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Exposure to a novel environment is psychologically and physically stressful for humans and animals. The response has been reported to involve enhanced sympathetic nervous system activity, but changes in nutrient levels under stress are not fully understood. As a form of exposure to a novel environment, repeated cage exchange (CE, four times at 2-h intervals for 8 h from 08:00 h) during the light phase with no restraint on movement was applied to A/J mice, a strain particularly prone to stress. Body temperature was measured with a temperature-sensing microchip implanted in the interscapular region. The stress conditions and anxiety level were evaluated by measuring urinary catecholamines and corticosterone and by performing an anxiety-like behavior test, respectively. Major nutrients such as glucose, fatty acids, and amino acids in the plasma were also examined. CE mice showed a significant increase in body temperature with each CE. They also showed a significantly greater reduction of body weight change, more water intake, and higher levels of urinary catecholamines and corticosterone and anxiety-like behavior score than control mice. The model revealed a significantly lower plasma glucose level and higher levels of several essential amino acids, such as branched-chain amino acids and phenylalanine, than those of control mice. Meanwhile, free fatty acids and several amino acids such as arginine, aspartic acid, proline, threonine, and tryptophan in both sets of mice were significantly decreased from the corresponding levels at 08:00 h, while similar plasma levels were exhibited between mice with and without CE. In conclusion, repeated CE stress was associated with changes in glucose and amino acids in plasma. Although further study is needed to clarify how these changes are specifically linked to anxiety-like behavior, this study suggests the potential for nutritional intervention to counter stress in humans exposed to novel environments.

BackgroundCapsule endoscopy has been widely used to investigate obscure gastrointestinal bleeding (OGIB) in the small intestine since its approval in 2001. However, the clinical features of OGIB remain unclear.AimWe retrospectively examined the clinical features and risk factors of OGIB in patients who underwent capsule endoscopy in our hospital.MethodsWe included 420 of the 431 patients who underwent capsule endoscopy from June 2014 to May 2021, in whom the small intestine could be observed. We retrospectively compared the clinical features and treatment of OGIB cases, with or without active small bowel bleeding (n = 173), with other cases (n = 247). Patient sex, age, diabetes mellitus, and heart failure histories were matched for the analysis.ResultsThe male/female ratio was 247/173 and the average age was 51.54 years. In multivariate analysis, the use of direct oral anticoagulants was significant (P = 0.016), and vascular lesions (P = 0.018) were observed in OGIB cases. When OGIB cases with and without active small bowel bleeding were compared, serum albumin level was lower in cases with active bleeding (P = 0.031). When treatment of OGIB cases were compared, those without vascular lesions could be treated conservatively (P = 0.0047). In the 1:1 propensity score matching analysis, serum creatinine level was elevated in cases of active bleeding (P = 0.029), and cases without vascular lesions were treated conservatively (P = 0.010).ConclusionsUse of direct oral anticoagulants is frequently associated with OGIB. OGIB patients without vascular lesions may be treated conservatively.

Abstract Background and Aims The early and reliable detection of chronic kidney disease is important. In the present study, we aimed to compare the diagnostic results for proteinuria and hematuria between the dipstick test used in primary occupational health examinations and the quantitative tests used in more thorough examinations in clinics. Methods We conducted a single‐center observational study of male staff (N = 573) at Kagoshima University who underwent a health examination in 2017. Both dipsticks and biochemical methods were used to assess proteinuria and hematuria. Results For the dipstick test, the sensitivity, specificity, and positive predictive value were 55.6%, 92.4% and 10.4% for proteinuria, and 64.3%, 98.3% and 66.7% for hematuria, respectively. Four participants for whom false‐negative results were obtained using dipsticks for proteinuria, and two of these had 3+ urinary glucose. Conclusion Qualitative tests for proteinuria and hematuria had low sensitivities and positive predictive values. Therefore, for the early and reliable detection of chronic kidney disease, the use of quantitative urine tests should be considered during occupational health examinations.

Human T-cell leukemia virus type 1 (HTLV-1) causes incurable adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have increased levels of HTLV-1-infected cells compared with asymptomatic HTLV-1 carriers. However, the roles of cellular genes in HTLV-1-infected CD4+ T cells await discovery. We performed microarray analysis of CD4+ T cells from HAM/TSP patients and found that the ABL1 is an important gene in HAM/TSP. ABL1 is a known survival factor for T- and B-lymphocytes and is part of the fused gene (BCR-ABL) known to be responsible for chronic myelogenous leukemia (CML). ABL1 tyrosine kinase inhibitors (TKIs), including imatinib, nilotinib, and dasatinib, are used clinically for treating CML. To evaluate whether ABL1 is indeed important for HAM/TSP, we investigated the effect of TKIs on HTLV-1-infected cells. We developed a propidium monoazide-HTLV-1 viability quantitative PCR assay, which distinguishes DNA from live cells and dead cells. Using this method, we were able to measure the HTLV-1 proviral load (PVL) in live cells alone when peripheral blood mononuclear cells (PBMCs) from HAM/TSP cases were treated with TKIs. Treating the PBMCs with nilotinib or dasatinib induced significant reductions in PVL (21.0% and 17.5%, respectively) in live cells. Furthermore, ABL1 siRNA transfection reduced cell viability in HTLV-1-infected cell lines, but not in uninfected cell lines. A retrospective survey based on our clinical records found a rare case of HAM/TSP who also suffered from CML. The patient showed an 84.2% PVL reduction after CML treatment with imatinib. We conclude that inhibiting the ABL1 tyrosine kinase specifically reduced the PVL in PBMCs from patients with HAM/TSP, suggesting that ABL1 is an important gene for the survival of HTLV-1-infected cells and that TKIs may be potential therapeutic agents for HAM/TSP.

Abstract Background Occupational stress is a known factor behind employee resignations; thus, early identification of individuals prone to such stress is important. Accordingly, in this pilot study we evaluated potential predictors of susceptibility to occupational stress in Japanese novice nurses. Methods Forty-two female novice nurses at Kagoshima University Hospital were recruited for the study population. Each underwent physical health and urinary examinations, and completed a lifestyle questionnaire at the time of job entry. Each also completed a Brief Job Stress Questionnaire (BJSQ), related to mental health status, at job entry and 5 months post-entry. Psychological stress, somatic symptoms, and combined BJSQ scores were determined for each time point. Results All three stress condition scores had significantly decreased at 5 months post-entry, suggesting occupational stress. Systolic blood pressure (r = −0.324, p

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the world and has a high risk of thromboembolism. The most effective approach, catheter ablation, requires evaluation by electrocardiography. The aim of our study was to investigate novel clinical markers that predict restoration of sinus rhythm (SR) after catheter ablation. Seventy-eight consecutive patients with AF underwent catheter ablation and were separated into 2 groups: restored SR and recurrent AF. The levels of 4 blood proteins (serum or plasma) and 3 mature microRNAs (miRNAs) and their primary miRNAs (pri-miRNAs) in serum were measured before and after ablation, and the associations between each parameter were analyzed statistically. Soluble thrombomodulin (s-TM) and plasminogen activator inhibitor-1 (PAI-1) levels increased above baseline after ablation in both the restored SR (s-TM 11.55 [2.92] vs 13.75 [3.38], P < .001; PAI-1 25.74 [15.25] vs 37.79 [19.56], P < .001) and recurrent AF (s-TM 10.28 [2.78] vs 11.67 [3.37], P < .001; PAI-1 26.16 [15.70] vs 40.74 [22.55], P < .001) groups. Levels of C-reactive protein and asymmetric dimethylarginine were not significantly changed. Pri-miR-126 levels significantly decreased after ablation in the recurrent AF group, but the other miRNAs and pri-miRNAs did not. The measurement of s-TM and pri-miR-126 in blood was a useful tool to reflect the condition of AF patients with catheter ablation.

Different involvement of leptin signaling in food intake (FI) and body temperature (BT) in pups and adults has been suggested. However, the leptin receptor (Lepr) long-form-deficient (db) mouse line has not been fully examined in pups. In the most available db mouse line, wild-type (WT) mice have a mutation in the dedicator of cytokinesis 7 gene, named misty, which was recently revealed to be involved in neuronal development. Therefore, we established a line of db mice without the misty mutation using natural mating. Adult (8 weeks of age) homozygous db/db mice displayed significantly higher core body weight (BW) and FI and significantly lower core BT than WT mice. However, postnatal (2 weeks of age) db/db mice displayed similar BW and milk intake and significantly lower core BT than WT mice. Correspondingly, adult and postnatal db/db mice exhibited altered mRNA levels of hypothalamic orexigenic and anorexigenic peptide in adults but not in pups. Additionally, db/db mice displayed significantly lower mRNA levels of brown adipose tissue uncoupling protein 1 at both ages. In conclusion, the db mouse line without the misty mutation clearly showed the different involvements of the Lepr long form in FI and BT in pups and adults.

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact MMP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis. Keywords:: atherosclerosis, cholesterol, diet, life-style, Microminipig

Background/Aim: Although nutritional risk factors for developing complications in type 2 diabetes mellitus (T2DM) have been examined, the effect of protein intake on nephropathy is debated, and there is little research on retinopathy. This cross-sectional case-series study aimed to examine the risk factors, including nutritional status, for complications in patients newly diagnosed with T2DM. Patients and Methods: Fifty-four patients were recruited, based on the results of examinations of blood glucose and/or glycated hemoglobin level for T2DM. To evaluate nutritional status, blood and urine examinations were performed and the Food Frequency Questionnaire was administered. Two-way analysis of variance, Fisher’s exact test and logistic regression analyses were performed. Results: The patients were categorized into four groups: 24 without albuminuria and without retinopathy, four without albuminuria with retinopathy, 21 with albuminuria without retinopathy, and five with albuminuria with retinopathy. Logistic analysis of albuminuria revealed that estimated sodium intake was significantly independent as the explanatory factors of age, sex, and body mass index. Patients with retinopathy had significantly higher blood urea nitrogen, and significantly lower plasma total protein levels than patients without retinopathy, suggesting that retinopathy is related to a higher catabolic state. Through a questionnaire on food intake, patients with retinopathy had a significantly lower intake of fat and monounsaturated fatty acids and a significantly higher intake of iodine based on intake of seaweed, corrected for energy intake, than patients without retinopathy. Conclusion: The present study may lead to planning a large cohort study for examining nutritional risk factors related to complications in patients newly diagnosed with T2DM in Japan. [ABSTRACT FROM AUTHOR]

Background/Aim: Smoking has been reported to be a risk factor for a variety of diseases. In Japan, the Brief Job Stress Questionnaire (BJSQ) has been administered by the Ministry of Health, Labour and Welfare since December 2015, but few reports have focused on its relationship with smoking. We investigated the current situation of smokers among staff of Kagoshima University who underwent a medical check-up. Patients and Methods: Of 2,478 people who underwent a medical check-up in May and June 2021, we targeted 2,237 workers who reported whether they smoked. We examined results of the medical check-up and BJSQ and the background of smokers (n=139, 6.2%). We compared smokers and non-smokers (n=2,098) using propensity score matching (PSM) for sex, age, drinking habits, medication for dyslipidaemia, and overtime working hours at a 1:1 ratio. Results: The results showed that white blood cell count (p=0.044), platelet count (p<0.001), glutamyl transferase (p=0.023), and triglyceride (p=0.027) were significantly higher among current smokers in comparison with current non-smokers. Smokers reported significantly more stress than non-smokers in terms of social support (p=0.027). Conclusion: As a result of PSM, several blood test items related to non-communicable diseases (lifestyle-related diseases) showed high values in current smokers, and these individuals reported significantly more stress than non-smokers. According to the emphasis on group analysis in the Total Health Promotion Plan revised in 2020, our findings can be helpful in enhancing smoking cessation programs in the workplace. [ABSTRACT FROM AUTHOR]

Background/aim: The effects of dietary protein and carbohydrate content on the plasma amino acid profile of patients with diabetes are not fully understood. Therefore, we examined whether there are effects of diets with differing proportions of protein and carbohydrate on the plasma amino acid concentrations of control (CT) mice and mice with type 2 diabetes (db). Materials and Methods: We used db mice as an animal model of type 2 diabetes which are genetically deficient in leptin receptor. Diets with differing proportions of protein and carbohydrates (L diet: low protein/carbohydrate ratio, H diet: high protein/carbohydrate ratio) were supplied. db Mice were fed with a restriction on the basis of the consumption by CT-L mice, such that equivalent amounts of energy and fat were consumed. In CT mice fed the L or H diets, there was no significant difference in ad libitum food intake. Results: There were significant interactions between diet and genotype with respect to water intake, urine volume, urinary glucose concentration, and plasma isoleucine, leucine, valine, branched-chain amino acids, and serine concentrations. db-H mice showed significantly higher water intake, urine volume, and urinary glucose than db-L mice. db Mice fed the L or H diets had similar plasma amino acid profiles, except for valine. In contrast, CT-H mice showed significantly higher valine and branched-chain amino acids and lower serine concentrations than CT-L mice. Thus, the CT-H mice were more similar to db mice fed either of the diets. Conclusion: There were different effects of the dietary protein or carbohydrate content on the plasma amino acid profiles between nondiabetic and diabetic mice. In particular, the profiles in nondiabetic conditions were different between the low- and high-protein diet conditions. [ABSTRACT FROM AUTHOR]

Background: Short QT syndrome is associated with an increased risk of cardiac arrhythmias and unexpected sudden death. Until now, only mutations in genes encoding the cardiac potassium and calcium channels have been implicated in early T-wave repolarization.Objective: The purpose of this study was to confirm a relationship between a short QT syndrome and carnitine deficiency.Methods: We report 3 patients affected by primary systemic carnitine deficiency and an associated short QT syndrome. Ventricular fibrillation during early adulthood was the initial symptom in 1 case. To confirm the relationship between carnitine, short QT syndrome, and arrhythmias, we used a mouse model of carnitine deficiency induced by long-term subcutaneous perfusion of MET88.Results: MET88-treated mice developed cardiac hypertrophy associated with a remodeling of the mitochondrial network. The continuous monitoring of electrocardiograms confirmed a shortening of the QT interval, which was negatively correlated with the plasma carnitine concentration. As in humans, such alterations coincided with the genesis of ventricular premature beats and ventricular tachycardia and fibrillation.Conclusion: Altogether, these results suggest that long-chain fatty acid metabolism influence the morphology and the electrical function of the heart. [ABSTRACT FROM AUTHOR]

Gastric and adipose tissue secrete a number of hormones that are involved in energy metabolism. The biological functions of these hormones, including their effects on aging, are currently under investigation. Adiponectin was shown to be directly involved in appetite and the control of body weight. However, the effects of aging of nesfatin-1, an appetite-suppressing peptide that was recently identified, have not yet been fully elucidated. The aim of this study was to determine the effects of aging on the plasma levels of nesfatin-1 and adiponectin. Our results demonstrated no significant differences in the nesfatin-1 plasma levels among three age groups (2, 6 and 24 months) of female BALB/c mice. The plasma nesfatin-1 levels/visceral fat (VF) ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In addition, there were no significant differences in the plasma adiponectin levels among the three age groups. The plasma adiponectin levels/VF ratio in the 24-month-old mice was significantly lower compared to that in the 2- and 6-month-old mice. In conclusion, there were no age-related changes in the plasma levels of nesfatin-1 and adiponectin, although the ratio of plasma levels of nesfatin-1 and adiponectin per VF was decreased with advancing age. Our results indicated that nesfatin-1 and adiponectin may be involved in controlling energy balance during aging. [ABSTRACT FROM AUTHOR]

Classical citrullinemia (CTLN1), a rare autosomal recessive disorder, is caused by mutations of the argininosuccinate synthetase (ASS) gene, localized on chromosome 9q34.1. ASS functions as a rate-limiting enzyme in the urea cycle. Previously, we identified 32 mutations in the ASS gene of CTLN1 patients mainly in Japan and the United States, and to date 34 different mutations have been described in 50 families worldwide. In the present study, we report ASS mutations detected in 35 additional CTLN1 families from 11 countries. By analyzing the entire coding sequence and the intron–exon boundaries of the ASS gene using RT-PCR and/or genomic DNA-PCR, we have identified 16 novel mutations (two different 1-bp deletions, a 67-bp insertion, and 13 missense) and have detected 12 known mutations. Altogether, 50 different mutations (seven deletion, three splice site, one duplication, two nonsense, and 37 missense) in 85 CTLN1 families were identified. On the basis of primary sequence comparisons with the crystal structure of E. coli ASS protein, it may be concluded that any of the 37 missense mutations found at 30 different positions led to structural and functional impairments of the human ASS protein. It has been found that three mutations are particularly frequent: IVS6–2A>G in 23 families (Japan: 20 and Korea: three), G390R in 18 families (Turkey: six, U.S.: five, Spain: three, Israel: one, Austria: one, Canada: one, and Bolivia: one), and R304W in 10 families (Japan: nine and Turkey: one). Most mutations of the ASS gene are “private” and are distributed throughout the gene, except for exons 5 and 12–14. It seems that the clinical course of the patients with truncated mutations or the G390R mutation is early-onset/severe. The phenotype of the patients with certain missense mutations (G362V or W179R) is more late-onset/mild. Eight patients with R86H, A118T, R265H, or K310R mutations were adult/late-onset and four of them showed severe symptoms during pregnancy or postpartum. However, it is still difficult to prove the genotype–phenotype correlation, because many patients were compound heterozygotes (with two different mutations), lived in different environments at the time of diagnosis, and/or had several treatment regimes or various knowledge of the disease. Hum Mutat 22:24–34, 2003. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]