Effects and safety of combined rTMS and action observation for recovery of function in the upper extremities in stroke patients: A randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) modulates cortical excitability and facilitates motor learning to improve motor recovery after stroke. Action observation (AO) therapy effectively facilitates physical training for motor memory formation. OBJECTIVE: To compare the effectiveness of rTMS alone with that of combined rTMS and AO for the functional recovery of upper extremity function in subacute stroke patients and to verify the safety of the interventions. METHODS: The present study was a prospective, randomized controlled trial involving subacute unilateral stroke patients. In total, 22 patients were randomly assigned to 2 groups: the trial group (rTMS with AO) and the control group (rTMS alone). Both groups received 1 Hz rTMS (intensity: 120% of resting motor threshold; rMT) over the contralesional primary motor cortex for 20 minutes on 10 consecutive days. Trial group received rTMS while watching a video of 5 different complex hand movements. The functional parameters were the Brunnstrom stage, Fugl-Meyer assessment (FMA) score of the upper extremity, Manual Function Test (MFT) score, and grip power. The following motor evoked potential (MEP) parameters were recorded from the abductor pollicis brevis muscle: rMT, latency, and amplitude. Both parameters were measured before and after the 2 week intervention. RESULTS: After the 2 week trial, the total FMA and MFT scores were significantly improved in both groups, but the MFT subscores of hand motor function and grip power were significantly improved in the combination therapy group only. In contrast, the changes (Δ) of FMA, MFT, grip power test, and MEP outcomes were not significantly different between the 2 groups. No adverse events or complications were reported. CONCLUSIONS: Distal upper extremity function, as measured by MFT and grip power, was improved after rTMS and AO in combination. The combination of rTMS with AO may be applied safely to improve upper extremity function after stroke.

A novel tubulin inhibitor STK899704 induces tumor regression in DMBA/TPA-induced skin carcinogenesis model.

Skin cancer is the most common type of cancer. The incidence rate of skin cancer has continuously increased over the past decades. In an effort to discover novel anticancer agents, we identified a novel tubulin inhibitor STK899704, which is structurally distinct from other microtubule-binding agents such as colchicine, vinca alkaloids and taxanes. STK899704 inhibited microtubule polymerization leading to mitotic arrest and suppressed the proliferation of various cancer cell lines as well as multidrug resistance cancer cell lines. In this study, our investigation is further extended into animal model to evaluate the effect of STK899704 on skin carcinogenesis in vivo. Surprisingly, almost 80% of the tumors treated with STK899704 were regressed with a one-fifth reduction in tumor volume. Furthermore, the efficacy of STK899704 was nearly 2 times higher than that of 5-fluorouracil, a widely used skin cancer therapeutic. Overall, our results suggest that STK899704 is a promising anticancer chemotherapeutic that may replace existing therapies, particularly for skin cancer.

Anticancer activity of a novel small molecule tubulin inhibitor STK899704.

We have identified the small molecule STK899704 as a structurally novel tubulin inhibitor. STK899704 suppressed the proliferation of cancer cell lines from various origins with IC50 values ranging from 0.2 to 1.0 µM. STK899704 prevented the polymerization of purified tubulin in vitro and also depolymerized microtubule in cultured cells leading to mitotic arrest, associated with increased Cdc25C phosphorylation and the accumulation of both cyclin B1 and polo-like kinase 1 (Plk1), and apoptosis. Unlike many anticancer drugs such as Taxol and doxorubicin, STK899704 effectively displayed antiproliferative activity against multidrug-resistant cancer cell lines. The proposed binding mode of STK899704 is at the interface between αß-tubulin heterodimer overlapping with the colchicine-binding site. Our in vivo carcinogenesis model further showed that STK 899704 is potent in both the prevention and regression of tumors, remarkably reducing the number and volume of skin tumor by STK899704 treatment. Moreover, it was significant to note that the efficacy of STK899704 was surprisingly comparable to 5-fluorouracil, a widely used anticancer therapeutic. Thus, our results demonstrate the potential of STK899704 to be developed as an anticancer chemotherapeutic and an alternative candidate for existing therapies.

Intraneural ganglion cysts: a systematic review and reinterpretation of the world's literature.

OBJECTIVE The etiology of intraneural ganglion cysts has been controversial. In recent years, substantial evidence has been presented to support the articular (synovial) theory for their pathogenesis. The authors sought to 1) perform a systematic review of the world's literature on intraneural cysts, and 2) reinterpret available published MR images in articles by other authors to identify unrecognized joint connections. METHODS In Part 1, all cases were analyzed for demographic data, duration of symptoms, the presence of a history of trauma, whether electromyography or nerve conduction studies were performed, the type of imaging, surgical treatment, presence of a joint connection, intraneural cyst recurrence, and postoperative imaging. Two univariate analyses were completed: 1) to compare the proportion of intraneural ganglion cyst publications per decade and 2) to assess the number of recurrences from 1914 to 2003 compared with the years 2004-2015. Three multivariate regression models were used to identify risk factors for intraneural cyst recurrence. In Part 2, the authors analyzed all available published MR images and obtained MR images from selected cases in which joint connections were not identified by the original authors, specifically looking for unrecognized joint connections. Two univariate analyses were done: 1) to determine a possible association between the identification of a joint connection and obtaining an MRI and 2) to assess the number of joint connections reported from 1914 to 2003 compared with 2004 to 2015. RESULTS In Part 1, 417 articles (645 patients) were selected for analysis. Joint connections were identified in 313 intraneural cysts (48%). Both intraneural ganglion cyst cases and cyst recurrences were more frequently reported since 2004 (statistically significant difference for both). There was a statistically significant association between cyst recurrence and percutaneous aspiration as well as failure to disconnect the articular branch or address the joint. In Part 2, the authors identified 43 examples of joint connections that initially went unrecognized: 27 based on their retrospective MR image reinterpretation of published cases and 16 of 16 cases from their sampling of original MR images from published cases. Overall, joint connections were more commonly found in patients who received an MRI examination and were more frequently reported during the years 2004 to 2015 (statistically significant difference for both). CONCLUSIONS This comprehensive review of the world's literature and the MR images further supports the articular (synovial) theory and provides baseline data for future investigators.

Referred pain patterns of the third and fourth dorsal interosseous muscles.

BACKGROUND: Myofascial pain (MP) is a common disorder that can involve any skeletal muscle in the human body. There are no published reports of the referred pain patterns of the third and fourth dorsal interosseous muscles. OBJECTIVE: To investigate the referred pain patterns of the third and fourth dorsal interosseous muscles. STUDY DESIGN: Prospective evaluation. SETTING: Academic medical center. METHODS: Twenty healthy adults participated in the study. Needle placement and injection of 0.2 mL 6% hypertonic saline solution into the midpoint of the interosseous muscles were performed under ultrasonographic (US) guidance. After the injections, the participants were instructed to wait until they felt the most pain and then draw a pain diagram. This drawing was transferred to the computer for analysis. RESULTS: The referred pain distributions for the third dorsal interosseous muscle were as follows: the interdigital space of the third and fourth fingers, 80%; the distal phalanx of the third and fourth fingers, 45%; and the ulnar side of the palm, 55%. Three and 6 participants reported pain on the volar side of the wrist and in the fifth finger, respectively. The referred pain distributions for the fourth dorsal interosseous muscle were as follows: the interdigital space of the fourth and fifth fingers, 80%; the hypothenar area, 65%; and the distal phalanx of the fourth and fifth fingers, 60%. Seven and 3 participants also reported pain on the ulnar side of the wrist and the ulnar side of the forearm, respectively. LIMITATION: This study is limited by its small sample size. CONCLUSION: Referred pain patterns of the third and fourth interosseous muscles resemble the pain experienced in C7 or C8 radiculopathies or the ulnar neuropathy. Thus, identification of the third and fourth interosseous muscle trigger point should be considered when patients experience pain on the ulnar aspect of the hand and wrist.

Characteristics of visual-perceptual function measured by the motor-free visual perception test-3 in korean adults.

OBJECTIVE: To adapt and standardize the Motor-Free Visual Perception Test-3 (MVPT-3) to Koreans and investigate the change in visual-perceptual function using the MVPT-3 in healthy Korean adults. METHODS: The Korean version of the MVPT-3 was developed through a cross-cultural adaptation process according to 6 steps, including translation, reconciliation, back translation, cognitive debriefing, feedback, and final reconciliation. A total of 321 healthy Korean volunteers (mean age, 51.05 years) were recruited. We collected participant demographic data, such as sex, age, and years of education, and performed the Korean version of the Mini-Mental State Examination (K-MMSE) and MVPT-3. Internal consistency of the MVPT-3 and the relationships between demographic data, K-MMSE and MVPT-3 scores were analyzed. The results of this study were compared with published data from western countries including the United States and Canada. RESULTS: Total score on the MVPT-3 was positively correlated with years of education (r=0.715, p<0.001) and K-MMSE score (r=0.718, p<0.001). However, it had a negative correlation with age (r=-0.669, p<0.001). A post-hoc analysis of MVPT-3 scores classified age into 5 groups of ≤49, 50-59, 60-69, 70-79, ≥80 years and years of education into 4 groups of 0, 1-9, 10-12, ≥13 years. No significant differences in MVPT-3 scores were observed according to sex or country. CONCLUSION: Visual perception was significantly influenced by age, years of education, and cognitive function. Reference values for the MVPT-3 provided in this study will be useful for evaluating and planning a rehabilitation program of visual perceptual function in patients with brain disorders.

Factors affecting the motor evoked potential responsiveness and parameters in patients with supratentorial stroke.

OBJECTIVE: To investigate the factors which affect the motor evoked potential (MEP) responsiveness and parameters and to find the correlation between the function of the upper extremities and the combined study of MEP with a diffusion tensor tractography (DTT) in patients with stroke. METHODS: A retrospective study design was used by analyzing medical records and neuroimaging data of 70 stroke patients who underwent a MEP test between June 2011 and March 2013. MEP parameters which were recorded from the abductor pollicis brevis muscle were the resting motor threshold, latency, amplitude, and their ratios. Functional variables, Brunnstrom stage of hand, upper extremity subscore of Fugl-Meyer assessment, Manual Function Test, and the Korean version of Modified Barthel Index (K-MBI) were collected together with the biographical and neurological data. The DTT parameters were fiber number, fractional anisotropy value and their ratios of affected corticospinal tract. The data were compared between two groups, built up according to the presence (MEP-P) or absence (MEP-N) of MEP on the affected hand. RESULTS: Functional and DTT variables were significantly different between MEP-P and MEP-N groups (p<0.001). Among the MEP-P group, the amplitude ratio (unaffected/affected) was significantly correlated with the Brunnstrom stage of hand (r=-0.427, p=0.013), K-MBI (r=-0.380, p=0.029) and the time post-onset (r=-0.401, p=0.021). The functional scores were significantly better when both MEP response and DTT were present and decreased if one or both of the two studies were absent. CONCLUSION: This study indicates MEP responsiveness and amplitude ratio are significantly associated with the upper extremity function and the activities of daily living performance, and the combined study of MEP and DTT provides useful information.

A derivative of chrysin suppresses two-stage skin carcinogenesis by inhibiting mitogen- and stress-activated kinase 1.

Mitogen- and stress-activated kinase 1 (MSK1) is a nuclear serine/threonine protein kinase that acts downstream of both extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in response to stress or mitogenic extracellular stimuli. Increasing evidence has shown that MSK1 is closely associated with malignant transformation and cancer development. MSK1 should be an effective target for cancer chemoprevention and chemotherapy. However, very few MSK1 inhibitors, especially natural compounds, have been reported. We used virtual screening of a natural products database and the active conformation of the C-terminal kinase domain of MSK1 (PDB id 3KN) as the receptor structure to identify chrysin and its derivative, compound 69407, as inhibitors of MSK1. Compared with chrysin, compound 69407 more strongly inhibited proliferation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells with lower cytotoxicity. Western blot data demonstrated that compound 69407 suppressed phosphorylation of the MSK1 downstream effector histone H3 in intact cells. Knocking down the expression of MSK1 effectively reduced the sensitivity of JB6 P+ cells to compound 69407. Moreover, topical treatment with compound 69407 before TPA application significantly reduced papilloma development in terms of number and size in a two-stage mouse skin carcinogenesis model. The reduction in papilloma development was accompanied by the inhibition of histone H3 phosphorylation at Ser10 in tumors extracted from mouse skin. The results indicated that compound 69407 exerts inhibitory effects on skin tumorigenesis by directly binding with MSK1 and attenuates the MSK1/histone H3 signaling pathway, which makes it an ideal chemopreventive agent against skin cancer.

Existence of lysogenic bacteriophages in Bacillus thuringiensis type strains.

We screened the existence of bacteriophages in 67 Bacillus thuringiensis type strains by phage DNA extraction and PCR using phage terminase small subunit (TerS)-specific primers to the supernatants and the precipitated pellets of Bt cultures, and by transmission electron microscopy. The various bacteriophages were observed from the supernatants of 22 type strains. Ten type strains showed the extracted phage DNAs and the amplified fragment by TerS PCR but 12 type strains showed only the phage DNAs. Their morphological characteristic suggests that they belong to Family Siphoviridae which had a long tail and symmetrical head.