Psychometrics of rating scales for externalizing disorders in Japanese outpatients: The ADHD-Rating Scale-5 and the Disruptive Behavior Disorders Rating Scale.

OBJECTIVES: This study validated the Japanese version of the Attention-Deficit/Hyperactivity Disorder-Rating Scale-5 (ADHD-RS-5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD-RS-5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. METHODS: We examined the internal consistency, test-retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6-18 years. RESULTS: The internal consistency and test-retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD-RS-5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher-ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent- and teacher-ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. CONCLUSION: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.

Effect of Intrathecal Urokinase Infusion on Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Vasospasm following an aneurysmal subarachnoid hemorrhage (SAH) causes serious neurological complications, despite surgical clipping of the aneurysm. Intrathecal urokinase (UK) infusion has been shown to effectively prevent symptomatic vasospasm in patients who have undergone endovascular obliteration of the ruptured aneurysms. OBJECTIVE: To investigate whether intrathecal UK infusion can prevent symptomatic vasospasm in patients undergoing surgical or endovascular treatment. METHODS: A total of 90 patients with severe aneurysmal SAH were enrolled and assigned to a surgical neck clipping (n = 56) or an endovascular coil embolization (n = 34) groups. After treatment, UK infusion from the lumbar drain was repeated in 32 patients in the surgical neck clipping group (group B) and all in the endovascular coil embolization group (group C) until complete resolution of the SAH was observed on computed tomography. The remaining 24 of the surgical neck clipping group, without UK infusion, were assigned to group A. RESULTS: Symptomatic vasospasm occurred in 7 (29.2%) patients in group A, 2 (6.3%) in group B, and none in group C (group A vs. group B [P = 0.02]; group B vs. group C [P = 0.14]). Excellent clinical outcomes (modified Rankin score, 0 or 1) were observed in 37.5%, 59.4%, and 76.5% of patients in group A, B, and C, respectively (group A vs. group B [P = 0.11]). CONCLUSION: Clearance of SAH via intrathecal UK infusion significantly reduced symptomatic vasospasm in patients in both UK groups, resulting in better clinical outcomes.

Clinical Significance of Early Venous Filling Detected via Preoperative Angiography in Glioblastoma.

Preoperative angiography in glioblastoma (GBM) often shows arteriovenous shunts and early venous filling (EVF). Here, we investigated the clinical implications of EVF in GBM as a prognostic and vascular mimicry biomarker. In this retrospective multicenter study, we consecutively enrolled patients who underwent angiography with a GBM diagnosis between 1 April 2013 and 31 March 2021. The primary and secondary endpoints were the differences in overall survival (OS) and progression-free survival (PFS), respectively, between cases with and without EVF. Of the 133 initially enrolled patients, 91 newly diagnosed with GBM underwent preoperative angiography and became the study population. The 6-year OS and PFS were significantly worse in the EVF than in the non-EVF group. Moreover, 20 GBM cases (10 with EVF and 10 without EVF) were randomly selected and evaluated for histological vascular mimicry. Except for two cases that were difficult to evaluate, the EVF group had a significantly higher frequency of vascular mimicry than the non-EVF group (0/8 vs. 5/10, p = 0.04). EVF on preoperative angiography is a robust prognostic biomarker for GBM and may help detect cases with a high frequency of histological vascular mimicry.

Psychometrics of the kiddie schedule for affective disorders and schizophrenia present and lifetime version for DSM-5 in Japanese outpatients.

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K-SADS-PL for DSM-5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the K-SADS-PL for DSM-5 in 137 Japanese outpatients. METHODS: Two of 12 experienced clinicians independently performed the K-SADS interview for each patient in a conjoint session, and the resulting consensus diagnosis was compared with a "best-estimate" diagnosis made by two of eight experienced clinicians using all available information for the patient. RESULTS: The inter-rater reliability was excellent, as shown by κ > 0.75 for all disorders, with the exception of current separation anxiety disorder. The criterion validity was fair to good, as shown by κ > 0.40 for all disorders, with the exception of current and lifetime agoraphobia. The construct validity was also good, as shown by theoretically expected associations between the K-SADS-PL diagnoses and subscales of the child behavior checklist. CONCLUSION: The K-SADS-PL for DSM-5, now available in Japanese, generates valid diagnoses in child and adolescent psychiatry.

Accuracy of Pedicle Screw Placement Comparing an Electronic Conductivity Device and a Multi-axis Angiography Unit with C-arm Fluoroscopy in Lumbar Fixation Surgery for Safety.

The aim of this study was to compare the accuracy, safety, and usefulness of percutaneous pedicle screw (PPS) placement for lumbar fixation using a multi-axis angiography unit (MAU) and an electronic conductivity device (ECD) with a cannulated Jamshidi needle with that using a conventional C-arm. Of 65 cases that underwent lumbar fixation (region between L1-S1) during April 2013 to March 2019, 57 cases that could be followed-up for more than 12 months after the procedure were included. Among them, 31 patients (150 screws) received treatment with MAU and ECD (MAU+ECD group) and 26 (117 screws) were treated with the conventional C-arm. We performed a retrospective study of the surgical techniques used in each group at our institute by assessing the accuracy of PPS using Gertzbin-Robbins classification and the Japanese Orthopedic Association (JOA) score for recovery. There was no significant difference in surgery outcome based on the JOA recovery rate. There was a significant difference between the two groups in terms of Accuracy-1 (Group A indicating accuracy and Groups B-E indicating inaccuracy), where the rates were 85.3% and 72.0% in the MAU+ECD group and C-arm group, respectively (P = 0.008). There was also a significant difference between the two groups in terms of Accuracy-2 (Groups A-B indicating accuracy; Groups C-E indicate inaccuracy), where the rates were 98.0% and 92.4% in the MAU+ECD and C-arm groups, respectively (P = 0.036). A combination of MAU and ECD is a safe and accurate method for inserting screws into the pedicle.

Relationship between auditory pathway fractional anisotropy and audibility in patients with cerebellopontine angle tumors on diffusion tensor imaging.

OBJECTIVE: Recent reports demonstrated that acoustic nerve disorders affect the auditory pathway on diffusion tensor imaging (DTI). The aim was to investigate whether auditory pathway fractional anisotropy (FA) values are associated with audibility in patients with cerebellopontine angle tumors. PATIENTS AND METHODS: Patients with cerebellopontine angle tumors were included in this retrospective study. Preoperatively, all patients underwent magnetic resonance imaging (MRI) including DTI. Two regions of interest on the lateral lemniscus (LL) and inferior colliculus (IC) were set bilaterally on DTI. FA values were calculated using software. Correlations between FA values and audibility were evaluated using Spearman's rank correlation coefficient. Statistical significance was defined as p < 0.05. RESULTS: Seventeen patients with cerebellopontine angle tumors were included in this study. FA values in the bilateral LL showed a significant negative correlation with hearing impairment severity (r = -0.758, -0.600, p < 0.05). FA values on the ipsilateral side of the IC showed a significant negative correlation with hearing impairment severity (r = -0.477, p < 0.05). FA values on the contralateral side of the IC did not correlate with hearing impairment severity (r = -0.201, p > 0.05). One patient with a low FA value on the contralateral side of the IC had postoperative hearing impairment despite good preoperative hearing ability. CONCLUSIONS: FA values in the bilateral LL and on the ipsilateral side of the IC reflected hearing impairment severity. Decreased FA values on the contralateral side of the IC might predict hearing impairment postoperatively.

Basic Gene Expression Characteristics of Glioma Stem Cells and Human Glioblastoma.

BACKGROUND: Glioma stem cells (GSCs) play important roles in the tumorigenesis of glioblastoma multiforme (GBM). Using a novel cellular bioinformatics pipeline, we aimed to characterize the differences in gene-expression profiles among GSCs, U251 (glioma cell line), and a human GBM tissue sample. MATERIALS AND METHODS: Total RNA was extracted from GSCs, U251 and GBM and microarray analysis was performed; the data were then applied to the bioinformatics pipeline consisting of a principal component analysis (PCA) with factor loadings, an intracellular pathway analysis, and an immunopathway analysis. RESULTS: The PCA clearly distinguished the three groups. The factor loadings of the PCA suggested that v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), dipeptidyl-peptidase 4 (DPP4), and macrophage migration-inhibitory factor (MIF) contribute to the stemness of GSCs. The intracellular pathway and immunopathway analyses provided relevant information about the functions of representative genes in GSCs. CONCLUSION: The newly-developed cellular bioinformatics pipeline was a useful method to clarify the similarities and differences among samples.

Coil Embolization for Cerebral Aneurysms Using a Semi-Jailing Technique and Open-Cell Stent.

BACKGROUND: Numerous reports have described the semi-jailing technique (SJT) using a closed-cell stent for stent-assisted coil embolization, revealing issues including poor expansion and thrombotic complications in curved vessels. This paper reports preliminary experience with SJT using an open-cell stent, a novel type of stent allowing stent placement from a microcatheter. METHODS: First, this research investigated differences between open- and closed-cell types in SJT using silicone vessel models. Next, 43 patients who underwent SJT for the internal carotid artery were divided into 2 groups to investigate treatment outcomes: 24 patients with placement of an open-cell stent (open-cell group) and 19 patients with closed-cell stents (closed-cell group). RESULTS: In the silicone vessel model, coils could be placed with the open-cell stent deployed with a shorter length than the closed-cell stent. No significant differences were found between groups in terms of maximum diameter of the aneurysm or dome-neck ratio. The open-cell group showed a trend toward higher complete embolization immediately after surgery (54.2% vs. 26.3%, P = 0.06), with few cases of stent malapposition (0% vs. 31.6%, P < 0.01). However, 1 case of ischemic complication in the closed-cell group and 1 case of hemorrhagic complication in open-cell group occurred. All cases of modified Rankin Scale scores at discharge were 0-1. CONCLUSIONS: Although the open-cell stent carries the disadvantage of an unresheathable design, coil placement with a shorter stent deployment length may be advantageous during SJT for internal carotid artery aneurysm embolization with favorable consequences for excellent vessel wall apposition.

Grading of astrocytomas using the PRESTO (principles of echo-shifting with a train of observations) magnetic resonance imaging sequence.

OBJECTIVE: Changes in brain tissue can be detected sensitively using PRESTO (principles of echo-shifting with a train of observations) magnetic resonance imaging (MRI). The aim of this study was to evaluate the correlation between the proliferative ability of astrocytoma and intratumoral spotty signal voids seen as hypo-intense dots on PRESTO MRI. PATIENTS AND METHODS: Fifty-seven astrocytic tumors, comprising 14 astrocytomas, 12 anaplastic astrocytomas, and 31 glioblastomas, were included in this retrospective study. The tumors were classified independently by blinded radiologists according to the number of spotty signal voids detected on PRESTO-MRI as follows: spot-free (grade 0), less than 3 spots (grade 1), or more than 3 spots or a large spot (grade 2). RESULTS: Thirteen patients (92.9%) with astrocytoma were classified as PRESTO grade 0 and 1 patient (7.1%) was classified as grade 1. Seven patients (58.3%) with anaplastic astrocytoma were classified as PRESTO grade 0, 1 (8.3%) as grade 1, and 4 as grade 2 (33.3%). Three patients (9.7%) with glioblastoma were classified as grade 0, 6 (19.4%) as grade 1, and 22 (70.9%) as grade 2. There was a strong correlation between PRESTO tumor grade and the mean MIB-1 index. CONCLUSIONS: These results indicate that a grading system based on the number of spotty signal voids detected on PRESTO images would be useful for the diagnosis of astrocytic tumors and predicting their proliferative ability.

Advantages and Disadvantages of Multi-axis Intraoperative Angiography Unit for Percutaneous Pedicle Screw Placement in the Lumbar Spine.

We analyzed clinical usefulness of the high resolution imaging system in a hybrid operation room (OR) for posterior lumbar interbody fusion. A total of 17 patients with lumbar spondylolisthesis between February 2014 and August 2016 were included. Multi-axis imaging system in a hybrid OR was used in 12 patients (hybrid OR group); the conventional C-arm fluoroscopy, in 5 patients (C-arm group). The time to confirm the first percutaneous pedicle screw (PPS) angle (hybrid OR, 80 vs C-arm, 249 s; P = 0.0026) and the second to the last PPS angle (77 vs 90 s; P = 0.040) were shorter in the hybrid OR group. Placement accuracy was higher in the hybrid OR group (88.0 vs 59.1%; P = 0.010). Irradiation dose was significantly lower in the C-arm group (462 vs 102 mGy; P = 0.0013). This study suggested that the accuracy of PPS placement and time to confirm the PPS angle are the advantages in a hybrid OR.

Juvenile Cerebral Infarction Caused by Bow Hunter's Syndrome during Sport: Two Case Reports.

We report two cases of juvenile cerebral infarction caused by bow hunter's syndrome (BHS) during sport. Case 1 was a 17-year-old male who developed a partial visual field defect after playing basketball. BHS was diagnosed because cervical ultrasonography demonstrated occlusion of the vertebral artery when the neck was rotated. After C1-2 posterior fixation was performed, his symptoms resolved. Case 2 was an 18-year-old male with recurrent visual disturbance after playing handball. Cerebral infarction occurred repeatedly despite antiplatelet therapy. After 3 years, vertebral artery dissection was diagnosed and stenting was performed, but his symptoms did not resolve. BHS was diagnosed when he was examined at our department. C1-2 posterior fixation was performed and his symptoms resolved. In these two cases, BHS was caused by sporting activity. For accurate diagnosis and treatment of BHS, neuroimaging with cervical rotation is mandatory.

Complementary and alternative medicine use by visitors to rural Japanese family medicine clinics: results from the international complementary and alternative medicine survey.

BACKGROUND: There is growing interest in the use of complementary and alternative medicine (CAM) throughout the world, however previous research done in Japan has focused primarily on CAM use in major cities. The purpose of this study was to develop and distribute a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q) to assess the use of CAM among people who visit rural Japanese family medicine clinics. METHODS: Using a Japanese version of the International Complementary and Alternative Medicine Questionnaire (I-CAM-Q), a cross-sectional survey was conducted in three rural family medicine clinics. All patients and those accompanying patients who met inclusion criteria were eligible to participate. Data were entered into SPSS Statistics and analyzed for use by age, gender, and location. RESULTS: Of the 519 respondents who participated in the project, 415 participants reported CAM use in the past 12 months (80.0%). When prayer is excluded, the prevalence of CAM use drops to 77.3% in the past year, or 403 respondents. The most common forms of CAM used by respondents were pain relief pads (n = 170, 32.8%), herbal medicines/supplements (n = 167, 32.2%), and massage by self or family (n = 166, 32.0%). Female respondents, individuals with higher levels of education, and those with poorer overall health status were more likely to use CAM than respondents without these characteristics. Only 22.8% of CAM therapies used were reported to physicians by survey participants. CONCLUSIONS: These data indicate that CAM use in rural Japan is common. The results are consistent with previous studies that show that Japanese individuals are more interested in forms of CAM such as pain relief pads and massage, than in mind-body forms of CAM like relaxation and meditation. Due to the high utilization of certain CAM practices, and given that most CAM users do not disclose their CAM use to their doctors, we conclude that physicians in rural Japan would benefit by asking about CAM use during patient interviews, and by familiarizing themselves with the potential benefits and risks of commonly used CAM modalities.

Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal nephron segment injuries.

BACKGROUND: Several proteins have been proposed as new urinary biomarkers of kidney injuries, but they are not always capable of identifying the kidney nephron segment that has been injured. Since calbindin 1 protein is exclusively localized in the kidney distal nephron segment, it is presumed that its expression is altered during distal nephron segment injuries, resulting in changes in its urinary excretion. METHODS: Calbindin 1 expression in normal rat kidneys was compared with that in the kidneys of rats that had suffered distal nephron segment injuries (unilateral ureteral obstruction [UUO] or anti-glomerular basement membrane glomerulonephritis [anti-GBM GN]) using immunohistochemical examinations and real-time polymerase chain reaction. The urinary calbindin 1 protein concentration of normal rats was also compared with that of anti-GBM GN rats and of cisplatin nephropathy rats using Western blotting. We also compared the kidney and urinary calbindin 1 protein concentrations of normal human subjects with those of proteinuric patients [immunoglobulin (Ig)A nephropathy; IgAN] with distal nephron segment injuries. RESULTS: Calbindin 1 mRNA expression in the renal cortices and calbindin 1 protein expression in the kidney distal nephron segments were decreased in the UUO and anti-GBM GN rat kidneys. The urinary calbindin 1 protein levels of the anti-GBM GN rats were also markedly decreased, whereas those of the cisplatin nephropathy rats were slightly decreased. The human IgAN patients displayed decreased renal calbindin 1 protein expression in their dilated distal tubules, and some patients displayed decreased urinary calbindin 1 levels. CONCLUSION: Since it has been demonstrated that decreased urinary calbindin 1 levels are indicative of decreased calbindin 1 kidney expression due to distal nephron segment injuries, calbindin 1 might be a useful urinary biomarker for identifying distal nephron segment injuries.

Overdosage of Hand2 causes limb and heart defects in the human chromosomal disorder partial trisomy distal 4q.

Partial trisomy distal 4q (denoted 4q+) is a human chromosomal disorder caused by duplication of the distal end of the long arm of chromosome 4 (Chr4). This disorder manifests typical phenotypes, including craniofacial, renal, heart and thumb developmental defects. Although these clinical features are likely caused by a dosage imbalance in the gene network involving the trisomic region, the causative gene or genes and the molecular bases are largely unknown. Here, we report mouse Recombination-induced mutation 4 (Rim4) as a model animal of 4q+. The Rim4 genome contains an insertion of a 6.5 Mb fragment from mouse chromosome 8 into chromosome 6. This insertion fragment contains 17 genes, including Hand2, that encode the basic helix-loop-helix transcription factor and is syntenic to the distal end of human Chr4, 4q32.3 to 4q34.1, which is responsible for 4q+. A comparison of phenotypes between patients with Rim4 and 4q+ revealed that Rim4 shows direct parallels with many phenotypes of 4q+ such as craniofacial, heart, cervical vertebra and limb deformities. Rebalancing the gene dosage by a genetic cross with Hand2 knockout mice ameliorated symptoms of the heart and limb deformities of Rim4. Conversely, an increase in copy number of Hand2 in wild-type mice recaptures the heart and limb deformities of Rim4. Our results collectively demonstrate that overdosage of Hand2 is a major cause for at least the limb and heart phenotypes of 4q+ and that mouse Rim4 provides a unique animal model for understanding the molecular bases underlying the complex phenotypes of 4q+.

PRKAR1A mutation affecting cAMP-mediated G protein-coupled receptor signaling in a patient with acrodysostosis and hormone resistance.

CONTEXT: Acrodysostosis is a rare autosomal dominant disorder characterized by short stature, peculiar facial appearance with nasal hypoplasia, and short metacarpotarsals and phalanges with cone-shaped epiphyses. Recently, mutations of PRKAR1A and PDE4D downstream of GNAS on the cAMP-mediated G protein-coupled receptor (GPCR) signaling cascade have been identified in acrodysostosis with and without hormone resistance, although functional studies have been performed only for p.R368X of PRKAR1A. OBJECTIVE: Our objective was to report a novel PRKAR1A mutation and its functional consequence in a Japanese female patient with acrodysostosis and hormone resistance. PATIENT: This patient had acrodysostosis-compatible clinical features such as short stature and brachydactyly and mildly elevated serum PTH and TSH values. RESULTS: Although no abnormality was detected in GNAS and PDE4D, a novel de novo heterozygous missense mutation (p.T239A) was identified at the cAMP-binding domain A of PRKAR1A. Western blot analysis using primary antibodies for the phosphorylated cAMP-responsive element (CRE)-binding protein showed markedly reduced CRE-binding protein phosphorylation in the forskolin-stimulated lymphoblastoid cell lines of this patient. CRE-luciferase reporter assays indicated significantly impaired response of protein kinase A to cAMP in the HEK293 cells expressing the mutant p.T239A protein. CONCLUSIONS: The results indicate that acrodysostosis with hormone resistance is caused by a heterozygous mutation at the cAMP-binding domain A of PRKAR1A because of impaired cAMP-mediated GPCR signaling. Because GNAS, PRKAR1A, and PDE4D are involved in the GPCR signal transduction cascade and have some different characters, this would explain the phenotypic similarity and difference in patients with GNAS, PRKAR1A, and PDE4D mutations.

3-benzylamino-ß-carboline derivatives induce apoptosis through G2/M arrest in human carcinoma cells HeLa S-3.

ß-carboline derivatives are known as the lead compounds for anti-tumor agents. To examine an optimal structure for anti-tumor activity, we synthesized a variety of ß-carboline derivatives, possessing a variety of substituents on the nitrogen atom of the amino group of 3-amino-ß-carboline, and evaluated their anti-tumor activity for HeLa S-3 cell line. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that an optimal structure for anti-tumor activity was 3-cyclohexylmethylamino (1e) or 3-benzylamino-ß-carboline (1f). An optimal counter anion of 2-methyl-3-benzylamino- ß-carbolinium salts was a triflate anion 2c. In addition, the introduction of a hydroxyl group on the meta-position of the benzyl group of 3-benzylamino-ß-carboline (3e) enhanced its anti-tumor activity. Hoechst 33342 staining and DNA fragmentation assay suggested that 1f, 2c and 3e induced cell death by apoptosis unlike 1e. Flow cytometry analysis showed that 1f, 2c and 3e induced cell apoptosis through arrest of the cell cycle in the G2/M phase.

Affinity regulates spatial range of EGF receptor autocrine ligand binding.

Proper spatial localization of EGFR signaling activated by autocrine ligands represents a critical factor in embryonic development as well as tissue organization and function, and ligand/receptor binding affinity is among the molecular and cellular properties suggested to play a role in governing this localization. We employ a computational model to predict how receptor-binding affinity affects local capture of autocrine ligand vis-a-vis escape to distal regions, and provide experimental test by constructing cell lines expressing EGFR along with either wild-type EGF or a low-affinity mutant, EGF(L47M). The model predicts local capture of a lower affinity autocrine ligand to be less efficient when the ligand production rate is small relative to receptor appearance rate. Our experimental data confirm this prediction, demonstrating that cells can use ligand/receptor binding affinity to regulate ligand spatial distribution when autocrine ligand production is limiting for receptor signaling.