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Objective: The main objective was to ascertain the acute responses in autonomic nervous activity and peripheral sensation induced by moderate-intensity treadmill exercise performed under different ambient temperatures. Methods: Twelve young healthy subjects underwent three sessions of moderate-intensity treadmill exercise (warming, 5 min and running, 25 min), on different days under 10°C, 20°C and 30°C room temperatures. Pre- and post-intervention, heart rate variability (HRV) and plantar vibrotactile perception threshold (VPT) were measured. Additionally, rate of perceived exertion (RPE) was recorded after intervention. Results: In comparison with the corresponding baseline values, after intervention, low frequency power (LF) and LF/high frequency power (HF) of HRV increased significantly and HF decreased significantly under the condition of 10°C only (p < .005). Following intervention, VPT increased significantly at the hallux for 31.5 Hz test frequency under 30°C and at the heel for 31.5 Hz test frequency under 10°C (both p < .05). In contrast, VPT decreased significantly at the hallux for 125 Hz test frequency under 10°C (p < .005). Exposure under the temperature of 20°C did not result in any significant change in VPT. After intervention, RPE under 30°C showed significantly higher values than those under 20°C (p < .01) and 10°C (p < .005) conditions with no difference between the latter two conditions. Conclusions: Treadmill exercise under 20°C ambient temperature did not exert any negative impacts on autonomic and peripheral nerve function and resulted in a perceived exertion of moderate intensity among the study participants. Therefore, an ambient temperature around 20°C might be recommended for the mentioned purpose.
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The published literature on the association of circulatory branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) with reduced kidney function is inconsistent or conflicting. Clarification of it might help to better understand the underlying pathophysiology and to determine potential biomarkers for early detection and evaluation of kidney function decline. Our main purpose was to explore and clarify the potential relationships of individual BCAAs and AAAs with estimated glomerular filtration rate (eGFR) decline. We included the data from 2804 healthy subjects and categorized them into three groups based on eGFR tertiles. The associations between individual amino acids and eGFR were explored by covariate-adjusted logistic regression models. There was a progressive increase in the concentrations of BCAAs and AAAs from the upper to the lower tertiles. We revealed significant positive associations of isoleucine, leucine, and phenylalanine with lower tertiles of eGFR in the adjusted models (p < 0.01-0.001). The findings hold a promising potential of using plasma isoleucine, leucine, and phenylalanine levels for evaluation of kidney function decline. Future longitudinal studies should investigate the causal association between altered levels of these amino acids and impaired kidney function and also the utility of the former as potential biomarkers for evaluating the risk and early detection of the latter.
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Unrelated bone marrow transplantation (uBMT) is performed to treat blood disorders, and it uses bone marrow from an unrelated donor as the transplant source. Although the importance of HLA matching in uBMT has been established, that of other genetic factors, such as single-nucleotide polymorphisms (SNPs), remains unclear. The application of immunoinhibitory receptors as anticancer drugs has recently been attracting attention. This prompted us to examine the importance of immunoinhibitory receptor SNPs in uBMT. We retrospectively genotyped five single-nucleotide polymorphisms (SNPs) in the immune checkpoint genes, BTLA, PD-1, LAG3, and CTLA4, and two SNPs in the methylase genes, DNMT1 and EZH2, in 999 uBMT donor-recipient pairs coordinated through the Japan Marrow Donor Program matched at least at HLA-A, -B, and -DRB1. No correlations were observed between these SNPs and post-uBMT outcomes (p > 0.005). This result questions the usefulness of these immune checkpoint gene polymorphisms for predicting post-BMT outcomes. However, the recipient EZH2 histone methyltransferase gene SNP, which encodes the D185H substitution, exhibited a low p-value in regression analysis of grade 2-4 acute graft-versus-host disease (p = 0.010). Due to a low minor allele frequency, this SNP warrants further investigation in a larger-scale study.
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Findings of the available studies regarding the roles of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in hypertension are inconsistent, conflicting and inconclusive. The purpose of this study was to explore and clarify the existence of any relationships of individual BCAAs and AAAs with hypertension with adjustments for potential relevant confounders. A total of 2805 healthy controls and 2736 hypertensive patients were included in the current analysis. The associations between individual amino acids and hypertension were explored by logistic regression analyses adjusted for potential confounding variables. Among the investigated amino acids, only the BCAAs showed consistently significant positive associations with hypertension in the adjusted models (p-trend < 0.05 to 0.001). However, compared with the corresponding lowest quartile of individual BCAAs, the positive association with hypertension remained significant only in the highest quartile (p < 0.01 to 0.001). We confirmed in a relatively large cohort of subjects that BCAAs, not AAAs, demonstrated consistent positive associations with hypertension. The results display the promising potential for the use of BCAAs as relevant and accessible biomarkers, and provide perspectives on interventions directed towards the reduction in plasma BCAA levels in the prevention and management of hypertension.
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Aminoácidos Aromáticos/sangue , Aminoácidos de Cadeia Ramificada/sangue , Hipertensão/etiologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
This paper presents experiences of integrating assistive robots in Japanese nursing care through semi-structured interviews and site observations at three nursing homes in Japan during the year 2019. The study looked at experiences with the robots Paro, Pepper, and Qoobo. The goal was to investigate and evaluate the current state of using robots within the nursing care context, which involved: firsthand experiences with intended and real users; and response from the elderly, and nursing staff. The qualitative analysis results pointed out user satisfaction, adjusted purpose, therapeutic and entertaining effects. The potentials of using robots to assist in elderly care has been evident. Limitations currently relate to the lack of ways to fully utilize and integrate robots.
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Recursos Humanos de Enfermagem , Humanos , Japão , Casas de Saúde , Satisfação Pessoal , RobóticaRESUMO
This paper presents experiences of integrating assistive robots in Japanese nursing care through semi-structured interviews and site observations at three nursing homes in Japan during the spring of 2019. The study looked at experiences with the robots Paro, Pepper, and Qoobo. The goal was to investigate and evaluate the current state of using robots in the nursing care context, firsthand experiences with intended and real use, as well as response from the elderly and nursing staff. The qualitative analysis results pointed out user satisfaction, adjusted purpose, therapeutic and entertaining effects. Potentials of robots to assist in elderly care is advantageous. Limitations currently relate to the lack of ways to fully utilized and integrate robots.
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Casas de Saúde , Robótica , Idoso , Humanos , JapãoRESUMO
BACKGROUND: Non-invasive application of whole-body vibration (WBV) has the potential for inducing improvements in impaired peripheral circulation, cutaneous sensation and balance among older adults. However, relevant studies have frequently applied high magnitudes of vibration and show conflicting and inconclusive results. Therefore, we attempted to ascertain the acute responses in those parameters from exposure of thirty older subjects to WBV of three different magnitudes, defined according to ISO 2631-1 (1997). METHODS: Each subject randomly underwent four sessions of intervention (three bouts of 1 min exposure with 1 min between-bout rests): WBV at 15, 20, or 25 Hz with a peak-to-peak displacement of 4 mm, or control condition. RESULTS: Both during and after intervention, dorsal foot skin blood flow increased significantly under 20 and 25 Hz exposure conditions with greater responses under the latter condition, the magnitude of which slightly exceeded the recommended value. Plantar vibrotactile perception showed significant increases after WBV exposure with overall greater responses under higher frequencies of vibration. In contrast, no WBV-induced change in balance was observed. CONCLUSIONS: WBV at 20 Hz with a magnitude within the recommended limit can be effective in inducing enhancements in peripheral blood flow; however, the same magnitude of vibration seems insufficient in improving balance among older adults.
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Extremidades/irrigação sanguínea , Modalidades de Fisioterapia , Equilíbrio Postural , Percepção do Tato , Vibração , Idoso , Feminino , Humanos , MasculinoRESUMO
The findings of the published studies investigating the changes in peripheral circulation induced by exposure to whole-body vibration (WBV) are not consensual or conclusive. Also, those studies did not consider the role of vibration magnitude on the peripheral circulatory responses making the interpretation of the observed findings difficult. We aimed to review the published literature investigating the effects of controlled WBV intervention on peripheral circulation by characterizing the relevant exposure conditions including vibration magnitudes, and ascertain the specific patterns of responses in peripheral circulation of the lower extremity from such exposure. A computerized search was performed in PubMed and Scopus using selected key search terms, and the relevant data were extracted. The vibration magnitude in the included studies frequently exceeded the limit specified in the International Standard ISO 2631-1 (1997) for such exposure. As observed, exposure to WBV with frequencies ≤30 Hz caused an improvement in peripheral blood flow (BF) and/or skin temperature (ST) of the lower extremity. In contrast, the responses in BF and ST from exposure to WBV of higher frequencies (31 Hz-50 Hz) produced conflicting results. The findings of this review indicate that WBV exposure with relatively lower frequency and magnitude can be safely and effectively used to induce improvements in peripheral circulation. For this purpose, the limits recommended by the ISO 2631-1 (1997) should be considered till safe and effective vibration-related parameters are established.
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Hemodinâmica , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Vibração/efeitos adversos , Vibração/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Fluxo Sanguíneo Regional , Temperatura Cutânea , Resultado do Tratamento , Adulto JovemRESUMO
The potential association between altered levels of plasma free amino acids (PFAAs) and uric acid (UA) with estimated glomerular filtration rate (eGFR) remains unknown among patients with hypertension. A total of 2804 healthy controls and 2455 hypertensive patients were included in the current analysis. eGFR was defined as reduced when it was <60 ml/min/1.73 m2. The associations between reduced eGFR and individual PFAAs and UA in the healthy control and hypertension groups were explored by logistic regression analyses adjusted for potential confounding variables. Results show that UA had a significant positive association with reduced eGFR in both healthy control and hypertension groups (P < 0.001). Among the PFAAs, citrulline, glycine and phenylalanine showed significant positive associations with reduced eGFR in both healthy control (P < 0.01 to 0.001) and hypertension (P < 0.001) groups. Moreover, alanine, asparagine and methionine achieved significant positive associations with reduced eGFR only in the hypertension group (P < 0.01 to 0.001). Conversely, serine showed significant inverse associations with reduced eGFR in the hypertension group only (P < 0.001). Our findings provide first evidence for a strong relationship between distinct patterns of PFAAs and elevated UA with reduced eGFR in hypertension. The findings may appear useful in developing effective strategies for the prevention or early detection and treatment of declined kidney function in hypertension.
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Aminoácidos/sangue , Taxa de Filtração Glomerular , Hipertensão/sangue , Ácido Úrico/sangue , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
Previous studies demonstrated independent contributions of plasma free amino acids (PFAAs) and high uric acid (UA) concentrations to increased risks of lifestyle-related diseases (LSRDs), but the important associations between these factors and LSRDs remain unknown. We quantified PFAAs and UA amongst Japanese subjects without LSRDs (no-LSRD, n = 2805), and with diabetes mellitus (DM, n = 415), dyslipidemia (n = 3207), hypertension (n = 2736) and metabolic syndrome (MetS, n = 717). The concentrations of most amino acids differed significantly between the subjects with and without hyperuricemia (HU) and also between the no-LSRD and LSRD groups (p < 0.05 to 0.001). After adjustment, the logistic regression analyses revealed that lysine in DM, alanine, proline and tyrosine in dyslipidemia, histidine, lysine and ornithine in hypertension, and lysine and tyrosine in MetS demonstrated significant positive associations with HU among the patients with LSRDs only (p < 0.05 to 0.005). By contrast, arginine, asparagine and threonine showed significant inverse associations with HU in the no-LSRD group only (p < 0.05 to 0.01). For the first time, we provide evidence for distinct patterns of association between PFAAs and HU in LSRDs, and postulate the possibility of interplay between PFAAs and UA in their pathophysiology.
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Aminoácidos/sangue , Diabetes Mellitus/sangue , Dislipidemias/sangue , Hipertensão/sangue , Hiperuricemia/sangue , Síndrome Metabólica/sangue , Adulto , Idoso , Glicemia/análise , Pressão Sanguínea , Colesterol/sangue , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Triglicerídeos/sangue , Ácido Úrico/sangueRESUMO
Innate immune factors exert widespread effects on cytokine secretion, cell survival, autophagy, and apoptosis. Nucleotide-binding and oligomerization domain-like receptors (NLRs) are members of the innate immune system in the cytosol that sense pathogens, endogenous danger molecules such as uric acid, and pollutants. Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and NOD2) are components of NLR family, and ligands of these factors are γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP) and muramyl dipeptide (MDP), respectively. Upon recognition of ligands, NOD1 and NOD2 induce the production of inflammatory cytokines and transcription factors including interleukin-6 (IL-6) and nuclear factor-κB (NF-κB). We examined the function of NOD1 and NOD2 in innate immunity, with a focus on their differing roles in disease pathogenesis between Japanese and Caucasian populations. Susceptibility to several immune-related diseases, including Crohn's disease, colorectal and breast cancers, and graft-versus-host-disease (GVHD) showed a correlation with genetic variants of NOD2 in Caucasian, but not in Japanese, populations. This difference may be primarily due to the fact that three major NOD2 SNPs (R702W, G908R, L1007insC) prevalent in Caucasians are rare or absent in Japanese populations. Because NLR has diverse effects on immune function, it is possible that many as yet uncharacterized immune-related diseases will also show different susceptibilities between races due to the different ratio of genetic variants in innate immune genes.
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Carcinogênese/genética , Carcinogênese/imunologia , Inflamação/genética , Inflamação/imunologia , Proteína Adaptadora de Sinalização NOD1 , Proteína Adaptadora de Sinalização NOD2 , Artrite , Doença de Crohn/genética , Doença de Crohn/imunologia , Citocinas , Etnicidade , Doença Enxerto-Hospedeiro , Humanos , Japão , Proteína Adaptadora de Sinalização NOD1/genética , Proteína Adaptadora de Sinalização NOD1/imunologia , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/imunologia , Sarcoidose , Sinovite , Uveíte , População BrancaRESUMO
BACKGROUND: Studies on the association of plasma-free amino acids with gout are very limited and produced conflicting results. Therefore, we sought to explore and characterize the plasma-free amino acid (PFAA) profile in patients with gout and evaluate its association with the latter. METHODS: Data from a total of 819 subjects (including 34 patients with gout) undergoing an annual health examination program in Shimane, Japan were considered for this study. Venous blood samples were collected from the subjects and concentrations of 19 plasma amino acids were determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Student's t-test was applied for comparison of variables between patient and control groups. The relationships between the presence or absence of gout and individual amino acids were investigated by logistic regression analysis controlling for the effects of potential demographic confounders. RESULTS: Among 19 amino acids, the levels of 10 amino acids (alanine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, tryptophan, valine) differed significantly (P < .001 to .05) between the patient and control groups. Univariate logistic regression analysis revealed that plasma levels of alanine, isoleucine, leucine, phenylalanine, tryptophan and valine had significant positive associations (P < .005 to .05) whereas glycine and serine had significant inverse association (P < .05) with gout. CONCLUSIONS: The observed significant changes in PFAA profiles may have important implications for improving our understanding of pathophysiology, diagnosis and prevention of gout. The findings of this study need further confirmation in future large-scale studies involving a larger number of patients with gout.
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Aminoácidos/sangue , Gota/sangue , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Cromatografia Líquida de Alta Pressão , Feminino , Gota/epidemiologia , Humanos , Japão , Masculino , Análise de Regressão , Fatores Sexuais , Fumar/epidemiologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: Recently, the association of plasma free amino acid (PFAA) profile and lifestyle-related diseases has been reported. However, few studies have been reported in large Asian populations, about the usefulness of PFAAs for evaluating disease risks. We examined the ability of PFAA profiles to evaluate lifestyle-related diseases in so far the largest Asian population. METHODS: We examined plasma concentrations of 19 amino acids in 8589 Japanese subjects, and determined the association with variables associated with obesity, blood glucose, lipid, and blood pressure. We also evaluated the PFAA indexes that reflect visceral fat obesity and insulin resistance. The contribution of single PFAA level and relevant PFAA indexes was also examined in the risk assessment of lifestyle-related diseases. RESULTS: Of the 19 amino acids, branched-chain amino acids and aromatic amino acids showed association with obesity and lipid variables. The PFAA index related to visceral fat obesity showed relatively higher correlation with variables than that of any PFAA. In the evaluation of lifestyle-related disease risks, the odds ratios of the PFAA index related to visceral fat obesity or insulin resistance with the diseases were higher than most of those of individual amino acid levels even after adjusting for potential confounding factors. The association pattern of the indexes and PFAA with each lifestyle-related disease was distinct. CONCLUSIONS: We confirmed the usefulness of PFAA profiles and indexes as markers for evaluating the risks of lifestyle-related diseases, including diabetes mellitus, metabolic syndrome, dyslipidemia, and hypertension in a large Asian population.
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Aminoácidos/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Hipertensão/sangue , Síndrome Metabólica/sangue , Adulto , Idoso , Povo Asiático , Biomarcadores , Glicemia , Pressão Sanguínea , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Japão/epidemiologia , Lipídeos/sangue , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/epidemiologia , Fatores de RiscoRESUMO
HLA matching is a well-known genetic requirement for successful bone marrow transplantation (BMT). However, the importance of non-HLA single-nucleotide polymorphisms (SNPs) remains poorly understood. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity, is associated with multiple diseases. We retrospectively genotyped SNPs of NLRP1-3 and caspase recruitment domain family member 8 (CARD8), which are implicated in the interleukin 1ß (IL-1ß) signaling, in 999 unrelated BMT donor-recipient pairs. We identified an association of the interaction between the recipient NLRP3 SNP CC genotype and total HLA mismatches with grade 2-4 acute graft-versus-host disease (AGVHD), and an association of the interaction between the donor NLRP3 SNP T allele and HLA-C mismatch with extensive chronic GVHD (ECGVHD), in both adjusted and unadjusted regressions (P < 0.005). Importantly, the ECGVHD risk associated with HLA-C mismatch was not elevated when the donor NLRP3 genotype was CC. We also identified an association of the interaction between recipient NLRP3 SNP and donor cytomegalovirus seropositivity with overall survival in adjusted regressions (P < 0.005). These results suggest the importance of certain SNP-covariate interactions in unrelated BMT. The three identified interactions may be useful for donor selection or outcome prediction.
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Doença Enxerto-Hospedeiro/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
Environmental pollutants (such as diesel exhaust particles and silica) cause disorders ranging from bronchial asthma to malignant tumors. In recent years, it has been reported that some of the signaling pathways in which environmental contaminants act in vivo are associated with innate immunity. Innate immunity recognizes ligands and induces inflammation. Those ligands are pathogen-associated molecular patterns (PAMPs: e.g., lipopolysaccharide) and danger-associated molecular patterns (DAMPs: e.g., cholesterol crystallization or uric acid crystal). Activation of innate immunity stimulates the acquired immunity system. Therefore, innate immunity regulates the strength of the general immune system. Furthermore, crystal silica, which is an environmental pollutant, activates innate immunity as a ligand. Innate immunity involves the membrane-bound Toll-like receptors (TLR) and cytoplasm-localized nucleotide-binding oligomerization domain (NOD)-like receptors (NLR). We reported the innate immunity-system-related diseases such as Crohn's disease, Blau syndrome, myelogenous leukemia, and sarcoidosis. An inflammasome complex containing NLR has attracted attention owing to its correlation with the onset of several diseases. It is reported that the inflammasome activation is related to the development of lifestyle-related diseases such as myocardial infarction and fatty liver. It is also reported that the mechanism by which crystal silica and asbestos cause inflammation involves the inflammasome activation. Analyzing the genes of innate immunity contributes to the clarification of the mechanism of disease onset caused by environmental pollutants.
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Poluentes Ambientais/imunologia , Sistema Imunitário/imunologia , Imunidade Inata/imunologia , Imunidade Adaptativa/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Amianto/imunologia , Cristalização , Humanos , Imunidade Inata/genética , Inflamassomos/imunologia , Moléculas com Motivos Associados a Patógenos/imunologia , Receptores Citoplasmáticos e Nucleares/imunologia , Dióxido de Silício/imunologia , Receptores Toll-Like/imunologiaRESUMO
BACKGROUND: The objective of this study was to clarify the relationship between feeling upon awakening (FA) and time spent using information technology (IT) devices by children in kindergartens, elementary schools, and junior high schools in Shimane, Japan. METHODS: In October 2008, a self-report survey was distributed to 2075 children in kindergartens (n = 261), elementary schools (n = 1162), and junior high schools (n = 652) in Shimane, Japan. The questionnaire gathered data on sex, school year, feeling upon awakening, and time spent using IT devices after school (television, videos on television, video games, personal computers, and cellular phones). After adjusting for sex and school year, data were analyzed by multivariate logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 2030 children completed this survey (response rate, 97.8%). Negative FA was associated with watching television more than 2 hours/day (OR = 1.51, 95% CI = 1.23-1.85), playing video games more than 30 minutes/day (1.50, 1.20-1.87), and using personal computers more than 30 minutes/day (1.35, 1.04-1.75). CONCLUSIONS: Time spent using IT devices affected the FA of children in kindergarten through junior high school. We propose the development of guidelines regarding the appropriate amount of time this population should spend using IT devices.
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Telefone Celular/estatística & dados numéricos , Emoções , Microcomputadores/estatística & dados numéricos , Televisão/estatística & dados numéricos , Jogos de Vídeo/estatística & dados numéricos , Vigília , Criança , Pré-Escolar , Intervalos de Confiança , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Razão de Chances , Inquéritos e Questionários , Fatores de TempoRESUMO
We investigated Candida albicans-induced mast cell degranulation in vitro and in vivo. Cell wall fraction but not culture supernatant and cell membrane fraction prepared from hyphally grown C. albicans induced ß-hexosaminidase release in RBL-2H3 cells. Cell wall mannan and soluble ß-glucan fractions also induced ß-hexosaminidase release. Histological examination of mouse forestomach showed that C. albicans gut colonization induces mast cell degranulation. However, intragastric administration of cell wall fraction failed to induce mast cell degranulation. We propose that cell wall polysaccharides are responsible for mast cell degranulation in the C. albicans-colonized gut.
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Members of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family participate in the innate immune system, exerting widespread effects on cytokine secretion, autophagy, and apoptosis. Recent studies in Caucasians revealed the association between mutants of NOD2, a member of the NLR family, and severity of acute graft-versus-host disease (GVHD). NOD2 polymorphism screening has been recommended for donor selection and risk assessment at bone marrow transplantation. To investigate whether NOD2 plays a role in the pathogenesis of GVHD in a Japanese population, we examined DNA from 142 bone marrow transplant patient/donor pairs to detect genetic variation in the NOD2 gene. No genetic variants of NOD2 were associated with the severity of acute GVHD in our patients. However, a weak association between a single nucleotide polymorphism in the NOD2 gene (R471C) and acute myeloid leukemia in the bone marrow patients (p = 0.029, odds ratio 4.08, 95% CI 1.22-13.67) was detected. This polymorphism was not prevalent in 479 Crohn's disease (CD) patients in Japan. These results suggest that, in the Japanese population, unlike the Caucasian, NOD2 is not a major contributor to susceptibility to severe acute GVHD.
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Predisposição Genética para Doença/genética , Doença Enxerto-Hospedeiro/genética , Proteína Adaptadora de Sinalização NOD2/genética , Alelos , Doença de Crohn/genética , Doença de Crohn/metabolismo , Regulação da Expressão Gênica , Genótipo , Células HEK293 , Humanos , Japão , Leucemia/genética , Leucemia/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
We examined whether Candida albicans gut colonization aggravates immune diseases in mice. Chronic and latent C. albicans gut colonization was established by the intragastric inoculation of C. albicans in mice fed as part of a purified diet. Allergic diarrhea was induced by repetitive intragastric administration of ovalbumin in sensitized BALB/c mice. Contact hypersensitivity was evaluated by measuring ear swelling after topical application of 2, 4-dinitrofluorobenzene in NC/Nga mice. Arthritis was induced by intradermal injection of bovine type-II collagen emulsified with complete Freund's adjuvant in DBA/1J mice. C. albicans gut colonization increased the incidence of allergic diarrhea, which was accompanied by gut hyperpermeability, as well as increased infiltration of inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by C. albicans gut colonization, as demonstrated by increased swelling, myeloperoxidase activity, and proinflammatory cytokines in ear auricles. Furthermore, C. albicans gut colonization promoted limb joint inflammation in collagen-induced arthritis, in an animal model of rheumatoid arthritis. These findings suggest that C. albicans gut colonization in mice aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues and underscores the necessity of investigating the pathogenic role of C. albicans gut colonization in immune diseases in humans.
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Candida albicans/patogenicidade , Candidíase/imunologia , Candidíase/patologia , Portador Sadio/imunologia , Portador Sadio/patologia , Trato Gastrointestinal/microbiologia , Animais , Doenças Autoimunes/patologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade/patologia , Inflamação/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBARESUMO
We recently found that dietary raffinose suppressed allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats. Using this model in the present study, we compared the efficacy of other oligosaccharides with that of raffinose. Brown Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt. 1, rats were fed a control diet or diets supplemented with different oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide, fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the fluid was significantly lower in rats fed raffinose and alpha-linked galactooligosaccharide diets than in those fed the control diet. Dietary fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia. In Expt. 2, i.p. administration of raffinose and alpha-linked galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide, suppressed airway eosinophilia in rats fed the control diet. In Expt. 3, suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide occurred in cecectomized rats administered neomycin. Reduced levels of interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the suppression of airway eosinophilia. We propose that indigestible oligosaccharides differ in their suppressive effect on allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats and that the effect appears not to be mediated by intestinal microflora.