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Patients with schizophrenia tend to have deficits in emotion recognition (ER) that affect their social function. However, the commonly-used ER measures appear incomprehensive, unreliable and invalid, making it difficult to comprehensively evaluate ER. The purposes of this study were to develop the Computerized Emotion Recognition Video Test (CERVT) evaluating ER ability in patients with schizophrenia. This study was divided into two phases. First, we selected candidate CERVT items/videos of 8 basic emotion domains from a published database. Second, we validated the selected CERVT items using Rasch analysis. Finally, the 269 patients and 177 healthy adults were recruited to ensure the participants had diverse abilities. After the removal of 21 misfit (infit or outfit mean square > 1.4) items and adjustment of the item difficulties of the 26 items with severe differential item functioning, the remaining 217 items were finalized as the CERVT items. All the CERVT items showed good model fits with small eigenvalues (≤ 2) based on the residual-based principal components analysis for each domain, supporting the unidimensionality of these items. The 8 domains of the CERVT had good to excellent reliabilities (average Rasch reliabilities = 0.84-0.93). The CERVT contains items of the 8 basic emotions with individualized scores. Moreover, the CERVT showed acceptable reliability and validity, and the scores were not affected by examinees' gender. Thus, the CERVT has the potential to provide a comprehensive, reliable, valid, and gender-unbiased assessment of ER for patients with schizophrenia., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The Fugl-Meyer assessment for upper extremity (FMA-UE) is a measure for assessing upper extremity motor function in patients with stroke. However, the considerable administration time of the assessment decreases its feasibility. This study aimed to develop an accumulative assessment system of upper extremity motor function (AAS-UE) based on the FMA-UE to improve administrative efficiency while retaining sufficient psychometric properties., Methods: The study used secondary data from 3 previous studies having FMA-UE datasets, including 2 follow-up studies for subacute stroke individuals and 1 test-retest study for individuals with chronic stroke. The AAS-UE adopted deep learning algorithms to use patients' prior information (ie, the FMA-UE scores in previous assessments, time interval of adjacent assessments, and chronicity of stroke) to select a short and personalized item set for the following assessment items and reproduce their FMA-UE scores., Results: Our data included a total of 682 patients after stroke. The AAS-UE administered 10 different items for each patient. The AAS-UE demonstrated good concurrent validity (r = 0.97-0.99 with the FMA-UE), high test-retest reliability (intra-class correlation coefficient = 0.96), low random measurement error (percentage of minimal detectable change = 15.6%), good group-level responsiveness (standardized response mean = 0.65-1.07), and good individual-level responsiveness (30.5%-53.2% of patients showed significant improvement). These psychometric properties were comparable to those of the FMA-UE., Conclusion: The AAS-UE uses an innovative assessment method, which makes good use of patients' prior information to achieve administrative efficiency with good psychometric properties., Impact: This study demonstrates a new assessment method to improve administrative efficiency while retaining psychometric properties, especially individual-level responsiveness and random measurement error, by making good use of patients' basic information and medical records., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The Fugl-Meyer motor scale (FM) is a well-validated measure for assessing upper extremity and lower extremity motor functions in people with stroke. The FM contains numerous items (50), which reduces its clinical usability. The purpose of this study was to develop a short form of the FM for people with stroke using a machine-learning methodology (FM-ML) and compare the efficiency (ie, number of items) and psychometric properties of the FM-ML with those of other FM versions, including the original FM, the 37-item FM, and the 12-item FM., Methods: This observational study with follow-up used secondary data analysis. For developing the FM-ML, the random lasso method of ML was used to select the 10 most informative items (in terms of index of importance). Next, the scores of the FM-ML were calculated using an artificial neural network. Finally, the concurrent validity, predictive validity, responsiveness, and test-retest reliability of all FM versions were examined., Results: The FM-ML used fewer items (80% fewer than the FM, 73% fewer than the 37-item FM, and 17% fewer than the 12-item FM) to achieve psychometric properties comparable with those of the other FM versions (concurrent validity: Pearson r = 0.95-0.99 vs 0.91-0.97; responsiveness: Pearson r = 0.78-0.91 vs 0.33-0.72; and test-retest reliability: intraclass correlation coefficient = 0.88-0.92 vs 0.93-0.98)., Conclusion: The findings preliminarily support the efficiency and psychometric properties of the 10-item FM-ML., Impact: The FM-ML has potential to substantially improve the efficiency of motor function assessments in patients with stroke., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The purposes of this study were to examine the practice effects and test-retest reliability of the Continuous Performance Test, Identical Pairs version (CPT-IP) over four serial assessments in patients with schizophrenia., Method: Fifty-six patients with schizophrenia were assessed with the CPT-IP four times, once per week. The CPT-IP contains four indices: "2-digit score," "3-digit score," "4-digit score," and "total score.", Results: The four indices showed trivial-to-small practice effects (Cohen's d = -0.13-0.24), good-to-excellent test-retest reliability (ICC = 0.62-0.88), and unacceptable random measurement error (MDC% = 33.8%-110.8%)., Conclusions: The total score had the best reliability among the four indices. Although practice effects of the four indices all appeared cumulative, all four CPT-IP indices reached a plateau after the second assessment. These results indicate that clinicians should interpret the change scores of the CPT-IP conservatively and use the total-score index in their routine repeated assessments., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: The d2 Test of Attention (D2) is a commonly used measure of selective attention for patients with schizophrenia. However, its test-retest reliability and minimal detectable change (MDC) are unknown in patients with schizophrenia, limiting its utility in both clinical and research settings. The aim of the present study was to examine the test-retest reliability and MDC of the D2 in patients with schizophrenia., Method: A rater administered the D2 on 108 patients with schizophrenia twice at a 1-month interval. Test-retest reliability was determined through the calculation of the intra-class correlation coefficient (ICC). We also carried out Bland-Altman analysis, which included a scatter plot of the differences between test and retest against their mean. Systematic biases were evaluated by use of a paired t-test., Results: The ICCs for the D2 ranged from 0.78 to 0.94. The MDCs (MDC%) of the seven subscores were 102.3 (29.7), 19.4 (85.0), 7.2 (94.6), 21.0 (69.0), 104.0 (33.1), 105.0 (35.8), and 7.8 (47.8), which represented limited-to-acceptable random measurement error. Trends in the Bland-Altman plots of the omissions (E1), commissions (E2), and errors (E) were noted, presenting that the data had heteroscedasticity., Conclusions: According to the results, the D2 had good test-retest reliability, especially in the scores of TN, TN-E, and CP. For the further research, finding a way to improve the administration procedure to reduce random measurement error would be important for the E1, E2, E, and FR subscores.

Objective: The purposes of this study were to examine the test-retest reliability, concurrent validity, and ecological validity of the Computerized Digit Vigilance Test (C-DVT) in patients with schizophrenia., Method: Each participant was assessed four times, with 1-week intervals. In each assessment, the participants completed both the C-DVT and the original DVT. The participants were also assessed using the Lawton Instrumental Activities of Daily Living Scale (LIADL) and the Personal and Social Performance Scale (PSP)., Results: Forty-nine participants were recruited in this study. The results showed that the test-retest agreement of the C-DVT was good-to-excellent (intraclass correlation coefficient = 0.71-0.89). The random measurement errors of the C-DVT were acceptable (percentages of minimal detectable change = 12.9%-24.1%). The practice effect of the C-DVT reached a plateau after three assessments (effect size <0.20). The concurrent validity of the C-DVT was good (r = .75-.79 with DVT) when we controlled for the randomized administration order of the two tests. The ecological validity of the C-DVT was good (r = -.44 with the LIADL; r = -.45 with the PSP)., Conclusions: The C-DVT had acceptable test-retest reliability, sound concurrent validity, and sound ecological validity in patients with schizophrenia. These findings indicate that the C-DVT has the potential to be a reliable and valid test of sustained attention in patients with schizophrenia., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

DNA recombination is required for effective segregation and diversification of genomes and for the successful completion of meiosis. Recent studies in various species hybrids have demonstrated a genetic link between DNA recombination and speciation. Consistent with this, we observed a striking suppression of recombination in the hybrids between two nematodes, the hermaphroditic Caenorhabditis briggsae and the gonochoristic C. nigoni. To unravel the molecular basis underlying the recombination suppression in their hybrids, we generated a C. nigoni genome with chromosome-level contiguity and produced an improved C. briggsae genome with resolved gaps up to 2.8 Mb. The genome alignment reveals not only high sequence divergences but also pervasive intra- and inter-chromosomal sequence re-arrangements between the two species, which are plausible culprits for the observed suppression. Comparison of recombination boundary sequences suggests that recombination in the hybrid requires extensive sequence homology, which is rarely seen between the two genomes. The new genomes and genomic libraries form invaluable resources for studying genome evolution, hybrid incompatibilities and sex evolution for this pair of model species.

Objective: The Conners' Continuous Performance Test II (CCPT-II) is one of the most commonly used tests of sustained attention in schizophrenia. To manage and monitor sustained attention deficits in schizophrenia, clinicians have to reliably assess the degree of attention impairment. The purpose of our study was to determine the relative and absolute reliability of the CCPT-II in schizophrenia., Method: The final sample was a total of 108 patients with schizophrenia. The primary measures in this study were the CCPT-II and the Clinical Global Impression-Severity (CGI-S). The CCPT-II was administered twice, 1 month apart, by a specially trained occupational therapist. We assessed two types of reliability: relative and absolute reliability. Relative reliability was determined with the intra-class correlation coefficient (ICC). Absolute reliability was quantified with standard error of measurement (SEM), minimal detectable change (MDC), and Bland-Altman's 95% limits of agreement (LOA)., Results: The ICCs for the five CCPT-II indexes (Omissions, Commissions, Hit RT, Hit RT Std Error, and Variability) ranged from 0.66 to 0.79. The MDCs (MDC%) of the five indices were 13.53 (156.78), 10.67 (47.85), 122.10 (34.16), 8.15 (106.82), and 25.81 (162.63), respectively., Conclusions: According to the results, the CCPT-II has limited reliability in monitoring the sustained attention function of patients with schizophrenia. Our results can be used as a reference for the measurement error of CCPT-II to help clinicians and researchers determine the true change between successive assessments of patients with schizophrenia., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The group-level responsiveness of the original, 30-item Stroke Rehabilitation Assessment of Movement measure (STREAM-30) is similar to that of the simplified STREAM (STREAM-15), even though the STREAM-30 has twice as many items as those of the STREAM-15., Objective: The purpose of this study was to compare the responsiveness of the STREAM-30 and STREAM-15 at both group and individual levels in patients with stroke. For the latter level, the Rasch-calibrated 27-item STREAM (STREAM-27) was used because the individual-level indexes of the STREAM-30 could not be estimated., Design: A repeated-measurements design was used. In total, 195 patients were assessed with the STREAM-30 at both admission and discharge., Methods: The Rasch scores of the STREAM-27 and STREAM-15 were estimated from the participants' responses on the STREAM-30. We calculated the paired t-test value, effect size, and standardized response mean as the indexes of group-level responsiveness. The significance of change for each participant was estimated as the individual-level responsiveness index, and the paired t test and test of marginal homogeneity were used for individual-level comparisons between the STREAM-27 and STREAM-15., Results: At the group level, the STREAM-30, STREAM-27, and STREAM-15 showed sufficient and comparable responsiveness. At the individual level, the STREAM-27 detected significantly more participants with significant improvement and fewer participants with no change or deterioration compared with the STREAM-15., Limitations: Few patients with subacute stroke showed deterioration at discharge, so the abilities of the 2 measures to detect deterioration remain inconclusive., Conclusions: The STREAM-27 detected more participants with significant recovery compared with the STREAM-15, although the group-level responsiveness of the 2 measures was the same. The STREAM-27 is recommended as an outcome measure to demonstrate the treatment effects of movement and mobility for patients with stroke., (© 2015 American Physical Therapy Association.)

The boundaries of R-loops are well-documented at immunoglobulin heavy chain loci in mammalian B cells. Within primary B cells or B cell lines, the upstream boundaries of R-loops typically begin early in the repetitive portion of the switch regions. Most R-loops terminate within the switch repetitive zone, but the remainder can extend a few hundred base pairs further, where G-density on the non-template DNA strand gradually drops to the genome average. Whether the G-density determines how far the R-loops extend is an important question. We previously studied the role of G-clusters in initiating R-loop formation, but we did not examine the role of G-density in permitting the elongation of the R-loop, after it had initiated. Here, we vary the G-density of different portions of the switch region in a murine B cell line. We find that both class switch recombination (CSR) and R-loop formation decrease significantly when the overall G-density is reduced from 46% to 29%. Short 50 bp insertions with low G-density within switch regions do not appear to affect either CSR or R-loop elongation, whereas a longer (150 bp) insertion impairs both. These results demonstrate that G-density is an important determinant of the length over which mammalian genomic R-loops extend., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Chronic kidney disease (CKD) is usually associated with cardiac apoptosis and/or cardiac hypertrophy. We hypothesized that exercise can reduce the CKD-induced cardiac damage., Methods and Results: The doxorubicin-induced CKD (DRCKD) model was used in rats to compare two exercise models: 60-min running and 60-min swimming. Results indicated that in healthy normal groups, the signals cardiotrophin-1 (CT-1), interleukin 6 (IL-6), leukaemia inhibitory factor receptor (LIFR), and gp130 were upregulated and janus kinase (JAK) and signal transducer and activation of transcription (STAT) were downregulated by both exercises. In contrast, all signals were highly upregulated in CKD. After exercise training, all signals (CT-1, IL-6, LIFR, gp130, and STAT) were downregulated, with JAK being only slightly upregulated in the running group but not in the swimming group. The myocyte death pathway (CT-1/IL-6 → LIFR/gp130 → PI3K → Akt → Bad) was excluded due to no change found for Bad. Nitric oxide (NO; normal, 15.63 ± 0.86 µmol/l) was significantly suppressed in CKD rats (2.95 ± 0.32 µmol/l), and both running and swimming training highly upregulated the NO level to 30.33 ± 1.03 µmol/l and 27.82 ± 2.47 µmol/l in normal subjects and 24.0 ± 3.2 µmol/l and 22.69 ± 3.79 µmol/l in the DRCKD rats, respectively. The endothelial progenic cells CD34 were significantly suppressed in DRCKD rats, which were not rescued significantly by exercise. In contrast, the CD 34 cells were only slightly suppressed in the healthy subjects by exercise., Conclusion: Both exercise regimens were beneficial by rescuing cardiac function in CKD victims. Its action mechanism was by way of inhibiting myocyte death and rescuing cardiac hypertrophy.

Reactive oxygen species (ROS)-induced DNA damage is repaired by the base excision repair pathway. However, the effect of chromatin structure on BER protein recruitment to DNA damage sites in living cells is poorly understood. To address this problem, we developed a method to specifically produce ROS-induced DNA damage by fusing KillerRed (KR), a light-stimulated ROS-inducer, to a tet-repressor (tetR-KR) or a transcription activator (TA-KR). TetR-KR or TA-KR, bound to a TRE cassette (∼ 90 kb) integrated at a defined genomic locus in U2OS cells, was used to induce ROS damage in hetero- or euchromatin, respectively. We found that DNA glycosylases were efficiently recruited to DNA damage in heterochromatin, as well as in euchromatin. PARP1 was recruited to DNA damage within condensed chromatin more efficiently than in active chromatin. In contrast, recruitment of FEN1 was highly enriched at sites of DNA damage within active chromatin in a PCNA- and transcription activation-dependent manner. These results indicate that oxidative DNA damage is differentially processed within hetero or euchromatin.

Background: The group-level responsiveness of the Postural Assessment Scale for Stroke Patients (PASS) is similar to that of the short-form PASS (SFPASS). This result is counterintuitive because the PASS has more items (12) and response levels (4) than does the SFPASS (5 items and 3 response levels)., Objective: The purpose of this study was to compare individual-level responsiveness between both measures to determine whether the SFPASS can detect change with as much sensitivity as the PASS., Study Design and Setting: Two hundred fifty-one patients were assessed using the PASS at 14 and 30 days after stroke onset in a medical center., Methods: The SFPASS scores were calculated from the patients' responses on the PASS. Individual-level responsiveness was calculated on the basis of the value of minimal detectable change (MDC). If a patient's change score was greater than the MDC of the PASS or SFPASS, his or her improvement was considered significant. The difference in the number of patients scoring greater than the MDC and the units of MDC (the MDC ratio) improved by the patients on both measures was examined., Results: Fifty-three percent of the patients scored greater than the MDC of the PASS, whereas 43.0% of the patients scored greater than the MDC of the SFPASS. The difference was significant. The mean (±SD) MDC ratio of the PASS (1.8±1.7) was significantly higher than that of the SFPASS (1.2±1.3)., Limitations: The scores of the SFPASS were retrieved from those of the PASS, which limits the generalization of our findings., Conclusions: The PASS has better individual-level responsiveness than does the SFPASS. To comprehensively report effects of clinical trials, future studies using the PASS should report the individual-level effect (eg, number of patients scoring greater than the MDC).

Background: The lack of knowledge about the responsiveness and predictive validity of a set of Hierarchical Balance Short Forms (the HBSF) in people with stroke limits the utility of the HBSF in both clinical and research settings., Objective: The purpose of this study was to investigate the responsiveness and predictive validity of the HBSF in people receiving inpatient rehabilitation after stroke., Design: A prospective cohort study was conducted., Methods: Sixty-six participants completed both the 6-item HBSF and the 12-item Postural Assessment Scale for Stroke (PASS) after admission to the rehabilitation ward and before hospital discharge. The standardized effect size (ES) and the standardized response mean (SRM) were used to investigate the internal responsiveness of the HBSF and the PASS. Changes in the Barthel Index and the mobility subscale of the Stroke Rehabilitation Assessment of Movement were used as the external criteria for examining external responsiveness. Moreover, the admission scores on the HBSF and the PASS and the discharge scores on the Barthel Index and mobility subscale of the Stroke Rehabilitation Assessment of Movement were analyzed to investigate the predictive validity of the 2 balance measures., Results: The internal responsiveness of the HBSF was high (ES>0.9, SRM>1.6). The SRM of the HBSF was significantly larger than that of the PASS, whereas the ES of the HBSF was not significantly larger than that of the PASS. The external responsiveness and predictive validity of the HBSF were sufficient and similar to those of the PASS (external responsiveness: r≥.35; predictive validity: r≥.67)., Limitations: The convenience sampling of people receiving inpatient rehabilitation after stroke may limit the generalization of the results., Conclusions: The HBSF has sufficient responsiveness and predictive validity in people receiving inpatient rehabilitation after stroke and is thus recommended for both clinicians and researchers.

Background: An efficient, reliable, and valid measure for assessing activities of daily living (ADL) function is useful to improve the efficiency of patient management and outcome measurement., Objective: The purpose of this study was to construct a computerized adaptive testing (CAT) system for measuring ADL function in outpatients with stroke., Design: Two cohort studies were conducted at 6 hospitals in Taiwan., Methods: A candidate item bank (44 items) was developed, and 643 outpatients were interviewed. An item response theory model was fitted to the data and estimated the item parameters (eg, difficulty and discrimination) for developing the ADL CAT. Another sample of 51 outpatients was interviewed to examine the concurrent validity and efficiency of the CAT. The ADL CAT, as the outcome measure, and the Barthel index (BI) and Frenchay Activities index (FAI) were administered on the second group of participants., Results: Ten items did not satisfy the model's expectations and were deleted. Thirty-four items were included in the final item bank. Two stopping rules (ie, reliability coefficient >.9 and maximum test length of 7 items) were set for the CAT. The participants' ADL scores had an average reliability of .93. The CAT scores were highly associated with those of the full 34 items (Pearson r=.98). The scores of the CAT were closely correlated with those of the combined BI and FAI (r=.82). The time required to complete the CAT was about one fifth of the time used to administer both the BI and FAI., Limitations: The participants were outpatients living in the community. Further studies are needed to cross-validate the results., Conclusions: The results demonstrated that the ADL CAT is quick to administer, reliable, and valid in outpatients with stroke.

An optimal culture system for human pluripotent stem cells should be fully defined and free of animal components. To date, most xeno-free culture systems require human feeder cells and/or highly complicated culture media that contain activators of the fibroblast growth factor (FGF) and transforming growth factor-β (TGFβ) signaling pathways, and none provide for replacement of FGF/TGFβ ligands with chemical compounds. The Wnt/β-catenin signaling pathway plays an important role in mouse embryonic stem cells in leukemia inhibitory factor-independent culture; however, the role of Wnt/β-catenin signaling in human pluripotent stem cell is still poorly understood and controversial because of the dual role of Wnts in proliferation and differentiation. Building on our previous investigations of small molecules modulating Wnt/β-catenin signaling in mouse embryonic stem cells, we identified a compound, ID-8, that could support Wnt-induced human embryonic stem cell proliferation and survival without differentiation. Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) is the target of the small molecule ID-8. Its role in human pluripotent cell renewal was confirmed by DYRK knockdown in human embryonic stem cells. Using Wnt and the DYRK inhibitor ID-8, we have developed a novel and simple chemically defined xeno-free culture system that allows for long-term expansion of human pluripotent stem cells without FGF or TGFβ activation. These culture conditions do not include xenobiotic supplements, serum, serum replacement, or albumin. Using this culture system, we have shown that several human pluripotent cell lines maintained pluripotency (>20 passages) and a normal karyotype and still retained the ability to differentiate into derivatives of all three germ layers. This Wnt-dependent culture system should provide a platform for complete replacement of growth factors with chemical compounds.

The Symbol Digit Modalities Test (SDMT) and Digit Vigilance Test (DVT), both well-recommended attention tests for schizophrenia, are measures of switching and sustained attention, respectively. The purpose of this study was to investigate the test-retest reliability of the two attention tests in schizophrenia. A rater administered both tests on 147 participants with schizophrenia twice at a 1-week interval. Test-retest reliability was determined through the calculation of the intra-class correlation (ICC) coefficient. We also carried out the Bland-Altman analysis, which include a scatter plot of the differences between test and retest against their mean. System biases were evaluated by use of a paired t-test. The ICC for the SDMT was 0.87 and that for the DVT was 0.83. The limits of agreement (LOAs) of the SDMT and DVT were 11.5 to -9.9 correct responses and 156.3 to -249.2 s, respectively. The mean difference scores of the SDMT and DVT were 1.5 (4.7% of the first session mean; p= .002) and -46.4 (7.6% of the first session mean; p< .001). The ICCs show that the SDMT and DVT are stable measures across assessment in different sessions in schizophrenia. However, the paired t-test indicates a practice effect, and the LOAs show large variations. Thus, the SDMT and DVT are reliable for a group of subjects but limited for individual subjects with schizophrenia in 1-week interval clinical trials.

The Symbol Digit Modalities Test (SDMT) is commonly used to evaluate an individual's switching attention and processing speed. However, its test-retest reliability and practice effect are not well known in patients with stroke, limiting its utility in both clinical and research settings. The present study examined the two aforementioned psychometric properties of the oral-format SDMT on a group of 30 outpatients with stroke. The oral-format SDMT demonstrated excellent test-retest reliability (ICC = 0.89) and a small practice effect (Cohen's d = 0.26) within a 1-week interval. A practice effect-corrected reliable change index [-5.29, 10.89] was also provided to help clinicians and researchers interpret their clients' test results. Patients' characteristics and the test-retest interval should be considered before applying the findings of the present study to clinical settings.

The centromere is a highly specialized chromosomal element that is essential for chromosome segregation during mitosis. Centromere integrity must therefore be properly preserved and is strictly dependent upon the establishment and maintenance of surrounding chromatin structure. Here we identify WDHD1, a WD40-domain and HMG-domain containing protein, as a key regulator of centromere function. We show that WDHD1 associates with centromeres in a cell cycle-dependent manner, coinciding with mid-to-late S phase. WDHD1 down-regulation compromises HP1α localization to pericentric heterochromatin and leads to altered expression of epigenetic markers associated with this chromatin region. As a consequence, such reduced epigenetic silencing is manifested in disrupted heterochromatic state of the centromere and a defective mitosis. Moreover, we demonstrate that a possible underlying mechanism of WDHD1's involvement lies in the proper generation of the small non-coding RNAs encoded by the centromeric satellite repeats. This role is mediated at the post-transcriptional level and likely through stabilizing Dicer association with centromeric RNA. Collectively, these findings suggest that WDHD1 may be a critical component of the RNA-dependent epigenetic control mechanism that sustains centromere integrity and genomic stability.

Background: The minimal detectable change (MDC) is the smallest amount of difference in individual scores that represents true change (beyond random measurement error). The MDCs of the Timed "Up & Go" Test (TUG) and the Dynamic Gait Index (DGI) in people with Parkinson disease (PD) are largely unknown, limiting the interpretability of the change scores of both measures., Objective: The purpose of this study was to estimate the MDCs of the TUG and the DGI in people with PD., Design: This investigation was a prospective cohort study., Methods: Seventy-two participants were recruited from special clinics for movement disorders at a university hospital. Their mean age was 67.5 years, and 61% were men. All participants completed the TUG and the DGI assessments twice, about 14 days apart. The MDC was calculated from the standard error of measurement. The percentage MDC (MDC%) was calculated as the MDC divided by the mean of all scores for the sample. Furthermore, the intraclass correlation coefficient was used to examine the reproducibility between testing sessions (test-retest reliability)., Results: The respective MDC and MDC% of the TUG were 3.5 seconds and 29.8, and those of the DGI were 2.9 points and 13.3. The test-retest reliability values for the TUG and the DGI were high; the intraclass correlation coefficients were .80 and .84, respectively., Limitations: The study sample was a convenience sample, and the participants had mild to moderately severe PD., Conclusions: The results showed that the TUG and the DGI have generally acceptable random measurement error and test-retest reliability. These findings should help clinicians and researchers determine whether a change in an individual patient with PD is a true change.

The purpose of this study was to identify the minimal detectable change (MDC) of the Sollerman hand function test (SHT) for patients with burned hands. Twelve subjects were studied, giving a total of 21 burned hands (10 right hands and 11 left hands). Each subject received two sessions of SHT assessment, held at 7- to 10-day intervals. Three raters were recruited to observe and assign scores for the patients' performance during the tests. The MDC was calculated based on standard measurement error, and the intraclass correlation coefficient was applied to examine relative reliability. Results showed that both intra- and interrater MDCs were acceptable (6.7 and 6.9 points, respectively) and that both intra- and interrater relative reliabilities were excellent (intraclass correlation coefficients = 0.98). According to this study, the SHT was found to have appropriate MDC and relative reliability in monitoring changes over time for patients with burned hands. The MDCs of SHT calculated in this study are useful in determining whether any change in score is the result of more than random error.

Background: An efficient and precise measure of balance is needed to improve administration efficiency and to reduce the assessment burden for patients., Objective: The purpose of this study was to develop a computerized adaptive testing (CAT) system for assessing balance function in an efficient, reliable, and valid fashion in patients with stroke., Design: Two cross-sectional prospective studies were conducted., Setting: This study was conducted in the departments of physical medicine and rehabilitation in 6 hospitals., Patients: The participants were inpatients and outpatients who were receiving rehabilitation., Measurements: A balance item pool (41 items) was developed on the basis of predefined balance concepts, expert opinions, and field testing. The items were administered by 5 raters to 764 patients. An item response theory model was fit to the data, and the item parameters were estimated. A simulation study was used to determine the performance (eg, reliability, efficiency) of the Balance CAT. The Balance CAT and the Berg Balance Scale (BBS) then were tested on another independent sample of 56 patients to determine the concurrent validity and time needed for administration., Results: Seven items did not meet the model's expectations and were excluded from further analysis. The remaining 34 items formed the item bank of the Balance CAT. Two stopping rules (ie, reliability coefficient > 0.9 or < or = 6 items) were set for the CAT. The simulation study showed that the patients' balance scores estimated by the CAT had an average reliability value of .94. The scores obtained from the CAT were closely associated with those of the full item set (Pearson r=.98). The scores of the Balance CAT were highly correlated with those of the BBS (Pearson r=.88). The average time needed to administer the Balance CAT (83 seconds) was only 18% of that of the BBS., Limitations: The convenience sampling of both samples may limit the generalization of the results. Further psychometric investigation of the Balance CAT is needed., Conclusion: The results provide strong evidence that the Balance CAT is efficient and has reliability and validity for patients with stroke.

Background: Functional limitation of the upper extremities is common in patients with stroke. An upper-extremity measure with sound psychometric properties is indispensable for clinical and research use., Objective: The purpose of this study was to compare the psychometric properties of 4 clinical measures for assessing upper-extremity motor function in people with stroke: the upper-extremity subscale of the Fugl-Meyer Motor Test (UE-FM), the upper-extremity subscale of the Stroke Rehabilitation Assessment of Movement, the Action Research Arm Test (ARAT), and the Wolf Motor Function Test., Design: This was a prospective, longitudinal study., Methods: Fifty-three people with stroke were evaluated with the 4 measures at 4 time points (14, 30, 90, and 180 days after stroke). Thirty-five participants completed all of the assessments. The ceiling and floor effects, validity (concurrent validity and predictive validity), and responsiveness of each measure were examined. Interrater reliability and test-retest reliability also were examined., Results: All measures, except for the UE-FM, had significant floor effects or ceiling effects at one or more time points. The Spearman rho correlation coefficient for each pair of the 4 measures was > or =.81, indicating high concurrent validity. The predictive validity of the 4 measures was satisfactory (Spearman rho, > or =.51). The responsiveness of the 4 measures at 14 to 180 days after stroke was moderate (.52 < or = effect size < or = .79). The 4 measures had good interrater reliability (intraclass correlation coefficient [ICC], > or =.92) and test-retest reliability (ICC, > or =.97). Only the minimal detectable changes of the UE-FM (8% of the highest possible score) and the ARAT (6%) were satisfactory., Limitations: The sample size was too small to conduct data analysis according to type or severity of stroke. In addition, the timed component of the Wolf Motor Function Test was not used in this study., Conclusions: All 4 measures showed sufficient validity, responsiveness, and reliability in participants with stroke. The UE-FM for assessing impairment and the ARAT for assessing disability had satisfactory minimal detectable changes, supporting their utility in clinical settings.

Cross-talk between TGF-beta and IL-6 has been shown to direct the differentiation of CD4(+) cells into special IL-17-secreting cells, which are termed Th17 cells. In this study, we demonstrated that TGF-beta and IL-6 could stimulate CD8(+) cells to differentiate into noncytotoxic, IL-17-producing cells in MLC. These IL-17-producing CD8(+) cells exhibit a unique granzyme B(-)IFN-gamma(-)IL-10(-) phenotype. The mRNA level of Th2/T cytotoxic 2 (Tc2) transcription factors GATA3 and Th1/Tc1 transcription factors T-box expressed in T cell (T-bet) as well as its target H2.O-like homeobox (Hlx) is decreased in CD8(+) cells from TGF-beta- and IL-6-treated MLC. In addition, these CD8(+) cells display a marked up-regulation of retinoic acid-related orphan receptor-gammat, a key IL-17 transcription factor. These results demonstrate that the existence of an IL-17-producing CD8(+) subset belongs to neither the Tc1 nor the Tc2 subset and can be categorized as a T noncytotoxic 17 (Tnc17) subset.

Background and Purpose: The psychometric properties of the Peabody Developmental Motor Scales-Second Edition (PDMS-2), a revised motor test to assess both gross motor and fine motor composites in children with cerebral palsy (CP), are largely unknown. The purpose of this study was to examine the test-retest reliability and the responsiveness of the PDMS-2 for children with CP., Subjects: A sample of 32 children who had CP (age=27-64 months) and who received intervention participated in this study., Methods: The PDMS-2 was administered to each child 3 times (at the beginning of the study, at 1 week, and at 3 months later) by a physical therapist. The agreement between the first 2 measurements was used to examine the reliability. The change between the first and the third measurements was used to examine the responsiveness., Results: The composite scores on the PDMS-2 had good test-retest reliability (intraclass correlation coefficient=.88-1.00). The sensitivity-to-change coefficients ranged from 1.6 to 2.1, and the responsiveness coefficients ranged from 1.7 to 2.3., Discussion and Conclusion: Our results provide strong evidence that the 3 composites of the PDMS-2 had high test-retest reliability and acceptable responsiveness. The PDMS-2 can be used as an evaluative motor measure for children with CP and aged 2 to 5 years.

Background and Purpose: An efficient, reliable, and valid instrument for assessing motor function in patients with stroke is needed by both clinicians and researchers. To improve administration efficiency, we applied the multidimensional Rasch model to the 30-item, 3-subscale Stroke Rehabilitation Assessment of Movement (STREAM) instrument to produce a concise, reliable, and valid instrument (simplified STREAM [S-STREAM]) for measuring motor function in patients with stroke., Subjects and Methods: The STREAM (consisting of 3 subscales: upper-limb movements, lower-limb movements, and mobility) was administered to 351 subjects with first stroke occurrence and a median time after stroke of 12.5 months. The unidimensionality of each subscale of the STREAM first was verified with unidimensional Rasch analysis. Each subscale of the STREAM then was simplified by deleting redundant items on the basis of expert opinion and the results of the Rasch analysis. The Rasch reliability of the S-STREAM and the concurrent validity of the S-STREAM with the STREAM were examined with multidimensional Rasch analysis and the intraclass correlation coefficient (ICC), respectively., Results: After deleting the items that did not fit the Rasch model, we found that the 8-item upper-limb movement subscale, the 9-item lower-limb movement subscale, and the 10-item mobility subscale assessed single, unidimensional upper-limb movements, lower-limb movements, and mobility, respectively. We selected 5 items from each subscale to construct the S-STREAM and found that the reliability of each subscale of the resulting simplified instrument was high (Rasch reliability coefficients of > or =.91). The agreement between the subscale scores (Rasch estimates) of the S-STREAM and those of the STREAM was excellent (ICC of > or =.99, with a lower limit for the 95% confidence interval of > or =.985), indicating good concurrent validity of the S-STREAM with the STREAM., Discussion and Conclusion: The S-STREAM demonstrates high Rasch reliability, unidimensionality, and concurrent validity with the STREAM in patients with stroke. Furthermore, the S-STREAM is efficient to administer, as it consists of only half the number of items in the original STREAM. Additional studies to examine other psychometric properties (eg, predictive validity and responsiveness) of the S-STREAM or its psychometric properties in various recovery stages after stroke are needed to further establish its utility in both clinical and research settings.

Background and Purpose: To improve the utility of the Berg Balance Scale (BBS), the aim of this study was to develop a short form of the BBS (SFBBS) that was psychometrically similar (including test reliability, validity, and responsiveness) to the original BBS for people with stroke., Subjects and Methods: A total of 226 subjects with stroke participated in this prospective study at 14 days after their stroke; 167 of these subjects also were examined at 90 days after their stroke. The BBS, Barthel Index, and Fugl-Meyer Motor Test were administered at these 2 time points. By reducing the number of tested items by more than half the number of items in the original BBS (ie, making 4-, 5-, 6-, and 7-item tests) and simplifying the scoring system of the original BBS (ie, collapsing the 5-level scale into a 3-level scale [BBS-3P]), we generated a total of 8 SFBBSs., Results: The distributions of scores for all 8 SFBBSs were acceptable but featured notable floor effects. The 4-item BBS, 5-item BBS, 5-item BBS-3P, and 7-item BBS-3P demonstrated good reliability. The subjects' scores on the 6-item BBS, 6-item BBS-3P, 7-item BBS, and 7-item BBS-3P showed excellent agreement with those on the original BBS. The 6-item BBS-3P and 7-item BBS-3P exhibited great responsiveness. Only the 7-item BBS-3P demonstrated both satisfactory and psychometric properties similar to those of the original BBS., Discussion and Conclusion: The 7-item BBS-3P was found to be psychometrically similar to the original BBS. The 7-item BBS-3P, compared with the original BBS, is simpler and faster to complete in either a clinical or a research setting and is recommended.

Background and Purpose: The trunk control items of the Postural Assessment Scale for Stroke Patients (PASS-TC) have been proposed for use in examining patients with stroke. The purpose of this study was to examine the discriminative and predictive validities and the evaluative properties of the PASS-TC at 14, 30, 90, and 180 days after stroke onset., Subjects and Methods: A total of 269 patients with stroke participated in this prospective study. The PASS-TC was administered at the 4 time points after stroke onset. The distributions of the PASS-TC scores were used to determine the discriminative ability to distinguish between individuals at the 4 time points. A comprehensive activities of daily living (CADL) measure was administered 1 year after stroke onset as an external criterion for examining the predictive ability of the PASS-TC. Changes in PASS-TC scores between the intervals of 14 to 30, 30 to 90, and 90 to 180 days after stroke onset were used to examine the evaluative properties of the measure., Results: The PASS-TC scores exhibited differences between the patients with disability and the patients without disability at the 4 time points. The scale, however, showed a notable ceiling effect at the 4 time points (>30% of the subjects), indicating a limited discriminative ability between individuals. The scores of the PASS-TC at the 4 time points were moderately correlated with the CADL scores at 1 year after stroke onset (Spearman rhof.5), evidence of its predictive validity. The responsiveness of the PASS-TC was moderate at 14 to 30 days after stroke (standardized response mean [SRM]=.65) and limited at 30 to 90 and 90 to 180 days after stroke (SRM=.42 and .02, respectively)., Discussion and Conclusion: The results provide evidence that the PASS-TC can predict CADL function at 1 year after a stroke, but the discriminative and evaluative abilities are limited over the first 6 months after a stroke. To promote the utility of the PASS-TC in stroke research, it will be necessary to reduce its ceiling effect and improve its evaluative ability.

Background and Purpose: To determine if the 3-level scales yield data as reliable and valid as data obtained for the original scales, 2 simplified 3-level measures of balance--a modified Berg Balance Scale (BBS-3P) and a modified Postural Assessment Scale for Stroke Patients (PASS-3P)--were proposed by the researchers, and psychometric properties of each were compared with those of the original measures (the Berg Balance Scale [BBS] and the Postural Assessment Scale for Stroke Patients [PASS], respectively) in patients with stroke., Subjects and Methods: The study consisted of 2 parts. The first part examined the reliability and concurrent and convergent validity of measurements obtained with these instruments. A total of 77 patients participated in this part of the study. The 3 levels in the center of the BBS were collapsed to a single level (ie, 0-2-4) to form the BBS-3P. Similarly, the 2 middle scores of the center of the PASS were averaged (ie, 0-1.5-3) to form the PASS-3P. In the second part of the study, the predictive validity and responsiveness of these measures were examined. The BBS and PASS scores of 226 patients were retrieved from the records of participants in the Quality of Life After Stroke Study, and these scores were converted into the proposed BBS-3P and PASS-3P scores., Results: The BBS-3P and PASS-3P showed high concurrent validity with the BBS and PASS, good predictive validity for disability, and moderate to high responsiveness. Importantly, the psychometric properties of the BBS-3P and PASS-3P were essentially identical to those of the original BBS and PASS., Discussion and Conclusion: The psychometric properties of both simplified 3-level balance measures were comparable to those of the full, nontruncated scales. Future study is needed to investigate how much meaningful utility can be gained from the scheme of simplification of scaling.

The vaccine-induced immune mechanisms that protect against Helicobacter pylori infection in the mouse model have not been identified. This study investigated the contribution of reactive oxygen and nitrogen intermediates to Helicobacter pathogenesis and immunity. Mice deficient in nicotinamide-adenine dinucleotide phosphate oxidase activity (gp91(phox-/-)), nitric oxide synthase activity (NOS2(-/-)), or both (gp91(phox-/-)/NOS2(-/-)) were infected with Helicobacter organisms and evaluated for inflammation and bacteria load. Infection of all 3 transgenic strains resulted in significantly more inflammation than found in infected C57BL/6 wild-type mice. However, only gp91(phox-/-) and gp91(phox-/-)/NOS2(-/-) mice had significantly reduced numbers of infected gastric glands. Intranasal immunization of NOS2(-/-) or gp91(phox-/-)/NOS2(-/-) mice against H. pylori resulted in protective immunity comparable to that seen in C57BL/6 control mice. Therefore, reactive oxygen species may play a role in limiting the inflammatory response associated with H. pylori infection of the gastric mucosa but may also limit the host's ability to eradicate Helicobacter organisms.

The random insertion of transgenes into the genomic DNA of mice usually leads to widely variable levels of expression in individual founder lines. To study the mechanisms that cause variegation, we designed a transgene that we expected to variegate, which consisted of a beta-globin locus control region 5' HS-2 linked in tandem to a tagged human beta-globin gene (into which a Lac-Z cassette had been inserted). All tested founder lines exhibited red blood cell-specific expression, but levels of expression varied >1000-fold from the lowest to the highest expressing line. Most of the variation in levels of expression appeared to reflect differences in the percentage of cells in the peripheral blood that expressed the transgene, which ranged from 0.3% in the lowest expressing line to 88% in the highest; the level of transgene expression per cell varied no more than 10-fold from the lowest to the highest expressing line. These differences in expression levels could not be explained by the location of transgene integration, by an effect of beta-galactosidase on red blood cell survival, by the half life of the beta-galactosidase enzyme or by the age of the animals. The progeny of all early erythroid progenitors (BFU-E colony-forming cells) exhibited the same propensity to variegate in methylcellulose-based cultures, suggesting that the decision to variegate occurs after the BFU-E stage of erythroid differentiation. Collectively, these data suggest that variegation in levels of transgene expression are due to local, integration site-dependent phenomena that alter the probability that a transgene will be expressed in an appropriate cell; however, these local effects have a minimal impact on the transgene's activity in the cells that initiate transcription.

Background and Purpose: The Action Research arm test (ARAT) was constructed for assessing recovery of upper extremity function after cortical injury. The objective of the study was to verify the inter-rater reliability and validity of the ARAT in stroke patients., Methods: 50 stroke patients participated in the study. For the purpose of inter-rater study, the ARAT was administered by three experienced raters on each patient within a 3-day period. Validity was assessed by comparing the patients' scores on the ARAT with those obtained for the other well-validated measurements evaluating upper extremity motor impairment and disability., Results: Intra-class correlation coefficient (ICC) for the total score was 0.98 indicating very high inter-rater reliability. ICCs were also very high in each of the subscales. The score of the ARAT was closely correlated with that of the upper extremity part of the motor assessment scale, the arm sub-score of the motricity index and the upper extremity movements of the modified motor assessment chart (Pearson r = 0.96, 0.87 and 0.94, respectively)., Conclusion: The preliminary results of this study support the value of the ARAT for measuring recovery of arm-hand function in stroke patients.

The antioxidant and free radical scavenging effects of dopamine, noradrenaline, tyramine, and tyrosine were investigated and compared with alpha-tocopherol. The antioxidant effect of dopamine and its related compounds on peroxidation of linoleic acid were in the order of dopamine > alpha-tocopherol = tyramine > tyrosine > noradrenaline as measured by the thiocyanate method. These amine compounds had reducing power, and a scavenging effect on reactive oxygen species, i.e., superoxide anion and hydroxyl radical. The results for reducing power and scavenging effect of these amine compounds had a similar trend as their inhibition of linoleic acid peroxidation. The antioxidant activity of these amine compounds in soybean oil was also evaluated by the Rancimat method. The induction time to reach 100 meq/kg peroxide value (POV) of soybean oil for dopamine, alpha-tocopherol, tyramine, tyrosine, noradrenaline, and control were 9.0, 8.2, 8.0, 6.4, 4.6, and 4.3 h, respectively. The antioxidant efficacy of amine compounds seems to be correlated with the numbers of hydroxy groups and their position on the phenolic ring.

In eukaryotic cells, a 5' flap DNA endonuclease activity and a ds DNA 5'-exonuclease activity exist within a single enzyme called FEN-1 [flap endo-nuclease and 5(five)'-exo-nuclease]. This 42 kDa endo-/exonuclease, FEN-1, is highly homologous to human XP-G, Saccharomyces cerevisiae RAD2 and S.cerevisiae RTH1. These structure-specific nucleases recognize and cleave a branched DNA structure called a DNA flap, and its derivative called a pseudo Y-structure. FEN-1 is essential for lagging strand DNA synthesis in Okazaki fragment joining. FEN-1 also appears to be important in mismatch repair. Here we find that human PCNA, the processivity factor for eukaryotic polymerases, physically associates with human FEN-1 and stimulates its endonucleolytic activity at branched DNA structures and its exonucleolytic activity at nick and gap structures. Structural requirements for FEN-1 and PCNA loading provide an interesting picture of this stimulation. PCNA loads on to substrates at double-stranded DNA ends. In contrast, FEN-1 requires a free single-stranded 5' terminus and appears to load by tracking along the single-stranded DNA branch. These physical constraints define the range of DNA replication, recombination and repair processes in which this family of structure-specific nucleases participate. A model explaining the exonucleolytic activity of FEN-1 in terms of its endonucleolytic activity is proposed based on these observations.