Cross-cultural adaptation, validity and reliability of the Japanese version of ABILHAND-kids for children with cerebral palsy using Rasch measurement model.

PURPOSE: The aim of this study was to develop the Japanese version of the ABILHAND-Kids and to examine its psychometric properties for Japanese children with cerebral palsy (CP). METHODS: The experimental version of 75 items was developed using forward-backward translation method. Parents of 137 children with CP answered it. Their responses were analyzed to successive items, and psychometric properties of the final version were investigated through the Rasch measurement model. RESULTS: The Japanese version of the ABILHAND-Kids contained 22 items. It showed valid item-patient targeting, no significant floor and ceiling effects, and no differential item functioning for demographic and clinical subgroups. All items contributed to the definition of one-dimensional measure. For internal consistency, the person separation index was 0.94. For test-retest reliability, the intraclass correlation coefficients were 0.96 (95% CI: 0.92-0.98). The minimal detectable difference was calculated with a logit score of 0.79 and a total raw score of 4.50. The logit score showed a strong correlation with the Manual Ability Classification System level (ρ= -0.70) and the Gross Motor Function Classification System level (ρ= -0.62). CONCLUSIONS: The Japanese version of the ABILHAND-Kids was found to be valid and reliable. It appears to be a good tool for assessing manual abilities in daily activities in children with CP.

Impairment of upper limb function affects participation and quality of life in children with cerebral palsy, and adequate assessment tools are essential to appropriate planning and evaluation of interventions.The Japanese version of the ABILHAND-Kids is a valid and reliable measure of manual ability in children with cerebral palsy.The Japan-specific items and calibrations allows for evaluation that takes Japanese culture into consideration.

Diagnostic Ultrasound: On-Site Diagnosis of Type B Aortic Dissection During Cataract Surgery.

We report a case of aortic dissection occurring during cataract surgery under local anesthesia, which was diagnosed on-site by point-of-care ultrasound. Intimal flaps were detected in the abdominal aorta, whereas the parasternal view showed no abnormalities in the aortic root or left ventricular function. According to these ultrasound findings, a Stanford type B aortic dissection was more likely than a type A aortic dissection, and imminent death was unlikely. Therefore, we decided to resume and complete the surgery. Subsequent computed tomography (CT) confirmed the point-of-care diagnosis. The patient was transferred to a tertiary hospital for medical treatment.

Clinicopathologic differences of gastric neoplasms between Helicobacter pylori-infected and -naïve patients: a multicenter retrospective analysis.

BACKGROUND: The incidence of gastric neoplasms in Helicobacter pylori (Hp)-naïve patients has recently increased due to a remarkable decrease in the Hp-infected population in Japan. We investigated the clinicopathologic differences between Hp-infected gastric neoplasms (HpIGNs) and Hp-naïve gastric neoplasms (HpNGNs) that have not been fully elucidated so far. METHODS: This retrospective multicenter study investigated 966 consecutive patients with 1131 gastric dysplasia or cancers who underwent endoscopic or surgical treatment for the recent decade. Clinicopathologic features were compared between HpIGN and HpNGN cases. RESULTS: One thousand and sixty-eight HpIGNs in 916 patients included 877 differentiated types and 191 undifferentiated types. Sixty-three HpNGNs in 50 patients included 57 differentiated types (35 foveolar types, 15 intestinal types, 6 fundic-gland types, and 1 other differentiated type) and 6 undifferentiated types. HpNGNs occurred in younger (59.5 vs. 71.8 years, p < 0.05) and female patients (40.0% vs. 26.5%, p < 0.05), were found more frequently in the proximal compartment (p < 0.05), and had smaller size (median 4.0 vs. 20.0 mm, p < 0.05). Histologically, HpNGNs and HpIGNs both primarily consisted of differentiated type (90.5% vs. 82.1%, p = 0.089) and HpNGNs showed lower prevalence of invasive cancer (11.1% vs. 37.6%, p < 0.05) and lymphovascular invasion (1.6% vs. 31.6%, p < 0.05). Nearly all HpNGNs (62/63, 98.4%) were diagnosed in early pathological stage, while 16.1% (172/1068) of HpIGNs were diagnosed in advanced stage (p < 0.05). CONCLUSIONS: HpNGNs is recently on the increase but shows lower malignant nature regardless of histologic type than HpIGN. Endoscopic gastric cancer screening will be reviewed via cost effectiveness for Hp-naïve individuals in future.

Treatment patterns and clinician stress related to care of out-of-hospital cardiac arrest patients with a do not attempt resuscitation order.

Objective: This research investigated treatment patterns for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders in Japanese emergency departments and the associated clinician stress. Methods: A cross-sectional survey was conducted at 9 hospitals in Okayama, Japan, targeting emergency department nurses and physicians. The questionnaire inquired about the last treated out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation. We assessed emotional stress on a 0-10 scale and moral distress on a 1-5 scale among clinicians. Results: Of 208 participants, 107 (51%) had treated an out-of-hospital cardiac arrest patient with a Do Not Attempt Resuscitation order in the past 6 months. Of these, 65 (61%) clinicians used a "slow code" due to perceived futility in resuscitation (42/65 [65%]), unwillingness to terminate resuscitation upon arrival (38/65 [59%]), and absence of family at the time of patient's arrival (35/65 [54%]). Female clinicians had higher emotional stress (5 vs. 3; P = 0.007) and moral distress (3 vs. 2; P = 0.002) than males. Nurses faced more moral distress than physicians (3 vs. 2; P < 0.001). Adjusted logistic regression revealed that having performed a "slow code" (adjusted odds ratio, 5.09 [95% CI, 1.68-17.87]) and having greater ethical concerns about "slow code" (adjusted odds ratio, 0.35 [95% CI, 0.19-0.58]) were associated with high stress levels. Conclusions: The prevalent use of "slow code" for out-of-hospital cardiac arrest patients with Do Not Attempt Resuscitation orders underscores the challenges in managing these patients in clinical practice.

An 83-year-old patient with RET fusion-positive non-small cell lung cancer experiencing severe hepatic disorder due to selpercatinib administration.

An 83-year-old woman with RET fusion-positive advanced lung adenocarcinoma was administered selpercatinib 320 mg/day. Despite the shrinking of the tumour, fever, fatigue, and anorexia developed on day 17. Selpercatinib administration was interrupted. On day 21, elevated blood aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were observed. On day 28, AST and ALT levels increased to demonstrate Grade 4 in CTCAE Ver.5. The patient received a glycyrrhizin-compounding agent and steroid treatment, and AST and ALT levels gradually decreased. On day 63, selpercatinib 160 mg/day was restarted after improvement of the hepatic disorder. Since then, selpercatinib was continued without any severe adverse events. Selpercatinib is a reasonable treatment option for RET fusion-positive advanced non-small cell lung cancer even in older patients. However, old age may be a risk factor for adverse events including hepatic disorders. For safe treatment in such patients, careful follow-up is required.

Effect of symbiotic N2 fixation on leaf protein contents, protein degradation and nitrogen resorption during leaf senescence in temperate deciduous woody species.

Nitrogen (N) resorption from senescing leaves enables plants to reuse N, making them less dependent on current N uptake from the environment, leading to higher fitness, particularly under low N supply. Species that form a symbiotic association with N2-fixing bacteria have not evolved proficient N resorption, i.e., they retain more N in the senesced leaves than non-N2-fixing species. However, the physiological mechanism underlying the difference is still unknown. Metabolic and structural protein contents in green and senesced leaves, as well as protein degradation during leaf senescence-a critical initial process for subsequent N resorption-were determined in four N2-fixing legumes and in four non-N2-fixers. The metabolic proteins were highly degraded in legumes and to a lesser extent in nonlegumes. Nonetheless, legumes retained more metabolic proteins in their senesced leaves than nonlegumes, because symbiotic N2 fixation improved the metabolic protein content in green leaves. Symbiotic N2 fixation did not change the structural protein content in green leaves. The structural proteins were moderately degraded in nonlegumes, and almost undegraded in legumes, and more structural proteins remained in the senesced leaves of legumes than in those of nonlegumes. The higher metabolic and structural protein contents in the senesced leaves of N2-fixing legumes properly explained the less proficient N resorption. This is an important step in unraveling molecular mechanisms of different N conservation strategies among plant functional types.

Emotional work stress reactions of emergency medical technicians involved in transporting out-of-hospital cardiac arrest patients with "do not attempt resuscitation" orders.

BACKGROUND: Emergency medical technicians (EMTs) may be subjected to emotional stress during patient treatment/transport. In Japan, dispatched EMTs must attempt resuscitation in all cases of out-of-hospital cardiac arrest (OHCA), including patients with "do not attempt resuscitation" (DNAR) orders and patients whose families do not support resuscitation. We described the characteristics, prevalence, and outcomes of OHCA/DNAR patients, and aimed to identify factors associated with EMT stress when treating them. METHODS: We included OHCA patients transported by EMTs in the city of Okayama from 2015 to 2019. We identified patients with DNAR orders based on emergency medical service (EMS) records, then EMTs completed questionnaires regarding the management of those patients and EMTs' emotions. RESULTS: Among 3079 eligible OHCA patients, 122 patients (4%) had DNAR orders (DNAR group), and 2957 (96%) patients had no DNAR orders (no DNAR group). Based on responses from 243 EMT participants involved in OHCA/DNAR transports, we divided EMTs into high stress (73/243, 30%) and low stress (170/243, 70%) groups. EMTs experienced emotional stress from treating patients with family physician orders to transport (AOR: 4.74, 95% CI: 2.35-9.56) and those for whom prehospital defibrillation was performed (AOR: 20.7, 95% CI: 3.10-137.9). CONCLUSIONS: Approximately 30% of EMTs providing resuscitation to OHCA/DNAR patients experienced high levels of stress. Establishment of a prehospital emergency system incorporating physician medical direction and updated guidelines for treating patients with DNAR orders may reduce the psychosocial stress of EMTs.

PRRX1 induced by BMP signaling decreases tumorigenesis by epigenetically regulating glioma-initiating cell properties via DNA methyltransferase 3A.

Glioma-initiating cells (GICs), a major source of glioblastoma recurrence, are characterized by the expression of neural stem cell markers and the ability to grow by forming nonadherent spheres under serum-free conditions. Bone morphogenetic proteins (BMPs), members of the transforming growth factor-ß family, induce differentiation of GICs and suppress their tumorigenicity. However, the mechanisms underlying the BMP-induced loss of GIC stemness have not been fully elucidated. Here, we show that paired related homeobox 1 (PRRX1) induced by BMPs decreases the CD133-positive GIC population and inhibits tumorigenic activity of GICs in vivo. Of the two splice isoforms of PRRX1, the longer isoform, pmx-1b, but not the shorter isoform, pmx-1a, induces GIC differentiation. Upon BMP stimulation, pmx-1b interacts with the DNA methyltransferase DNMT3A and induces promoter methylation of the PROM1 gene encoding CD133. Silencing DNMT3A maintains PROM1 expression and increases the CD133-positive GIC population. Thus, pmx-1b promotes loss of stem cell-like properties of GICs through region-specific epigenetic regulation of CD133 expression by recruiting DNMT3A, which is associated with decreased tumorigenicity of GICs.

Visualization of the cancer cell cycle by tissue-clearing technology using the Fucci reporter system.

Tissue-clearing technology is an emerging imaging technique currently utilized not only in neuroscience research but also in cancer research. In our previous reports, tissue-clearing methods were used for the detection of metastatic tumors. Here, we showed that the cell cycles of primary and metastatic tumors were visualized by tissue-clearing methods using a reporter system. First, we established cancer cell lines stably expressing fluorescent ubiquitination-based cell cycle indicator (Fucci) reporter with widely used cancer cell lines A549 and 4T1. Fluorescence patterns of the Fucci reporter were investigated in various tumor inoculation models in mice. Interestingly, fluorescence patterns of the Fucci reporter of tumor colonies were different between various organs, and even among colonies in the same organs. The effects of antitumor drugs were also evaluated using these Fucci reporter cells. Of the three antitumor drugs studied, 5-fluorouracil treatment on 4T1-Fucci cells resulted in characteristic fluorescent patterns by the induction of G2 /M arrest both in vitro and in vivo. Thus, the combination of a tissue-clearing method with the Fucci reporter is useful for analyzing the mechanisms of cancer metastasis and drug resistance.

Anti-pyroptotic function of TGF-ß is suppressed by a synthetic dsRNA analogue in triple negative breast cancer cells.

Development of innovative therapeutic modalities would address an unmet clinical need in the treatment of triple negative breast cancer (TNBC). Activation of retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) such as melanoma differentiation-associated gene 5 (MDA5) and RIG-I in cancer cells is suggested to suppress tumor progression by inducing cell death. Transfection of polyI:C, a conventionally used synthetic double-stranded RNA (dsRNA) analogue that activates RLRs, has been evaluated in clinical trials. However, detailed mechanisms of tumor suppression by RLRs, especially interactions with other signaling pathways, remain elusive. Here, we showed that transfection of polyI:C suppressed transforming growth factor-ß (TGF-ß) signaling in a MDA5- and RIG-I-dependent manner. We found that suppression of TGF-ß signaling by polyI:C promoted cancer cell death, which was attenuated by forced expression of constitutively active Smad3. More detailed analysis suggested that cell death by polyI:C transfection exhibited characteristics of pyroptosis, which is distinct from apoptosis. Therapeutic efficacy of polyI:C transfection was also demonstrated using a mouse model. These results indicated that intratumor administration of polyI:C and related dsRNA analogues may be promising treatments for TNBC through inhibition of the anti-pyroptotic function of TGF-ß.

BMP signaling is a therapeutic target in ovarian cancer.

BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.

Species-specific nitrogen resorption proficiency in legumes and nonlegumes.

Nitrogen (N) resorption from senescing leaves enables plants to reuse N, thereby making them less dependent on current N uptake from the environment. Therefore, N resorption is important for survival and fitness, particularly for plants growing under low N supply. We studied N resorption from senescing leaves of 25 legumes and 25 nonlegumes in a temperate region of Japan to test the hypothesis that high N resorption has not evolved in legumes that fix atmospheric N2. The extent of N resorption was quantified by N resorption proficiency that is measured as the level to which leaf N concentration was reduced during senescence, i.e., the lower the senesced leaf N concentration, the lower the N loss through leaf fall and higher the N resorption proficiency. In support of the hypothesis, senesced leaf N concentration was higher in legumes than in nonlegumes, but there was considerable overlap between the groups. The higher senesced leaf N concentration of legumes was associated with a lower proportion of leaf N resorbed during senescence, particularly in species with higher leaf N concentrations. According to a hierarchical partitioning analysis, there was a large contribution of species to the total variance in the senesced leaf N concentration as opposed to a minor contribution of functional group (legume/nonlegume). This study reveals that legumes are not proficient at resorbing N from senescing leaves but that N2-fixation might not be the single most important determinant of N resorption.

Tyrosine kinase Eph receptor A6 sensitizes glioma-initiating cells towards bone morphogenetic protein-induced apoptosis.

Bone morphogenetic protein (BMP) signaling plays important roles in glioblastoma multiforme (GBM), a lethal form of brain tumor. BMP reduces GBM tumorigenicity through its differentiation- and apoptosis-inducing effects on glioma-initiating cells (GIC). However, some GIC do not respond to the tumor suppressive effects of BMP. Using a phosphoreceptor tyrosine kinase array, we found that EPHA6 (erythropoietin-producing hepatocellular carcinoma receptor A6) phosphorylation was regulated by BMP-2 signaling in some GIC. Analysis of The Cancer Genome Atlas showed that EPHA6 expression was lower in patients with GBM than in the normal brain, and that high EPHA6 expression was correlated with better prognosis. EPHA6 receptor increased the susceptibility of both sensitive and resistant GIC to BMP-2-induced apoptosis. The cooperative effect on apoptosis induction depended on the kinase activity of BMP type I receptor but was independent of EPHA6 kinase function. Overexpression of the EPHA6 receptor in GIC resulted in the formation of a protein complex of EPHA6 receptor and the BMP type I receptor ALK-2, which was associated with BMP-induced apoptosis in GIC. Intracranial injection of GIC into nude mice showed that gain-of-function of EPHA6 together with BMP-2 pretreatment slowed GBM tumor progression in the mouse brain and promoted mouse survival. In summary, EPHA6 together with BMP-2 signaling led to apoptotic cell death in GIC, and thus is a putative tumor suppressor in GBM.

Higher enhanced computed tomography attenuation value of the aorta is a predictor of massive transfusion in blunt trauma patients.

OBJECTIVE: Several scoring systems have been developed to identify patients who require massive transfusion (MT) after major trauma to improve survival. The primary goal of this study was to investigate the usefulness of enhanced computed tomography attenuation values (CTAVs) of major vessels to determine the need for MT in patients with major blunt trauma. METHODS: This single-center retrospective cohort study evaluated patients aged 16 years or older who underwent contrast-enhanced computed tomography scan of the torso after major blunt trauma. The CTAVs of six major vessel points in both the arterial and portal venous phases at initial computed tomography examination were assessed and compared between the MT and the no MT group. The capability of enhanced CTAVs to predict the necessity for MT was estimated based on the area under the receiver operating characteristic curve. RESULTS: Of the 254 eligible patients, 36 (14%) were in the MT group. Patients in the MT group had significantly higher CTAVs at all sites except the inferior vena cava in both the arterial and portal venous phases than that in the no MT group. The descending aorta in the arterial phase had the highest accuracy for predicting MT, with an AUROC of 0.901 (95% confidence interval, 0.855 to 0.947; P<0.001). CONCLUSION: Initial elevation of enhanced CTAV of the aorta is a predictor for the need for MT. A higher CTAV of the aorta should alert the trauma surgeon or emergency physician to activate their MT protocol.

Image quality of a novel light-emitting diode (LED)-illuminated colonoscope.

BACKGROUND AND STUDY AIMS: Light-emitting diodes (LEDs) are used widely for their high luminous efficiency and durability. We developed a novel prototype high definition endoscope with white LEDs and evaluated the image quality it produced against a commercial endoscope with conventional light source. PATIENTS AND METHODS: The specifications of both colonoscopes were identical, except for the LED light source at the tip of the prototype. We examined 20 patients with rectal or sigmoid colon lesions and the image quality was evaluated in 40 images (one image from the LED colonoscope and one from the conventional colonoscope for each lesion) by three endoscopists. We additionally evaluated the 17 videos recorded with the LED colonoscope that were available. Image quality, mucosal and vascular color, and luminous distribution and intensity were scored on a 5-point scale. RESULTS: The mean score for vascular color given by one evaluator was significantly higher using the LED colonoscope than using the conventional colonoscope. The mean scores for mucosal color and luminous intensity from another evaluator were significantly lower with the LED colonoscope than with the conventional colonoscope. There were no significant differences in the luminous distribution scores for any of the evaluators. The image quality of the videos was evaluated as being similar with both colonoscopes. CONCLUSIONS: Image quality from the LED and conventional colonoscopes were similar, although the luminous intensity of the LEDs is inferior to that of the conventional light source at the present time.

Utility of computed tomographic enteroclysis/enterography for the assessment of mucosal healing in Crohn's disease.

Aim. When determining therapeutic strategy, it is important to diagnose small intestinal lesions in Crohn's disease (CD) precisely and to evaluate mucosal healing as well as clinical remission in CD. The purpose of this study was to compare findings from computed tomographic enteroclysis/enterography (CTE) with those from the mucosal surface and to determine whether the state of mucosal healing can be determined by CTE. Materials and Methods. Of the patients who underwent CTE for CD, 39 patients were examined whose mucosal findings could be confirmed by colonoscopy, capsule endoscopy, balloon endoscopy, or with the resected surgical specimens. Results. According to the CTE findings, patients were determined to be in the active CD group (n = 31) or inactive CD group (n = 8). The proportion of previous surgery, clinical remission, stenosis, and CDAI score all showed significant difference between groups. Mucosal findings showed an association with ulcer in 93.6% of active group patients but in only 12.5% of inactive group patients (P < 0.0001), whereas mucosal healing was found in 62.5% of inactive group patients but in only 3.2% of active group patients (P < 0.0001). Conclusion. CTE appeared to be a useful diagnostic method for assessment of mucosal healing in Crohn's disease.

Effect of capsule placement with transnasal endoscopy.

AIM: One of the prohibiting factors in achieving complete small bowel capsule endoscopy is slow gastric transit of the capsule. The present study retrospectively investigated the success rate of, and the time required for, transnasal endoscope-assisted capsule placement to assess its clinical utility. METHODS: In 24 of 27 patients who underwent capsule placement assisted by a transnasal endoscope, the capsule was successfully transported to and released in the duodenum (capsule placement group). For each patient in the capsule placement group, three age- and sex-matched patients who underwent conventional capsule endoscopy were assigned as controls (n=72). Gastric transit time, small bowel transit time, and rate of capsule arrival at the cecum within 8h were compared between the two patient groups. RESULTS: Among the 27 patients in whom capsule placement was carried out, the capsule was successfully placed in the duodenum in 24 patients (88.9% success rate). In the capsule placement group, gastric transit time was significantly shorter (10.5 vs 46.2min, P=0.0021), small bowel transit time was significantly longer (354.7 vs 301.3min, P=0.0134), and completion rate (capsule arrival at the cecum within 8h) was significantly higher (83.3 vs 61.1%, P=0.0455) than in the control group. There were no procedural accidents associated with capsule placement. CONCLUSION: Transnasal endoscope-assisted capsule placement appears to be a safe and reliable procedure, achieving complete small bowel capsule endoscopy, and is considered clinically useful.

Correlations between obesity/metabolic syndrome-related factors and risk of developing colorectal tumors.

BACKGROUND/AIMS: Colorectal cancer/adenoma development may correlate with obesity/metabolic syndrome in the Japanese. We sought to clarify the relation between colorectal adenoma prevalence and various factors to develop a better colorectal tumor screening strategy. METHODOLOGY: Of 2668 patients who underwent colonoscopy, medical records of 837 patients (467 men, 370 women; age, 40-80 years) with available data on measured values of body mass index, waist circumference, body fat percentage, and prior history of hypertension, diabetes and hyperlipidemia were reviewed and analyzed. RESULTS: Of these patients, 460 (55.0%) had colorectal tumor or prior history thereof (lesions >=1mm). Multivariate analysis revealed significant differences in gender, age and waist circumference between patients with/without colorectal adenoma, with men at significantly higher risk than women of developing colorectal tumor (OR=2.57, 95% CI: 1.84-4.65; p<0.001). In patients with/without colorectal tumor, age, waist circumference and body fat percentage were significantly different among men, but only age was significantly different among women. CONCLUSIONS: Present findings that waist circumference and body fat percentage correlated with prevalence of colorectal tumor among men may contribute to more accurate prediction of colorectal tumor risk and an efficient colorectal cancer screening system.