A Randomized Controlled Trial of Repetitive Peripheral Magnetic Stimulation applied in Early Subacute Stroke: Effects on Severe Upper-limb Impairment.

OBJECTIVES: Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive method that activates peripheral nerves and enhances muscle strength. This study aimed to investigate the effect of rPMS applied in early subacute stroke on severe upper extremity impairment. DESIGN: Randomized controlled trial. SETTING: Rehabilitation department of a university hospital. SUBJECTS: People aged 30-80 years with no practical arm function within four weeks of a first stroke. INTERVENTIONS: Participants were randomly assigned to either the rPMS group (n = 24, 20Hz and 2400 pulses of rPMS to triceps brachii and extensor digitorum muscles daily for two weeks in addition to conventional physiotherapy) or the control group (n = 20, conventional physiotherapy). MAIN MEASURES: The primary outcome was the upper extremity motor section of Fugl-Meyer Assessment after treatment. Secondary outcomes included Barthel Index and root mean square of surface electromyography for muscle strength and stretch-induced spasticity of critical muscles of the upper extremity. Data presented: mean (SD) or median (IQR). RESULTS: The rPMS group showed more significant improvements in the Fugl-Meyer Assessment (12.5 (2.5) vs. 7.0 (1.4), P < 0.001), Barthel Index (15 (5) vs. 10 (3.7), P < 0.001), and strength-root mean square (biceps brachii: 20.5 (4.8) vs. 6.2 (2.7), p < 0.001; triceps brachii: 14.9 (5.8) vs. 4.3 (1.2), p < 0.001; flexor digitorum: 5.1 (0.8) vs. 4.0 (1.1), p < 0.001) compared with the control group. CONCLUSION: In patients with no functional arm movement, rPMS of upper limb extensors improves arm function and muscle strength for grip and elbow flexion and extension.

Reduction of bacterial adhesion on titanium-doped diamond-like carbon coatings.

A range of titanium doped diamond-like carbon (Ti-DLC) coatings with different Ti contents were prepared on stainless steel substrates using a plasma-enhanced chemical vapour deposition technique. It was found that both the electron donor surface energy and the surface roughness of the Ti-DLC coatings increased with increasing Ti contents in the coatings. Bacterial adhesion to the coatings was evaluated against Escherichia coli WT F1693 and Pseudomonas aeruginosa ATCC 33347. The experimental data showed that bacterial adhesion decreased with the increases of the Ti content, the electron donor surface energy and surface roughness of the coatings, while the bacterial removal percentage increased with the increases of these parameters. The Ti-DLC coatings reduced bacterial attachment by up to 75% and increased bacterial detachment from 15 to 45%, compared with stainless steel control.

Overexpression of miR-18a negatively regulates myocyte enhancer factor 2D to increase the permeability of the blood-tumor barrier via Krüppel-like factor 4-mediated downregulation of zonula occluden-1, claudin-5, and occludin.

miR-18a represses angiogenesis and tumor evasion by weakening vascular endothelial growth factor and transforming growth factor-ß signaling to prolong the survival of glioma patients, although it is thought to be an oncogene. This study investigates the potential effects of miR-18a on the permeability of the blood-tumor barrier (BTB) and its possible molecular mechanisms. An in vitro BTB model was successfully established. The endogenous expression of miR-18a in glioma vascular endothelial cells (GECs) was significantly lower than that in normal vascular ECs, and the overexpression of miR-18a significantly increased the permeability of the BTB as well as downregulating the mRNA and protein expressions of tight junction-related proteins zonula occluden-1 (ZO-1), claudin-5, and occludin in GECs. Dual luciferase reporter assays revealed that miR-18a bound to the 3'-untranslated region (3'UTR) of myocyte enhancer factor 2D (MEF2D). The overexpression of both miR-18a and MEF2D with the 3'UTR significantly weakened the effect caused by miR-18a of decreasing the mRNA and protein expressions of ZO-1, claudin-5 and occludin and of increasing the permeability of the BTB. Chromatin immunoprecipitation showed that MEF2D could directly bind to KLF4 promoter. This study shows that miR-18a targets and negatively regulates MEF2D, which further regulates tight junction-related proteins ZO-1, claudin-5, and occludin through transactivation of KLF4 and, finally, changes the permeability of the BTB. MiR-18a should garner growing attention because it might serve as a potential target in opening the BTB and providing a new strategy for the treatment of gliomas.

Efficacy of coupling intermittent theta-burst stimulation and 1 Hz repetitive transcranial magnetic stimulation to enhance upper limb motor recovery in subacute stroke patients: A randomized controlled trial.

BACKGROUND: Both 1 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are reported to benefit upper limb motor function rehabilitation in patients with stroke. However, the efficacy of combining 1 Hz rTMS and iTBS has not been adequately explored. OBJECTIVE: We aimed to compare the effects of 1 Hz rTMS and the combination of 1 Hz rTMS and iTBS on the upper limb motor function in the subacute phase post-stroke. METHODS: Twenty-eight participants were randomly assigned to three groups: Group A (1 Hz rTMS over the contralesional primary motor cortex (M1) and iTBS over the ipsilesional M1), Group B (contralesional 1 Hz rTMS and ipsilesional sham iTBS), and Group C (contralesional sham 1 Hz rTMS and ipsilesional sham iTBS). The participants received the same conventional rehabilitation accompanied by sessions of transcranial magnetic stimulation for two weeks (5 days one week). Motor-evoked potential (MEP), upper extremity Fugl-Meyer Assessment (UE-FMA), and Barthel Index (BI) were performed before and after the sessions. RESULTS: Group A showed greater UE-FMA, BI, and MEP amplitude improvement and more significant decrement in MEP latency compared to Group B and Group C in testable patients. Correlation analyses in Group A revealed a close relation between ipsilesional MEP amplitude increment and UE-FMA gain. CONCLUSIONS: The combining of 1 Hz rTMS and iTBS protocol in the present study is tolerable and more beneficial for motor improvement than the single use of 1 Hz rTMS in patients with subacute stroke.

Effects of high-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex on motor recovery in severe hemiplegic stroke: A randomized clinical trial.

BACKGROUND: The contralesional hemisphere compensation may play a critical role in the recovery of stroke when there is extensive damage to one hemisphere. There is little research on the treatment of hemiplegia by high-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the contralesional cortex. OBJECTIVE: We conducted a 2-week randomized, sham-controlled, single-blind trial to determine whether high-frequency rTMS (HF-rTMS) over the contralesional motor cortex can improve motor function in severe stroke patients. METHODS: Forty-five patients with ischemic or hemorrhagic stroke in the middle cerebral artery territory were randomly assigned to treatment with 10 Hz rTMS (HF group), 1 Hz rTMS (LF group) or sham rTMS (sham group) applied over the contralesional motor cortex (M1) before physiotherapy daily for two weeks. The primary outcome was the change in the Fugl-Meyer Motor Assessment (FMA) Scale score from baseline to 2 weeks. The secondary endpoints included root mean square of surface electromyography (RMS-SEMG), Barthel Index (BI), and contralesional hemisphere cortical excitability. RESULTS: The HF group showed a more significant improvement in FMA score (p < 0.05), BI (p < 0.005), contralesional hemisphere cortical excitability and conductivity (p < 0.05), and RMS-SEMG of the key muscles (p < 0.05) compared with the LF group and sham group. There were no significant differences between the LF group and sham group. There was a positive correlation between cortical conductivity of the uninjured hemisphere and recovery of motor impairment (p = 0.039). CONCLUSIONS: HF-rTMS over the contralesional cortex was superior to low-frequency rTMS and sham stimulation in promoting motor recovery in patients with severe hemiplegic stroke by acting on contralesional cortex plasticity. TRIAL REGISTRATION: Clinical trial registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn/showproj.aspx?proj=23264 (ChiCTR-IPR-17013580).

MiR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of ZO-1, occludin and claudin-5.

The purposes of this study were to investigate the possible molecular mechanisms of miR-18a regulating the permeability of blood-tumor barrier (BTB) via down-regulated expression and distribution of runt-related transcription factor 1 (RUNX1). An in vitro BTB model was established with hCMEC/D3 cells and U87MG cells to obtain glioma vascular endothelial cells (GECs). The endogenous expressions of miR-18a and RUNX1 were converse in GECs. The overexpression of miR-18a significantly impaired the integrity and increased the permeability of BTB, which respectively were detected by TEER and HRP flux assays, accompanied by down-regulated mRNA and protein expressions and distributions of ZO-1, occludin and claudin-5 in GECs. Dual-luciferase reporter assay was carried out and revealed RUNX1 is a target gene of miR-18a. Meanwhile, mRNA and protein expressions and distribution of RUNX1 were downregulated by miR-18a. Most important, miR-18a and RUNX1 could reversely regulate the permeability of BTB as well as the expressions and distributions of ZO-1, occludin and claudin-5. Finally, chromatin immunoprecipitation verified that RUNX1 interacted with "TGGGGT" DNA sequence in promoter region of ZO-1, occludin and claudin-5 respectively. Taken together, our present study indicated that miR-18a increased the permeability of BTB via RUNX1 mediated down-regulation of tight junction related proteins ZO-1, occludin and claudin-5, which would attract more attention to miR-18a and RUNX1 as potential targets of drug delivery across BTB and provide novel strategies for glioma treatment.