Comparison Between Movement-Based and Task-Based Mirror Therapies on Improving Upper Limb Functions in Patients With Stroke: A Pilot Randomized Controlled Trial

Objective: The aim of this trial was to compare the effect of movement-based mirror therapy (MMT) and task-based mirror therapy (TMT) on improving upper limb functions in patients with stroke.Methods: A total of 34 patients with sub-acute stroke with mildly to moderately impaired upper limb motor functions. The participants were randomly allocated to one of three groups: MMT, TMT, and conventional treatment (CT). The MMT group underwent movement-based mirror therapy for around 30 min/day, 5 days/week, for 4 weeks, whereas the TMT group underwent dose-matched TMT. The CT group underwent only conventional rehabilitation. The MMT and TMT groups underwent CT in addition to their mirror therapy. Blinded assessments were administered at baseline and immediately after the intervention. Upper limb motor functions, measured using Fugl-Meyer Assessment-upper extremity (FMA-UE), Wolf Motor Function Test (WMFT), and hand grip strength; upper limb spasticity, measured using the modified Ashworth scale (MAS); and activities of daily living, measured using the modified Barthel index (MBI).Results: A significant time-by-group interaction effect was noted in FMA-UE. Post-hoc analysis of change scores showed that MMT yielded a better effect on improving FMA-UE than the other two therapies, at a marginally significant level (P = 0.050 and 0.022, respectively). No significant interaction effect was noted in WMFT, hand grip strength, MAS, and MBI.Conclusion: Both MMT and TMT are effective in improving the upper limb function of patients with mild to moderate hemiplegia due to stroke. Nevertheless, MMT seems to be superior to TMT in improving hemiplegic upper extremity impairment. Further studies with larger stroke cohorts are expected to be inspired by this pilot trial.Trial registration number: No. ChiCTR1800019043 (http://www.chictr.org.cn/index.aspx

Effects of facet joint degeneration on stress alterations in cervical spine C5–C6: A finite element analysis

It has been demonstrated that articular facet degeneration can cause local strain alterations and induce neck pain. This study aims to quantify the biomechanical effects of normal and degenerated C5–C6 articular facets, and evaluate the correlation of mechanical strain between healthy and degenerated spine. A 3-dimensional finite element (FE) model of the C5–C6 cervical spine was developed [Model 0 (M0)]. The asymmetric models of C5–C6 bilateral articular facet joint were established separately to mimic articular facet joint degeneration. The capsule ligament stiffness of C5–C6 unilateral facet joint was altered with minimum and maximum threshold to simulate capsule ligaments' lesion and calcification [Model 1 (M1) and Model 2 (M2), respectively]. Besides, the cervical C5–C6 unilateral articular facet joint direction was changed by 5° and 10° forward to imitate the moderate joint hyperplasia and severe osteophyte (Model 3 and Model 4 respectively). M1 increased the rotation range of ipsilateral side (left), while M2 reduced, and both had limited effect on the contralateral side (right). The angle increased in Model 3 (M3) (61°) and Model 4 (M4) (55°) comparing to M0 during the axial rotation, and the angle of M4 was larger. M3 and M4 increased the nucleus pulposus pressure with and without controlled angular displacement during axial rotation. The pressure of nucleus pulpous increased during M1 rotating to the abnormal side but decreased when rotating to the other side, but the results of M2 were opposite. The capsule ligament stiffness made an impact on segmental mobility and vertebral spatial position, and the sagittal angle of articular facet joint exerted an influence on disc pressure distribution

A Residue at the Cytoplasmic Entrance of BK-Type Channels Regulating Single-Channel Opening by Its Hydrophobicity

Single large-conductance calcium-activated K+ (BK) channels encoded by the mSlo gene usually have synchronous gating, but a Drosophila dSlo (A2/C2/E2/G5/10) splice variant (dSlo1A) exhibits very flickery openings. To probe this difference in gating, we constructed a mutant I323T. This channel exhibits four subconductance levels similar to those of dSlo1A. Rectification of the single-channel current-voltage relation of I323T decreased as [Ca2+ ]in increased from 10 to 300 μM. Mutagenesis suggests that the hydrophobicity of the residue at the position is important for the wild-type gating; i.e., increasing hydrophobicity prolongs open duration. Molecular dynamics simulation suggests that four hydrophobic pore-lining residues at position 323 of mSlo act cooperatively in a “shutter-like” mechanism gating the permeation of K+ ions. Rate-equilibrium free energy relations analysis shows that the four I323 residues in an mSlo channel have a conformation 65% similar to the closed conformation during gating. Based on these observations, we suggest that the appearance of rectification and substates of BK-type channels arise from a reduction of the cooperativity among these four residues and a lower probability of being open

CRISPR-mediated direct mutation of cancer genes in the mouse liver

The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem (ES) cells1. Here we describe a new method of cancer model generation using the CRISPR/Cas system in vivo in wild-type mice. We have used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs)2–4 to the liver and directly target the tumor suppressor genes Pten5 and p536, alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre-LoxP technology7, 8. Simultaneous targeting of Pten and p53 induced liver tumors that mimicked those caused by Cre-loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumor tissue revealed insertion or deletion (indel) mutations of the tumor suppressor genes, including bi-allelic mutations of both Pten and p53 in tumors. Furthermore, co-injection of Cas9 plasmids harboring sgRNAs targeting the β-Catenin gene (Ctnnb1) and a single-stranded DNA (ssDNA) oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-Catenin. This study demonstrates the feasibility of direct mutation of tumor suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics

A Biomechanical Comparison of Two Intramedullary Implants for Subtrochanteric Fracture in Two Healing Stages: A Finite Element Analysis

Background. The biomechanical effect of two implants, namely, proximal femoral nail antirotation for Asia (PFNA-II) and Expert Asian Femoral Nail (A2FN), for treating subtrochanteric fracture during healing stages, is still unclear. Methods. A 3D finite element model of an intact femur was constructed and validated. The fractured and postoperative models were accordingly produced. The postoperative models were loaded with the peak joint forces during gait for the soft and hard callus stages. The effects of stress distribution on the implants, femoral head and callus, and the deformation of the proximal femur were examined. Results. Both implants showed similar biomechanical effect in two healing stages. As the healing duration increased, the von Mises stress of two implants and the tensile stress of the femoral head decreased, whereas the compressive stress of the femoral head increased. However, the PFNA-II operation resulted in higher stress on the implant, lower stress on the proximal femur, and lower compressive stress and higher tensile stress on the callus than A2FN operation. Conclusions. The A2FN implant may provide a biomechanically superior construct for subtrochanteric fracture healing. However, the upper screw of the A2FN implant may be more likely to be loose in the healing process

Peak Vertical Ground Reaction Force during Two-Leg Landing: A Systematic Review and Mathematical Modeling

Objectives. (1) To systematically review peak vertical ground reaction force (PvGRF) during two-leg drop landing from specific drop height (DH), (2) to construct a mathematical model describing correlations between PvGRF and DH, and (3) to analyze the effects of some factors on the pooled PvGRF regardless of DH. Methods. A computerized bibliographical search was conducted to extract PvGRF data on a single foot when participants landed with both feet from various DHs. An innovative mathematical model was constructed to analyze effects of gender, landing type, shoes, ankle stabilizers, surface stiffness and sample frequency on PvGRF based on the pooled data. Results. Pooled PvGRF and DH data of 26 articles showed that the square root function fits their relationship well. An experimental validation was also done on the regression equation for the medicum frequency. The PvGRF was not significantly affected by surface stiffness, but was significantly higher in men than women, the platform than suspended landing, the barefoot than shod condition, and ankle stabilizer than control condition, and higher than lower frequencies. Conclusions. The PvGRF and root DH showed a linear relationship. The mathematical modeling method with systematic review is helpful to analyze the influence factors during landing movement without considering DH