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Secreted protein acidic and rich in cysteine (SPARC), an exercise-induced myokine, has been suggested as a potential endogenous factor that suppresses colon tumorigenesis. However, the effects of different exercise protocols on circulating SPARC levels are unclear. The main purpose of this study was to examine the effects of both exercise intensity and duration on circulating SPARC levels. This study also examined the relationship between responsiveness of SPARC levels and physical characteristics, including body composition and skeletal muscle function. Nineteen healthy adult men participated in four experimental interventions: two 30-min exercises at workloads corresponding to 60% (W60) and 40% (W40) peak oxygen uptake (VO2peak), a 45-min session of W40, and a 30-min session of complete rest. Blood SPARC and lactate concentrations were measured before and after each session. Only W60 significantly increased serum SPARC levels (p < 0.05), and a significant correlation was found between changes in SPARC levels and lactate concentrations (r = 0.411, p < 0.05). The relative changes in SPARC levels during W60 demonstrated significant positive correlations with skeletal muscle mass and knee extensor muscle strength (both p < 0.05). The increase in serum SPARC levels might be mediated by lactate accumulation and might not, hence, be induced during exercise at the intensity of the first ventilatory threshold levels even though the duration is prolonged. Our results provide fundamental insight into exercise prescription of both exercise intensity and duration for SPARC response, leading to a better understanding of the preventive effects of exercise on colon cancer. This study found that the increase in serum secreted protein acidic and rich in cysteine (SPARC) levels might be mediated by lactate accumulation and might, hence, be influenced by exercise intensity rather than exercise duration. An association was found between SPARC response to exercise and skeletal muscle mass. Our results provide a better understanding of the preventive effects of exercise on colon cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of dysphagia on long‐term survival and swallowing function outcomes in patients with idiopathic inflammatory myopathy other than inclusion body myositis. Methods: We retrospectively evaluated consecutive patients with idiopathic inflammatory myopathy other than inclusion body myositis to investigate the impact of dysphagia and its severity assessed using the Food Intake LEVEL Scale on survival and swallowing function outcomes. Time‐to‐event analyses were used, including Kaplan‐Meier curves with log‐rank (trend) test, cumulative incidence with Gray's test, and Cox proportional hazards models. Results: Of the 254 patients, 26 were dysphagic, including eight severe (Food Intake LEVEL Scale [FILS] score 2, 3) and six most severe (FILS score 1) cases; 210 were non‐dysphagic, and 18 were indeterminate cases. During the 5 years after myositis diagnosis, 15 (57.7%) dysphagic and 31 (14.8%) non‐dysphagic patients died, and dysphagic patients had significantly shorter survival. However, multivariate analysis showed that shorter survival was significantly associated with baseline age‐adjusted Charlson Comorbidity Index (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.36‐1.82]), but not with dysphagia (HR 1.46, 95% CI 0.69‐3.10). Dysphagia severity was significantly associated with delayed recovery of dysphagia. In 20 non‐severe or severe dysphagic cases, 19 restored swallowing function within 1 year. The most severe cases had a significantly higher cumulative probability of death before recovery from dysphagia than severe cases. Conclusion: The poor survival of dysphagic myositis patients was largely confounded by advanced age and comorbid malignancies. However, patients with the most severe dysphagia had a significantly worse swallowing function and survival prognosis than those with milder dysphagia. [ABSTRACT FROM AUTHOR]

Objective: Coatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA. We identified a novel COPA variant in 4 patients in one family. We undertook this study to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these 4 patients and by analyzing results from a gene‐targeted mouse model. Methods: We performed whole‐exome sequencing in 7 family members and measured the type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and in Copa mutant mice that were generated. Results: We identified a heterozygous variant of COPA (c.725T>G, p.Val242Gly) in the 4 affected members of the family. The IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G, as well as the previously reported disease‐causing variants, augmented stimulator of interferon genes (STING)–induced type I IFN promoter activities. CopaV242G/+ mice manifested interstitial lung disease and STING‐dependent elevation of IFN‐stimulated gene expression. In CopaV242G/+ dendritic cells, the STING pathway was not constitutively activated but was hyperactivated upon stimulation, leading to increased type I IFN production. Conclusion: V242G, a novel COPA variant, was found in 4 patients from one family. In gene‐targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We examined the association between hemoglobin A1c (HbA1c) and anemia, which was categorized into three groups according to mean corpuscular volume (MCV), as well as the association between hemoglobin in the non‐anemic range and HbA1c. Materials and Methods: We used the 2016 health checkup data from 36,422 workers without diabetes. Anemic people were divided into three groups based on MCV: <80, 80–90 and >90 fL. Non‐anemic people were divided into four groups based on their hemoglobin levels. We carried out multiple linear regression models to estimate the means and 95% confidence intervals (CIs) of HbA1c. Results: For men, 0.2% had anemia with MCV <80 fL, 0.5% had anemia with MCV 80–90 fL, 0.9% had anemia with MCV >90 fL and 98.4% had no anemia. For women, the corresponding values were 6.1, 6.4, 2.8 and 84.7%, respectively. The adjusted mean HbA1c (%) values for men with anemia with MCV <80, 80–90 and >90 fL were 5.67 (95% CI 5.60–5.74), 5.58 (95% CI 5.54–5.62) and 5.41 (95% CI 5.37–5.44), respectively. Among men without anemia, HbA1c (%) increased from 5.36 (95% CI 5.34–5.39) in those with hemoglobin ≥17.5 mg/dL to 5.45 (95% CI 5.45–5.46) in those with hemoglobin 13.0 to <14.5 mg/dL (P for trend <0.001). The HbA1c values were higher in men with anemia with MCV <80 fL or MCV 80–90 fL, but lower in men with MCV >90 fL, compared with non‐anemic men with hemoglobin 13.0 to <14.5 mg/dL (All P < 0.001). Similar findings were observed in women. Conclusions: We observed elevated HbA1c among anemic people with MCV <80 fL or MCV 80–90 fL, and decreased HbA1c among anemic people with MCV >90 fL, suggesting that different types of anemia might influence HbA1c differently. In addition, non‐anemic people with lower hemoglobin levels had higher HbA1c levels, suggesting that hemoglobin levels are in need of consideration when interpreting HbA1c values among non‐anemic people. [ABSTRACT FROM AUTHOR]

Objective: In contrast to the association between excess weight and sickness absence (SA), the association in relation to underweight has been under-researched. This study aimed to examine the effects of BMI at both extremes of its distribution on SA.Methods: Data came from the Japan Epidemiology Collaboration on Occupational Health study of 77,760 workers aged 20 to 59 years (66,166 males, 11,594 females). Information was collected on medically certified long-term SA (LTSA) (i.e., SA lasting ≥ 30 consecutive days) from April 2012 to March 2017. A sex-specific Cox proportional hazards model was used to investigate the associations.Results: Among males, both obesity (hazard ratio [HR] = 1.81, 95% CI: 1.50-2.17) and underweight (HR = 1.56, 95% CI: 1.23-1.96) were significantly associated with LTSA compared with normal weight. This U-shaped association between BMI categories and LTSA was observed both for mental and physical disorders. Among females, an elevated risk was observed among those with overweight (HR = 1.54, 95% CI: 1.16-2.05).Conclusions: In a cohort of the Japanese working-age population, both obesity and underweight were associated with a greater risk of LTSA in males. Future research should not overlook the excess risk of LTSA associated with underweight. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We examined a prospective association between serum creatinine levels and diabetes. Materials and Methods: The present study included 31,343 male workers without diabetes, and aged between 20 and 64 years at baseline. We calculated the cumulative average of their serum creatinine over the study period. We defined diabetes as either glycated hemoglobin levels ≥6.5%, random glucose levels ≥200 mg/dL, fasting glucose levels ≥126 mg/dL or receiving antidiabetic treatment. Cox proportional hazards regression analysis was carried out to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: With a median observation of 7.7 years, 2,509 participants developed diabetes. After adjusting for age, smoking, body mass index, hypertension and dyslipidemia, lower cumulative average serum creatinine levels were related to a greater diabetes risk: HRs were 1.56 (95% CI 1.35–1.82), 1.22 (1.09–1.35) and 1.06 (0.96–1.17) for the participants with serum creatinine <0.70, 0.70–0.79 and 0.80–0.89 mg/dL, respectively, compared with those with 0.90–1.20 mg/dL (P for trend <0.001). The serum creatinine‐diabetes association was more pronounced among older adults (serum creatinine <0.70 vs 0.90–1.20 mg/dL, HR 1.66, 95% CI 1.37–2.00) than younger adults (HR 1.32, 95% CI 1.02–1.71; P for interaction by age group = 0.001). Conclusions: Low serum creatinine is associated with an increased risk of diabetes. Screening serum creatinine levels can be used to identify those who are at high risk of diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Brain-derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE. Methods: Thirteen healthy adult men participated in four experimental sessions; a 30-min CE, a 30-min cycling PE at an intensity of 60% peak oxygen uptake, a 30-min CCPE at the same intensity as PE, and a 30-min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session. Results: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05). Conclusions: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: We previously developed a 3‐year diabetes risk score in the working population. The objective of the present study was to develop and validate flexible risk models that can predict the risk of diabetes for any arbitrary time‐point during 7 years. Materials and Methods: The participants were 46,198 Japanese employees aged 30–59 years, without diabetes at baseline and with a maximum follow‐up period of 8 years. Incident diabetes was defined according to the American Diabetes Association criteria. With routine health checkup data (age, sex, abdominal obesity, body mass index, smoking status, hypertension status, dyslipidemia, glycated hemoglobin and fasting plasma glucose), we developed non‐invasive and invasive risk models based on the Cox proportional hazards regression model among a random two‐thirds of the participants, and used another one‐third for validation. Results: The range of the area under the receiver operating characteristic curve increased from 0.73 (95% confidence interval 0.72–0.74) for the non‐invasive prediction model to 0.89 (95% confidence interval 0.89–0.90) for the invasive prediction model containing dyslipidemia, glycated hemoglobin and fasting plasma glucose. The invasive models showed improved integrated discrimination and reclassification performance, as compared with the non‐invasive model. Calibration appeared good between the predicted and observed risks. These models performed well in the validation cohort. Conclusions: The present non‐invasive and invasive models for the prediction of diabetes risk up to 7 years showed fair and excellent performance, respectively. The invasive models can be used to identify high‐risk individuals, who would benefit greatly from lifestyle modification for the prevention or delay of diabetes. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of low-intensity exercise training using belt electrode skeletal muscle electrical stimulation on muscle strength and cardiorespiratory fitness in healthy subjects. Nineteen healthy subjects were allocated into control or intervention groups; in both groups the participants kept regular physical activity while the intervention group underwent 30 min B-SES training at 3–4 METs for four weeks. Knee extensor muscle strength and cardiorespiratory endurance during incremental exercise test were measured at baseline and after four weeks for all participants. The relative change of knee extensor muscle strength in the intervention group was significantly higher than control group (p < .05). Also, oxygen uptake at ventilator threshold and peak oxygen uptake during incremental exercise test significantly increased in the intervention group when compared with control group (p < .05). This study showed that prolonged low-intensity B-SES training resulted in significant increases in muscle strength and cardiorespiratory fitness in healthy subjects. Our present work suggested that B-SES training could assist patients who might have difficulty performing adequate voluntary exercise because of excessive obesity, orthopaedic problems and chronic diseases such as cardiovascular disease and type 2 diabetes. An intervention study conducted for such patients is strongly recommended. [ABSTRACT FROM PUBLISHER]

ABSTRACT Introduction: We investigated the motor unit (MU) firing pattern in type 2 diabetes mellitus (T2DM) patients by means of multichannel surface electromyography (SEMG). Methods: Eight T2DM patients and 8 age-matched, healthy men performed a ramp-up contraction to 20% of maximal voluntary contraction (MVC). They also performed a sustained contraction at 10% of MVC during isometric knee extension. Multichannel SEMG signals recorded from the vastus lateralis muscle were decomposed with the convolution kernel compensation technique to extract individual MU firing patterns. Results: During the ramp contraction, the extent of MU firing modulation was significantly attenuated in T2DM. Variability of MU firing rate was significantly higher in T2DM at later periods during the sustained contraction. Conclusions: Our findings suggest that T2DM patients manifest characteristic MU activity patterns due possibly to some degree of neuromuscular impairment affecting the integrity of MU firing modulation. Muscle Nerve 48:806-813, 2013 [ABSTRACT FROM AUTHOR]

. Purpose: To identify symptoms potentially related to glaucomatous visual field abnormalities (VFAs) in a population-based setting, and to assess the applicability of using these symptoms to identify persons at risk of developing glaucoma. Methods: In this study, 10 214 Japanese male general workers (mean age, 45.3 ± 8.8 years) filled out a self-administered questionnaire and underwent frequency doubling technology (FDT) perimetry testing. The questionnaire inquired about whether the participant was suffering from any of nine symptoms, with scores for each response graded on a four-item Likert scale: 0 (none), 1 (rarely), 2 (sometimes), and 3 (always). Results from the questionnaire were compared among three groups: participants without any VFAs (9767), participants with VFAs as determined by the FDT test (FDT-VFA; 447), and 227 participants (of the 447 FDT-VFA participants) with glaucomatous VFAs who were newly diagnosed by ophthalmologic examinations. Results: The mean summed scores for the total items were significantly (p < 0.01) higher in FDT- and glaucomatous VFA groups than in normal subjects. In particular, responses citing the symptoms 'feeling of something in the front of the eye' and 'feeling of hardness to see in dark places' were significantly (p < 0.05) more frequent in subjects with FDT- and glaucomatous VFAs than among normal participants. However, the respective areas under the receiver operating characteristic curve of summed scores for the nine total items and for the two items which showed significant differences for the glaucoma groups were 0.57 (95% confidence interval = 0.53-0.60) and 0.58 (95% confidence interval = 0.54-0.61). Conclusion: Although the symptoms 'feeling of hardness to see in dark places' and 'feeling of something in the front of the eye' could be associated with glaucomatous VFA in a population-based setting, inquiring about symptoms is of little aid in identifying subjects with glaucomatous VFA as a strategy for public health. [ABSTRACT FROM AUTHOR]

Urinary 8-hydroxydeoxyguanosine (8-OH-dG) and 7-methylguanine (m7Gua) were measured by a column-switching high performance liquid chromatography method as markers of oxidative and methylating DNA damage, respectively. We investigated the associations between urinary 8-OH-dG or m7Gua and various lifestyle and demographic factors, such as age and sex. The urinary 8-OH-dG excretion level was positively correlated with cigarette smoking, but inversely correlated with fruit consumption, physical activity and total energy consumed per day. A multiple regression analysis revealed that daily physical activity and healthy meal combinations decreased the urinary 8-OH-dG level, whereas alcohol consumption increased it. In terms of the urinary m7Gua measurement, cigarette smoking, age and consumption of meat, fish, egg, soybean, etc. were positively correlated with the urinary m7Gua level, whereas body weight, BMI, physical activity, and dietary index score, which indicates good nutritional balance, were negatively correlated with the amount of m7Gua. Based on a multiple regression analysis, cigarette smoking and age correlated with the m7Gua level, while high BMI and healthy meal combinations have significant reducing effects on m7Gua level. Therefore, the urinary m7Gua level is considered to be a useful marker of DNA methylation, not only from smoking, but also from aging and unhealthy dietary habits. ( Cancer Sci 2009; 100: 715–721) [ABSTRACT FROM AUTHOR]

Aim Little is known about the relationship between near falls and substantial falls in older adults. Clarifying this relationship would be helpful to assess fall risk in greater detail. The purpose of the present study was to clarify whether near falls predict future falls. Methods This was designed to be a prospective cohort study. Participants were recruited from a community apartment for older adults. After a baseline physical assessment, participants were asked to record the incidence of near falls in a diary for 3 months. After the survey period, participants were followed for 6 months by telephone contact every 2 months. Cox proportional hazards regression models were used to analyze the association between near falls and falls. Results A total of 60 participants were included in the analysis. During the initial 3 months, 23 participants (38%) experienced near falls. Eight participants (13%) experienced substantial falls during the following 6 months. Cox proportional hazards regression models adjusted for age, body mass index, sex and physical frailty showed that experience of near falls (hazards regression 6.0, 95% confidence intervals 1.1-31.7; P < 0.05) was significantly associated with incidence of future falls. Conclusions Experience of near falls among older adults is an independent predictor of substantial falls irrespective of the physical frailty status. Clinicians might need to focus on near falls to appropriately assess the fall risk in older adults. Geriatr Gerontol Int 2017; 17: 1477-1480. [ABSTRACT FROM AUTHOR]