[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Optical coherence tomography and coronary angioscopy assessment of healed coronary plaque components.

PURPOSE: Histopathological or intracoronary image assessment of healed plaques (HPs) has been reported. However, the lesion characteristics of HPs remains undetermined yet. We assessed the healed plaque components in patients with coronary artery lesions using multiple imaging modalities. METHODS: We enrolled 33 stable angina pectoris (SAP) patients with 36 native coronary culprit lesions with angiography severe stenosis and without severe calcification undergoing pre-intervention optical coherence tomography (OCT) and coronary angioscopy (CAS). HPs were defined as layered phenotype on OCT. Lesion morphologies and plaque characteristics of HPs were assessed using OCT and CAS. RESULTS: HPs were observed in 19 lesions (52.8%). HP lesions had higher frequent B2/C lesions (89.4% vs. 52.9%, p = 0.02), worse pre-PCI coronary flow (corrected thrombolysis in myocardial infarction count 21.6 ± 13.5 vs. 13.8 ± 6.2, p = 0.047) and greater lumen-area stenosis (79.6 ± 10.6% vs. 68.0 ± 21.6%, p = 0.047) than non-HP lesions. HP lesions had higher prevalence of OCT-thin-cap fibroatheroma (TCFA) (31.6% vs. 0.0%, p = 0.02), OCT-macrophage (89.5% vs. 41.2%, p = 0.004), and CAS-red thrombus (89.5% vs. 41.2%, p = 0.004) than non-HP lesions. The combination of 3 features including OCT-TCFA, macrophages, and CAS-red thrombus showed higher predictive valuer for HPs on OCT than each single variable. Post-PCI irregular tissue protrusion was more frequently observed in lesions with HPs than in those without (52.6% vs. 13.3%, p = 0.03). CONCLUSIONS: SAP lesions with HPs might have more frequent vulnerable plaques with intraplaque inflammation and thrombus than those without, suggesting that layered phenotype on OCT might reflect not only healing process but also potential risks for future coronary events.

Assessment of the VDW interaction converting DMAPS from the thermal-motion form to the hydrogen-bonded form.

Assessment of van der Waals (VDW) interactions is fundamental to all of the central quest of structure that regulates the biological function. VDW interactions contributing to intramolecular weak hydrogen bonding are regarded as an important force to regulate the thermal stimuli-sensitive function of sulfobetaine methacrylate, DMAPS. We present here the conversion from the thermal-motion form at room temperature to the weak-hydrogen-bonded form against thermal motion as a terahertz spectral change with a definite isosbestic point from an absorption peak of one form to the other. Vibrational absorptions are used as a probe for assessing VDW interactions in conjunction with highly reliable and well-established density functional theory (DFT) calculations for analysis. Complicated spectral features and uncertain conformations of DMAPS in the amorphous state are clearly resolved under the polarizable continuum model and the dispersion correction for the pure DFT calculations.

[Animal welfare and corporate welfare in pharmaceutical R&D - the future of third-party assessment].

For research and development (R&D) of new drugs, animal experimentation is indispensable, and research institutes, pharmaceutical companies, or contract research organizations routinely conduct preclinical studies of efficacy, safety, or metabolism using laboratory animals. However, animal experimentation entails some organizational risks. One is the suspension of R&D of a new drug, because in the course of clinical studies it becomes apparent that the drug has limited efficacy, unexpected side effects, and/or unexpected metabolites. Another risk is damage to the company image by development of an unfavorable reputation. Society has accepted animal experimentation as a necessary evil, but if such experimentation is not conducted with adequate concern for animal welfare, social sanctions will against that institute, company or organization will result. Once this happens, it is difficult to recover a good public image. Therefore, pharmaceutical companies must conduct animal experiments so as to obtain highly useful data without sacrificing public favor. One way to maintain a good reputation is through third-party accreditation, which verifies that the institute, company or organization and its researchers value animal welfare appropriately.

The relationship between energy cost and the center of gravity trajectory during sit-to-stand motion.

[Purpose] The purpose of this study was to examine the relationship between jerk cost and the formation of the center of gravity trajectory during sit-to-stand motion with asymmetrical foot placement. [Subjects] Nineteen male volunteers were included (age: 21 ± 1 years). [Methods] The subjects moved from a sitting position to a standing position under two different foot placement conditions: (1) 0 degrees of dorsiflexion on the non-dominant side and 20 degrees of dorsiflexion on the dominant side (P1) and (2) 20 degrees of plantarflexion on the non-dominant side and 20 degrees of dorsiflexion on the dominant side (P2). Two standing conditions were used: (1) natural movement and (2) instructed movement, with instructions to increase weight bearing on the non-dominant side. The center of gravity trajectory and its jerk cost were calculated at each axis: front and back (jerk-x), right and left (jerk-y), and vertical (jerk-z). [Results] Jerk-x and jerk-y were significantly larger during instructed movement than natural movement in both P1 and P2. Jerk-z was not significantly different between instructed and natural movement in P1 or P2. [Conclusion] These results indicate that energy cost influences the formation of the center of gravity trajectory during sit-to-stand motion with asymmetrical foot placement.

Factors decreasing caregiver burden to allow patients with cerebrovascular disease to continue in long-term home care.

BACKGROUND: This study attempted to assess continued long-term home care by examining patients' independent activities of daily living (ADLs) and caregivers' free time. METHODS: We surveyed the main caregivers of 52 patients with cerebrovascular disease with continuous home care from 1999 to 2010. Survey items were patients' ADLs, the frequency of use of care services, care requirements, and caregiver sense of burden. We compared the survey results between years. RESULTS: ADLs of excretory control, verbal expression, verbal comprehension, and range of activities showed significant deterioration from 1999 to 2010. Patient need for care increased significantly but use of care services did not. Main caregivers were typically spouses who aged together with the patients. Main caregivers rarely changed; occasionally, a son or daughter-in-law became the main caregiver. Patients typically required less than 3 hours of care daily, which did not change over time. Caregivers had significantly more difficulty maintaining their own health in 2010 than 1999. However, they did not identify increases in difficulties with housework or coping with work. They felt that caregiving was a burden but did not indicate that the family relationship had deteriorated. CONCLUSIONS: Regardless of degree of independence of patients' ADLs, caregiver burden was severe. To decrease caregiver burden, it is necessary to use care services, reduce care time, and allow caregivers free time. In addition, it is possible to continue long-term home care by maintaining their relationships.

A novel gas chromatography mass spectrometry-based serum diagnostic and assessment approach to ulcerative colitis.

BACKGROUND & AIMS: To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. METHODS: Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. RESULTS: The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (rs=0.7371, P<0.0001) in the validation set. CONCLUSIONS: Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.

Assessment of cyclic changes in the diameter of the aortic annulus using speckle-tracking trans-esophageal echocardiography.

It is uncertain whether dynamic variation in the diameter of the aortic annulus occurs during the cardiac cycle in humans. The purpose of this study was to analyze cyclic changes of the aortic annulus using speckle-tracking trans-esophageal echocardiography. The subjects were 40 patients with aortic stenosis and 40 controls. Absolute and relative changes in the diameter of the aortic annulus and the times at which the maximum and minimum diameters occurred during the cardiac cycle were determined using speckle-tracking trans-esophageal echocardiography. The maximum and minimum diameters were 22.9 ± 2.7 and 20.0 ± 2.9 mm, respectively, in controls. The change in diameter of the aortic annulus was 2.9 ± 0.7 mm, and the relative change was 12.9 ± 3.5%. The maximum aortic annulus diameter was reached at the onset of aortic valve opening, and the minimum diameter occurred in the rapid filling phase. The change in diameter of the aortic annulus was significantly smaller (2.2 ± 0.6 mm vs. 2.9 ± 0.7 mm, p < 0.0001), and the time to reach the maximum diameter was significantly longer (98.5 ± 17.5 ms vs. 83.4 ± 18.2 ms, p = 0.0004), in the aortic stenosis group than in the control group. The study found that dynamic changes of the aortic annulus occur in the cardiac cycle and can be measured using speckle-tracking trans-esophageal echocardiography. We also found that aortic stenosis has an effect on the extent and timing of these changes. This suggests that accurate assessment of aortic annulus diameter requires consideration of the timing of the cardiac cycle.

Accuracy of the centenarian numbers in Okinawa and the role of the Okinawan diet on longevity: responses to Le Bourg about the article "Exploring the impact of climate on human longevity".

This response letter addresses two points raised by le Bourg when discussing our previous paper entitled "Exploring the impact of climate on human longevity". First, the arguments explaining the accuracy of the numbers of centenarian in Okinawa are developed, and second the composition and healthfulness of the traditional Okinawan diet are described as well as the changes in dietary pattern and their impact on longevity.

Exploring the impact of climate on human longevity.

The purpose of this study was to examine the impact of physical geographic factors and climate conditions on human longevity. The centenarian rate (CR) in 2005 was computed for Japan's 47 prefectures, whose geography and climate vary greatly. Several pathways, such as excess winter mortality, land use and agricultural production, possibly linking physical and climate factors with extreme longevity, were explored. The probability of becoming a centenarian varies significantly among the Japanese prefectures. In particular, the computation of CR(70) demonstrated that the actual probability for individuals 70 years old in 1975 of becoming centenarians in 2005 was 3 times higher, on average, in Okinawa, both for males and females, than in Japan as a whole. About three quarters of the variance in CR(70) for females and half for males is explained by the physical environment and land use, even when variations in the level of socio-economic status between prefectures are controlled. Our analysis highlighted two features which might have played an important role in the longevity observed in Okinawa. First, there is virtually no winter in Okinawa. For instance, the mean winter temperature observed in 2005 was 17.2°C. Second, today, there is almost no rice production in Okinawa compared to other parts of Japan. In the past, however, production was higher in Okinawa. If we consider that long term effects of harsh winters can contribute to the mortality differential in old age and if we consider that food availability in the first part of the 20th century was mainly dependent on local production, early 20th century birth cohorts in Okinawa clearly had different experiences in terms of winter conditions and in terms of food availability compared to their counterparts in other parts of Japan. This work confirms the impact of climate conditions on human longevity, but it fails to demonstrate a strong association between longevity and mountainous regions and/or air quality.

Impact of cilostazol on left ventricular geometry and function: assessment by tissue Doppler imaging and two-dimensional speckle-tracking echocardiography.

OBJECTIVES: Cilostazol, a type III phosphodiesterase inhibitor, is an antiplatelet agent with vasodilating properties. Positive inotropic and chronotropic effects are frequently observed with cilostazol, but there are few reports on the influence of cilostazol on left ventricular function. The aim of this study was to assess this effect using tissue Doppler imaging (TDI) and two-dimensional speckle-tracking echocardiography (2D-STE). METHODS: Thirty-five patients with normal left ventricular ejection fraction were enrolled in the study. Left ventricular cardiac function was assessed by TDI and 2D-STE before and after oral administration of cilostazol. Peak strain was defined using the peak radial strain (PRS), peak circumferential strain (PCS) and peak longitudinal strain (PLS). Time to peak strain was defined based on the times to PRS, PCS, and PLS, as T-PRS, T-PCS, and T-PLS, respectively. RESULTS: After cilostazol administration, there were significant decreases in the left ventricular end-diastolic and end-systolic diameters (47.3 ± 5.2 vs. 43.3 ± 4.9 mm, P < 0.0001; 29.3 ± 6.4 vs. 26.0 ± 5.5 mm, P < 0.0001, respectively), and significant increases in the left ventricular ejection fraction (70.6 ± 9.5 vs. 72.7 ± 7.8%, P = 0.0381) and peak systolic annular velocity (7.9 ± 1.7 vs. 9.5 ± 3.1 cm/sec, P < 0.0001). PRS, PCS, and PLS all increased significantly and T-PRS, T-PCS, and T-PLS all decreased significantly after cilostazol administration. CONCLUSION: Positive inotropic and chronotropic effects of cilostazol were found based on assessment by TDI and 2D-STE. We suggest that periodic echocardiographic assessment should be performed before and after oral administration of cilostazol.

Assessment of Chemosensitivity-related Aberrant Methylation of Nonsmall Cell Lung Cancer by EBUS-TBNA.

BACKGROUND: Multigene aberrant methylation profiling may predict response to chemotherapy in lung cancer. The purpose of this study was to analyze the feasibility of detecting aberrant methylation in biopsy samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). METHODS: Lymph node samples from 30 patients with nonsmall cell lung cancer diagnosed as metastatic carcinoma by EBUS-TBNA were analyzed. Histologic cores obtained by EBUS-TBNA were separately stored at -80°C. DNA was extracted from EBUS-TBNA samples and bisulfate modification was performed. We evaluated the methylation status of a panel of 6 genes (FANCF, Reprimo, TMS1/ASC, activated protein-2α, CHFR, and ATM) using methylation-specific polymerase chain reaction. Twenty-four patients with adenocarcinoma or squamous cell carcinoma metastasis received platinum-based combination chemotherapy. We reviewed their response to chemotherapy in correlation to the methylation status. RESULTS: Bisulfate modification was successfully performed in all samples using DNA obtained from EBUS-TBNA samples by checking p16 unmethylation expression. Aberrant methylation was detected as follows: 9 cases of FANCF (30.0%), 14 cases of Reprimo (46.7%), 10 cases of TMS1/ASC (33.3%), and 19 cases of activated protein-2α (63.3%). In response to chemotherapy, there were 1 complete response, 6 partial response, 12 stable disease, and 5 progressive disease (PD) cases. The number of methylated genes was significantly smaller in the PD group than in the non-PD groups (P=0.0435). CONCLUSIONS: Aberrant methylation analysis can be performed in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows for genetic evaluations of tumor cells and may help to guide the most effective treatment strategies in the near future.

Assessment of epidermal growth factor receptor mutation by endobronchial ultrasound-guided transbronchial needle aspiration.

BACKGROUND: The presence of somatic mutations in epidermal growth factor receptor (EGFR) predicts the effectiveness of EGFR tyrosine kinase inhibitors (TKIs). It would be ideal if an EGFR mutation could be detected in biopsy samples, since the majority of non-small cell lung cancer patients are inoperable at the time of presentation. We have reported the usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the lymph node staging of lung cancer. EBUS-TBNA enables the sampling of histologic cores, which can be used for genetic analysis. METHODS: The purpose of this study was to develop and analyze the feasibility of detecting EGFR mutations in samples obtained by EBUS-TBNA. Forty-six patients with primary lung cancer in whom metastatic adenocarcinoma in the hilar and/or mediastinal lymph node was diagnosed by EBUS-TBNA were enrolled into the study. DNA was extracted from paraffin-embedded samples, and the EGFR mutation was analyzed in exons 19 and 21 using a newly developed loop-hybrid mobility shift assay. The results were confirmed by direct sequencing. RESULTS: Forty-three cases were eligible for analysis and in 11 cases, EGFR mutation (25.6%) was detected; one case was an in-frame deletion (E746-A750del) of exon 19, nine cases were point mutations (L858R) of exon 21, and one case was a double point mutation (L858R+L861V). All cases with EGFR mutations were confirmed by direct sequencing. CONCLUSIONS: EGFR mutation can easily be detected in metastatic lymph nodes sampled by EBUS-TBNA. EBUS-TBNA allows genetic evaluations of tumor cells within the lymph node and may provide us with indications for EGFR-TKI therapy in the near future.