Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [⁶⁴Cu]DPA and investigated the tumor engagement of [⁶⁴Cu/⁶⁸Ga]DPA in mouse models. Our results revealed that intact [⁶⁴Cu/⁶⁸Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [⁶⁴Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

BACKGROUND: Among former Olympic-level athletes, engagement in different sport disciplines has been associated with mortality risk in subsequent years. However, limited evidence is available on whether engagement in different sport disciplines at a young age is associated with locomotive syndrome (LS) risk later in life. This study examined the relationship between engagement in different sport disciplines during university years and LS risk in older age among former university athletes. METHODS: Participants were 274 middle-aged and 294 older men alumni who graduated from a school of physical education in Japan. LS risk was defined as answering "yes" to any of the Loco-check questions. Data on university sports club membership were collected using questionnaires. University clubs were classified into three groups of cardiovascular intensity (low, moderate, high), following the classification system of sport disciplines by the American College of Cardiology. This classification considers the static and dynamic components of an activity, which correspond to the estimated percent of maximal voluntary contraction reached and maximal oxygen uptake achieved, respectively. University clubs were grouped based on the risk of bodily collision (no, yes) and extent of physical contact (low, moderate, high). Relationships between engagement in different sport disciplines and LS risk were analyzed using Cox proportional hazards models, and adjusted for age, height, weight, joint disease, habitual exercise, and smoking and drinking status. RESULTS: Adjusted hazard ratios and 95% confidence intervals associated with the low, moderate, and high cardiovascular intensity sports were 1.00 (reference), 0.48 (0.22-1.06, P = 0.070), and 0.44 (0.20-0.97, P = 0.042) in older men, respectively; however, there was no significant association between these parameters among middle-aged men. Engagement in sports associated with physical contact and collision did not affect LS risk in either group. CONCLUSIONS Engagement in sports associated with high cardiovascular intensity during university years may reduce the risk of LS in later life. Encouraging young people to participate in such activities might help reduce LS prevalence among older populations.
Adult ; Aged ; Aged, 80 and over ; Athletes/statistics & numerical data* ; Exercise ; Geriatric Assessment ; Humans ; Japan/epidemiology* ; Locomotion ; Male ; Middle Aged ; Mobility Limitation ; Motor Disorders/etiology* ; Postural Balance ; Prevalence ; Proportional Hazards Models ; Risk Factors ; Sports/statistics & numerical data* ; Syndrome ; Young Adult

Objective：The English version of the Characterizing Freezing of Gait questionnaire (C-FOGQ) that is used to assess detailed information of freezing of gait was developed by Ehgoetz Martens et al. This study aims to develop the Japanese version of the C-FOGQ using guidelines for cross-cultural adaptation and to conduct the pretesting study.Methods：The C-FOGQ was translated with permission into Japanese according to the following guidelines for cross-cultural adaptation： (1) translation (English to Japanese), (2) back-translation (Japanese to English), and (3) pretesting. Thirty-nine patients with parkinsonism-related disorders participated in the pretesting study.Results：There was no significant linguistic problem in the process of translation and back-translation. In pretesting, the average response time of the Japanese version of the C-FOGQ was 526.8 seconds. The error/no-response rate was less than 1%. The average score for section II of the Japanese version of the C-FOGQ was 20.0 points.Conclusion：A linguistically-validated Japanese version of the FOGQ was developed according to the guidelines of cross-cultural adaptation. It seems to be possible to use this questionnaire for detailed evaluation of gait freezing in Japan as well as in the West.

Objective：The English version of the Characterizing Freezing of Gait questionnaire (C-FOGQ) that is used to assess detailed information of freezing of gait was developed by Ehgoetz Martens et al. This study aims to develop the Japanese version of the C-FOGQ using guidelines for cross-cultural adaptation and to conduct the pretesting study.Methods：The C-FOGQ was translated with permission into Japanese according to the following guidelines for cross-cultural adaptation：(1) translation (English to Japanese), (2) back-translation (Japanese to English), and (3) pretesting. Thirty-nine patients with parkinsonism-related disorders participated in the pretesting study.Results：There was no significant linguistic problem in the process of translation and back-translation. In pretesting, the average response time of the Japanese version of the C-FOGQ was 526.8 seconds. The error/no-response rate was less than 1%. The average score for section II of the Japanese version of the C-FOGQ was 20.0 points.Conclusion：A linguistically-validated Japanese version of the FOGQ was developed according to the guidelines of cross-cultural adaptation. It seems to be possible to use this questionnaire for detailed evaluation of gait freezing in Japan as well as in the West.

Background/Aims: There are few published registry studies from Asia on pediatric inflammatory bowel disease (IBD). Registry network data enable comparisons among ethnic groups. This study examined the characteristics of IBD in Japanese children and compared them with those in European children. Methods: This was a cross-sectional multicenter registry study of newly diagnosed Japanese pediatric IBD patients. The Paris classification was used to categorize IBD features, and results were compared with published EUROKIDS data. Results: A total of 265 pediatric IBD patients were initially registered, with 22 later excluded for having incomplete demographic data. For the analysis, 91 Crohn’s disease (CD), 146 ulcerative colitis (UC), and 6 IBD-unclassified cases were eligible. For age at diagnosis, 20.9% of CD, 21.9% of UC, and 83.3% of IBD-unclassified cases were diagnosed before age 10 years. For CD location, 18.7%, 13.2%, 64.8%, 47.3%, and 20.9% were classified as involving L1 (ileocecum), L2 (colon), L3 (ileocolon), L4a (esophagus/stomach/duodenum), and L4b (jejunum/proximal ileum), respectively. For UC extent, 76% were classified as E4 (pancolitis). For CD behavior, B1 (non-stricturingon-penetrating), B2 (stricturing), B3 (penetrating), and B2B3 were seen in 83.5%, 11.0%, 3.3%, and 2.2%, respectively. A comparison between Japanese and European children showed less L2 involvement (13.2% vs. 27.3%, P< 0.01) but more L4a (47.3% vs. 29.6%, P< 0.01) and L3 (64.8% vs. 52.7%, P< 0.05) involvement in Japanese CD children. Pediatric perianal CD was more prevalent in Japanese children (34.1% vs. 9.7%, P< 0.01). Conclusions Upper gastrointestinal and perianal CD lesions are more common in Japanese children than in European children.

BACKGROUND: Lymphaticovenous anastomosis is an important surgical treatment for lymphedema, with lymphaticovenous side-to-end anastomosis (LVSEA) and lymphaticovenous end-to-end anastomosis being the most frequently performed procedures. However, LVSEA can cause lymphatic flow obstruction because of regurgitation and tension in the anastomosis. In this study, we introduce a novel and simple procedure to overcome this problem. METHODS: Thirty-five female patients with lower extremity lymphedema who underwent lymphaticovenous anastomosis at our hospital were included in this study. Eighty-five LVSEA procedures were performed, of which 12 resulted in insufficient venous blood flow. For these 12 anastomoses, the proximal lymphatic vessel underwent clipping after the anastomotic procedure and the venous inflow was monitored. Subsequently, the proximal ligation after side-to-end anastomosis recovery (PLASTER) technique, which involves ligating the proximal side of the lymphatic vessel, was applied. A postoperative evaluation was performed using indocyanine green 6 months after surgery. RESULTS: Despite the clipping procedure, three of the 12 anastomoses still showed poor venous inflow. Therefore, it was not possible to apply the PLASTER technique in those cases. Among the nine remaining anastomoses in which the PLASTER technique was applied, three (33%) were patent. CONCLUSIONS: Our findings show that achieving patent anastomosis is challenging when postoperative venous inflow is poor. We achieved good results by performing proximal ligation after LVSEA. Thus, the PLASTER technique is a particularly useful recovery technique when LVSEA does not result in good run-off.
Edema ; Female ; Humans ; Indocyanine Green ; Ligation ; Lower Extremity ; Lymphatic Diseases ; Lymphatic Vessels ; Lymphedema ; Microsurgery

Effects of three plant extracts (Hordeum vulgare L., Apocynum Venetum L., Brasenia schreberi J.F.G mel.) on human gingival fibroblasts were examined. As a result, we observed the promoting effect of the extract of Hordeum vulgare L. and the extract of Apocynum Venetum L. respectively on FGF2 and FGF7 production. Moreover, the mixture of the three plant extracts showed the effect of improving the changes in type I collagen gene expression and matrix metalloproteinase 1 gene expression by LPS addition. Next, a dentifrice containing the three plant extracts was subjected to human efficacy trials. We measured periodontal pocket depth, attachment level, bleeding on probing and saliva TNFα as an indicator of periodontal disease. The results suggest that the dentifrice formulated with the three plant extracts were effective for the improvement of periodontal disease.

　　Chronic kidney disease (CKD) has recently been reported to be an independent risk factor for stroke. However, a detailed analysis was yet to be conducted according to stroke subtype. We attempted to determine the risk factors for stroke using data from the “specific health checkup” for metabolic syndrome conducted by the 9 hospitals affiliated with the Akita Prefectural Federation of Agricultural Cooperatives, and evaluate and determine the risk factors for stroke. There were 401 patients who had undergone metabolic syndrome checkups from 2007 and 2010 and suffered from stroke afterwards within 3 years after the screening. The controls were all 69,407 subjects who were screened during the same period. The predictors examined were sex, age, blood pressure, BMI, cholesterol values (HDL・LDL), history of diabetes mellitus, presence of atrial fibrillation, CKD, and drinking and smoking habits. Analysis was conducted using logistic regression. The risk factors for stroke as a whole were male sex, age, blood pressure, diabetes, atrial fibrillation, CKD, and smoking history. For cerebral infarction, the risk factors were male sex, age, blood pressure, diabetes, atrial fibrillation, CKD, and smoking habit. The risk factors for cerebral hemorrhage were age, blood pressure, and CKD. For subarachnoid hemorrhage, the risk factors were female sex, age, blood pressure, low HDLemia, and CKD. In conclusion, CKD is an independent risk factor for the 3 subtypes of stroke, and in particular plays an important role as a higher risk factor for cerebral hemorrhage. Smoking cessation and controls of blood pressure, diabetes and atrial fibrillation are the important measures for stroke prevention. In addition, the further intervention should also be targeted to those with the result of CKD revealed by specific health checkups.

Purpose: Bone is one of the most common sites of metastases in patients with advanced lung cancer. Skeletal complications may cause significant morbidity and decrease performance status (PS). Such complications, referred to as skeletal related events (SREs), include severe bone pain, pathological fractures, spinal cord compression, and hypercalcemia of malignancy. We assessed the clinical impact of SREs in non-small lung cancer (NSCLC) patients with bone metastases. Methods: We retrospectively investigated the clinical records of all 120 patients who were diagnosed advanced NSCLC with bone metastases between June 1998 and March 2009. Results: A total of 23 patients (26.7%) were found to have SREs at the time of initial diagnosis. The median survival time (MST) was 123 days for patients with SREs, while it increased to 276 days for those without SREs. The MST of the patients with SREs were significantly shorter than that of the patients without SREs (p<0.001). We also studied the SREs during clinical courses of 89 patients whose records were available over 3 months. A total of 39 patients (43.8%) were found to have SREs during clinical courses. Conclusion: The patients in NSCLC with bone metastases were often found to have SREs. SREs cause significant morbidity and deterioration of PS. Systemic chemotherapy could not decrease SREs during their clinical courses. Further studies evaluating bisphosphonates in combination with chemotherapy are warranted. Palliat Care Res 2010; 5(2): 145-151