Psychometric properties of the Chinese version of the Arm Activity Measure in people with chronic stroke

IntroductionThe Arm Activity Measure was developed to assess active and passive functions of the upper limb in people with unilateral paresis, but a Chinese version is not available and its psychometric properties have not been specifically tested in people with stroke. This study aimed to translate and culturally adapt the Chinese version of the Arm Activity Measure (ArmA-C) and establish its psychometric properties in people with chronic stroke.MethodsThe psychometric properties of ArmA-C were determined in 100 people with chronic stroke.ResultsThe ArmA-C had good test–retest reliability (intraclass correlation coefficients [ICC] = 0.87–0.93; quadratic weighted Kappa coefficients = 0.53–1.00). A floor effect was identified in section A of the ArmA-C. The content validity and internal consistency (Cronbach's alpha coefficients = 0.75–0.95) were good. The construct validity of the ArmA-C was supported by acceptable fit to the two-factor structure model and significant correlations with the Fugl-Meyer Assessment for Upper Extremity score, grip strength, the Wolf Motor Function Test score, the Trail Walking Test completion time, and the Oxford Participation and Activities Questionnaire scores.ConclusionsThe ArmA-C is reliable and valid for assessing active and passive functions in people with chronic stroke

Intermediate filament–membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength

By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF–membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF–membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion

VI-Band Follow-Up Observations of Ultra-Long-Period Cepheid Candidates in M31

The ultra-long period Cepheids (ULPCs) are classical Cepheids with pulsation periods exceeding $\approx 80$ days. The intrinsic brightness of ULPCs are ~1 to ~3 mag brighter than their shorter period counterparts. This makes them attractive in future distance scale work to derive distances beyond the limit set by the shorter period Cepheids. We have initiated a program to search for ULPCs in M31, using the single-band data taken from the Palomar Transient Factory, and identified eight possible candidates. In this work, we presented the VI-band follow-up observations of these eight candidates. Based on our VI-band light curves of these candidates and their locations in the color-magnitude diagram and the Period-Wesenheit diagram, we verify two candidates as being truly ULPCs. The six other candidates are most likely other kinds of long-period variables. With the two confirmed M31 ULPCs, we tested the applicability of ULPCs in distance scale work by deriving the distance modulus of M31. It was found to be $\mu_{M31,ULPC}=24.30\pm0.76$ mag. The large error in the derived distance modulus, together with the large intrinsic dispersion of the Period-Wesenheit (PW) relation and the small number of ULPCs in a given host galaxy, means that the question of the suitability of ULPCs as standard candles is still open. Further work is needed to enlarge the sample of calibrating ULPCs and reduce the intrinsic dispersion of the PW relation before re-considering ULPCs as suitable distance indicators.Comment: 13 pages, with 14 Figures and 4 Tables (one online table). AJ accepte

Oral Delivery of the P2Y12 Receptor Antagonist Ticagrelor Prevents Loss of Photoreceptors in an ABCA4−/− Mouse Model of Retinal Degeneration

PURPOSE. Accumulation of lysosomal waste is linked to neurodegeneration in multiple diseases, and pharmacologic enhancement of lysosomal activity is hypothesized to reduce pathology. An excessive accumulation of lysosomal-associated lipofuscin waste and an elevated lysosomal pH occur in retinal pigment epithelial cells of the ABCA4 mouse model of Stargardt\u27s retinal degeneration. As treatment with the P2Y12 receptor antagonist ticagrelor was previously shown to lower lysosomal pH and lipofuscin-like autofluorescence in these cells, we asked whether oral delivery of ticagrelor also prevented photoreceptor loss. METHODS. Moderate light exposure was used to accelerate photoreceptor loss in albino ABCA4 mice as compared to BALB/c controls. Ticagrelor (0.1%–0.15%) was added to mouse chow for between 1 and 10 months. Photoreceptor function was determined with electroretinograms, while cell survival was determined using optical coherence tomography and histology. RESULTS. Protection by ticagrelor was demonstrated functionally by using the electroretinogram, as ticagrelor-treated ABCA4 mice had increased a-and b-waves compared to untreated mice. Mice receiving ticagrelor treatment had a thicker outer nuclear layer, as measured with both optical coherence tomography and histologic sections. Ticagrelor decreased expression of LAMP1, implicating enhanced lysosomal function. No signs of retinal bleeding were observed after prolonged treatment with ticagrelor. CONCLUSIONS. Oral treatment with ticagrelor protected photoreceptors in the ABCA4 mouse, which is consistent with enhanced lysosomal function. As mouse ticagrelor exposure levels were clinically relevant, the drug may be of benefit in preventing the loss of photoreceptors in Stargardt’s disease and other neurodegenerations associated with lysosomal dysfunction. © 2019 The Authors. All rights reserved

A review of the MSCA ITN ECOSTORE - Novel complex metal hydrides for efficient and compact storage of renewable energy as hydrogen and electricity

Hydrogen as an energy carrier is very versatile in energy storage applications. Developments in novel, sustainable technologies towards a CO2-free society are needed and the exploration of all-solid-state batteries (ASSBs) as well as solid-state hydrogen storage applications based on metal hydrides can provide solutions for such technologies. However, there are still many technical challenges for both hydrogen storage material and ASSBs related to designing low-cost materials with low-environmental impact. The current materials considered for all-solid-state batteries should have high conductivities for Na+, Mg2+ and Ca2+, while Al3+-based compounds are often marginalised due to the lack of suitable electrode and electrolyte materials. In hydrogen storage materials, the sluggish kinetic behaviour of solid-state hydride materials is one of the key constraints that limit their practical uses. Therefore, it is necessary to overcome the kinetic issues of hydride materials before discussing and considering them on the system level. This review summarizes the achievements of the Marie Skłodowska-Curie Actions (MSCA) innovative training network (ITN) ECOSTORE, the aim of which was the investigation of different aspects of (complex) metal hydride materials. Advances in battery and hydrogen storage materials for the efficient and compact storage of renewable energy production are discussed

On-ward participation of a hospital pharmacist in a Dutch intensive care unit reduces prescribing errors and related patient harm: an intervention study

Introduction: Patients admitted to an intensive care unit (ICU) are at high risk for prescribing errors and related adverse drug events (ADEs). An effective intervention to decrease this risk, based on studies conducted mainly in North America, is on-ward participation of a clinical pharmacist in an ICU team. As the Dutch Healthcare System is organized differently and the on-ward role of hospital pharmacists in Dutch ICU teams is not well established, we conducted an intervention study to investigate whether participation of a hospital pharmacist can also be an effective approach in reducing prescribing errors and related patient harm (preventable ADEs) in this specific setting. Methods: A prospective study compared a baseline period with an intervention period. During the intervention period, an ICU hospital pharmacist reviewed medication orders for patients admitted to the ICU, noted issues related to prescribing, formulated recommendations and discussed those during patient review meetings with the attending ICU physicians. Prescribing issues were scored as prescribing errors when consensus was reached between the ICU hospital pharmacist and ICU physicians. Results: During the 8.5-month study period, medication orders for 1,173 patients were reviewed. The ICU hospital pharmacist made a total of 659 recommendations. During the intervention period, the rate of consensus between the ICU hospital pharmacist and ICU physicians was 74%. The incidence of prescribing errors during the intervention period was significantly lower than during the baseline period: 62.5 per 1,000 monitored patient-days versus 190.5 per 1,000 monitored patient-days, respectively (P < 0.001). Preventable ADEs (patient harm, National Coordinating Council for Medication Error Reporting and Prevention severity categories E and F) were reduced from 4.0 per 1,000 monitored patient-days during the baseline period to 1.0 per 1,000 monitored patient-days during the intervention period (P = 0.25). Per monitored patient-day, the intervention itself cost (sic)3, but might have saved (sic)26 to (sic)40 by preventing ADEs. Conclusions: On-ward participation of a hospital pharmacist in a Dutch ICU was associated with significant reductions in prescribing errors and related patient harm (preventable ADEs) at acceptable costs per monitored patient-da

Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults

Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath’s EAA (1.69-years; 95% CI 0.72, 2.67), Hannum’s EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (− 0.04-kb; 95% CI − 0.08, − 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort