高齢者の手段的ADL低下に対するスポーツと文化的趣味活動の交互作用－藤原京スタディー

Background: Maintenance of instrumental activities of daily living (IADL) and social role (SR) is crucial to keep independent life because the decline in SR and IADL was a significant predictor of dependence in basic ADL in later. The independent effect of physical and cultural leisure activities and their effect modification on the IADL remains unknown. Methods: We prospectively observed 3241 elderly with intact IADL at baseline for 5 years. Higher level functional capacity such as IADL and SR was assessed using the Tokyo Metropolitan Institute of Gerontology Index of competence (TMIG index). Results: The mean age of the participants was 72.3 years (standard deviation 5.1), and 46.9% were male, and 90.9% of them received a follow-up assessment. Of the participants, 10.4% developed an IADL decline. Engagement in leisure physical activity was associated with a significantly lower risk of IADL decline (adjusted risk ratio, 0.73; 95% confidence interval [CI], 0.60 to 0.89), and cultural leisure activity was also associated with lower risk of IADL decline (adjusted risk ratio, 0.77; 95% CI, 0.63 to 0.95) independent of potential confounders. We also found significant and positive interaction between physical and cultural leisure activities at risk for IADL decline (P = 0.024) and SR decline (P = 0.004). Conclusions: We found an independent association of physical and cultural leisure activities with a lower risk for functional decline in IADL and SR with positive interaction. Combined engagement in physical and cultural activities may effectively prevent from IADL decline and SR decline.博士（医学）・乙第1456号・令和2年3月16日© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

白内障手術既往のある高齢者は視力と独立して高い認知機能を維持する : 平城京コホート研究横断解析

Cataract surgery improves visual acuity and drastically increases the capacity for light reception to the retina. Although previous studies suggested that both light exposure and visual acuity were associated with cognitive function, the relationships between cataract surgery, visual acuity, and cognitive function have not been evaluated in large populations. In this cross-sectional study, we measured cognitive function using the Mini-Mental State Examination and best-corrected visual acuity in pseudophakic (previous cataract surgery) and phakic (no previous cataract surgery) elderly individuals. Of 945 participants (mean age 71.7 years), 166 (17.6%) had pseudophakia and 317 (33.5%) had impaired cognitive function (score ≤26). The pseudophakic group showed significantly better visual acuity than the phakic group (p = 0.003) and lower age-adjusted odds ratio (ORs) for cognitive impairment (OR 0.66; p = 0.038). Consistently, in multivariate logistic regression models, after adjusting for confounding factors, including visual acuity and socioeconomic status, ORs for cognitive impairment were significantly lower in the pseudophakic group than in the phakic group (OR 0.64; 95% confidence interval 0.43-0.96; p = 0.031). This association remained significant in sensitivity analysis, excluding participants with low cognitive score ≤23 (n = 36). In conclusion, in a general elderly population, prevalence of cognitive impairment was significantly lower in pseudophakic individuals independently of visual acuity. The association was also independent of several major causes of cognitive impairment such as aging, gender, obesity, socioeconomic status, hypertension, diabetes, sleep disturbances, depressive symptoms, and physical inactivity.博士（医学）・甲第666号・平成29年3月15日© Mary Ann Liebert, Inc.This is a non-final version of an article published in final form in "http://dx.doi.org/10.1089/rej.2015.1718

ATTED-II: a database of co-expressed genes and cis elements for identifying co-regulated gene groups in Arabidopsis

Publicly available database of co-expressed gene sets would be a valuable tool for a wide variety of experimental designs, including targeting of genes for functional identification or for regulatory investigation. Here, we report the construction of an Arabidopsis thaliana trans-factor and cis-element prediction database (ATTED-II) that provides co-regulated gene relationships based on co-expressed genes deduced from microarray data and the predicted cis elements. ATTED-II () includes the following features: (i) lists and networks of co-expressed genes calculated from 58 publicly available experimental series, which are composed of 1388 GeneChip data in A.thaliana; (ii) prediction of cis-regulatory elements in the 200 bp region upstream of the transcription start site to predict co-regulated genes amongst the co-expressed genes; and (iii) visual representation of expression patterns for individual genes. ATTED-II can thus help researchers to clarify the function and regulation of particular genes and gene networks

Relationship of tooth loss to mild memory impairment and cognitive impairment: findings from the fujiwara-kyo study

<p>Abstract</p> <p>Background</p> <p>This cross-sectional study investigated the relationship between the number of remaining teeth to mild memory impairment (MMI), which is a preclinical stage of dementia, and to cognitive impairment.</p> <p>Methods</p> <p>The subjects were aged 65 years or older and were grouped according to their score for the Mini-Mental State Examination (MMSE), the three-word delayed recall test in the MMSE, and the Geriatric Depression Scale into the control group (n = 3,696), the MMI group (n = 121), and the low MMSE score (23 or lower) group (n = 214). We collected data on the number of remaining teeth, the length of the edentulous period, health-related lifestyle, medical history, blood pressure, height, and body weight. Fasting venous blood samples were also obtained.</p> <p>Results</p> <p>Multiple logistic regression analysis, adjusted for depressive symptoms, age, sex, length of education, and other explanatory variables, revealed that the odds ratios of 0-10 remaining teeth to 22-32 remaining teeth were 1.679 (95% CI 1.073-2.627) for MMI and 2.177 (95% CI 1.510-3.140) for a low MMSE score. A significant relationship was also found between the length of the edentulous period and the risk of a low MMSE score (odds ratio 3.102, 95% CI 1.432-6.720) (15 years or more/less than 15 years).</p> <p>Conclusions</p> <p>Our findings suggest that tooth loss is associated with cognitive function.</p

USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes

K63-linked ubiquitin chains attached to plasma membrane proteins serve as tags for endocytosis and endosome-to-lysosome sorting. USP8 is an essential deubiquitinase for the maintenance of endosomal functions. Prolonged depletion of USP8 leads to cell death, but the major effects on cellular signaling pathways are poorly understood. Here, we show that USP8 depletion causes aberrant accumulation of K63-linked ubiquitin chains on endosomes and induces immune and stress responses. Upon USP8 depletion, two different decoders for K63-linked ubiquitin chains, TAB2/3 and p62, were recruited to endosomes and activated the TAK1-NF-κB and Keap1-Nrf2 pathways, respectively. Oxidative stress, an environmental stimulus that potentially suppresses USP8 activity, induced accumulation of K63-linked ubiquitin chains on endosomes, recruitment of TAB2, and expression of the inflammatory cytokine. The results demonstrate that USP8 is a gatekeeper of misdirected ubiquitin signals and inhibits immune and stress response pathways by removing K63-linked ubiquitin chains from endosomes.</p

Insulin-like growth factor 1 predicts decompensation and long-term prognosis in patients with compensated cirrhosis

AimInsulin-like growth factor 1 (IGF-1), which is primarily produced in hepatocytes and is associated with liver functional reserve, plays a crucial role in the pathological condition of cirrhosis. This study aimed to investigate the usefulness of serum IGF-1 levels for predicting the long-term prognosis and decompensation development in patients with cirrhosis.MethodsWe retrospectively evaluated 148 patients with cirrhosis and divided them into three groups according to baseline IGF-1 levels: low (L)-, intermediate (I)-, and high (H)-IGF-1 groups. The cumulative survival rates were compared among these groups in compensated and decompensated cirrhosis, respectively. Significant and independent factors associated with mortality and decompensation development were identified using Cox proportional hazards regression analysis.ResultsThe median observation period was 57.1 (41.7–63.2) months. Thirty (20.3%) patients died of liver disease-related events and 21 (22.3%) patients with compensated cirrhosis developed decompensation. Multivariate analysis identified low serum IGF-1 levels as a significant and independent factor associated with mortality (all patients: hazard ratio [HR], 0.967; p = 0.004; patients with compensated cirrhosis: HR, 0.927; p = 0.002). The cumulative survival rates were significantly lower in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (all patients: p &lt; 0.001 and = 0.009; patients with compensated cirrhosis: p = 0.012 and 0.003, respectively). However, in decompensated cirrhosis, the cumulative survival rates demonstrated no significant differences among the three groups. The cumulative decompensation incidence rates were significantly higher in the L-IGF-1 group than in the H-IGF-1 and I-IGF-1 groups (p &lt; 0.001 and = 0.009, respectively). Low serum IGF-1 levels were significantly and independently associated with decompensation development (HR, 0.939; p &lt; 0.001).ConclusionLow serum IGF-1 levels were significantly and independently associated with decompensation development and poor long-term prognosis in patients with compensated cirrhosis. Therefore, IGF-1 may be useful for predicting decompensation-related events and should be regularly monitored in the management of compensated phase

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain–truncated form (HBΔtm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBΔtm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control

Consensus Statement on the Pathology of IgG4-Related Disease

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD