Association Between Nonadherence and Transient Hyperuricemia in Pediatric Kidney Transplantation.

BACKGROUND: Nonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center. METHODS: This retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period. RESULTS: Nonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx. CONCLUSIONS: Transient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.

Randomized, double-blind, crossover, placebo-controlled clinical trial to evaluate the effects of chicken hot water extract on insulin secretion.

OBJECTIVE: Essence of chicken (EOC), a hot water extract of chicken, is widely consumed in Southeast Asia as a beverage. EOC has an inhibitory effect on the elevation of blood glucose levels and a secretagogue effect on insulin. However, the mechanism by which EOC promotes insulin secretion is unknown. We aimed to verify the postprandial hyperglycemic inhibitory effect and the insulin secretory effect of EOC in healthy adults under appropriate placebo settings. In addition, we aimed to understand the mechanism underlying the insulin secretory effect of EOC. PATIENTS AND METHODS: Thirty-four healthy Japanese adults were fed 68 mL of EOC or control food, followed by 200 g of cooked rice. Blood glucose and plasma insulin levels were measured at 30, 45, 60, 90, and 120 min after the participants ate cooked rice. The trial had a randomized, double-blind, crossover, placebo-controlled design. RESULTS: The ingestion of EOC induced an increase in the maximum blood concentration (Cmax) of insulin and shortened the time required to reach the maximum blood concentration following rice consumption. Ingestion of the test beverage resulted in a significantly higher insulinogenic index than that obtained after ingestion of the control beverage. No side effects were observed in this study. Mechanistic experiments revealed that EOC stimulated significant (p < 0.05) secretion of GLP-1 from NCI-H716 human intestinal L cells at 0.1, 1, and 10 mg/mL. CONCLUSIONS: Consuming EOC when eating rice supports pancreatic function. Daily consumption of EOC could elevate the early-phase insulin response; therefore, it could prevent diabetes in Asians with low insulin secretion.

Degree of improving TMS focality through a geometrically stable solution of an inverse TMS problem.

The Transcranial Magnetic Stimulation (TMS) inverse problem (TMS-IP) investigated in this study aims to focus the TMS induced electric field close to a specified target point defined on the gray matter interface in the M1HAND area while otherwise minimizing it. The goal of the study is to numerically evaluate the degree of improvement of the TMS-IP solutions relative to the well-known sulcus-aligned mapping (a projection approach with the 90∘ local sulcal angle). In total, 1536 individual TMS-IP solutions have been analyzed for multiple target points and multiple subjects using the boundary element fast multipole method (BEM-FMM) as the forward solver. Our results show that the optimal TMS inverse-problem solutions improve the focality - reduce the size of the field "hot spot" and its deviation from the target - by approximately 21-33% on average for all considered subjects, all observation points, two distinct coil types, two segmentation types, two intracortical observation surfaces under study, and three tested values of the field threshold. The inverse-problem solutions with the maximized focality simultaneously improve the TMS mapping resolution (differentiation between neighbor targets separated by approximately 10 mm) although this improvement is quite modest. Coil position/orientation and conductivity uncertainties have been included into consideration as the corresponding de-focalization factors. The present results will change when the levels of uncertainties change. Our results also indicate that the accuracy of the head segmentation critically influences the expected TMS-IP performance.

Deep-learning-based image reconstruction in dynamic contrast-enhanced abdominal CT: image quality and lesion detection among reconstruction strength levels.

AIM: To evaluate the use of deep-learning-based image reconstruction (DLIR) algorithms in dynamic contrast-enhanced computed tomography (CT) of the abdomen, and to compare the image quality and lesion conspicuity among the reconstruction strength levels. MATERIALS AND METHODS: This prospective study included 59 patients with 373 hepatic lesions who underwent dynamic contrast-enhanced CT of the abdomen. All images were reconstructed using four reconstruction algorithms, including 40% adaptive statistical iterative reconstruction-Veo (ASiR-V) and DLIR at low, medium, and high-strength levels (DLIR-L, DLIR-M, and DLIR-H, respectively). The signal-to-noise ratio (SNR) of the abdominal aorta, portal vein, liver, pancreas, and spleen and the lesion-to-liver contrast-to-noise ratio (CNR) were calculated and compared among the four reconstruction algorithms. The diagnostic acceptability was qualitatively assessed and compared among the four reconstruction algorithms and the conspicuity of hepatic lesions was compared between <5 and ≥5 mm lesions. RESULTS: The SNR of each anatomical structure (p<0.0001) and CNR (p<0.0001) were significantly higher in DLIR-H than the other reconstruction algorithms. Diagnostic acceptability was significantly better in DLIR-M than the other reconstruction algorithms (p<0.0001). The conspicuity of hepatic lesions was highest when using 40% ASiR-V and tended to lessen as the reconstruction strength level was getting higher in DLIR, especially in <5 mm lesions; however, all hepatic lesions could be detected. CONCLUSIONS: DLIR improved the SNR, CNR, and image quality compared with 40% ASiR-V, while making it possible to decrease lesion conspicuity using higher reconstruction strength.

Acetazolamide-Loaded Dynamic 7T MR Quantitative Susceptibility Mapping in Major Cerebral Artery Steno-Occlusive Disease: Comparison with PET.

BACKGROUND AND PURPOSE: Dynamic changes in cerebrovascular reactivity after acetazolamide administration vary markedly among patients with major cerebral arterial steno-occlusive disease. MR quantitative susceptibility mapping can dynamically quantify the cerebral magnetic susceptibility. The purpose of this study was to determine whether dynamic changes in susceptibility after administration of acetazolamide on 7T quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in the cerebral hemispheres with major cerebral arterial steno-occlusive disease. MATERIALS AND METHODS: Sixty-five patients underwent 7T MR imaging at baseline and at 5, 10, 15, and 20 minutes after acetazolamide administration. Differences between the susceptibility of venous structures and surrounding brain tissue were calculated in the quantitative susceptibility mapping images. Susceptibility differences at 5, 10, 15, and 20 minutes after acetazolamide administration relative to baseline were calculated in 97 cerebral hemispheres with major cerebral arterial steno-occlusive disease. CBV and the cerebral metabolic rate of oxygen were also calculated using 15O-gas PET in the resting state. RESULTS: Dynamic changes of susceptibility after acetazolamide administration were classified into 3 patterns: abnormally increasing 5 or 10 minutes after acetazolamide administration; abnormally decreasing within 20 minutes after acetazolamide administration; and remaining unchanged after acetazolamide administration. CBV was significantly greater in the first pattern than in the latter 2. The cerebral metabolic rate of oxygen differed significantly in descending order from the first to middle to last pattern. CONCLUSIONS: Dynamic changes of susceptibility after acetazolamide administration on 7T MR quantitative susceptibility mapping are associated with pre-existing states of CBV and the cerebral metabolic rate of oxygen in major cerebral arterial steno-occlusive disease.

Electron Bernstein waves driven by electron crescents near the electron diffusion region.

The Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth's magnetopause. The EDR is characterized by agyrotropic electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.

Subjective Evaluation of Denture Adhesives: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Many reports show that denture adhesives improve the retention and stability of dentures. However, few randomized controlled trials have examined the effects of denture adhesives. OBJECTIVE: This 10-center randomized controlled trial with parallel groups involving 200 edentulous patients wearing complete dentures aimed to evaluate the effects of short-term use of cream and powder denture adhesives. METHODS: Patients were allocated into 2 cream- and powder-type adhesive groups and 1 control group. Intervention groups were treated with the 2 adhesives (1 each), and the control group received saline solution. Adhesive or control was applied to the denture-mucosal surface for 4 d, and data at baseline and after day 4 of intervention (i.e., 8 meals) were obtained. Patient satisfaction was evaluated with a 100-mm visual analog scale. Oral health-related quality of life was measured with the Japanese version of the Oral Health Impact Profile for Edentulous Patients. Perceived chewing ability was evaluated by a questionnaire regarding ease of chewing and swallowing food. Between-group comparisons were performed with Kruskal-Wallis tests with the Mann-Whitney U test adjusted by Bonferroni correction. Within-group comparisons of pre- and postintervention measurements were performed with the Wilcoxon signed-rank test. Intention-to-treat analysis was also performed. RESULTS: Between-group comparisons showed no significant differences for general satisfaction or Oral Health Impact Profile for Edentulous Patients. However, significant differences in satisfaction with various denture functions with cream- and powder-type adhesives were seen in pre- and postintervention comparisons (P < 0.05). Significant differences were also observed for perceived chewing ability of hard foods (P < 0.05). CONCLUSION: These results suggest that although denture adhesives do not invariably improve denture function, they do affect subjective evaluations and possibly chewing of hard foods. Therefore, the effects of denture adhesive use are insufficient to resolve any fundamental dissatisfaction with dentures ( ClinicalTrials.gov NCT01712802 ). KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that denture adhesives should be applied under certain conditions; however, an appropriate diagnosis is important before application. These practice-based data provide information to establish evidence-based guidelines for applying denture adhesives.

Development and validation of the comprehensive assessment scale for chemotherapy-induced peripheral neuropathy in survivors of cancer.

BACKGROUND: Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity. METHODS: We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach's α. RESULTS: Factor analysis showed that the structure consisted of 15 items in four dimensions: "Threatened interference in daily life by negative feelings", "Impaired hand fine motor skills", "Confidence in choice of treatment/management," and "Dysesthesia of the palms and soles." The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity. CONCLUSIONS: The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.

FEASIBILITY STUDY ON THE FUSION OF PHITS SIMULATIONS AND THE DLNN ALGORITHM FOR A NEW QUANTITATIVE METHOD OF IN-SITU MULTIPLE-CHANNEL DEPTH DISTRIBUTION SPECTROMETRY.

We have recently have developed an in-situ multiple-channel depth distribution spectrometer (DDS) that can easily acquire on-site measurements of the depth distribution of specific radioactivities of Cs-134 and Cs-137 underground. Despite considerable improvements in the hardware developed for this device, the quantitative method for determining of radioactivities with this DDS device cannot yet achieve satisfactory performance for practical use. For example, this method cannot discriminate each γ-ray spectra of Cs-134 and Cs-137 acquired by the 20 thallium-doped caesium iodine CsI(Tl) scintillation crystal detectors of the DDS device from corresponding depth levels of underground soil. Therefore, we have applied deep learning neural network (DLNN) as a novel radiation measurement technique to discriminate the spectra and to determine the specific radioactivities of Cs-134 and Cs-137. We have developed model soil layers on a virtual space in Monte-Carlo based PHITS simulations and transported γ-ray radiation generated from a particular single soil layer or multiple layers as radiation sources; next, we performed PHITS calculations of those specific radioactivity measurements for each soil layer using DDS device based on machine learning via the DLNN algorithm. In this study, we obtained informative results regarding the feasibility of the proposal innovative radiation measurement method for further practical use in on-site applications.

Frequency and risk factors of thoracic metastases and optimisation of the use of cross-sectional chest imaging in follow-up patients with cervical cancer.

AIM: To optimise cross-sectional chest imaging usage by identifying frequency and risk factors associated with thoracic metastases in cervical cancer patients after initial definitive treatment. MATERIALS AND METHODS: This study, conducted during 2004-2015, examined 361 consecutive patients with histopathologically proven cervical carcinoma with at least 1 year of follow-up. Electronic medical records and all available imaging modes were used to record and assess patient and tumour characteristics and timing of thoracic metastases. Associations with these characteristics and thoracic metastases were assessed using univariate and multivariable Cox proportional hazards modelling. RESULTS: Of the 361 patients, 31 developed thoracic metastases. Multivariate regression results showed that adeno/adenosquamous carcinomas (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.06 to 5.72), other histology (HR, 5.61; 95% CI, 1.81 to 17.42), high International Federation of Gynaecology and Obstetrics (FIGO) stage (HR, 2.84; 95% CI, 1.09 to 7.37), and presence of initial intra-abdominal lymph node metastases (HR, 2.46; 95% CI, 1.02 to 5.90) were associated significantly and independently with thoracic metastases. The second analysis among the subgroup of surgical treatment identified intermediate-high risk classification of recurrence (HR, 5.12; 95% CI, 1.14 to 22.94), high FIGO stage (HR, 2.73; 95% CI, 1.05 to 7.13), and other histology (HR, 11.51; 95% CI, 3.66 to 36.19) as independent predictors of thoracic metastases. Two of the 361 and 2/313 patients with thoracic metastases who did not correspond to the conditions above were in the respective evaluation groups. CONCLUSION: Assessment of negative prognostic factors for thoracic metastases might contribute to reduced need for chest cross-sectional chest computed tomography examinations.

Automated detection of outbreaks of antimicrobial-resistant bacteria in Japan.

BACKGROUND: Hospital outbreaks of antimicrobial-resistant (AMR) bacteria should be detected and controlled as early as possible. AIM: To develop a framework for automatic detection of AMR outbreaks in hospitals. METHODS: Japan Nosocomial Infections Surveillance (JANIS) is one of the largest national AMR surveillance systems in the world. For this study, all bacterial data in the JANIS database were extracted between 2011 and 2016. WHONET, a free software for the management of microbiology data, and SaTScan, a free cluster detection tool embedded in WHONET, were used to analyse 2015-2016 data of eligible hospitals. Manual evaluation and validation of 10 representative hospitals around Japan were then performed using 2011-2016 data. FINDINGS: Data from 1031 hospitals were studied; mid-sized (200-499 beds) hospitals accounted for 60%, followed by large hospitals (≥500 beds; 24%) and small hospitals (<200 beds; 16%). More clusters were detected in large hospitals. Most of the clusters included five or fewer patients. From the in-depth analysis of 10 hospitals, ∼80% of the detected clusters were unrecognized by infection control staff because the bacterial species involved were not included in the priority pathogen list for routine surveillance. In two hospitals, clusters of more susceptible isolates were detected before outbreaks of more resistant pathogens. CONCLUSION: WHONET-SaTScan can automatically detect clusters of epidemiologically related patients based on isolate resistance profiles beyond lists of high-priority AMR pathogens. If clusters of more susceptible isolates can be detected, it may allow early intervention in infection control practices before outbreaks of more resistant pathogens occur.

Microbes Culture System Using Cellulose Tubes and Photocatalyst-Coated Glass Balls.

Currently, microbes are utilized in many fields, such as medicine, food and environment etc. For more application of microbes, we need a new culture system, which can culture target microbes in large quantities at low cost. Thereupon, we propose a culture system using cellulose tubes. Target microbes are encapsulated inside the cellulose tubes, where they acquire nutrients and oxygen through nano pores of the tubes and are protected from competitive microbes even in open environment. To further increase the amount of oxygen and nutritions available for the target microbes, we propose photocatalyst-coated glass balls (PCGB) to sterilize competing microbes outside the tubes. We experimentally verified the effectiveness of the proposed culture system by culturing Coryne gultamicum as the target microbes.

Acquired undescended testis and possibly associated testicular torsion in children with cerebral palsy or neuromuscular disease.

INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not well recognized by primary care physicians or healthcare providers. OBJECTIVE: The objective of this study was to highlight the clinical importance of torsion of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with testicular torsion of a UDT operated on at the study institute between 1991 and 2015 were identified. The records of seven children (63.6%) associated with CP or NMD were retrospectively reviewed. Clinical findings of testicular torsion were assessed along with the treatment outcome and testicular salvageability. RESULTS: All seven children were not identified with a UDT by public health checkup for infant and young children. No children with CP or NMD had torsion of a descended testis during the present study period. Median age at surgery was 15 years (range, 1-20 years). The testis location was at the external inguinal ring in five patients, in the inguinal canal in one, and in the superficial inguinal pouch in one. Of the contralateral testes, four were a UDT, one was a retractile testis, and two were descended testes. Orchiectomy was performed in six patients (85.7%). In the remaining patients, the testis was preserved but became atrophic. DISCUSSION: This study demonstrated that children with CP or NMD may be affected with torsion of a UDT with peak at around puberty with the poor salvage rate, even if the testes appear descended in infancy and young children. Shortcomings of this study were the retrospective design and a small series of children undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to educate primary care physicians and healthcare providers in the recognition of acquired UDTs and possibly associated testicular torsion in children with CP and NMD. Genital examination should be continued regularly until adolescence in these children to detect acquired UDT. These children should be referred to pediatric urologists to promote surgery as soon as the diagnosis of acquired UDT is carried out. It is believed that it is perhaps the best approach to prevent loss of the testis in children with CP and NMD.

Baseline biomarkers of connectome disruption and atrophy predict future processing speed in early multiple sclerosis.

The development of accurate prognoses in multiple sclerosis is difficult, as the disease is characterized by heterogeneous patterns of brain abnormalities that relate in an unclear way to future impairments. Here, we use a statistical modeling approach to determine if the baseline pattern of connectome disruption due to T2-FLAIR lesions could predict a patient's future processing speed, as measured using the Symbol Digits Modality Test scores. Imaging data, demographics and Symbol Digits Modality Test scores were collected from 61 early relapsing remitting multiple sclerosis patients. The Network Modification Tool was used to estimate damage to the connectome by quantifying white matter abnormalities' effects on 1) global network properties, 2) regional connectivity and 3) connectivity between pairs of regions. MS subjects showed significant improvement of processing speed between baseline and follow-up (t = -2.6, p = 0.0096); however, both baseline (t = -4.01, p = 0.00012) and follow-up (t = -2.10, p = 0.038) processing speed were significantly lower than age-matched healthy controls. Partial Least Squares Regression was used to create models that predict future processing speed from between baseline imaging metrics and demographics. The model based on region-pair disconnection and gray matter atrophy had the lowest AIC and highest prediction accuracy (R2 = 0.79) compared to models based on global (R2 = 0.41) or regional (R2 = 0.66) disconnection and gray matter atrophy, overlap with an ROI-based atlas and gray matter atrophy (R2 = 0.73) or gray matter atrophy alone (R2 = 0.71). We found that baseline measures of connectivity disruption in various parietal, temporal, occipital and subcortical regions and atrophy in the putamen were important predictors of future processing speed. We conclude that information about disruptions to pairwise brain connections is more informative of future processing speed than regional or global metrics or gray matter atrophy alone. The combination of quantitative disconnectome metrics, gray matter atrophy and statistical modeling approaches could enable clinicians in developing more accurate, individualized prognoses of future cognitive status in multiple sclerosis patients.

Rikkunshito simultaneously improves dyspepsia correlated with anxiety in patients with functional dyspepsia: A randomized clinical trial (the DREAM study).

BACKGROUND: Functional dyspepsia (FD), a heterogeneous disorder, involves multiple pathogenetic mechanisms. Developing treatments for FD has been challenging. We performed a randomized, placebo-controlled, double-blind clinical trial to determine the efficacy of rikkunshito, a Japanese herbal medicine, in FD patients. METHODS: FD patients (n = 192) who met the Rome III criteria without Helicobacter pylori infection, predominant heartburn, and depression were enrolled at 56 hospitals in Japan. After 2 weeks of single-blind placebo treatment, 128 patients with continuous symptoms were randomly assigned to 8 weeks of rikkunshito (n = 64) or placebo (n = 61). The primary efficacy endpoint was global assessment of overall treatment efficacy (OTE). The secondary efficacy endpoints were improvements in upper gastrointestinal symptoms evaluated by the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), the Global Overall Symptom scale (GOS), and the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (m-FSSG), and psychological symptoms evaluated by the Hospital Anxiety and Depression Scale (HADS). KEY RESULTS: Rikkunshito increased OTE compared to placebo at 8 weeks (P = .019). Rikkunshito improved upper gastrointestinal symptoms (PAGI-SYM, GOS, and m-FSSG) at 8 weeks, especially postprandial fullness/early satiety (P = .015 and P = .001) and bloating (P = .007 and P = .002) of the PAGI-SYM subscales at 4 weeks and 8 weeks. Improvement of HADS at 8 weeks (P = .027) correlated with those of PAGI-SYM (r = .302, P = .001), GOS (r = .186, P = .044), and m-FSSG (r = .462, P < .001), postprandial fullness/early satiety (r = .226, P = .014), dyspepsia (r = .215, P = .019), and PDS (r = .221, P = .016). CONCLUSION & INFERENCES: Rikkunshito may be beneficial for FD patients to simultaneously treat gastrointestinal and psychological symptoms.

Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma.

Somatic G17V RHOA mutations were found in 50-70% of angioimmunoblastic T-cell lymphoma (AITL). The mutant RHOA lacks GTP binding capacity, suggesting defects in the classical RHOA signaling. Here, we discovered the novel function of the G17V RHOA: VAV1 was identified as a G17V RHOA-specific binding partner via high-throughput screening. We found that binding of G17V RHOA to VAV1 augmented its adaptor function through phosphorylation of 174Tyr, resulting in acceleration of T-cell receptor (TCR) signaling. Enrichment of cytokine and chemokine-related pathways was also evident by the expression of G17V RHOA. We further identified VAV1 mutations and a new translocation, VAV1-STAP2, in seven of the 85 RHOA mutation-negative samples (8.2%), whereas none of the 41 RHOA mutation-positive samples exhibited VAV1 mutations. Augmentation of 174Tyr phosphorylation was also demonstrated in VAV1-STAP2. Dasatinib, a multikinase inhibitor, efficiently blocked the accelerated VAV1 phosphorylation and the associating TCR signaling by both G17V RHOA and VAV1-STAP2 expression. Phospho-VAV1 staining was demonstrated in the clinical specimens harboring G17V RHOA and VAV1 mutations at a higher frequency than those without. Our findings indicate that the G17V RHOA-VAV1 axis may provide a new therapeutic target in AITL.

Evolution of spall-damage in iron caused by repeated plate impacts: Ultrasonic evaluation.

This paper focuses on the developed of spall-damage that occurs in pure iron as a result of repeated impact. The employed low-frequency scanning acoustic microscopy (LF-SAM) observations combined with the measurements of ultrasonic wave velocity, attenuation, backscattering intensity and amplitude spectrum of the reflected wave, enabled us to provide a nondestructive evaluation. The spall-damage distribution was analyzed in the C-scan images, and we found the spall-damage increase with impact stress when the latter exceeds the characteristic spall-threshold stress. Moreover, we recorded the decreased sound velocity, amplitude ratio, and the increase of backscattering intensity, significant attenuation (the high frequency component of the reflected wave) for enhanced impact stress. It was also demonstrated that the tiny cracks generated in iron develop significantly during subsequent impacts either with lower or higher impact stress. Since the presented results concern for the first time the multiple-impact experiments, we contend that the applied ultrasonic investigations constitute the effective method of nondestructive spall-damage evaluation.

Development of 19F-NMR chemical shift detection of DNA B-Z equilibrium using 19F-NMR.

Various DNA conformational changes are in correlation with biological events. In particular, DNA B-Z equilibrium showed a high correlation with translation and transcription. In this study, we developed a DNA probe containing 5-trifluoromethylcytidine or 5-trifluoromethylthymidine to detect DNA B-Z equilibrium using 19F-NMR. Its probe enabled the quantitative detection of B-, Z-, and ss-DNA based on 19F-NMR chemical shift change.