Search

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.

Tau pathology of the noradrenergic locus coeruleus (LC) is a hallmark of several age-related neurodegenerative disorders, including Alzheimer’s disease. However, a comprehensive neuropathological examination of the LC is difficult due to its small size and rod-like shape. To investigate the LC cytoarchitecture and tau cytoskeletal pathology in relation to possible propagation patterns of disease-associated tau in an unprecedented large-scale three-dimensional view, we utilized volume immunostaining and optical clearing technology combined with light sheet fluorescence microscopy. We examined AT8+ pathological tau in the LC/pericoerulear region of 20 brains from Braak neurofibrillary tangle (NFT) stage 0–6. We demonstrate an intriguing morphological complexity and heterogeneity of AT8+ cellular structures in the LC, representing various intracellular stages of NFT maturation and their diverse transition forms. We describe novel morphologies of neuronal tau pathology such as AT8+ cells with fine filamentous somatic protrusions or with disintegrating soma. We show that gradual dendritic atrophy is the first morphological sign of the degeneration of tangle-bearing neurons, even preceding axonal lesions. Interestingly, irrespective of the Braak NFT stage, tau pathology is more advanced in the dorsal LC that preferentially projects to vulnerable forebrain regions in Alzheimer’s disease, like the hippocampus or neocortical areas, compared to the ventral LC projecting to the cerebellum and medulla. Moreover, already in the precortical Braak 0 stage, 3D analysis reveals clustering tendency and dendro-dendritic close appositions of AT8+ LC neurons, AT8+ long axons of NFT-bearing cells that join the ascending dorsal noradrenergic bundle after leaving the LC, as well as AT8+ processes of NFT-bearing LC neurons that target the 4th ventricle wall. Our study suggests that the unique cytoarchitecture, comprised of a densely packed and dendritically extensively interconnected neuron, QC 20230523

© 2020, The Author(s). Background: Cross-education refers to increased motor output (i.e., force generation, skill) of the opposite, untrained limb following a period of unilateral exercise training. Despite extensive research, several aspects of the transfer phenomenon remain controversial. Methods: A modified two-round Delphi online survey was conducted among international experts to reach consensus on terminology, methodology, mechanisms of action, and translational potential of cross-education, and to provide a framework for future research. Results: Through purposive sampling of the literature, we identified 56 noted experts in the field, of whom 32 completed the survey, and reached consensus (75% threshold) on 17 out of 27 items. Conclusion: Our consensus-based recommendations for future studies are that (1) the term ‘cross-education’ should be adopted to refer to the transfer phenomenon, also specifying if transfer of strength or skill is meant; (2) functional magnetic resonance imaging, short-interval intracortical inhibition and interhemispheric inhibition appear to be promising tools to study the mechanisms of transfer; (3) strategies which maximize cross-education, such as high-intensity training, eccentric contractions, and mirror illusion, seem worth being included in the intervention plan; (4) study protocols should be designed to include at least 13–18 sessions or 4–6 weeks to produce functionally meaningful transfer of strength, and (5) cross-education could be considered as an adjuvant treatment particularly for unilateral orthopedic conditions and sports injuries. Additionally, a clear gap in views emerged between the research field and the purely clinical field. The present consensus statement clarifies relevant aspects of cross-education including neurophysiological, neuroanatomical, and methodological characteristics of the transfer phenomenon, and provides guidance on how to improve the quality and usability of future cross-education studies.

Background: Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner. Methods: We retrospectively identified patients who had a histological diagnosis of medulloblastoma and complete data about extent of resection and survival from centres participating in the Medulloblastoma Advanced Genomics International Consortium. We collected from resections done between April, 1997, and February, 2013, at 35 international institutions. We established medulloblastoma subgroup affiliation by gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. We classified extent of resection on the basis of postoperative imaging as gross total resection (no residual tumour), near-total resection (<1·5 cm2 tumour remaining), or sub-total resection (≥1·5 cm2 tumour remaining). We did multivariable analyses of overall survival and progression-free survival using the variables molecular subgroup (WNT, SHH, group 4, and group 3), age (<3 vs ≥3 years old), metastatic status (metastases vs no metastases), geographical location of therapy (North America/Australia vs rest of the world), receipt of chemotherapy (yes vs no) and receipt of craniospinal irradiation (<30 Gy or >30 Gy vs no craniospinal irradiation). The primary analysis outcome was the effect of extent of resection by molecular subgroup and the effects of other clinical variables on overall and progression-free survival. Findings: We included 787 patients with medulloblastoma (86 with WNT tumours, 242 with SHH tumours, 163 with group 3 tumours, and 296 with group 4 tumours) in our multivariable Cox mod

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Little is known regarding the modulation and the plasticity of the neural pathway interconnecting elements of the central nervous system and skeletal muscle in resistant-trained individuals. The aim of the study was to compare corticospinal and spinal responses measured during dynamic muscle contractions of the tibialis anterior in resistance trained (RT) and un-trained (UT) males. Nine UT and 10 RT male volunteers reported to the laboratory 24 h following a familiarisation session. Motor evoked potentials (MEPs) and the cortical silent period were evoked using transcranial magnetic stimulation at a range of contraction intensities and was delivered as the ankle passed 90 during shortening and lengthening contractions. The Hoffmann reflex (H-reflex) and V-waves were evoked with peripheral nerve stimulation. Despite the RT group being significantly stronger during shortening (28%; P = 0.023: CI = 1.27–15.1 N m), lengthening (25%; P = 0.041: CI = 0.27–17.0 N m) and isometric muscle actions (20%; P = 0.041; CI = 0.77–14.9 N m), no differences between the groups existed for corticospinal or spinal variables. Lack of detectable differences between RT and UT individuals may be linked to minimal exposure to task specific, isolated high intensity resistance training of the TA muscle.