Monitoring of Cellular Changes in the Bone Marrow following PTH(1-34) Treatment of OVX Rats Using a Portable Stray-Field NMR Scanner

Osteoporosis is characterized by reduction in trabecular bone in conjunction with increased marrow cell adiposity. While these changes occur within weeks, monitoring of treatment efficacy as performed by DEXA is sensitive only to long-term changes. MRI is sensitive to bone marrow changes but is less affordable. In a recent study, we have shown that a stray-field NMR can monitor bone marrow cellular changes that are related to osteoporosis. Objectives. To demonstrate sensitivity of a low-field tabletop NMR scanner to bone marrow dynamics following hormonal treatment in rats. Methods. Two-month-old female rats (n=36) were ovariectomized (OVX) and dosed for the ensuing 3 or 5 weeks with 20 mg/kg of PTH(1-34). Hind limbs femurs and tibiae were isolated and underwent ex vivo microradiography and histology and NMR relaxometry at 6 weeks (preventive experiment) and 11 weeks (therapeutic treatment experiment) after OVX. Results. OVX rats developed osteoporotic changes including adipogenic marrow compared to Sham and PTH treated rats. T2 and ADC NMR relaxation coefficients were found to correlate with marrow composition. Conclusions. This study suggests that stray-field NMR, an affordable method that is sensitive to the rapid cellular changes in bone marrow, may have a clinical value in monitoring hormonal treatment for osteoporosis

Promoting independence in Lewy body dementia through exercise: the PRIDE study

Background: Lewy body dementia (LBD) is an aggressive type of dementia of rapid, fluctuating disease trajectory, higher incidence of adverse events, and poorer functional independence than observed in Alzheimer’s disease dementia. Non-pharmacological treatments such as progressive, high-intensity exercise are effective in other neurological cohorts but have been scarcely evaluated in LBD. Methods: The Promoting Independence in Lewy Body Dementia through Exercise (PRIDE) trial was a non-randomised, non-blinded, crossover pilot trial involving older adults with LBD consisting of a baseline assessment, an 8-week wait-list, and an 8-week exercise intervention. The aims of this study were to evaluate the determinants of the primary outcome functional independence, as measured by the Movement Disorder Society Unified Parkinson’s Disease Rating Scale, and the feasibility and preliminary efficacy of an exercise intervention on this outcome. Additionally, important clinical characteristics were evaluated to explore associations and treatment targets. The exercise intervention was supervised, clinic-based, high-intensity progressive resistance training (PRT), challenging balance, and functional exercises, 3 days/week. Results: Nine participants completed the baseline cross-sectional study, of which five had a diagnosis of Parkinson’s disease dementia (PDD), and four dementia with Lewy Bodies (DLB). Six completed the exercise intervention (three PDD, three DLB). The cohort was diverse, ranging from mild to severe dementia and living in various residential settings. Greater functional independence at baseline was significantly associated with better physical function, balance, cognition, quality of life, muscle mass ratio, walking endurance, faster walking speed and cadence, and lower dementia severity (p 80% adherence), and only one minor exercise-related adverse event occurred. Conclusions: PRIDE is the first exercise trial conducted specifically within individuals diagnosed with LBD, and provides important insight for the design of larger, randomized trials for further evaluation of progressive, high-intensity exercise as a valuable treatment in LBD. Trial registration: The PRIDE trial protocol has previously been prospectively registered (08/04/2016, ANZCTR: ACTRN12616000466448)

Quantification of daily-living gait quantity and quality using a wrist-worn accelerometer in Huntington's Disease

Background: Huntington's disease (HD) leads to altered gait patterns and reduced daily-living physical activity. Accurate measurement of daily-living walking that takes into account involuntary movements (e.g. chorea) is needed. Objective: To evaluate daily-living gait quantity and quality in HD, taking into account irregular movements. Methods: Forty-two individuals with HD and fourteen age-matched non-HD peers completed clinic-based assessments and a standardized laboratory-based circuit of functional activities, wearing inertial measurement units on the wrists, legs, and trunk. These activities were used to train and test an algorithm for the automated detection of walking. Subsequently, 29 HD participants and 22 age-matched non-HD peers wore a tri-axial accelerometer on their non-dominant wrist for 7 days. Measures included gait quantity (e.g., steps per day), gait quality (e.g., regularity) metrics, and percentage of walking bouts with irregular movements. Results: Measures of daily-living gait quantity including step counts, walking time and bouts per day were similar in HD participants and non-HD peers (p > 0.05). HD participants with higher clinician-rated upper body chorea had a greater percentage of walking bouts with irregular movements compared to those with lower chorea (p = 0.060) and non-HD peers (p < 0.001). Even after accounting for irregular movements, within-bout walking consistency was lower in HD participants compared to non-HD peers (p < 0.001), while across-bout variability of these measures was higher (p < 0.001). Many of the daily-living measures were associated with disease-specific measures of motor function. Conclusions: Results suggest that a wrist-worn accelerometer can be used to evaluate the quantity and quality of daily-living gait in people with HD, while accounting for the influence of irregular (choreic-like) movements, and that gait features related to within- and across-bout consistency markedly differ in individuals with HD and non-HD peers

Is every-day walking in older adults more analogous to dual-task walking or to usual walking? Elucidating the gaps between gait performance in the lab and during 24/7 monitoring

Contains fulltext : 203576.pdf (publisher's version ) (Open Access

Protonet 4.0: A Hierarchical Classification of One Million Protein Sequences

ProtoNet is an automatic hierarchical classification of the protein sequence space. In 2004, the ProtoNet (version 4.0) presents the analysis of over one million proteins merged from SwissProt and TrEMBL databases. In addition to rich visualization and analysis tools to navigate the clustering hierarchy, we incorporated several improvements that allow a simplified view of the scaffold of the proteins. An unsupervised, biologically valid method that was developed resulted in a condensation of the ProtoNet hierarchy to only 12% of the clusters. A large portion of these clusters was automatically assigned high confidence biological names according to their correspondence with functional annotations. ProtoNet is available at: http://www.protonet.cs.huji.ac.il

Tossing and Turning in Bed: Nocturnal Movements in Parkinson's Disease

Contains fulltext : 220357.pdf (Publisher’s version ) (Closed access