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Background: Although diets rich in carotenoids are associated with muscle health and a reduced risk of disability, the relationship between carotenoids and low lean body mass has not been fully elucidated., Objectives: This study aimed to clarify the relationship between serum carotenoid concentrations and low lean body mass over 4 y in older Japanese community-dwellers., Methods: A total of 750 adults aged ≥60 y participated in the National Institute for Longevity Sciences-Longitudinal Study of Aging. Individuals with a low lean body mass and muscle strength or gait speed at baseline were excluded. Baseline serum α-carotene, β-carotene, β-cryptoxanthin, zeaxanthin, lutein, and lycopene were measured. Low lean body mass was defined as appendicular lean mass relative to the measured height (ALM/ht 2 ) of <7.0 kg/m 2 in males and <5.4 kg/m 2 in females, according to the criteria of the Asian Working Group for Sarcopenia 2019. A generalized estimating equation was used to estimate the odds ratio and 95% confidence interval for low lean body mass according to tertiles of total and individual carotenoids at baseline, adjusted for sex, age, season, follow-up months, education years, economic status, current smoking status, a history of ischemic heart disease, stroke, hypertension, dyslipidemia, diabetes mellitus, and metabolic equivalents., Results: Low serum total carotenoids were associated with low ALM/ht 2 , and the odds ratios of low ALM/ht 2 in the third tertile of total carotenoids were significantly lower than those in the first tertile after adjusting for covariates. The odds ratios of low ALM/ht 2 in the third tertile of β-cryptoxanthin were significantly associated with those in the first tertile after adjusting for covariates (P = 0.03); however, no trend was observed for this relationship., Conclusions: These findings indicate that low serum total carotenoids and serum β-cryptoxanthin are associated with low lean body mass in older Japanese community-dwellers., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Objective: Balloon kyphoplasty (BKP) is an effective procedure for osteoporotic vertebral compression fractures; however, there is limited data regarding its outcomes in patients aged ≥81 years. This study investigated the treatment outcomes and prognostic factors for BKP in this age group., Methods: A retrospective analysis was conducted on 115 patients with osteoporotic vertebral compression fracture undergoing single-level BKP after failed conservative treatment, classified into the <81 years (n=70) and ≥81 years (n=45) groups. Surgical results were evaluated as good outcomes (independent indoors 1 year postoperatively) and poor outcomes, followed by univariate and multivariate analyses to determine prognostic factors correlating with these outcomes., Results and Conclusion: The majority of patients (<81 years: 85.7%; ≥81 years: 73.3%) had a good degree of independence at 1 year postoperatively, which was comparable in both groups. Further analysis of patients aged ≥81 years showed that longer duration from onset to surgery, more subsequent vertebral fractures, and lower preoperative body mass index were correlated with poorer outcomes postoperatively, and low body mass index, time from onset to surgery, and female sex were independent risk factors for these outcomes (area under the receiver operating characteristics curve: 0.91)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In transplantation using allogeneic induced pluripotent stem cells (iPSCs), strategies focused on major histocompatibility complexes were adopted to avoid immune rejection. We showed that minor antigen mismatches are a risk factor for graft rejection, indicating that immune regulation remains one of the most important issues. In organ transplantation, it has been known that mixed chimerism using donor-derived hematopoietic stem/progenitor cells (HSPCs) can induce donor-specific tolerance. However, it is unclear whether iPSC-derived HSPCs (iHSPCs) can induce allograft tolerance. We showed that 2 hematopoietic transcription factors, Hoxb4 and Lhx2, can efficiently expand iHSPCs with a c-Kit + Sca-1 + Lineage - phenotype, which possesses long-term hematopoietic repopulating potential. We also demonstrated that these iHSPCs can form hematopoietic chimeras in allogeneic recipients and induce allograft tolerance in murine skin and iPSC transplantation. With mechanistic analyses, both central and peripheral mechanisms were suggested. We demonstrated the basic concept of tolerance induction using iHSPCs in allogeneic iPSC-based transplantation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ken-ichiro Seino reports financial support was provided by MEXT. Ken-ichiro Seino has patent pending to Licensee. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

The blockade of the CD154-CD40 pathway with anti-CD154 monoclonal antibody has been a promising immunomodulatory approach to prevent allograft rejection. However, clinical trials of immunoglobulin G1 antibodies targeting this pathway revealed thrombogenic properties, which were subsequently shown to be mediated by crystallizable fragment (Fc)-gamma receptor IIa-dependent platelet activation. To prevent thromboembolic complications, an immunoglobulin G4 anti-CD154 monoclonal antibody, TNX-1500, which retains the fragment antigen binding region of ruplizumab (humanized 5c8, BG9588), was modified by protein engineering to decrease Fc binding to Fc-gamma receptor IIa while retaining certain other effector functions and pharmacokinetics comparable with natural antibodies. Here, we report that TNX-1500 treatment is not associated with platelet activation in vitro and consistently inhibits kidney allograft rejection in vivo without clinical or histologic evidence of prothrombotic phenomena. We conclude that TNX-1500 retains efficacy similar to that of 5c8 to prevent kidney allograft rejection while avoiding previously identified pathway-associated thromboembolic complications., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: No previous study has established the factors associated with intracranial aneurysm growth using imaging data obtained before the appearance of morphological changes. Therefore, we investigated the factors related to future aneurysm growth in posterior communicating artery (Pcom) aneurysms., Methods: Using a longitudinal database of intracranial aneurysm cases, we reviewed the findings for consecutive patients with unruptured Pcom aneurysms admitted to our institute from 2012 to 2021. Magnetic resonance images obtained over time were used to evaluate aneurysm growth. Aneurysms showing growth over time (group G) and unchanged aneurysms (group U) were compared in terms of background data and morphological factors., Results: 93 Pcom aneurysms (group G: 25 aneurysms, 25%; group U: 68 aneurysms, 75%) were eligible for the present study. Six aneurysm rupture events occurred in group G (24%). Among morphological factors, Pcom diameter (1.2 ± 0.3 mm vs. 0.8 ± 0.7 mm, P < 0.01), bleb formation (group G: 39% vs. group U: 10%; odds ratio, 5.6; P = 0.01), and the lateral projection of the dome (group G: 52% vs. group U: 13%; odds ratio, 3.2; P = 0.023) were significantly different between the 2 groups. The sensitivity and specificity of a cutoff Pcom diameter of 0.73 mm for predicting enlargement were 96% and 53%, respectively., Conclusions: Pcom diameter, bleb formation, and lateral dome projection were associated with growth of Pcom aneurysms. Aneurysms with these risk factors require careful follow-up imaging, which may facilitate early detection of aneurysm growth and prevention of rupture through therapeutic interventions., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: A balanced diet integrating several foods and nutrients may promote the maintenance of brain function. Previous studies have substantiated the above hypothesis in the regional population in Japan. This study aimed to investigate the potential effect of dietary diversity on the risk of disabling dementia in a nationwide large-scale cohort of the Japanese population., Methods: A total of 38,797 participants (17,708 men and 21,089 women) aged 45-74 years were followed up for a median of 11.0 years. The daily frequencies of the consumption of each of the 133 food and beverage items listed on a food frequency questionnaire (excluding five alcoholic beverages) were measured. The dietary diversity score was calculated as the number of food items consumed per day. Multivariable adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of the dietary diversity score quintile groups., Results: We documented 4302 participants with disabling dementia (11.1%) during the follow-up period. Among women, the dietary diversity score was inversely associated with disabling dementia (highest quintile HR [with the lowest quintile as the reference]: 0.67; 95% CI: 0.56-0.78; Q1-Q5 p for trend <0.001), but this was not true among men (highest quintile HR: 1.06; 95% CI: 0.87-1.29; Q1-Q5 p for trend = 0.415). These results did not change substantially when using disabling dementia with stroke as the outcome; the association remained significant among women but was absent among men., Conclusions: Our findings indicate that eating a variety of foods may prevent disabling dementia only among women. Thus, the habit of consuming a variety of food items has important public health implications for women., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We developed a colorimetric analytical method for favipiravir (FPV), a promising treatment for COVID-19. FPV forms yellow complexes with ferrihydrite (Fh) by a ligand substitution reaction with the iron (III) hydroxyl surface groups in Fh. Fh-coated microbeads were packed into a capillary tube with an inner diameter of 1 mm. FPV-spiked serum after pretreatment was drawn into the capillary packed with Fh-coated microbeads. The intensities of the yellow-color complexes on the microbeads were transformed into red-green-blue (RGB) pixels using Image-J software 1.8, and the difference between green and blue was used as the analytical signal. The signal increased with increasing FPV concentration. The proposed method showed good linearity (R 2  = 0.9907) over a concentration range of 25-200 μg/mL. The RSD (n = 3) and the LOD (3σ) values were estimated to be 2.8-15.4% and 16.91 μg/mL, respectively. The proposed method enables us to quantify FPV rapidly and easily without the need for expensive equipment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The relationship between age-related brain atrophy and long-chain polyunsaturated fatty acid (LCPUFA) intake is not fully understood. This study investigated the association of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) intake and brain atrophy in non-demented older Japanese people (n = 810, aged 60-89 years) using data sets of a 2-year longitudinal study. Brain volumes were measured using 3D-MRI in the baseline and follow-up periods. The associations of multivariate-adjusted changes in brain volumes with baseline LCPUFA intake were assessed using a general linear model. Higher ARA intake was associated with a smaller decrease in frontal cortex volumes, which was accompanied by a lower risk of cognitive decline among the participants. In the subgroup analysis for low DHA and EPA intake, accounting for one-third of Japanese intake, DHA and EPA intake was positively correlated with preservation of the temporal cortex volume. These findings suggest that appropriate intake of LCPUFA may decelerate age-related brain atrophy and lead to the maintenance of brain health in older people., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: The amount of breakfast protein intake is important for maintaining muscle strength. However, the effect of breakfast protein quality (ie, bioavailability) remains unclear. We investigated the association between breakfast protein quality and the incidence of muscle weakness., Design: Longitudinal study., Setting and Participants: Healthy older adults age 60-83 years without stroke, arthritis, Parkinson disease, or muscle weakness at baseline (maximum follow-up period and participations were 9.2 years and 5 times, respectively)., Methods: Weakness was defined by the Asian Working Group for Sarcopenia 2019 criteria, using grip strength. Breakfast protein quality was evaluated using the protein digestibility-corrected amino acid score (PDCAAS), where higher scores represent higher quality, calculated from 3-day dietary records. Participants were classified according to sex-stratified tertiles of breakfast PDCAAS (ie, low to high groups). The association between PDCAAS and incident weakness was analyzed using the generalized estimating equation, after adjusting for sex, age, follow-up time, grip strength, body mass index, physical activity, cognition, education, smoking, economics, medical history, lunch and dinner PDCAASs, and energy and protein intake during 3 regular meals at baseline., Results: Overall, 14.4% of the initial sample was excluded owing to a diagnosis of weakness-related diseases, and 58.3% (n = 701) had at least 1 follow-up measurement for inclusion in the analysis. The mean ± SD follow-up period was 6.9 ± 2.1 years; the cumulative number of participants was 3019, and 282 developed weakness. Using the low PDCAAS group as the reference, the adjusted odds ratios (95% CIs) for incident weakness in the middle and high PDCAAS groups were 0.71 (0.43-1.18) and 0.50 (0.29-0.86), respectively., Conclusions and Implications: Higher breakfast protein quality was associated with a reduction in incident weakness in older adults, independent of protein intake. These findings may highlight the role of protein quality for muscle health in older adults., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The prevalence of osteoporotic vertebral compression fracture (OVCF) is increasing. The indications for and efficacy of balloon kyphoplasty (BKP) are controversial. We sought to identify predictors of outcome after BKP in patients with OVCF., Methods: Between January 2001 and December 2019, 152 patients underwent BKP for painful OVCFs at our institution. This study included 115 patients who were followed for >12 months, and their data were retrospectively analyzed. With regard to the degree of independent living 1 year after BKP, patients were divided into a good outcome group (composed of patients who could independently go indoors) and a poor outcome group. We analyzed factors associated with outcome and subsequent OVCF., Results: Mean age of patients was 77.9 years, 58.2% were female, 81% had a good outcome, and 19% had a poor outcome. Univariable analysis revealed significant differences in age, bone mineral density, preoperative vertebral body decompression rate, body mass index (BMI), preoperative Japanese Orthopaedic Association score, preoperative modified Rankin Scale score, and subsequent OVCF. Multivariable logistic analysis showed that low BMI (odds ratio 1.415, 95% confidence interval 1.06-1.87, P = 0.046) and subsequent OVCF (odds ratio 0.13, 95% confidence interval 0.02-0.69, P = 0.044) were independent risk factors. The incidence of subsequent OVCF was also lower among patients with higher BMI (odds ratio 0.83, 95% confidence interval 0.72-0.95, P = 0.001)., Conclusions: BMI and subsequent OVCF are the most influential predictors of independent living 1 year after BKP for OVCF., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The long-term benefits of "free" gastroepiploic artery (GEA) grafts remain unclear. The aim of this study is to investigate the long-term patency and clinical results of en bloc free GEA grafts., Methods: Of the 1478 patients undergoing coronary artery bypass graft surgery at our institution between January 1997 and December 2009, 137 patients underwent en bloc free GEA grafting. Graft patency, late survival, and freedom from major adverse cardiovascular events were examined. Propensity score matching was used to compare the patency of free GEA grafts with the saphenous vein grafts, and 134 matched pairs were generated., Results: The early patency rate of free GEA grafts was 98.6%. The long-term patency rates of the free GEA grafts was 96.5% at 5 years, 95% at 10 years, and 86.6% at 15 years. In the 134 matched pairs, the long-term patency rates of free GEA grafts anastomosed to the right coronary artery were significantly higher than those of saphenous vein grafts to the right coronary artery (97% vs 91.8% at 5 years; 95.3% vs 79.6% at 10 years; 85.9% vs 61.7% at 15 years; P < .001). Survival was 94% at 5 years, 86.6% at 10 years, and 66.8% at 15 years; and freedom from major adverse cardiovascular events was 93.2% at 5 years, 91.3% at 10 years, and 73.1% at 15 years., Conclusions: En bloc free GEA grafts had favorable long-term performance and can be considered as an effective option for patients who need to receive as many arterial grafts as possible., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment., Design: Multi-institutional prospective single-arm observational study., Setting and Participants: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan., Methods: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA)., Results: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement., Conclusions and Implications: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) are multipotent cells that exist in mesenchymal tissues such as bone marrow and are able to differentiate into osteocytes, chondrocytes, and adipocytes. MSCs are generally collected as adherent cells on a plastic dish, and are positive for markers such as CD44, CD73, CD90, CD105 and CD166, and negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD79a and HLA-DR. MSCs have been established from many kinds of mammals, but MSCs from amphibians have not yet been reported. We cultured adherent cells from the bone marrow of Xenopus laevis by modifying the protocol for culturing mammalian MSCs. The morphology of these cells was similar to that of mammalian MSCs. The amphibian MSCs were positive for cd44, cd73, cd90 and cd166, and negative for cd11b, cd14, cd19, cd31, cd34, cd45, cd79a and hla-dra. Moreover, they could be induced to differentiate into osteocyte-, chondrocyte-, and adipocyte-lineage cells by cytokine induction systems that were similar to those used for mammalian MSC differentiation. Thus, they are considered to be similar to mammalian MSCs. Unlike mammals, amphibians have high regenerative capacity. The findings from the present study will allow for future research to reveal how Xenopus MSCs are involved in the amphibian regenerative capacity and to elucidate the differences in the regenerative capacity between mammals and amphibians., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The relationship between physical frailty and regional gray matter volume in the brain was investigated among community-dwelling older Japanese people., Methods: Participants (N = 835; age range 65-89 years) were community-dwelling older adults in Obu City and Higashiura Town in Aichi Prefecture, Japan. Physical frailty was determined by the modified criteria of the Cardiovascular Health Study, which included weight loss, slowness, weakness, exhaustion, and low physical activity. Regional gray matter volumes were evaluated from 3-dimensional T1-weighted magnetic resonance images by statistical parametric mapping. The relationship between physical frailty and regional gray matter volume was analyzed with an analysis of covariance design using statistical parametric mapping adjusting for age, sex, and education level., Results: The voxel-based analyses showed that physical frailty per se was not significantly associated with any brain region. However, weakness was associated with reduced gray matter volumes in the hippocampus, amygdala, and fusiform gyrus, and slowness was associated with reduced gray matter volumes in the hippocampus, amygdala, fusiform gyrus, medial prefrontal and orbitofrontal cortex, inferior frontal gyrus, primary somatosensory cortex, insula, superior temporal sulcus, and cerebellum. Other components of physical frailty were not associated with the gray matter volumes in any regions., Conclusions and Implications: The weakness and slowness components of physical frailty were linked to reduced gray matter volume in brain regions associated with not only physical mobility but also cognitive functions and social processes. This study addressed the underlying mechanisms in the progression of physical, cognitive, and social frailty, from the perspective of brain structures that are associated with frailty., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Some mechanical thrombectomy techniques for acute ischemic stroke use a combination of an aspiration catheter and stent retriever. We experienced a rare case of aspiration catheter coil breakage and subsequent retrieval using a stent retriever., Case Description: A 79-year-old man suddenly developed somnolence, global aphasia, and right hemiplegia. Magnetic resonance imaging revealed acute infarction of the left frontal lobe and occlusion of the left common carotid artery. Thus, using an aspiration catheter and a stent retriever, mechanical thrombectomy was performed. The stent retriever was deployed from the middle cerebral artery to the internal carotid artery and retracted into the aspiration catheter placed in the internal carotid artery proximal to the thrombus. The catheter was bent during retraction of the stent retriever. After thrombus aspiration, the internal carotid and anterior and middle cerebral arteries were successfully reperfused; however, the stent retriever captured a broken section of the winding coil of the aspiration catheter. We suspected that an X-ray marker on the stent retriever broke the winding coil at the bent segment of the aspiration catheter and the stent captured the broken coil., Conclusions: The combined use of an aspiration catheter and a stent retriever may cause unexpected device breakage, especially when the catheter is bent., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: This study examined the association between frailty development and physical activity including the number of steps, the time of light-intensity physical activity (LPA) with <3.0 metabolic equivalents (METs), and the time of moderate- to vigorous-intensity physical activity (MVPA) with ≥3.0 METs in community-dwelling older Japanese adults., Design, Setting, and Participants: Study subjects were 401 older adults at the baseline examination (April 2000-May 2002) who participated at least once in the follow-up examination of the longitudinal study of aging. Their 1787 cumulative data points (mean number of repeat visits, 3.5) were used for analysis., Measures: The number of steps, time of LPA, and time of MVPA were recorded at baseline using a uniaxial accelerometer. Frailty was defined according to 5 frailty criteria: shrinking, exhaustion, low physical activity, low grip strength, and slow gait speed., Results: The fully adjusted odds ratio for frailty among subjects walking <5000 steps was 1.85 [95% confidence interval (CI), 1.10-3.11]. The fully adjusted odds ratio for frailty among subjects with MVPA for <7.5 minutes was 1.80 (95% CI, 1.05-3.09). No significant association was observed between frailty and LPA., Conclusions and Implications: The risk for developing frailty was substantially lower in older people walking ≥5000 steps/d or exercising for at least 7.5 minutes/d at an intensity >3.0 METs. These data could be applicable to the community interventions that aim to prevent frailty., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Aims: Pigmented lesions such as of seborrheic keratosis and senile lentigo, which are commonly seen on skin of people>50years of age, are considered unattractive and disfiguring because of their negative psychological impact. Drug therapy using all-trans retinoic acid (ATRA) is an attractive option for self-treatment at home. We have developed an ATRA-loaded microneedle patch (ATRA-MN) and confirmed the pharmacological effects of ATRA-MN application in mice. Here, we describe a clinical study to evaluate the safety and efficacy of ATRA-MN in subjects with seborrheic keratosis or senile lentigo., Main Methods: ATRA-MN was applied to the lesion site of each subject for 6h once per week for 4weeks. The skin irritation reaction was scored to assess adverse reactions and blood tests were performed to evaluate the presence of systemic adverse reactions. To assess the treatment effect using ATRA-MN, the desquamation and whitening ability of the investigational skin was observed., Key Findings: Desquamation of the stratum corneum was observed following four ATRA-MN applications at 1-week intervals, but ATRA-MN applications did not induce severe local or systemic adverse effects., Significance: These results showed that ATRA-MN treatment is promising as a safe and effective therapy for seborrheic keratosis and senile lentigo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Dipeptidyl peptidase 4 inhibitors are widely used in patients with type 2 diabetes mellitus to accomplish glycemic control through an increase in the blood glucagon-like peptide 1 (GLP-1) concentration. These agents also inhibit vascular inflammation (eg, in atherosclerosis). This study was undertaken to determine whether and how vildagliptin (a potent dipeptidyl peptidase 4 inhibitor) might reduce intimal hyperplasia in vein grafts., Methods: Twelve rabbits were randomly divided into two groups; one group received vildagliptin orally (10 mg/kg/d; n = 6), whereas the control group (n = 6) did not. Vildagliptin administration was started 7 days before rabbits underwent interposition reversed autologous jugular vein grafting and ended at graft harvesting (28 days after the operation). Histochemical changes in the vascular wall were examined, as were changes in the acetylcholine-induced effects on the endothelial Ca(2+) concentration ([Ca(2+)]i) and endothelium-dependent relaxation., Results: Under fasting conditions, vildagliptin increased the plasma GLP-1 concentration, without affecting plasma glucose or insulin. Acetylcholine induced endothelium-dependent relaxation only in the vildagliptin group, and this was blocked by the nitric oxide synthase inhibitor N(ω)-nitro-l-arginine. Acetylcholine did not modify the endothelial [Ca(2+)]i in either the control or vildagliptin group. Intimal hyperplasia was significantly less in the vildagliptin group (0.11 ± 0.02 mm, n = 5) than in the controls (0.31 ± 0.06 mm, n = 4; P < .01)., Conclusions: Vildagliptin increased the plasma GLP-1 concentration. It also enhanced acetylcholine-induced [Ca(2+)]i-independent endothelial nitric oxide release and reduced vein graft intimal hyperplasia, independently of any glycemic control action., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: To examine the association of intrahepatic fat with homeostasis model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, in Japanese adults, and whether intrahepatic fat is associated with insulin resistance independent of waist circumference and other measures of obesity., Methods: Fifty-three individuals aged 37-69 were studied. Spectrum obtained using a 3-T magnetic resonance imager was analysed with LCModel to quantify intrahepatic fat. Blood levels of insulin, glucose and other biochemical markers were obtained after 8h or more fasting. Percent body fat was estimated by a bioelectrical impedance analyzer. HOMA-IR and intrahepatic fat content were log-transformed in the analysis., Results: We found a positive correlation between intrahepatic fat and HOMA-IR, which was independent of the anthropometric measures of obesity. In contrast, significant and positive correlations of body mass index, percent body fat, and waist circumference with HOMA-IR were largely explained by their associations with intrahepatic fat. Intrahepatic fat was positively associated with alanine transaminase and triglycerides even after adjustment for HOMA-IR., Conclusion: Intrahepatic fat was associated with insulin resistance independent of age, sex, and measures of obesity in Japanese adults. Hypertriglyceridemia and liver injury may directly occur subsequent to intrahepatic fat accumulation., (Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: It is not known whether salt intake decreases over time in the same population. This study attempts to describe salt intake for 8 years according to age groups, and examines whether salt intake changes over time in community-dwelling middle-aged and elderly Japanese subjects., Methods: Data were collected as part of the National Institute for Longevity Sciences Longitudinal Study of Aging. Participants included 544 men and 512 women who participated in and completed all nutrition surveys from the first (1997-2000) to fifth (2006-2008) study waves. Each study wave was conducted for 2 years; in individuals, the entire follow-up period was 8 years. Salt and energy intake were calculated from 3-day diet records with photographs. The mixed-effects regression model was used for analysis of repeated measures of salt intake., Results: Mean age and salt intake for study participants at first participation in the survey were 56.5 ± 9.3 years and 12.8 ± 3.3 g/day in men and 55.8 ± 9.4 years and 10.6 ± 2.5 g/day in women, respectively. Mean energy intake decreased in men and women in all age groups from the first to fifth study waves. Eight-year longitudinal data showed that salt intake decreased in men. In stratified analyses by age, mean salt intake in men decreased 0.08 g/year among 40- to 49-year-olds, 0.09 g/year among 50- to 59-year-olds, 0.16 g/year among 60- to 69-year-olds, and 0.14 g/year among 70- to 79-year-olds. For women, mean salt intake decreased 0.08 g/year among 70- to 79-year-olds (P = 0.098). After adjusting for energy intake, salt intake was decreased among 60- to 69-year-old men (P = 0.049) and increased among 50- to 59-year-old women (P = 0.015)., Conclusions: Absolute salt intake was decreased among all age groups from 40 to 70 years in men and from 70 to 79 years in women. An increased focus on reducing energy intake resulted in only a modest decrease in salt intake. Although we observed a decline, salt intake still exceeded recommended levels. Efforts that focus on salt reduction are needed to address this important public health problem., (Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the validity of self-reported medical history of several diseases among the Japanese population, and to clarify to what extent the self-reported year of diagnosis for chronic diseases is different from the physician's reports., Study Design and Setting: Subjects were 8,947 persons who responded to questions about medical history in a self-administered questionnaire. Of them, 854 subjects reported one or more medical histories and gave permission to contact their physician. The physicians were then requested to provide information on 809 subjects. Valid responses of 714 subjects were collected. We compared the self-reported medical histories with those reported by the physician., Results: Of 15 persons who reported myocardial infarction, 13 (87%) were confirmed. Angina pectoris was verified in eight out of the 11 (73%). The confirmation proportions of hypertension, diabetes, hyperlipidemia, and hyperuricemia were 97%, 96%, 95%, and 95%, respectively. The self-reported year of diagnosis was 1.70-2.49 years earlier than the physician-reported year for chronic diseases. Agreement between the self-reported and the physician-reported years was higher, the more recent the self-reported year was., Conclusion: Self-reported medical histories were generally accurate, especially for diseases with clear diagnostic criteria. However, investigators should be aware of the errors in reporting the year of diagnosis.

Background: Circulating C-reactive protein (CRP) is a marker of inflammation and is associated with the incidence of cardiovascular events. Although it has been known that adiponectin protects, whereas leptin accelerates, the development of atherosclerotic diseases, the comparative strength of their reciprocal effects on circulating CRP remains unclear., Methods: We studied a population of 2049 Japanese men aged 35 to 66. For all subjects, multiple regression analysis performed with log-transformed CRP concentration as the dependent variable, and with log-transformed leptin, log-transformed adiponectin, age, BMI, smoking status, and components of metabolic syndrome as independent variables., Results: Both leptin (positively) and adiponectin (negatively) were significantly and independently associated with CRP concentration. The absolute value of the standardized regression coefficient (st-beta) of leptin (st-beta=0.201) was higher than that of adiponectin (st-beta=-0.082). After subjects were stratified by current BMI level, both of the adipocytokines were significantly associated with CRP concentration among subjects with BMI <25 kg/m(2), whereas only leptin was significantly associated with CRP concentration among subjects with BMI >=25 kg/m(2)., Conclusions: Both leptin and adiponectin were independently associated with CRP concentration. Leptin was more strongly related to CRP levels than adiponectin was, especially among obese subjects.

Background: Despite a close association of adiponectin with metabolic syndrome (MetS), its usefulness as an additional MetS factor has not been well investigated., Methods: We studied 2327 apparently healthy Japanese male office workers aged 35 to 66 years old and investigated cross-sectionally whether categorization by serum adiponectin distinguished participants' levels of high-sensitivity C-reactive protein (CRP) beyond the conventional MetS., Results: In a linear regression analysis, adiponectin was associated with CRP independently of all MetS factors (beta=-0.192, P<0.001). Furthermore, a graded decrease in CRP level was observed with elevation of adiponectin in every stratum characterized by the presence or absence of each MetS component (trend P<0.05 in all strata except those of decreased high-density lipoprotein cholesterol or hyperglycemia). Similarly, geometric means of CRP levels (mg/l) decreased as adiponectin increased from the lowest to the highest tertile in all strata classified by the number of MetS components, though a P value did not reach statistical significance in those with 3 MetS components (the stratum of 0 MetS component: 0.41 [95% confidence interval, 0.34-0.49], 0.32 [0.28-0.37] and 0.26 [0.23-0.30], trend P<0.001; 1 component: 0.45 [0.39-0.52], 0.38 [0.34-0.43], and 0.32 [0.28-0.36], trend P<0.001; 2 components: 0.58 [0.50-0.67], 0.51 [0.44-0.60], and 0.46 [0.38-0.55], trend P=0.043; 3 components: 0.80 [0.66-0.96], 0.69 [0.55-0.87], and 0.58 [0.39-0.85], trend P=0.139)., Conclusions: Adiponectin evaluation provides additional inflammatory information on conventional MetS, supporting the potential of hypoadiponectinemia as an additional MetS component for identifying high-risk individuals for cardiovascular disease.

We report the orthodontic treatment of a 31-year-old man with severe skeletal Class II malocclusion and documented obstructive sleep apnea (OSA). He had a retrognathic profile with an overbite of 4 mm and an overjet of 14 mm. Mandibular distraction osteogenesis was performed to lengthen the small, retruded mandible by 18 mm and improve the symptoms of OSA. Orthodontic treatment after the mandibular distraction osteogenesis procedure lasted 3 years 1 month. An acceptable occlusion was obtained, and the patient's OSA was significantly alleviated. Although the patient was satisfied with the treatment, condylar resorption was observed. The relevance of condylar resorption with reference to a comprehensive evaluation of the treatment outcome is discussed.

Introduction: The aim of this study was to objectively and prospectively assess whether oral appliances (OAs) alter occlusal function in patients treated for snoring or obstructive sleep apnea., Methods: The occlusal contact area (OCA) and bite force (Bf) of 12 patients who used OAs were measured with pressure-sensitive sheets in the morning and evening with the Dental Prescale Occluzer System. OCA and Bf were compared in each measurement period by using ANOVA. Percentage changes in the morning relative to the evening (OCA(M-E) and Bf(M-E)) were compared between the 2 periods by using the Wilcoxon signed rank test. Correlations between percentage changes in pretreatment and posttitration ((Pre-Post)OCA and (Pre-Post)Bf), age, and cephalometric variables were also assessed., Results: Patients showed significant decreases in OCA and Bf when posttitration readings were compared with corresponding pretreatment measurements. OCA(M-E) and Bf(M-E) were significantly different between pretreatment and posttitration, suggesting that OCA and Bf tend to be smaller in the morning with OA use. (Pre-Post)Bf measured in the evening correlated with age., Conclusions: Effects on occlusal function after OA use were observed. These results suggest that practitioners should pay attention to the possible side effects of OAs on the dentition when treating patients with snoring or obstructive sleep apnea.

Purpose: Low birth weight has been associated with metabolic and vascular diseases, but the precise mechanism is debated. Adiponectin is one of the key molecules in metabolic disease, and a decrease in level precedes the onset of type 2 diabetes and development of atherosclerosis. Our aim is to examine whether low birth weight is associated with adiponectin concentration in adult., Methods: We conducted a population-based cross-sectional study of 2277 subjects (1661 men and 616 women) aged 35 to 66 years who had their self-reported birth weights and adiponectin concentrations measured as adults., Results: After adjusting for potential confounders, including age, sex, current body mass index (BMI), smoking status, alcohol consumption, and exercise, geometric mean adiponectin levels were 6.63, 6.45, 6.86, 7.05, 6.75, and 7.22 microg/mL for subjects with birth weights less than 2500, 2500 to less than 2800, 2800 to less than 3000, 3000 to less than 3200, 3200 to less than 3500, and greater than 3500 g, respectively. A positive association was found between birth weight and adiponectin concentration (trend p = 0.002). Stratified by current BMI of 25 kg/m2, a positive association was not observed for subjects with a BMI less than 25 kg/m2, but was pronounced in those with a BMI of 25 kg/m2 or greater., Conclusion: This study indicates that low birth weight contributes to decreased adiponectin concentrations in adult life independently of current BMI, especially for obese subjects.

Objective: An inverse association between adiponectin and C-reactive protein (CRP) has been shown in certain pathological states including obesity, diabetes, and coronary artery disease, which themselves might have confounded this association. This study investigated the association between adiponectin and CRP among substantially healthy subjects., Methods and Results: A population of 2347 middle-aged Japanese men with no medical history of cardiovascular disease, cancer, diabetes, hypertension, or hyperlipidemia was evaluated. Those with some metabolic syndrome components from serological and anthropometric tests were excluded, leaving 714 men for analysis. Serum adiponectin and CRP were significantly correlated (r = -0.21, P < 0.001). After categorization into quartiles from the lowest to the highest adiponectin concentration (Q1 to Q4), the CRP level was found to be significantly higher in Q1 than in Q2, Q3 and Q4 (0.41 mg/L versus 0.30, 0.25 and 0.24 mg/L, P = 0.043, P < 0.001 and P < 0.001, respectively). These associations remained significant even after adjustment for covariates. Moreover, multiple linear regression analysis revealed that adiponectin contributed more strongly to CRP than other factors, including the index of insulin resistance., Conclusions: An inverse and strong association between adiponectin and CRP in substantially healthy subjects implies that decreased serum adiponectin might be fundamentally associated with the early stage of low-grade inflammation.

Objectives: The feasibility of detecting persistent regional left ventricular abnormal relaxation due to myocardial ischemia using strain echocardiography several minutes after exercise was investigated., Methods: Consecutive 27 patients (mean age 65 +/- 9 years, 21 males, 6 females) with suspected coronary artery disease were enrolled. Strain echocardiographic images were acquired at the mid segments of the left ventricular wall before and 5 min after exercise in the apical long-axis, two-chamber and four-chamber views. Strain curves were obtained at each segment, and peak values of strain at the closure of aortic valve (A) and at one third of diastolic duration (B) were measured. Strain diastolic index (SDI) was calculated as (A - B)/A X 100%. The ratio of SDI before exercise to that after exercise was defined as the SDI ratio and compared with exercise thallium-201 single photon emission computed tomography (SPECT) as the reference standard to detect myocardial ischemia., Results: A total of 162 segments were evaluated. Based on the results of exercise SPECT, 119 segments were classified as non-ischemic segments, and 43 as ischemic segments. Ischemic segments showed significant decreases in SDI before and after exercise, whereas non-ischemic segments showed no significant differences in SDI before and after exercise. SDI ratio was significantly decreased in ischemic segments, but not in non-ischemic segments. SDI ratio with a cut off value of 0.51 had a sensitivity of 91% and a specificity of 89% to detect myocardial ischemia in the receiver-operating characteristics. Conclusions. Strain echocardiography can provide quantitative assessment of myocardial ischemia by detecting post-ischemic regional left ventricular delayed relaxation even 5 min after exercise.

Introduction: Side effects observed in the occlusion and dental arches of patients using an oral appliance (OA) to treat snoring or sleep apnea for more than 5 years have not yet been investigated., Methods: Stone casts trimmed in centric occlusion before appliance placement and after an average of 7.4 +/- 2.2 years of OA use in 70 patients were compared visually by 5 orthodontists., Results: Of these patients, 14.3% had no occlusal changes, 41.4% had favorable changes, and 44.3% had unfavorable changes. Significant changes in many variables were found. Patients with greater initial overbites and Class II Division 1 and Class II Division 2 malocclusions were more likely to have favorable or no changes. More favorable changes in overbite occurred in subjects with large baseline overbites. A greater baseline overjet and more distal mandibular canine relationship were correlated to favorable changes. A greater initial overjet was correlated to a more favorable change, a decrease in mandibular crowding, a smaller change in anterior crossbite, and a greater change in overjet., Conclusions: OA wear after a mean of 7.4 years induces clinically relevant changes in the dental arch and the occlusion.

Introduction: This retrospective study compared cephalometric variables between responders and nonresponders to a titratable oral appliance (OA) in a group of subjects matched for sex, pretreatment age, and body mass index (BMI)., Methods: Nine nonresponders as defined by an improvement in the apnea hypopnea index (AHI; <20%) and their individually matched responders were selected for this study. The difference in age for each matched pair was +/-5 years, and, for BMI, the difference was +/-15%. The pretreatment AHI was matched to the same category (moderate, >15 to < or =30; severe I, >30 to < or =45; and severe II, >45 AHI)., Results: Middle and inferior airway space and oropharyngeal airway cross-sectional area were significantly larger in the nonresponders. Position of the mandible relative to the cervical spine was the only significant skeletal variable and was larger in nonresponders. Changes in BMI between the groups were statistically significant; the averages were a 2.9% increase in the nonresponders and a 0.5% decrease in responders. The wider airway in nonresponders might reflect an enhanced neuromuscular compensation while awake. The weight gain in nonresponders was relatively small, but it might have reduced the effectiveness of the OA., Conclusion: When treating OSA patients with OA therapy, clinicians should pay particular attention to airway size and weight changes.

Introduction: Oral appliances (OAs) have been widely used to treat snoring and sleep apnea, but their effects on craniofacial structures in patients after 5 years or more of wear have not yet been quantified., Methods: Seventy-one patients who had worn adjustable mandibular repositioners to treat snoring or sleep apnea were evaluated. Upright lateral cephalometric radiographs in centric occlusion taken before treatment and after a mean of 7.3 +/- 2.1 years of OA use were compared. Baseline sleep studies and patient demographic data were included in the analysis., Results: Cephalometric analyses after long term OA use showed significant (P < .01) changes in many variables, including increases in mandibular plane and ANB angles; decreases in overbite and overjet; retroclined maxillary incisors; proclined mandibular incisors; increased lower facial height; and distally tipped maxillary molars with mesially tipped and erupted mandibular molars. The initial deep overbite group had a significantly greater decrease in overbite. Duration of OA use correlated positively with variables such as decreased overbite and increased mandibular plane angle; changes in the dentition appeared to be progressive over time., Conclusions: After long-term use, OAs appear to cause changes in tooth positions that also might affect mandibular posture.

Objectives: The usefulness of coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography to detect myocardial ischemia was compared with exercise thallium-201 single photon emission computed tomography (SPECT)., Methods: Transthoracic Doppler echocardiography was performed in 110 patients with suspected coronary artery disease. Color Doppler signals of the left circumflex coronary artery flow in the apical four-chamber view were identified, and the velocities at rest and during hyperemia recorded for calculation of coronary flow reserve by the pulsed Doppler method. All patients underwent SPECT within 1 week of the transthoracic Doppler echocardiographic study., Results: Coronary flow reserve in the left circumflex coronary artery was measured in 79 (72%) of 110 patients. SPECT revealed reversible perfusion defect in the left circumflex coronary artery territories in 12 of 69 patients excluding those with multivessel disease. Coronary flow reserve < 2.0 had a sensitivity of 92% and specificity of 96% for reversible perfusion defect detected by SPECT., Conclusions: Noninvasive coronary flow reserve measurement in the left circumflex coronary artery by transthoracic Doppler echocardiography can estimate myocardial ischemia in the left ventricular lateral regions.

The aim of this study was to examine adaptive changes in the cross-sectional area of the upper airway during mandibular advancement and jaw opening and to explore whether these changes are directly related to morphologic features of the mandible. Fourteen nonapneic men participated in this study. A custom-made oral device was used to keep the mandible at 0% (F(0)V(0)), 50% (F(50)V(0)), 75% (F(75)V(0)), or 100% (F(100)V(0)) of maximum advancement, and at 50% (F(75)V(50)), 75% (F(75)V(75)), or 100% (F(75)V(100)) of maximum gape at F(75)V(0). Magnetic resonance imaging was used to investigate differences in the upper-airway cross-sectional area in these 7 positions. To eliminate excessive individual variation, changes in the mean (mean%) and minimum (min%) cross-sectional area of the upper airway were calculated as percentages of those at F(0)V(0). Cephalograms were taken to analyze morphologic features of the mandible. A dose-dependent change was seen when the mandible was advanced. The min% in F(100)V(0) was significantly greater than those in F(50)V(0) and F(75)V(0). The change in the upper airway size varied between subjects during jaw opening. At F(75)V(0), the min% of the whole upper airway was significantly associated with morphologic features of the mandible, such as the mandibular plane angle and lengths of the mandibular body and ramus.