A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

Correlation of Hemispatial Neglect with White Matter Tract Integrity: A DTI Study.

We investigated the diffusion tensor image (DTI) parameters of superior longitudinal fasciculus (SLF) and inferior fronto-occipital fasciculus (IFOF), and their relationships with hemispatial neglect. Thirteen patients with first-ever ischemic stroke who had the right hemispheric lesion were included. Neglect was assessed using the Albert test and figure discrimination test of Motor-free Visual Perception Test 3 (MVPT-3). The SLF and IFOF were separated by diffusion tensor tractography (DTT) and tract volume (TV) was calculated. We measured the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values in the total area, seed region of interest (ROI), and target ROI, respectively. Among thirteen patients, seven demonstrated signs of hemispatial neglect on neglect test. Tractography reconstruction showed significantly low TV of the right IFOF in patients with hemispatial neglect. FA values of the right SLF and the right IFOF were significantly lower in neglect patients. ADC values were not significantly different in two groups. This study suggests that damage of SLF and IFOF is associated with hemispatial neglect in right hemispheric stroke patients. DTI may be useful for predicting the severities of hemispatial neglect using values such as TV and FA of each tract.

The Korean Version of the Cognitive Assessment Scale for Stroke Patients (K-CASP): A Reliability and Validity Study.

OBJECTIVE: To develop the Korean version of the Cognitive Assessment Scale for Stroke Patients (K-CASP) and to evaluate the test reliability and validity of the K-CASP in stroke patients. METHODS: The original CASP was translated into Korean, back-translated into English, then reviewed and compared with the original version. Thirty-three stroke patients were assessed independently by two examiners using the K-CASP twice, with a one-day interval, for a total of four test results. To evaluate the reliability of the K-CASP, intra-class correlation coefficients were used. Pearson correlations were calculated and simple regression analyses performed with the Korean version of Mini-Mental State Examination (K-MMSE) and the aphasia quotient (AQ) to assess the validity. RESULTS: The mean score was 24.42±9.47 (total score 36) for the K-CASP and 21.50±7.01 (total score 30) for the K-MMSE. The inter-rater correlation coefficients of the K-CASP were 0.992 on the first day and 0.995 on the second day. The intra-rater correlation coefficients of the K-CASP were 0.997 for examiner 1 and 0.996 for examiner 2. In the Pearson correlation analysis, the K-CASP score significantly correlated with the K-MMSE score (r=0.825, p<0.001). The coefficients of determination (r2) of the AQ were 0.586 for the K-MMSE and 0.513 for the K-CASP in the simple regression analysis. CONCLUSION: The K-CASP is a reliable and valid instrument for cognitive dysfunction screening in post-stroke patients. It is more applicable than other cognitive assessment tools in stroke patients with aphasia.

Korean Version of the Mini-Mental State Examination Using Smartphone: A Validation Study.

BACKGROUND: Stroke often leads to disability, and poststroke survivors often have limited accessibility to medical facilities. INTRODUCTION: For such patients, mobile videoconferencing technology offers an opportunity to perform follow-up assessment and appropriate management of cognitive impairment. We aimed to determine the validity of the Korean version of the Mini-Mental State Examination (MMSE-K) when administered using a smartphone. MATERIALS AND METHODS: Thirty patients with ischemic or hemorrhagic stroke were included in this study (20 males, 10 females; mean age, 69.8 ± 12.9 years). Both face-to-face and remote assessments of cognitive function through MMSE-K were performed for each patient at an interval of at least 3 days. Additionally, an in-person collaborator evaluated the MMSE-K score during the remote assessment. A smartphone and a tablet were used by the patient and the examiner, respectively, and remote connection was mediated using a dedicated videoconferencing application. The MMSE-K scores obtained through face-to-face, remote, and in-person assessments were compared using the Wilcoxon signed rank test and the Spearman correlation analysis. RESULTS: There was good agreement between face-to-face and remote assessments, as well as between remote assessment and in-person collaborator's evaluation regarding total MMSE-K score and subscores for each MMSE-K domain (orientation, memory, attention/calculation, language, and visuospatial function). DISCUSSION: Remote assessment can be a useful clinical evaluation method, and this study confirmed the validity. CONCLUSIONS: The smartphone represents a promising tool for the assessment of cognitive function in clinical practice, but further research into the intra- and inter-rater reliability of observations is warranted.

Reliability and Validity of Korean Version of Apraxia Screen of TULIA (K-AST).

OBJECTIVE: To evaluate the reliability and validity of Korean version of AST (K-AST) as a bedside screening test of apraxia in patients with stroke for early and reliable detection. METHODS: AST was translated into Korean, and the translated version received authorization from the author of AST. The performances of K-AST in 26 patients (21 males, 5 females; mean age 65.42±17.31 years) with stroke (23 ischemic, 3 hemorrhagic) were videotaped. To test the reliability and validity of K-AST, the recorded performances were assessed by two physiatrists and two occupational therapists twice at a 1-week interval. The patient performances at admission in Korean version of Mini-Mental State Examination (K-MMSE), self-care and transfer categories of Functional Independence Measure (FIM), and motor praxis area of Loewenstein Occupational Therapy Cognitive Assessment, the second edition (LOTCA-II) were also evaluated. Scores of motor praxis area of LOTCA-II was used to assess the validity of K-AST. RESULTS: Inter-rater reliabilities were 0.983 (p<0.001) at the first assessment and 0.982 (p<0.001) at the second assessment. For intra-rater (test-retest) reliabilities, the values of four raters were 0.978 (p<0.001), 0.957 (p<0.001), 0.987 (p<0.001), and 0.977 (p<0.001). K-AST showed significant correlation (r=0.758, p<0.001) with motor praxis area of LOTCA-II test. K-AST also showed positive correlations with the total FIM score (r=0.694, p<0.001), the selfcare category of FIM (r=0.705, p<0.001) and the transfer category of FIM (r=653, p<0.001). CONCLUSION: K-AST is a reliable and valid test for bedside screening of apraxia.

Effects of Extracorporeal Shock Wave Therapy on Spasticity in Patients after Brain Injury: A Meta-analysis.

[Purpose] The purpose of this meta-analysis was to assess the effects of extracorporeal shock wave therapy (ESWT) on reducing spasticity immediately and 4 weeks after application of ESWT. [Subjects and Methods] We searched PubMed, TCL, Embase, and Scopus from their inception dates through June 2013. The key words "muscle hypertonia OR spasticity" were used for spasticity, and the key words "shock wave OR ESWT" were used for ESWT. Five studies were ultimately included in the meta-analysis. [Results] The Modified Ashworth Scale (MAS) grade was significantly improved immediately after ESWT compared with the baseline values (standardized mean difference [SMD], -0.792; 95% confidence interval [CI], -1.001 to -0.583). The MAS grade at four weeks after ESWT was also significantly improved compared with the baseline values (SMD, -0.735; 95% CI, -0.951 to -0.519). [Conclusion] ESWT has a significant effect on improving spasticity. Further standardization of treatment protocols including treatment intervals and intensities needs to be established and long-term follow up studies are needed.

Korean version of the scale for the assessment and rating of ataxia in ataxic stroke patients.

OBJECTIVE: To investigate the intra-rater and inter-rater reliability and usefulness of the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) in ataxic stroke patients. METHODS: The original SARA was translated into Korean, back translated to English, and compared to the original version. Stroke patients (n=60) with ataxia were evaluated using the K-SARA by one physiatrist and one occupational therapist. All subjects were rated twice. We divided the subjects into 5 groups by Functional Ambulation Category (FAC) and 3 groups based on the ataxia subscale of the National Institutes of Health Stroke Scale (NIHSS). The mean K-SARA scores representing each group of FAC and the ataxia subscale of NIHSS were compared. RESULTS: The test-retest correlation coefficient of the K-SARA was 0.997 by the therapist and 1.00 by the physiatrist (p<0.001). The inter-rater correlation coefficient of the K-SARA was 0.985 (p<0.001). The ataxia subscale of NIHSS did not correlate with K-SARA. There was a significant difference in the mean K-SARA score by FAC (p<0.001). CONCLUSION: K-SARA is a reliable and valid measure of ataxia in stroke patients in Korea.

The cervical range of motion as a factor affecting outcome in patients with congenital muscular torticollis.

OBJECTIVE: To investigate the factors affecting rehabilitation outcomes in children with congenital muscular torticollis (CMT). METHODS: We retrospectively reviewed the medical records of 347 patients who were clinically suspected as having CMT and performed neck ultrasonography to measure sternocleidomastoid (SCM) muscle thickness. Fifty-four patients met the inclusion criteria. Included were demographic characteristics as well as measurements of cervical range of motion (ROM), SCM muscle thickness, and the abnormal/normal (A/N) ratio, defined as the ratio of SCM muscle thickness on the affected to the unaffected side. RESULTS: Subjects were divided into three groups depending on degree of cervical ROM (group 1A: ROM>60, n=12; group 1B: 60≥ROM>30, n=31; group 1C: ROM≤30, n=11), the SCM muscle thickness (Th) (group 2A: Th<1.2 cm, n=23; group 2B: 1.2≤Th<1.4 cm, n=18; group 2C: Th≥1.4 cm, n=13), and the A/N ratio (R) (group 3A: R<2.2, n=19; group 3B: 2.2≤R<2.8, n=20; group 3C: R≥2.8, n=15). We found that more limited cervical ROM corresponded to longer treatment duration. The average treatment duration was 4.55 months in group 1A, 5.87 months in group 1B, and 6.50 months in group 1C. SCM muscle thickness and the A/N ratio were not correlated with treatment duration. CONCLUSION: Infants with CMT who were diagnosed earlier and had an earlier intervention had a shorter duration of rehabilitation. Initial cervical ROM is an important prognostic factor for predicting the rehabilitation outcome of patients with CMT.

Use of videofluoroscopic swallowing study in patients with aspiration pneumonia.

OBJECTIVE: To investigate the clinical characteristics of dysphagic elderly Korean patients diagnosed with aspiration pneumonia as well as to examine the necessity of performing a videofluoroscopic swallowing study (VFSS) in order to confirm the presence of dysphagia in such patients. METHOD: The medical records of dysphagic elderly Korean subjects diagnosed with aspiration pneumonia were retrospectively reviewed for demographic and clinical characteristics as well as for VFSS findings. RESULTS: In total, medical records of 105 elderly patients (81 men and 24 women) were reviewed in this study. Of the 105 patients, 82.9% (n=87) were admitted via the emergency department, and 41.0% (n=43) were confined to a bed. Eighty percent (n=84) of the 105 patients were diagnosed with brain disorders, and 68.6% (n=72) involved more than one systemic disease, such as diabetes mellitus, cancers, chronic cardiopulmonary disorders, chronic renal disorders, and chronic liver disorders. Only 66.7% (n=70) of the 105 patients underwent VFSS, all of which showed abnormal findings during the oral or pharyngeal phase, or both. CONCLUSION: In this study, among 105 dysphagic elderly patients with aspiration pneumonia, only 66.7% (n=70) underwent VFSS in order to confirm the presence of dysphagia. As observed in this study, the evaluation of dysphagia is essential in order to consider elderly patients with aspiration pneumonia, particularly in patients with poor functional status, brain disorders, or more than one systemic disease. A greater awareness of dysphagia in the elderly, as well as the diagnostic procedures thereof, particularly VFSS, is needed among medical professionals in Korea.