adults' balance and muscle strength/ power. Objectives The objective of this systematic review and meta-analysis was to quantify the effectiveness of supervised vs. unsupervised balance and/or resistance training programs on measures of balance and muscle strength/ power in healthy older adults. In addition, the impact of supervision on training-induced adaptive processes was evaluated in the form of dose-response relationships by analyzing randomized controlled trials that compared supervised with unsupervised trials. Data Sources A computerized systematic literature search was performed in the electronic databases PubMed, Web of Science, and SportDiscus to detect articles examining the role of supervision in balance and/or resistance training in older adults. Study Eligibility Criteria The initially identified 6041 articles were systematically screened. Studies were included if they examined balance and/or resistance training in adults aged >= 65 years with no relevant diseases and registered at least one behavioral balance (e.g., time during single leg stance) and/or muscle strength/ power outcome (e.g., time for 5-Times-Chair-Rise-Test). Finally, 11 studies were eligible for inclusion in this meta-analysis. Study Appraisal Weighted mean standardized mean differences between subjects (SMDbs) of supervised vs. unsupervised balance/resistance training studies were calculated. The included studies were coded for the following variables: number of participants, sex, age, number and type of interventions, type of balance/strength tests, and change (%) from pre- to post-intervention values. Additionally, we coded training according to the following modalities: period, frequency, volume, modalities of supervision (i.e., number of supervised/unsupervised sessions within the supervised or unsupervised training groups, respectively). Heterogeneity was computed using I 2 and chi(2) statistics. The methodological quality of the included studies was evaluated using the Physiotherapy Evidence Database scale. Results Our analyses revealed that in older adults, supervised balance/resistance training was superior compared with unsupervised balance/resistance training in improving measures of static steady-state balance (mean SMDbs = 0.28, p = 0.39), dynamic steady-state balance (mean SMDbs = 0.35, p = 0.02), proactive balance (mean SMDbs = 0.24, p = 0.05), balance test batteries (mean SMDbs = 0.53, p = 0.02), and measures of muscle strength/power (mean SMDbs = 0.51, p = 0.04). Regarding the examined dose-response relationships, our analyses showed that a number of 10-29 additional supervised sessions in the supervised training groups compared with the unsupervised training groups resulted in the largest effects for static steady-state balance (mean SMDbs = 0.35), dynamic steady-state balance (mean SMDbs = 0.37), and muscle strength/power (mean SMDbs = 1.12). Further, >= 30 additional supervised sessions in the supervised training groups were needed to produce the largest effects on proactive balance (mean SMDbs = 0.30) and balance test batteries (mean SMDbs = 0.77). Effects in favor of supervised programs were larger for studies that did not include any supervised sessions in their unsupervised programs (mean SMDbs: 0.28-1.24) compared with studies that implemented a few supervised sessions in their unsupervised programs (e.g., three supervised sessions throughout the entire intervention program; SMDbs: -0.06 to 0.41). Limitations The present findings have to be interpreted with caution because of the low number of eligible studies and the moderate methodological quality of the included studies, which is indicated by a median Physiotherapy Evidence Database scale score of 5. Furthermore, we indirectly compared dose-response relationships across studies and not from single controlled studies. Conclusions Our analyses suggest that supervised balance and/or resistance training improved measures of balance and muscle strength/power to a greater extent than unsupervised programs in older adults. Owing to the small number of available studies, we were unable to establish a clear dose-response relationship with regard to the impact of supervision. However, the positive effects of supervised training are particularly prominent when compared with completely unsupervised training programs. It is therefore recommended to include supervised sessions (i.e., two out of three sessions/week) in balance/resistance training programs to effectively improve balance and muscle strength/power in older adults.

Comprehensive molecular characterization of and novel therapeutic approaches to glioblastoma have been explored as a result of advancements in biotechnologies. In this study, we aimed to bring basic research discoveries closer to clinical practice and ultimately incorporate molecular classification into the routine histopathological evaluation of grade IV gliomas. Integrated results of genome-wide sequencing, transcriptomic and epigenomic analyses by The Cancer Genome Atlas Network defined the classic, proneural, neural and mesenchymal subtypes of this tumor. In a retrospective cohort, we analyzed selected subgroup-defining molecular markers in formalin-fixed paraffin-embedded surgical specimens by immunohistochemistry. Quantitative and qualitative scores of marker expression were tested in hierarchical cluster analyses to evaluate segregations of the molecular subgroups, which then were correlated with clinical parameters including patients' age, gender and overall survival. Our study has confirmed the separation of molecular glioblastoma subgroups with clear trends regarding clinical correlations. Future analyses in a larger, prospective cohort using similar methods are expected to facilitate the development of a molecular diagnostic panel that may complement routine histological work up and support prognostication as well as treatment decisions in glioblastoma.

Aims The aim of this study was to examine the effects of gender on the relationship between Functional Movement Screen (FMS) and treadmill-based gait parameters. Methods Twenty elite junior athletes (10 women and 10 men) performed the FMS tests and gait analysis at a fixed speed. Between-gender differences were calculated for the relationship between FMS test scores and gait parameters, such as foot rotation, step length, and length of gait line. Results Gender did not affect the relationship between FMS and treadmill-based gait parameters. The nature of correlations between FMS test scores and gait parameters was different in women and men. Furthermore, different FMS test scores predicted different gait parameters in female and male athletes. FMS asymmetry and movement asymmetries measured by treadmill-based gait parameters did not correlate in either gender. Conclusion There were no interactions between FMS, gait parameters, and gender; however, correlation analyses support the idea that strength and conditioning coaches need to pay attention not only to how to score but also how to correctly use FMS.

Study Design: Eighteen healthy male adults were assigned to either an intervention or control group.Objectives: Isogai dynamic therapy (IDT) is one of Japanese stretching interventions and has been practiced for over 70 years. However, its scientific quantitative evidence remains unestablished. The objective of this study was to determine whether IDT could modify lumbar curvature in healthy young adults compared with stretching exercises used currently in clinical practice.Summary of Background Data: None of previous studies have provided data that conventional stretching interventions could modify spinal curvatures. However, this study provides the first evidence that a specific form of a Japanese stretching intervention can acutely modify the spinal curvatures.Methods: We compared the effects of IDT, a Japanese stretching intervention (n= 9 males), with a conventional stretching routine (n= 9 males) used widely in clinics to modify pelvic tilt and lumbar lordosis (LL) angle. We measured thoracic kyphosis (TK) and LL angles 3 times during erect standing using the Spinal Mouse before and after each intervention. IDT consisted of: (1) hip joint correction, (2) pelvic tilt correction, (3) lumbar alignment correction, and (4) squat exercise stretch. The control group performed hamstring stretches while (1) standing and (2) sitting.Results: IDT increased LL angle to 25.1 degrees (+/- 5.9) from 21.2 degrees (+/- 6.9) (P= 0.047) without changing TK angle (pretest: 36.8 degrees [+/- 6.9]; posttest: 36.1 degrees [+/- 6.5]) (P= 0.572). The control group showed no changes in TK (P= 0.819) and LL angles (P= 0.744).Conclusions: IDT can thus be effective for increasing LL angle, hence anterior pelvic tilt. Such modifications could ameliorate low back pain and improve mobility in old adults with an unfavorable pelvic position.

It is unclear how old age affects the neuronal mechanisms of motor learning. We reviewed the neuronal mechanisms of how healthy old and young adults acquire motor skills as assessed with transcranial magnetic stimulation. Quantitative meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed by upper extremity muscles in 132 healthy old and 128 young adults, revealed that the motor practice-induced increase in corticospinal excitability (CSE) is task-dependent but not age-dependent, with an increase in CSE in both age groups after visuomotor but not ballistic training. In addition, short-interval intracortical inhibition (SICI) is reduced in old but not young adults, but only after visuomotor practice. In addition, correlation analyses in 123 old and 128 young adults showed that the magnitude of motor skill acquisition did not correlate with increases in CSE or decreases in SICI in either age group. Thus, there are subtle age-related differences in use-dependent plasticity but increases in CSE or decreases in SICI are not related to motor skill acquisition in healthy young or old adults.

// Balazs Murnyak 1 , Mahan C. Kouhsari 1 , Rotem Hershkovitch 1 , Bernadette Kalman 2, 3 , Gyorgy Marko-Varga 4 , Almos Klekner 5 and Tibor Hortobagyi 1, 6 1 Division of Neuropathology, Institute of Pathology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary 2 Institute of Diagnostics, Faculty of the Health Sciences, University of Pecs, Pecs, Hungary 3 Molecular Pathology Unit, Markusovszky Teaching Hospital, Szombathely, Hungary 4 Division of Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden 5 Department of Neurosurgery, Faculty of Medicine, University of Debrecen, Debrecen, Hungary 6 Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK Correspondence to: Tibor Hortobagyi, email: hortobagyi@med.unideb.hu , tibor.hortobagyi@kcl.ac.uk Keywords: glioma, glioblastoma, p53, PARP1 Received: December 27, 2016 Accepted: April 24, 2017 Published: May 19, 2017 ABSTRACT Overexpression of PARP1 exists in various cancers, including glioblastoma (GBM). Although PARP1 inhibition is a promising therapeutic target, no comprehensive study has addressed PARP1’s expression characteristics and prognostic role regarding molecular heterogeneity in astrocytomas including GBM. Our aim was to evaluate PARP1’s associations with survival, WHO grade, lineage specific markers, and GBM transcriptomic subtypes. We collected genomic and clinical data from the latest glioma datasets of The Cancer Genome Atlas and performed PARP1, ATRX, IDH1, and p53 immunohistochemistry on GBM tissue samples. We demonstrated that PARP1 gain and increased mRNA expression are characteristics of high-grade astrocytomas, particularly of Proneural and Classical GBM subtypes. Additionally, higher PARP1 levels exhibited an inverse correlation with patient survival (p

Purpose Our ability to flexibly coordinate the available degrees of freedom allows us to perform activities of daily living under various task constraints. Healthy old adults exhibit subclinical peripheral and central nervous system dysfunctions, possibly compromising the flexibility in inter-joint coordination during voluntary movements and the ability to adapt to varying task constraints.Method We examined how healthy old (75.4 +/- 5.2 years, n = 14) compared with young adults (24.3 +/- 2 years, n = 15) make use of the available motor flexibility to adapt to physical and dexterity constraints during a rapid goal-directed reaching task. We manipulated physical and dexterity demands by changing, respectively, external resistance and target size. Motor flexibility was quantified by an uncontrolled manifold (UCM) analysis.Results We found that healthy young and old adults employ similar motor flexibility as quantified by the ratio between goal equivalent and non-goal equivalent variability (V-Ratio) and were similarly able to adapt to increases in physical and dexterity demands during goal-directed rapid reaching (V-Ratio: p = .092; young: 0.548 +/- 0.113; old: 0.264 +/- 0.117). Age affected end-effector kinematics. Motor flexibility and end-effector kinematics did not correlate.Conclusions The data challenge the prevailing view that old age affects movement capabilities in general and provide specific evidence that healthy old adults preserve motor flexibility during a reaching task. Future studies applying UCM analysis should examine if experimental set-ups limit movement exploration, leaving possible age differences undetected.

Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus. Cells co-expressing astrocyte and microglia markers were also detected in the in vitro LPS activation/injury model and in sections from human brain affected by stroke, Alzheimer's disease, and Lewy body dementia. Our findings indicate that injury and chronic neurodegeneration lead to the appearance of cells that share molecular characteristics of both microglia and astrocytes, 2 cell types with distinct embryologic origin and function.

Objectives: To determine the effects of exergaming on quality of life (QoL), motor, and clinical symptoms in subacute stroke patients.Design: A pseudorandomized controlled trial, using a before-after test design.Setting: University hospital.Participants: Subacute, ischemic stroke outpatients (N=3857), 680 of whom were randomized and 641 completed the study.Interventions: We determined the effects of 5 times a week twice daily (EX2; 50 sessions; n=286) and once daily (EX1; 25 sessions; n=272) exergaming and low-intensity standard care (control [CON]; 25 sessions; n=83) on clinical, mobility, blood pressure (BP), and QoL outcomes.Main Outcome Measures: The primary outcome was Modified Rankin Scale. Secondary outcomes were activities of daily living, 5 aspects of health-related QoL, Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), and static balance (center of pressure).Results: During exercise, the peak heart rate was 134, 134, and 126 beats per minute in the EX2, EX1, and CON groups, respectively. mRS improved similarly in the EX2 (–1.8; effect size, d=–4.0) and EX1 (–1.4; d=–2.6) groups, but more than in the CON group (–0.7; d=–0.6). QoL, Barthel Index, BBS, 6MWT, and standing posturography improved more in the EX2 group and the same in the EX1 and CON groups. Systolic and diastolic resting BP decreased more in the EX2 and EX1 groups than in the CON group. The intervention effects did not differ between men (n=349) and women (n=292).Conclusions: Twice daily compared with once daily high-intensity exergaming or once daily lower intensity standard care produced superior effects on clinical and motor symptoms, BP, and QoL in male and female subacute ischemic stroke participants.

Different therapies can improve clinical and motor symptoms of multiple sclerosis (MS) similarly, but studies comparing the effects of different exercise therapies on clinical and motor outcomes are scant. We compared the effects of exergaming (EXE), balance (BAL), cycling (CYC), proprioceptive neuromuscular facilitation (PNF), and a standard care wait-listed control group (CON) on clinical and motor symptoms and quality of life (QoL) in people with MS (PwMS).PwMS (n = 68, 90% female; age, 47.0 yr; Expanded Disability Status Scale score 5-6) were randomized into five groups. Before and after the interventions (five times a week for 5 wk), PwMS were tested for MS-related clinical and motor symptoms (Multiple Sclerosis Impact Scale-29 (MSIS-29), primary outcome), QoL (EuroQol Five Dimensions Questionnaire), symptoms of depression, gait and balance ability (Tinetti Assessment Tool), static and dynamic balance and fall risk (Berg Balance Scale), walking capacity (6-min walk test), and standing posturography on a force platform.EXE, BAL, and CYC improved the MSIS-29 scores similarly. EXE and CYC improved QoL and walking capacity similarly but more than BAL. Only EXE improved gait and balance scores (Tinetti Assessment Tool). EXE and BAL improved fall risk and standing balance similarly but more than CYC. PNF and CON revealed no changes. The EuroQol Five Dimensions Questionnaire moderated the exercise effects on the MSIS-29 scores only in EXE. Changes in QoL and changes in the MSIS-29 scores correlated (R = 0.73) only in EXE.In conclusion, BAL and CYC but EXE in particular, but not PNF, can improve clinical and motor symptoms and QoL in PwMS (Expanded Disability Status Scale score 5 to 6), expanding the evidence-based exercise options to reduce mobility limitations in PwMS.

Aim: Right-handed young adults perform target-matching tasks more accurately with the non-dominant (ND) compared to the dominant (D) limb, but it is unclear if age affects this disparity. We determined if age affects target-matching asymmetry in right-side dominant healthy adults. Method: Young (n = 12, age: 23.6 y, 6 females) and older (n = 12; age: 75.1 y, 7 females) adults performed a passive joint position-matching task with the D and ND leg in a randomized order. Result: Age affected absolute, constant, and variable knee JPS errors but, contrary to expectations, it did not affect target-matching asymmetries between the D and ND knees. However, older participants tended to underestimate while young subjects overestimated the target angles. Moreover, older as compared to young subjects performed the target-matching task with higher variability. Conclusion: Altogether, age seems to affect passive knee target-matching behaviour in right-side dominant healthy adults. The present data indicate that healthy aging produces age-specific modifications in passive joint position sense.

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.

Athletes use compression garments (CGs) to improve sport performance, accelerate rehabilitation from knee injuries or to enhance joint position sense (JPS). The position of CGs around the knee may affect knee JPS but the data is inconsistent. The purpose of the present study was to determine the effects of CG position on healthy adults' knee joint position sense acuity. In a counterbalanced, single-blinded study, 16 healthy young adults (8 female, age: 25.5 y) performed an active knee joint position-matching task with and without (CON) a below-knee (BK), above-knee (AK), or whole-knee (WK) CG in a randomized order on the dominant (CompDom) or the non-dominant leg (CompNon-Dom). We also determined the magnitude of tissue compression by measuring anatomical thigh and calf cross sectional area (CSA) in standing using magnetic resonance imaging (MRI). Subjects had less absolute repositioning error (magnitude of error) in BK compared with CON condition. On the other hand, the analysis of the direction of error (constant error) revealed that in each condition subjects tended to underestimate the target position (AK, BK and CON: 75%; WK: 94%). In WK condition there was a significantly larger negative error (-2.7 +/- 3.4) as compared with CON (-1.6 +/- 3.7) condition. There also was less variable error, in WK compared to BK and CON conditions, indicating less variability in their position sense using a WK CG, regardless of the underestimation. CG reduced thigh CSA by 4.5 cm(2) or 3% and calf CSA by Delta 1.3 cm(2) or 1%. The position of CG relative to the knee modifies knee JPS. The findings helps us better understand how the application of a WK CG may support athletic activities.

In standing, coordinated activation of lower extremity muscles can be simplified by common neural inputs to muscles comprising a functional synergy. We examined the effect of task difficulty on common inputs to agonist-agonist (AG-AG) pairs supporting direction specific reciprocal muscle control and agonist-antagonist (AG-ANT) pairs supporting stiffness control. Since excessive stiffness is energetically costly and limits the flexibility of responses to perturbations, compared to AG-ANT, we expected greater AG-AG common inputs and a larger increase with increasing task difficulty. We used coherence analysis to examine common inputs in three frequency ranges which reflect subcortical/spinal (0–5 and 6–15 Hz) and corticospinal inputs (6–15 and 16–40 Hz). Coherence was indeed higher in AG-AG compared to AG-ANT muscles in all three frequency bands, indicating a predilection for functional synergies supporting reciprocal rather than stiffness control. Coherence increased with increasing task difficulty, only in AG-ANT muscles in the low frequency band (0–5 Hz), reflecting subcortical inputs and only in AG-AG group in the high frequency band (16–40 Hz), reflecting corticospinal inputs. Therefore, common neural inputs to both AG-AG and AG-ANT muscles increase with difficulty but are likely driven by different sources of input to spinal alpha motor neurons.

Made available in DSpace on 2020-12-12T02:26:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-01 Background: Gait adaptability in old age can be examined by responses to various perturbations. Fatigability due to mental or muscle exercises can perturb internal cognitive and muscle resources, necessitating adaptations in gait. Research question: What are the effects of age and mental and muscle fatigability on stride outcomes and gait variability? Methods: Twelve older (66–75yrs) and twelve young (20–25 yrs) adults walked at 1.2 m/s before and after two fatigue conditions in two separate sessions. Fatigue conditions were induced by repetitive sit-to-stand task (RSTS) and by 30-min of mental tasks and randomized between days (about a week apart). We calculated the average and coefficient of variation of stride length, width, single support, swing time and cadence, and the detrended fluctuations analysis (DFA) based on 120 strides time intervals. We also calculated multi-scale sample entropy (MSE) and the maximal Lyapunov exponent (λmax) of mediolateral (ML) and anteroposterior (AP) of the Center of Pressure (CoP) trajectories. Results: In both age groups, RSTS modestly affected stride length, single support time, cadence, and CV of stride length (p ≤ 0.05), while the mental task did not affect gait. After fatigability, λmax - ML increased (p ≤ 0.05), independent of fatigue condition. All observed effects were small (η²: 0.001 to 0.02). Significance: Muscle and mental fatigability had minimal effects on gait in young and healthy older adults possibly because treadmill walking makes gait uniform. It is still possible that age-dependent muscle activation underlies the uniform gait on the treadmill. Age- and fatigability effects might be more overt during real life compared with treadmill walking, creating a more effective model for examining gait and age adaptability to fatigability perturbations. University of Groningen University Medical Center Groningen Center for Human Movement Sciences São Paulo State University (UNESP) Post-graduation Program in Movement Sciences Institute of Biosciences Posture and Gait Studies Laboratory (LEPLO) Department of Biomedical Sciences of Cells and Systems University of Groningen University Medical Center Groningen São Paulo State University (UNESP) Post-graduation Program in Movement Sciences Human Movement Research Laboratory (MOVI-LAB) Department of Physical Education São Paulo State University (UNESP) Post-graduation Program in Movement Sciences Institute of Biosciences Posture and Gait Studies Laboratory (LEPLO) São Paulo State University (UNESP) Post-graduation Program in Movement Sciences Human Movement Research Laboratory (MOVI-LAB) Department of Physical Education

A joint moment also causes motion at other joints of the body. This joint coupling-perspective allows more insight into two age-related phenomena during gait. First, whether increased hip kinetic output compensates for decreased ankle kinetic output during positive joint work. Second, whether preserved joint kinetic patterns during negative joint work in older age have any functional implication. Therefore, we examined how age and surface inclination affect joint moment strategies to accelerate and/or decelerate individual leg joints during walking. Healthy young (age: 22.5 ± 4.1 years, n = 18) and older (age: 76.0 ± 5.7 years, n = 22) adults walked at 1.4 m/s on a split-belt instrumented treadmill at three grades (0%, 10%, −10%). Lower-extremity moment-induced angular accelerations were calculated for the hip (0% and 10%) and knee (0% and −10%) joints. During level and uphill walking, both age groups showed comparable ankle moment-induced ipsilateral (p = 0.774) and contralateral (p = 0.047) hip accelerations, although older adults generated lower ankle moments in late stance. However, ankle moment-induced contralateral hip accelerations were smaller (p = 0.001) in an older adult subgroup (n = 13) who showed larger hip extension moments in early stance than young adults. During level and downhill walking, leg joint moment-induced knee accelerations were unaffected by age (all p > 0.05). These findings suggest that during level and uphill walking increased hip flexor mechanical output in older adults does not arise from reduced ankle moments, contrary to increased hip extensor mechanical output. Additionally, results during level and downhill walking imply that preserved eccentric knee extensor function is important in maintaining knee stabilization in older age.

Introduction/Purpose: Little is known about the comparative effectiveness of exercise programs, especially when delivered at a high intensity, in mobility-limited older adults. We compared the effects of 25 sessions of high-intensity agility exergaming (EXE) and stationary cycling (CYC) at the same cardiovascular load on measured and perceived mobility limitations, balance, and health-related quality of life in mobility-limited older adults. Methods: Randomized to EXE (n = 28) and CYC (n = 27), mobility-impaired older adults (age 70 yr) exercised five times per week for 5 wk at 80% of age-predicted maximal heart rate. Waitlisted controls did not exercise (n = 28). Results: Groups did not differ at baseline in any outcomes (P > 0.05). The primary outcomes (The Short Form-36-Health Survey: EXE, 6.9%; effect size, 2.2; CYC, 5.5%, 1.94; Western Ontario and McMaster Universities Osteoarthritis Index: EXE, -27.2%, -3.83; CYC, -17.2, -2.90) improved similarly (P > 0.05). Secondary outcomes, including body mass (-3.7%), depression (-18%), and walking capacity (13.5%) also improved (P 0.05). Conclusions: When matched for cardiovascular and perceived effort, two diverse high-intensity exercise programs improved health-related quality of life, perceived mobility limitation, and walking capacity similarly and balance outcomes more in mobility-limited older adults, expanding these older adults' evidence-based exercise options to reduce mobility limitations.

Background: Aging is associated with slowed gait and old compared with young adults generally walk with greater positive hip work (H1) and reduced positive ankle work (A2). The role of exercise interventions on old adults' gait mechanics that underlie training-induced improvements in gait velocity is unclear. We examined the effects of lower extremity power training and detraining on old adults' gait kinetics.Methods: As part of the Potsdam Gait Study (POGS), healthy old adults completed a no-intervention control period (69.1 +/- 4A yrs, n =14) or a power training program followed by detraining (72.9 +/- 5.4 yrs, n = 15).We measured isokinetic knee extensor and plantarflexor power and measured hip, knee and ankle kinetics at habitual, fast and standardized walking speeds.Results: Power training significantly increased isokinetic knee extensor power (25%), plantarflexor power (43%), and fast gait velocity (5.9%). Gait mechanics underlying the improved fast gait velocity included increases in hip angular impulse (29%) and H1 work (37%) and no changes in positive knee (K2) and A2 work. Detraining further improved fast gait velocity (4.7%) with reductions in H1(-35%), and increases in K2 (36%) and A2 (7%).Conclusion: Power training increased fast gait velocity in healthy old adults by increasing the reliance on hip muscle function and thus further strengthened the age-related distal-to-proximal shift in muscle function. (C) 2016 Elsevier B.V. All rights reserved.

Slow gait predicts many adverse clinical outcomes in old adults, but the mechanisms of how power training can minimize the age-related loss of gait velocity is unclear. We examined the effects of 10 wk of lower extremity power training and detraining on healthy old adults' lower extremity muscle power and gait kinematics.As part of the Potsdam Gait Study, participants started with 10 wk of power training followed by 10 wk of detraining (n = 16), and participants started with a 10-wk control period followed by 10 wk of power training (n = 16). We measured gait kinematics (stride characteristic and joint kinematics) and isokinetic power of the ankle plantarflexor (20°·s, 40°·s, and 60°·s) and knee extensor and flexor (60°·s, 120°·s, and 180°·s) muscles at weeks 0, 10, and 20.Power training improved isokinetic muscle power by ~30% (P ≤ 0.001) and fast (5.9%, P0.05) but not habitual gait velocity. Ankle plantarflexor velocity measured during gait at fast pace decreased by 7.9% (P0.05). The changes isokinetic muscle power and joint kinematics did not correlate with increases in fast gait velocity. The mechanisms that increased fast gait velocity involved higher cadence (r = 0.86, P ≤ 0.001) rather than longer strides (r = 0.49, P = 0.066). Detraining did not reverse the training-induced increases in muscle power and fast gait velocity.Because increases in muscle power and modifications in joint kinematics did not correlate with increases in fast gait velocity, kinematic mechanisms seem to play a minor role in improving healthy old adults' fast gait velocity after power training.

There is controversy whether age-related neuroanatomical and neurophysiological changes in the central nervous system affect healthy old adults' abilities to acquire and retain motor skills. We examined the effects of age on motor skill acquisition and retention and potential underlying mechanisms by measuring corticospinal and intracortical excitability, using transcranial magnetic stimulation. Healthy young (n = 24, 22 years) and old (n = 22, 71 years) adults practiced a wrist flexion-extention visuomotor task or only watched the templates as an attentional control for 20 minutes. Old compared with young adults performed less well at baseline. Although the absolute magnitude of skill acquisition and retention was similar in the 2 age groups (age x intervention x time, p - 0.425), a comparison of baseline-similar age sub-groups revealed impaired skill acquisition but not retention in old versus young. Furthermore, the neuronal mechanisms differed as revealed by an opposite direction of associations in the age-groups between relative skill acquisition and intracortical facilitation during the task, and opposite changes during skill retention in corticospinal excitability at rest and during the task and intracortical inhibition during the task. (C) 2016 Elsevier Inc. All rights reserved.

Objectives The vast majority of literature on the frequency of the haemorrhagic transformation of ischaemic stroke is based on imaging studies. The purpose of the present study was to assess the added value of autopsy and neuropathological analysis in a neurology centre with emphasis on acute stroke care. Methods We retrospectively analysed the findings of 100 consecutive brain autopsies followed by detailed clinical correlation. Results The clinical diagnosis was confirmed by neuropathology in every patient with intracerebral haemorrhage and with non-cerebrovascular neurological disorders (e.g. primary tumours, metastases, infections). At admission 64 patients (age 62 years, SD 6.5) were diagnosed with acute ischaemic stroke. In 10 of these patients (16%) haemorrhagic transformation was diagnosed clinically by a second CT. In 24 cases (38%) haemorrhagic transformation was detected only at autopsy. The distribution of haemorrhagic transformation in our material was the following: small petechiae in 26.5%, more confluent petechiae in 29.4%, ≤ 30% of the infarcted area with some mild space-occupying effect in 29.4% and > 30% of the infarcted area with significant space-occupying effect or clot remote from infarcted area in 14.7%. Most of the PH1–2 transformations developed in thrombolysed patients and all of the PH2 type transformations were diagnosed already clinically. Conclusions We demonstrated that haemorrhagic transformation is frequent and often undiscovered in vivo. Our findings underline the importance of post-mortem neuropathological examination also in the era of advanced imaging techniques and prove that autopsy is the ultimate yardstick of our diagnostic and therapeutic efforts. The high number of haemorrhagic transformations diagnosed only after death is an important novel finding with clinical implications.