Development and feasibility of first- and third-person motor imagery for people with stroke living in the community

Background: Impairment of arm movement occurs in up to 85% of people post-stroke, affecting daily living activities, and quality of life. Mental imagery effectively enhances hand and daily function in people with stroke. Imagery can be performed when people imagine themselves completing the movement or imagine another person doing it. However, there is no report on the specific use of first-person and third-person imagery in stroke rehabilitation. Aims: To develop and assess the feasibility of the First-Person Mental Imagery (FPMI) and the Third-Person Mental Imagery (TPMI) programs to address the hand function of people with stroke living in the community. Methods: This study comprises phase 1—development of the FPMI and TPMI programs, and phase 2—pilot-testing of the intervention programs. The two programs were developed from existing literature and reviewed by an expert panel. Six participants with stroke, living in the community, participated in the pilot-testing of the FPMI and TPMI programs for 2 weeks. Feedback collected included the suitability of the eligibility criteria, therapist’s and participant’s adherence to intervention and instructions, appropriateness of the outcome measures, and completion of the intervention sessions within the specified time. Results: The FPMI and TPMI programs were developed based on previously established programs and included 12 hand tasks. The participants completed four 45-min sessions in 2 weeks. The treating therapist adhered to the program protocol and completed all the steps within the specified time frame. All hand tasks were suitable for adults with stroke. Participants followed the instructions given and engaged in imagery. The outcome measures selected were appropriate for the participants. Both programs showed a positive trend towards improvement in participants’ upper extremity and hand function and self-perceived performance in activities of daily living. Conclusions: The study provides preliminary evidence that these programs and outcome measures are feasible for implementation with adults with stroke living in the community. This study outlines a realistic plan for future trials in relation to participant recruitment, training of therapists on the intervention delivery, and the use of outcome measures

Effectiveness of action observation and motor imagery on relearning upper extremity function after stroke : a systematic review and meta-analysis

The effectiveness of action observation (AO) and motor imagery (MI) in high-quality studies with less risk of bias is rarely reported together. This systematic review evaluates the effectiveness of AO and MI on improving upper extremity function among people after stroke by combining evidence of studies with high methodological quality. Randomised controlled trials, with a score of 6 or above in the PEDro Scale, that examined the effects of AO or MI for people with stroke were selected. A narrative analysis and meta-analysis were conducted using the PRISMA guidelines. Ten randomised controlled trials from 11 articles met the inclusion criteria. The results of meta-analysis showed that AO had a small to moderate statistically significant effect on improving upper extremity motor function (standardized mean difference, SMD=0.34; confidence interval, CI=0.08, 0.59; P=0.35; I2=0.00%) and no significant effect on MI (SMD=0.08; CI=-0.26, 0.42; P=0.65; I2=0.00%) when compared with the control intervention. Evidence was found in support of AO and it is recommended for people with acute or sub-acute stroke

Modulating Integrin αIIbβ3 Activity through Mutagenesis of Allosterically Regulated Intersubunit Contacts

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Biochemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.biochem.9b00430.Integrin αIIbβ3, a transmembrane heterodimer, mediates platelet aggregation when it switches from an inactive to an active ligand-binding conformation following platelet stimulation. Central to regulating αIIbβ3 activity is the interaction between the αIIb and β3 extracellular stalks, which form a tight heterodimer in the inactive state and dissociate in the active state. Here, we demonstrate that alanine replacements of sensitive positions in the heterodimer stalk interface destabilize the inactive conformation sufficiently to cause constitutive αIIbβ3 activation. To determine the structural basis for this effect, we performed a structural bioinformatics analysis and found that perturbing intersubunit contacts with favorable interaction geometry through substitutions to alanine quantitatively accounted for the degree of constitutive αIIbβ3 activation. This mutational study directly assesses the relationship between favorable interaction geometry at mutation-sensitive positions and the functional activity of those mutants, giving rise to a simple model that highlights the importance of interaction geometry in contributing to the stability between protein–protein interactions.NIH P01 HL40387NIH R35 GM122603National Science Foundation 1709506National Science Foundation 165011

Actinobacillus Actinomycetemcomitans Leukotoxin Requires Lipid Microdomains for Target Cell Cytotoxicity

Actinobacillus actinomycetemcomitans produces a leukotoxin (Ltx) that kills leukocyte function-associated antigen-1 (LFA-1)-bearing cells from man, the Great Apes and Old World monkeys. The unique specificity of Ltx for the β2 integrin, LFA-1, suggests it is capable of providing insight into the pathogenic mechanisms of Ltx and other RTX toxins. Using the Jurkat T cell line and an LFA-1-deficient Jurkat mutant (Jβ2.7) as models, we found the initial effect of Ltx is to elevate cytosolic Ca2+ [Ca2+]c, an event that is independent of the Ltx/LFA-1 interaction. [Ca2+]c increases initiate a series of events that involve the activation of calpain, talin cleavage, mobilization to, and subsequent clustering of, LFA-1 in cholesterol and sphingolipid-rich regions of the plasma membrane known as lipid rafts. The association of Ltx and LFA-1 within lipid rafts is essential for cell lysis. Jβ2.7 cells fail to accumulate Ltx in their raft fractions and are not killed, while cholesterol depletion experiments demonstrate the necessity of raft integrity for Ltx function. We propose that toxin-induced Ca2+ fluxes mobilize LFA-1 to lipid rafts where it associates with Ltx. These findings suggest that Ltx utilizes the raft to stimulate an integrin signalling pathway that leads to apoptosis of target cells

Musculoskeletal Strength, Balance Performance, and Self-Efficacy in Elderly Ving Tsun Chinese Martial Art Practitioners: Implications for Fall Prevention

Objectives. To (1) compare the bone strength, lower limb muscular strength, functional balance performance, and balance self-efficacy between Ving Tsun (VT) martial art practitioners and nonpractitioners and (2) identify the associations between lower limb muscular strength, functional balance performance, and balance self-efficacy among the VT-trained participants. Methods. Thirty-five VT practitioners (mean age ± SD = 62.7 ± 13.3 years) and 49 nonpractitioners (mean age ± SD = 65.9 ± 10.5 years) participated in the study. The bone strength of the distal radius, lower limb muscular strength, functional balance performance, and balance self-efficacy were assessed using an ultrasound bone sonometer, the five times sit-to-stand test (FTSTS), the Berg balance scale (BBS), and the Chinese version of the activities-specific balance confidence scale, respectively. A multivariate analysis of covariance was performed to compare all the outcome variables between the two groups. Results. Elderly VT practitioners had higher radial bone strength on the dominant side (P<0.05), greater lower limb muscular strength (P=0.001), better functional balance performance (P=0.003), and greater balance confidence (P<0.001) than the nonpractitioners. Additionally, only the FTSTS time revealed a significant association with the BBS score (r=-0.575, P=0.013). Conclusions. VT may be a suitable health-maintenance exercise for the elderly. Our findings may inspire the development of VT fall-prevention exercises for the community-dwelling healthy elderly

Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.

Cancer progression represents an evolutionary process where overall genome level changes reflect system instability and serve as a driving force for evolving new systems. To illustrate this principle it must be demonstrated that karyotypic heterogeneity (population diversity) directly contributes to tumorigenicity. Five well characterized in vitro tumor progression models representing various types of cancers were selected for such an analysis. The tumorigenicity of each model has been linked to different molecular pathways, and there is no common molecular mechanism shared among them. According to our hypothesis that genome level heterogeneity is a key to cancer evolution, we expect to reveal that the common link of tumorigenicity between these diverse models is elevated genome diversity. Spectral karyotyping (SKY) was used to compare the degree of karyotypic heterogeneity displayed in various sublines of these five models. The cell population diversity was determined by scoring type and frequencies of clonal and non-clonal chromosome aberrations (CCAs and NCCAs). The tumorigenicity of these models has been separately analyzed. As expected, the highest level of NCCAs was detected coupled with the strongest tumorigenicity among all models analyzed. The karyotypic heterogeneity of both benign hyperplastic lesions and premalignant dysplastic tissues were further analyzed to support this conclusion. This common link between elevated NCCAs and increased tumorigenicity suggests an evolutionary causative relationship between system instability, population diversity, and cancer evolution. This study reconciles the difference between evolutionary and molecular mechanisms of cancer and suggests that NCCAs can serve as a biomarker to monitor the probability of cancer progression

Acute Effects of Tai Chi Training on Cognitive and Cardiovascular Responses in Late Middle-Aged Adults: A Pilot Study

This study explored the immediate effects of Tai Chi (TC) training on attention and meditation, perceived stress level, heart rate, oxygen saturation level in blood, and palmar skin temperature in late middle-aged adults. Twenty TC practitioners and 20 nonpractitioners volunteered to join the study. After baseline measurements were taken, the TC group performed TC for 10 minutes while their cognitive states and cardiovascular responses were concurrently monitored. The control group rested for the same duration in a standing position. Both groups were then reassessed. The participants’ attention and meditation levels were measured using electroencephalography; stress levels were measured using Perceived Stress Scale; heart rate and blood oxygenation were measured using an oximeter; and palmar skin temperature was measured using an infrared thermometer. Attention level tended to increase during TC and dropped immediately thereafter (p<0.001). Perceived stress level decreased from baseline to posttest in exclusively the TC group (p=0.005). Heart rate increased during TC (p<0.001) and decreased thereafter (p=0.001). No significant group, time, or group-by-time interaction effects were found in the meditation level, palmar skin temperature, and blood oxygenation outcomes. While a 10-minute TC training could temporarily improve attention and decrease perceived stress levels, it could not improve meditation, palmar skin temperature, or blood oxygenation among late middle-aged adults

Nuclear-Targeted Deleted in Liver Cancer 1 (DLC1) Is Less Efficient in Exerting Its Tumor Suppressive Activity Both In Vitro and In Vivo

BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We herein provide new evidence that DLC1 protein, which predominantly associated with focal adhesions and localized in cytosol, dynamically shuttled between cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1, we identified amino acids 600-700 of DLC1 as a novel region that is important for its nuclear localization. The tumor suppressive activity of nuclear DLC1 was directly assessed by employing a nuclear localization signal (NLS) fusion variant of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC cells, expression of NLS-DLC1 failed to suppress colony formation and actin stress fiber formation in vitro. The abrogated tumor suppressive activity of nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed tumors when compared with the non-nuclear targeted DLC1. CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in different cellular compartments both in vitro and in vivo