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Background Extracellular vesicles are small vesicles that are released from many cells, including neurons. α-Synuclein has recently been described in extracellular vesicles derived from the central nervous system and may contribute to the spreading of disease pathology in α-synuclein-related neurodegeneration. Objectives We aimed to examine the potential diagnostic value of α-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD). Methods Preanalytical variables were studied to establish an optimized assay for preparation of plasma extracellular vesicles and detection of extracellular vesicle-derived α-synuclein. Plasma samples were obtained from 2 independent cohorts. The Tubingen cohort contained 96 patients with PD, 50 patients with dementia with Lewy bodies, 50 patients with progressive supranuclear palsy (PSP), and 42 healthy controls; the Kassel cohort included 47 patients with PD, 43 patients with dementia with Lewy bodies, and 36 controls with secondary parkinsonian syndromes. Extracellular vesicles were prepared from total plasma by size exclusion chromatography and quantified by nanoparticle tracking analysis, α-synuclein content was measured by an electrochemiluminescence assay. Results α-Synuclein concentration in plasma extracellular vesicles provided the best discrimination between PD, dementia with Lewy bodies, PSP, and healthy controls, with an area under the curve of 0.804 (PD vs dementia with Lewy bodies), 0.815 (PD vs. PSP), and 0.769 (PD vs healthy controls) in the Tubingen cohort. Results were validated in the Kassel cohort. Conclusions The concentration of α-synuclein in plasma extracellular vesicles may serve as a potential diagnostic biomarker for PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A study of Mg-based bulk metallic glasses (BMGs) as biodegradable bone implants is presented. The implantation site can affect performance, so the BMGs were evaluated in vivo in rat femurs using mu-CT scans at various times for more than 90 days. Estimates of H2 evolution correlate well with previous in vitro studies and boneimplant contact is similar to that for Ti pins. One potential drawback of Mg-based BMGs in this application is embrittlement due to structural relaxation. Here, relaxation at 20 and 37?degrees C is examined, and an increase in the characteristic relaxation time, from 10 to 30 days at 20?degrees C, is observed as Zn increases from 29 to 32?at.%, correlating with dramatically reduced hydrogen evolution.

Aim Information on the timing and long-term outcome of single-event multilevel surgery in children with bilateral spastic cerebral palsy (CP) walking with flexed knee gait is limited. Based on our clinical experience, we hypothesized that older children with bilateral spastic CP would benefit more from single-event multilevel surgery than younger children. Moreover, any improvement in older children could be maintained with fewer additional surgery events. Method We performed a retrospective analysis of the long-term outcomes of single-event multilevel surgery. Thirty-two children (17 males, 15 females) who had received single-event multilevel surgery between 1995 and 2000 with a mean age at the time of surgery of 10 years 6 months (range 5y 8mo–15y 6mo; SD 3y 1mo) and in Gross Motor Function Classification System level II (n=12) or III (n=20) were included in the study. The inclusion criteria required that all children were ambulatory with spastic bilateral CP, had a flexed knee gait, had a full set of data for single-event multilevel surgery preoperatively and at 1 year and 10 years postoperatively, had not had previous surgery on their lower limbs, had not had any treatment with botulinum toxin A before gait assessment, and had not received intrathecal baclofen medication. The follow-up time lasted for over 10 years until the participants reached adulthood (mean age at the last follow-up 21 years 4 months, SD 3y 4mo). Data were collected on six separate occasions: preoperatively, at 1 year, at 2 to 3 years, at 5 years, at 7 to 8 years, and at 10 or more years postoperatively. The primary outcome was the Gait Deviation Index, and the secondary outcomes were the number and type of initial and additional surgeries. A linear mixed model and Spearman’s rank correlation coefficient were used to prove the hypothesis. Results The older the child was at the time of the surgery, the better the long-term result (Age,Time=0.15; p=0.03). We did not find any correlation between age at the time of surgery and the number of bony or soft-tissue procedures performed initially as well as during the 10 years of follow-up. Interpretation Children with CP who require single-event multilevel surgery at an older age fare better in the long term than those who are younger at the time of surgery. The pubertal growth spurt is discussed as a contributing factor to gait deterioration.