Normative data and psychometric properties of the strengths and difficulties questionnaire among Japanese school-aged children

Background

Although child mental health problems are among the most important worldwide issues, development of culturally acceptable mental health services to serve the clinical needs of children and their families is especially lacking in regions outside Europe and North America. The Strengths and Difficulties Questionnaire (SDQ), which was developed in the United Kingdom and is now one of the most widely used measurement tools for screening child psychiatric symptoms, has been translated into Japanese, but culturally calibrated norms for Japanese schoolchildren have yet to be established. To this end, we examined the applicability of the Japanese versions of the parent and teacher SDQs by establishing norms and extending validation of its psychometric properties to a large nationwide sample, as well as to a smaller clinical sample.

Methods

The Japanese versions of the SDQ were completed by parents and teachers of schoolchildren aged 7 to 15 years attending mainstream classes in primary or secondary schools in Japan. Data were analyzed to describe the population distribution and gender/age effects by informant, cut-off scores according to banding, factor structure, cross-scale correlations, and internal consistency for 24,519 parent ratings and 7,977 teacher ratings from a large nationwide sample. Inter-rater and test-retest reliabilities and convergent and divergent validities were confirmed for a smaller validation sample (total n?=?128) consisting of a clinical sample with any mental disorder and community children without any diagnoses.

Results

Means, standard deviations, and banding of normative data for this Japanese child population were obtained. Gender/age effects were significant for both parent and teacher ratings. The original five-factor structure was replicated, and strong cross-scale correlations and internal reliability were shown across all SDQ subscales for this population. Inter-rater agreement was satisfactory, test-retest reliability was excellent, and convergent and divergent validities were satisfactory for the validation sample, with some differences between informants.

Conclusions

This study provides evidence that the Japanese version of the SDQ is a useful instrument for parents and teachers as well as for research purposes. Our findings also emphasize the importance of establishing culturally calibrated norms and boundaries for the instrument’s use.     

From the Cover: Salt stress-induced Ca2+ waves are associated with rapid,long-distance root-to-shoot signaling in plants

Their sessile lifestyle means that plants have to be exquisitely sensitive to their environment, integrating many signals to appropriate developmental and physiological responses. Stimuli ranging from wounding and pathogen attack to the distribution of water and nutrients in the soil are frequently presented in a localized manner but responses are often elicited throughout the plant. Such systemic signaling is thought to operate through the redistribution of a host of chemical regulators including peptides, RNAs, ions, metabolites, and hormones. However, there are hints of a much more rapid communication network that has been proposed to involve signals ranging from action and system potentials to reactive oxygen species. We now show that plants also possess a rapid stress signaling system based on Ca²⁺ waves that propagate through the plant at rates of up to ∼400 µm/s. In the case of local salt stress to the Arabidopsis thaliana root, Ca²⁺ wave propagation is channeled through the cortex and endodermal cell layers and this movement is dependent on the vacuolar ion channel TPC1. We also provide evidence that the Ca²⁺ wave/TPC1 system likely elicits systemic molecular responses in target organs and may contribute to whole-plant stress tolerance. These results suggest that, although plants do not have a nervous system, they do possess a sensory network that uses ion fluxes moving through defined cell types to rapidly transmit information between distant sites within the organism.Plants are constantly tailoring their responses to current environmental conditions via a complex array of chemical regulators that integrate developmental and physiological programs across the plant body. Environmental stimuli are often highly localized in nature, but the subsequent plant response is often elicited throughout the entire organism. For example, soil is a highly heterogeneous environment and the root encounters stimuli that are presented in a patchy manner. Thus, factors including dry or waterlogged regions of the soil, variations in the osmotic environment, and stresses such as elevated levels of salt are all likely to be encountered locally by individual root tips, but the information may have to be acted on by the plant as a whole.In animals, long-range signaling to integrate activities across the organism occurs through rapid ionic/membrane potential-driven signaling through the nervous system in addition to operating via long-distance chemical signaling. Plants have also been proposed to possess a rapid, systemic communication network, potentially mediated through signals ranging from changes in membrane potential/ion fluxes (1–3) and levels of reactive oxygen species (ROS) (4, 5) to altered hydraulics in the vasculature (6). Even so, the molecular mechanisms behind rapid, systemic signaling in plants and whether such signals indeed carry regulatory information remains largely unknown. Suggestions that Ca²⁺ channels play a role in signals that occlude sieve tube elements (7), or that mediate systemic electrical signaling (2) in response to remote wounding, highlight Ca²⁺-dependent signaling events as a strong candidate for mediating some of these long-range responses. Similarly, cooling of roots elicits Ca²⁺ increases in the shoot within minutes (8), suggesting systemic signals can elicit Ca²⁺-dependent responses at distal sites within the plant. However, despite extensive characterization of Ca²⁺ signals (reviewed in ref. 9), their roles in a possible plant-wide communication network remain poorly understood. Therefore, to visualize how Ca²⁺ might act in local and systemic signaling, we generated Arabidopsis plants expressing the highly sensitive, GFP-based, cytoplasmic Ca²⁺ sensor YCNano-65 (10). We observed that a range of abiotic stresses including H₂O₂, touch, NaCl, and cold shock triggered Ca²⁺ increases at the point of application. However, NaCl also elicited a Ca²⁺ increase that moved away from the point of stress application. Propagation of this Ca²⁺ increase was associated with subsequent systemic changes in gene expression. We also report that this salt stress-induced long-distance Ca²⁺ wave is dependent on the activity of the ion channel protein Two Pore Channel 1 (TPC1), which also appears to contribute to whole-plant stress tolerance.     

Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized,controlled, double-blind,Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study

Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (?37.5 ± 48.7 vs ?24.7 ± 29.4 ml), and LV end-systolic volume (?41.9 ± 43.0 vs ?29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.     

Allogeneic hematopoietic stem cell transplantation for aplastic anemia with pre-transplant conditioning using fludarabine,reduced-dose cyclophosphamide,and low-dose thymoglobulin: A KSGCT prospective study

The optimal pre-transplant conditioning for aplastic anemia (AA) remains unclear. We performed a prospective study on allogeneic transplantation from a related or unrelated donor for adult patients with AA. We assessed whether reduced-dose cyclophosphamide (CY) could decrease toxicity while maintaining engraftment, and low-dose thymoglobulin could safely prevent graft-vs-host disease (GVHD). The pre-transplant conditioning regimen consisted of fludarabine 120 mg/m², CY 100 mg/kg, and thymoglobulin 2.5 mg/kg with or without 2 Gy of total body irradiation. Twenty-seven patients with a median age of 36 years were analyzed. Sixteen patients received graft from related donors. The stem cell source was bone marrow in 26 patients. All of the patients but one, who died early, achieved neutrophil engraftment at a median of 19 days. Mixed chimerism was observed in six and five patients at days 30 and 90, respectively. Only one patient experienced secondary engraftment failure with complete donor-type chimerism. None of the patients developed severe acute GVHD. The cumulative incidence of chronic GVHD was 37.7% at 1 year. The overall survival rate was 96.3% at 1 year and 3 years. A high EB virus-DNA load was detected in one patient at days 60. No one developed EBV-lymphoproliferative disorder within a year. The results suggest that the conditioning regimen in this study was safe and effective. However, relatively high incidence of chronic GVHD needs further improvement.     

Evaluation of Coronary Artery Disease in Patients with Atrial Fibrillation by Cardiac Computed Tomography for Catheter Ablation: CADAF-CT Trial 2

Objective We recently reported that routine cardiac computed tomography (CT) scans for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) could steadily detect coronary artery lesions (CALs) and could accurately detect myocardial ischemia in 9% of patients with AF who underwent RFCA of AF. The aim of this study was to identify the independent risk factor (s) of myocardial ischemia in those patients. Methods Patient characteristics, blood test, CALs, Ordinal coronary calcium scoring (OCCS), and myocardial Ischemia (MI) were evaluated in 757 consecutive patients who underwent RFCA of AF. Results There were 685 and 72 patients without and with myocardial ischemia, respectively. A univariate analysis and multivariate statistical analysis revealed that a male gender (Odds ratio 2.11), a high number of co-existing coronary risk factors (NCCRF ≥3) (Odds ratio 2.03), an elevated brain natriuretic peptide level (BNP ≥100 pg/mL) (Odds ratio 3.37), an enlarged left atrial volume (≥90 mL) (Odds ratio 2.91), and a high OCCS (≥4) (Odds ratio 13.0) were independent risk factors of myocardial ischemia in patients undergoing RFCA of AF. Conclusion The high OCCS (≥4) by cardiac CT was the strongest independent risk factor of myocardial ischemia in those patients. However, physicians may be able to find the high risk patients of myocardial ischemia by evaluating a male gender, in the presence of a high NCCRF (≥3) and elevated BNP (≥100 pg/mL) without OCCS by cardiac CT in patients undergoing RFCA of AF.     

Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism

Background

In a genome-wide association study of autism, zinc finger protein 804A (ZNF804A) single nucleotide polymorphisms (SNPs) were found to be nominally associated in verbally deficient individuals with autism. Zinc finger protein 804A copy number variations (CNVs) have also been observed in individuals with autism. In addition, ZNF804A is known to be involved in theory of mind (ToM) tasks, and ToM deficits are deemed responsible for the communication and social challenges faced by individuals with autism. We hypothesized that ZNF804A could be a risk gene for autism.

Methods

We examined the genetic association and CNVs of ZNF804A in 841 families in which 1 or more members had autism. We compared the expression of ZNF804A in the postmortem brains of individuals with autism (n = 8) and controls (n = 13). We also assessed in vitro the effect of ZNF804A silencing on the expression of several genes known to be involved in verbal efficiency and social cognition.

Results

We found that rs7603001 was nominally associated with autism (p = 0.018). The association was stronger (p = 0.008) in the families of individuals with autism who were verbally deficient (n = 761 families). We observed ZNF804A CNVs in 7 verbally deficient boys with autism. In ZNF804A knockdown cells, the expression of synaptosomal-associated protein, 25kDa (SNAP25) was reduced compared with controls (p = 0.009). The expression of ZNF804A (p = 0.009) and SNAP25 (p = 0.009) were reduced in the anterior cingulate gyrus (ACG) of individuals with autism. There was a strong positive correlation between the expression of ZNF804A and SNAP25 in the ACG (p < 0.001).

Limitations

Study limitations include our small sample size of postmortem brains.

Conclusion

Our results suggest that ZNF804A could be a potential candidate gene mediating the intermediate phenotypes associated with verbal traits in individuals with autism.     

High-dose-rate brachytherapy and hypofractionated external beam radiotherapy combined with long-term hormonal therapy for high-risk and very high-risk prostate cancer: outcomes after 5-year follow-up

The purpose of this study was to report the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiotherapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for National Comprehensive Cancer Network (NCCN) criteria-defined high-risk (HR) and very high-risk (VHR) prostate cancer. Data from 178 HR (n = 96, 54%) and VHR (n = 82, 46%) prostate cancer patients who underwent ¹⁹²Ir-HDR brachytherapy and hypofractionated EBRT with long-term ADT between 2003 and 2008 were retrospectively analyzed. The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After five fractions of HDR treatment, EBRT with 10 fractions of 3 Gy was administered. All patients initially underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT was continued for 36 months after EBRT. The median follow-up was 61 months (range, 25–94 months) from the start of radiotherapy. The 5-year biochemical non-evidence of disease, freedom from clinical failure and overall survival rates were 90.6% (HR, 97.8%; VHR, 81.9%), 95.2% (HR, 97.7%; VHR, 92.1%), and 96.9% (HR, 100%; VHR, 93.3%), respectively. The highest Radiation Therapy Oncology Group-defined late genitourinary toxicities were Grade 2 in 7.3% of patients and Grade 3 in 9.6%. The highest late gastrointestinal toxicities were Grade 2 in 2.8% of patients and Grade 3 in 0%. Although the 5-year outcome of this tri-modality approach seems favorable, further follow-up is necessary to validate clinical and survival advantages of this intensive approach compared with the standard EBRT approach.