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1.
Proc Natl Acad Sci U S A ; 120(31): e2308750120, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37487068

RESUMEN

Adipose tissue is central to regulation of energy homeostasis. Adaptive thermogenesis, which relies on mitochondrial oxidative phosphorylation (Ox-Phos), dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to type 2 diabetes and obesity. Here, we show that nuclear factor I-A (NFIA), a transcriptional regulator of brown and beige adipocytes, improves glucose homeostasis by upregulation of Ox-Phos and reciprocal downregulation of inflammation. Mice with transgenic expression of NFIA in adipocytes exhibited improved glucose tolerance and limited weight gain. NFIA up-regulates Ox-Phos and brown-fat-specific genes by enhancer activation that involves facilitated genomic binding of PPARγ. In contrast, NFIA in adipocytes, but not in macrophages, down-regulates proinflammatory cytokine genes to ameliorate adipose tissue inflammation. NFIA binds to regulatory region of the Ccl2 gene, which encodes proinflammatory cytokine MCP-1 (monocyte chemoattractant protein-1), to down-regulate its transcription. CCL2 expression was negatively correlated with NFIA expression in human adipose tissue. These results reveal the beneficial effect of NFIA on glucose and body weight homeostasis and also highlight previously unappreciated role of NFIA in suppressing adipose tissue inflammation.


Asunto(s)
Diabetes Mellitus Tipo 2 , Factores de Transcripción NFI , Humanos , Animales , Ratones , Adipocitos , Homeostasis , Inflamación , Tejido Adiposo Pardo , Citocinas
2.
J Infect Chemother ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39173741

RESUMEN

INTRODUCTION: Since the first report of a novel coronavirus infection caused by SARS-CoV-2 in late 2019, the infection has spread rapidly and had a significant impact on our lives. In the early stages of the COVID-19 pandemic, there was no adequate testing system in place, despite an urgent need for infection control measures in student dormitories. METHODS: We have been monitoring SARS-CoV-2 in wastewater as part of our infection control efforts in the university facilities since fall 2020. In the four dormitories, absorbent cotton was placed in the drains that the facility wastewater passed through, and samples were collected twice a week and processed by RT-PCR for SARS-CoV-2. The dormitory residents were informed of the monitoring results the next morning. RESULTS: The positivity of residents in the dormitories was highly consistent with the positivity of wastewater. Wastewater was positive in 89 % of cases before any residents were tested and found positive. Facility wastewater monitoring showed sensitivities of 80.4 % and specificities of 87.6 %. No traceable resident-to-resident transmission of infection within the facility was confirmed during the study period. CONCLUSION: Sampling a single wastewater outlet in a building for SARS-CoV-2 PCR can effectively indicate the presence or absence of COVID-19 cases and be very useful for infection control of a facility. This simple and effective monitoring is applicable to future outbreaks of both emerging and re-emerging infectious diseases.

3.
Blood ; 136(26): 3018-3032, 2020 12 24.
Artículo en Inglés | MEDLINE | ID: mdl-32992343

RESUMEN

Activating mutations in the Vav guanine nucleotide exchange factor 1 (VAV1) gene are reported in various subtypes of mature T-cell neoplasms (TCNs). However, oncogenic activities associated with VAV1 mutations in TCNs remain unclear. To define them, we established transgenic mice expressing VAV1 mutants cloned from human TCNs. Although we observed no tumors in these mice for up to a year, tumors did develop in comparably aged mice on a p53-null background (p53-/-VAV1-Tg), and p53-/-VAV1-Tg mice died with shorter latencies than did p53-null (p53-/-) mice. Notably, various TCNs with tendency of maturation developed in p53-/-VAV1-Tg mice, whereas p53-/- mice exhibited only immature TCNs. Mature TCNs in p53-/-VAV1-Tg mice mimicked a subtype of human peripheral T-cell lymphoma (PTCL-GATA3) and exhibited features of type 2 T helper (Th2) cells. Phenotypes seen following transplantation of either p53-/-VAV1 or p53-/- tumor cells into nude mice were comparable, indicating cell-autonomous tumor-initiating capacity. Whole-transcriptome analysis showed enrichment of multiple Myc-related pathways in TCNs from p53-/-VAV1-Tg mice relative to p53-/- or wild-type T cells. Remarkably, amplification of the Myc locus was found recurrently in TCNs of p53-/-VAV1-Tg mice. Finally, treatment of nude mice transplanted with p53-/-VAV1-Tg tumor cells with JQ1, a bromodomain inhibitor that targets the Myc pathway, prolonged survival of mice. We conclude that VAV1 mutations function in malignant transformation of T cells in vivo and that VAV1-mutant-expressing mice could provide an efficient tool for screening new therapeutic targets in TCNs harboring these mutations.


Asunto(s)
Transformación Celular Neoplásica , Neoplasias Hematológicas , Linfoma de Células T Periférico , Mutación , Proteínas Proto-Oncogénicas c-vav , Animales , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patología , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/metabolismo , Linfoma de Células T Periférico/patología , Ratones , Ratones Noqueados , Proteínas Proto-Oncogénicas c-vav/genética , Proteínas Proto-Oncogénicas c-vav/metabolismo , Proteína p53 Supresora de Tumor/deficiencia , Proteína p53 Supresora de Tumor/metabolismo
4.
Nutr Neurosci ; 25(12): 2528-2535, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34590989

RESUMEN

BACKGROUND: The hypothalamus receives ingested nutrient information via ascending gut-related projections and plays a significant role in the regulation of food intake. Human neuroimaging studies have observed changes in the activity or connectivity of the hypothalamus in response to nutrient ingestion. However, previous neuroimaging studies have not yet assessed differences in temporal changes of hypothalamic responses to various nutrients in humans. Thus a repeated measures functional magnetic resonance imaging (fMRI) study using 30-min scans was designed to examine differences in hypothalamic responses to various nutrients. METHODS: In this study, 18 healthy adults (mean age, 22.4 years; standard deviation, 4.8; age range, 19-39 years; 11 males and seven females) underwent fMRI sessions. On the day of each session, one of the four solutions (200 ml of monosodium glutamate, glucose, safflower oil emulsion, or saline) was administered to participants while fMRI scanning. RESULTS: Infused amino acid and glucose, but not lipid emulsion, increased lateral hypothalamic responses as compared to a saline infusion ([x, y, z] = [4, -4, -10], z = 2.96). In addition, only hypothalamic responses to saline, but not those to the infusion of other nutrients, elicited a subjective sensation of hunger. CONCLUSION: These findings suggest that lateral hypothalamic responses to ingested nutrients may mediate homeostatic sensations in humans.


Asunto(s)
Glucosa , Hipotálamo , Masculino , Adulto , Femenino , Humanos , Adulto Joven , Emulsiones , Hipotálamo/metabolismo , Imagen por Resonancia Magnética/métodos , Nutrientes
5.
J Infect Chemother ; 28(2): 266-272, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34887175

RESUMEN

INTRODUCTION: The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. METHODS: From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. RESULTS: After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. CONCLUSIONS: In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Voluntarios Sanos , Humanos , Inmunoglobulina G , Inmunoglobulina M , Estudios Seroepidemiológicos
6.
AIDS Res Ther ; 18(1): 30, 2021 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-34044856

RESUMEN

BACKGROUND: Antiretrovirals, including tenofovir, can suppress human immunodeficiency virus (HIV) infection but cannot completely eradicate it. Patients with HIV infection are administered antiretroviral drugs over a long term; thus, managing consequent adverse drug reactions, such as renal dysfunction and bone mineral loss, is important. Currently, highly sensitive biomarkers that can detect adverse drug reactions early have not been well studied. METHODS: This single-center, prospective, observational study explored changes in the biomarkers of renal function, bone metabolism, and lipid profile before and after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with HIV infection. RESULTS: All 31 enrolled patients had been treated with antiretrovirals for more than 5 years. The rate of proteinuria decreased significantly after starting TAF-containing antiretroviral regimen. The urinary liver-type fatty acid binding protein (L-FABP)/creatinine ratio was significantly decreased at 3 and 6 months after switching to TAF compared with that before switching to TAF (- 0.5 µg/g Cr at 3 months, and - 0.8 µg/g Cr at 6 months; p < 005 for both at 3 and 6 months). The urinary N-terminal telopeptide (NTx)/creatinine ratio decreased over the study period, and the ratios were significantly different between 3 and 6 months (- 11 nmol/mmol Cr at 3 months, - 15.2 nmol/mmol Cr at 6 months; p = 0.0069 at 3 months, p < 0.0001 at 6 months). Low density lipoprotein-cholesterol level significantly increased at 3 (+ 26 mg/dL) and 6 months (+ 13 mg/dL) compared with that at the baseline (p < 0.0001). CONCLUSIONS: Switching from TDF to TAF decreased the levels of renal and bone biomarkers, such as urinary L-FABP and NTx, but increased low density lipoprotein-cholesterol levels. Future studies should evaluate if these biomarkers, such as urinary L-FABP and NTx, truly detect serious adverse drug reactions early.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Alanina , Fármacos Anti-VIH/efectos adversos , Biomarcadores , Fumaratos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Riñón/fisiología , Lípidos , Estudios Prospectivos , Tenofovir/efectos adversos , Tenofovir/análogos & derivados
7.
J Infect Chemother ; 27(9): 1342-1349, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34158239

RESUMEN

INTRODUCTION: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to date. Given that some of the patients with coronavirus disease 2019 (COVID-19) are asymptomatic, antibody tests are useful to determine whether there is a previous infection with SARS-CoV-2. In this study, we measured IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects in The University of Tokyo, Japan. METHODS: From June 2020, we recruited participants, who were students, staff, and faculty members of The University of Tokyo in the project named The University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS). Following blood sample collection, participants were required to answer an online questionnaire about their social and health information. We measured IgG and IgM titers against SARS-CoV-2 using iFlash-SARS-CoV-2 IgM and IgG detection kit which applies a chemiluminescent immunoassay (CLIA) for the qualitative detection. RESULTS: There were 6609 volunteers in this study. After setting the cutoff value at 10 AU/mL, 32 (0.48%) were positive for IgG and 16 (0.24%) for IgM. Of six participants with a history of COVID-19, five were positive for IgG, whereas all were negative for IgM. The median titer of IgG was 0.40 AU/mL and 0.39 AU/mL for IgM. Both IgG and IgM titers were affected by gender, age, smoking status, and comorbidities. CONCLUSIONS: Positive rates of IgG and IgM titers were relatively low in our university. Serum levels of these antibodies were affected by several factors, which might affect the clinical course of COVID-19.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Estudios Epidemiológicos , Humanos , Inmunoglobulina G , Inmunoglobulina M , Japón/epidemiología
8.
Clin Exp Nephrol ; 24(2): 151-156, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31734818

RESUMEN

BACKGROUND: Urine dipstick tests are often used to evaluate proteinuria during health checkups. We examined the dipstick's accuracy in assessing the proteinuria levels among Japanese workers. METHODS: We assessed subjects aged ≥ 18 years who had a health checkup at the University of Tokyo in 2016 or 2017 (n = 5383). Proteinuria was stratified by urine protein-to-creatinine ratio (PCR): A1, < 150 mg/gCre; A2, 150-499 mg/gCre; and A3, ≥ 500 mg/gCre. The accuracy of a dipstick result of ± or higher to detect a PCR level of ≥ A2 was examined. We compared changes in dipstick results and PCR level in 136 subjects evaluated twice with a median interval of 119 days. RESULTS: The subjects' mean age was 40 years, and half were women. The dipstick results were - in 94.9%, ± in 4.1%, and ≥ 1 + in 1.0%. The PCR level was A1, A2, A3 in 98.6%, 1.2%, and 0.2% of the subjects, respectively. The sensitivity, specificity, and positive and negative predictive values of a ± or higher dipstick result to detect A2 or higher were 66.2%, 95.6%, 17.5%, and 99.5%, respectively. Among the 136 subjects examined twice, 134 (98.5%) had no change in PCR level (A1 in all cases) despite a decrease or increase in dipstick results. CONCLUSION: Urine dipstick results of ± or above had a high specificity but low sensitivity and positive predictive value to detect PCR proteinuria of A2 or higher. Confirmation by quantitative protein measurement should be recommended for individuals at high risk of chronic kidney disease.


Asunto(s)
Salud Laboral , Proteinuria/diagnóstico , Tiras Reactivas , Insuficiencia Renal Crónica/diagnóstico , Urinálisis/instrumentación , Biomarcadores/orina , Creatinina/orina , Humanos , Valor Predictivo de las Pruebas , Proteinuria/epidemiología , Proteinuria/orina , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/orina , Reproducibilidad de los Resultados , Tokio/epidemiología
9.
Respir Res ; 20(1): 138, 2019 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-31277661

RESUMEN

Although pleural thickening is a common finding on routine chest X-rays, its radiological and clinical features remain poorly characterized. Our investigation of 28,727 chest X-rays obtained from annual health examinations confirmed that pleural thickening was the most common abnormal radiological finding. In most cases (92.2%), pleural thickening involved the apex of the lung, particularly on the right side; thus, it was defined as a pulmonary apical cap. Pleural thickening was more common in males than in females and in current smokers or ex-smokers than in never smokers. The prevalence increased with age, ranging from 1.8% in teenagers to 9.8% in adults aged 60 years and older. Moreover, pleural thickening was clearly associated with greater height and lower body weight and body mass index, suggesting that a tall, thin body shape may predispose to pleural thickening. These observations allowed us to speculate about the causative mechanisms of pleural thickening that are attributable to disproportionate perfusion, ventilation, or mechanical forces in the lungs.


Asunto(s)
Radiografías Pulmonares Masivas/métodos , Pleura/diagnóstico por imagen , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/epidemiología , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Humanos , Masculino , Radiografías Pulmonares Masivas/normas , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/normas , Adulto Joven
10.
J Infect Chemother ; 23(6): 410-414, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28188094

RESUMEN

Kodamaea ohmeri is a rare yeast pathogen that has recently emerged as an important cause of fungemia in immunocompromised patients. However, appropriate therapy for this infection remains unclear. We report a case of catheter-related blood stream infection caused by K. ohmeri in a 58-year-old patient who improved after removal of the central venous catheter and administration of micafungin. Considering the antibiotic susceptibility of this pathogen and reviewing literature, echinocandins may be the first choice for an empiric therapy for this pathogen.


Asunto(s)
Bacteriemia , Infecciones Relacionadas con Catéteres , Micosis , Saccharomycetales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Equinocandinas/farmacología , Equinocandinas/uso terapéutico , Femenino , Humanos , Lipopéptidos/farmacología , Lipopéptidos/uso terapéutico , Micafungina , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Saccharomycetales/efectos de los fármacos , Saccharomycetales/genética
11.
BMC Pulm Med ; 17(1): 177, 2017 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-29216862

RESUMEN

BACKGROUND: Patients with primary spontaneous pneumothorax (PSP) usually complain of sudden-onset dyspnea and pleuritic chest pain. However, asymptomatic PSP has been incidentally detected on chest X-rays. In this study, we analyzed the incidence, characteristics, risk factors, and prognosis of asymptomatic PSP detected during regular medical check-ups in university students. METHODS: In this study, 101,709 chest X-rays were performed during medical check-ups for students at the University of Tokyo between April 2011 and March 2016. Among them, 43 cases of asymptomatic PSP (0.042%) were detected. We calculated the lung collapse rate of pneumothorax using Kircher's method. We also analyzed risk factors associated with asymptomatic PSP using characteristics inspected in medical check-ups. RESULTS: The incidence of asymptomatic PSP was significantly higher in men than in women (0.050% vs 0.018%). Multivariate analysis revealed an association of younger age, greater height, lower body mass index, and greater height growth per year with an increased risk of asymptomatic PSP in male students. Mild lung collapse (<10%) was present in 22 of 43 students with asymptomatic PSP; among these, eight students eventually underwent an invasive therapy. CONCLUSIONS: The prevalence of asymptomatic PSP among university students was as high as 0.042%. In addition to known risk factors for conventional PSP, greater height growth was a risk factor for asymptomatic PSP. Careful follow-up is very important because a considerable number of patients with mild lung collapse eventually require an invasive medical procedure.


Asunto(s)
Enfermedades Asintomáticas/epidemiología , Neumotórax/epidemiología , Adolescente , Factores de Edad , Estatura , Índice de Masa Corporal , Femenino , Humanos , Incidencia , Hallazgos Incidentales , Japón/epidemiología , Modelos Logísticos , Masculino , Análisis Multivariante , Neumotórax/diagnóstico por imagen , Prevalencia , Radiografía Torácica , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Estudiantes , Universidades , Adulto Joven
12.
J Infect Chemother ; 21(12): 868-72, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26298039

RESUMEN

Lymphocytic interstitial pneumonia (LIP) is a rare opportunistic illness in human immunodeficiency virus (HIV)-infected adults, although it is relatively common among HIV-infected children. Most adult cases have been reported in African and Afro-Caribbean patients and few cases have been reported from Asia. Acute exacerbation of HIV-related LIP has not been well described. Here we report a pathologically proven case of acute exacerbation of adult-onset HIV-related LIP. The patient was an African immigrant living in Japan who presented with chronic dyspnea and diffuse bilateral pulmonary infiltrates. His clinical, radiological, and pathological findings were consistent with those of LIP. After a diagnostic surgical lung biopsy, his hypoxemia and pulmonary infiltrates exacerbated rapidly over a few days, although his condition had not progressed during the previous year. LIP may be an important differential diagnosis among adult patients in Asian countries, especially patients of non-Asian ethnicity.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/virología , Esteroides/uso terapéutico , Humanos , Japón , Masculino , Persona de Mediana Edad
13.
J Clin Med ; 13(20)2024 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-39458036

RESUMEN

Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: "1 time or less", "twice", and "3 times or more". For the duration of each toothbrushing session, they were classified into three groups: "1 min or less", "2-3 min", and "4 min or more". A statistical analysis was performed by Pearson's χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366-0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578-0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567-0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health.

14.
Sci Rep ; 14(1): 25091, 2024 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-39443615

RESUMEN

Alcohol consumption increases oxidative stress and imbalances in the antioxidant system, even with ethanol (EtOH) exposure at a young age. This study assessed changes in the antioxidant system following young EtOH exposure in peripheral immunity and measured sensitive indicators of heavy alcohol consumption. We used peripheral blood mononuclear cells (PBMCs) from 197 male university students without smoking habits to examine changes in antioxidant-related gene expression in vitro and in PBMCs. In vitro, the antioxidant system was impaired by EtOH. Next, we examined the expression of 84 antioxidant-related genes in the PBMCs of 162 young adults, among which the superoxide dismutase (SOD) 1 expression was most negatively correlated with alcohol consumption degree. The plasma SOD1 level had the highest area under the curve value (0.806) for heavy alcohol consumption. Our data demonstrated that a decreased SOD1 level is a sensitive indicator of an impaired antioxidant system and heavy alcohol consumption with early EtOH exposure.


Asunto(s)
Consumo de Bebidas Alcohólicas , Antioxidantes , Etanol , Leucocitos Mononucleares , Superóxido Dismutasa-1 , Humanos , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Masculino , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Adulto Joven , Consumo de Bebidas Alcohólicas/efectos adversos , Antioxidantes/metabolismo , Estrés Oxidativo/efectos de los fármacos , Adulto , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/sangre , Superóxido Dismutasa/genética
15.
Eur J Prev Cardiol ; 31(10): 1277-1285, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-38386694

RESUMEN

AIMS: The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes. METHODS AND RESULTS: Using the UK Biobank cohort, we investigated the effect of type 2 diabetes genetic risk-physical activity interaction on three-point and four-point major adverse cardiovascular events (MACE), in 25 701 diabetic participants. We used a polygenic risk score for type 2 diabetes (PRS_T2D) as a measure of genetic risk for type 2 diabetes. We observed a significant interaction between PRS_T2D and physical activity on cardiovascular outcomes (three-point MACE: P trend for interaction = 0.0081; four-point MACE: P trend for interaction = 0.0037). Among participants whose PRS_T2D was in the first or second quartile, but not in the third or fourth quartile, each 10 metabolic equivalents (METs) hours per week of physical activity decreased the risk of three-point or four-point MACE. Furthermore, restricted cubic spline analysis indicated that intense physical activity (>80 METs hours per week, which was self-reported by 12.7% of participants) increased the risk of cardiovascular outcomes among participants whose PRS_T2D was in the fourth quartile. Sub-group analysis suggested that negative impact of intense physical activity was observed only in non-insulin users. CONCLUSION: The beneficial effect of physical activity on cardiovascular outcomes disappeared among those with high genetic risk for type 2 diabetes.


The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, whether genetic risk for type 2 diabetes influences the effect of physical activity on cardiovascular outcomes in individuals with diabetes remains elusive. We aimed to investigate interaction between genetic risk for type 2 diabetes and physical activity on major adverse cardiovascular events (MACE) in individuals with diabetes.The beneficial effect of physical activity on cardiovascular outcomes disappeared among diabetic individuals with high genetic risk for type 2 diabetes, due to significant gene­environment interaction; in this subpopulation, intense physical activity was associated with increased risk of cardiovascular outcomes.Personalized exercise recommendations tailored to avoid excessively intense exercise, in combination with genetic screening of high-risk individuals, would be required.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Ejercicio Físico , Predisposición Genética a la Enfermedad , Humanos , Diabetes Mellitus Tipo 2/genética , Masculino , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/genética , Femenino , Persona de Mediana Edad , Medición de Riesgo , Anciano , Reino Unido/epidemiología , Herencia Multifactorial , Conducta de Reducción del Riesgo , Factores de Riesgo , Adulto , Factores Protectores , Factores de Riesgo de Enfermedad Cardiaca
16.
PLOS Digit Health ; 3(3): e0000460, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38489375

RESUMEN

The purpose of this study is to demonstrate the use of a deep learning model in quantitatively evaluating clinical findings typically subject to uncertain evaluations by physicians, using binary test results based on routine protocols. A chest X-ray is the most commonly used diagnostic tool for the detection of a wide range of diseases and is generally performed as a part of regular medical checkups. However, when it comes to findings that can be classified as within the normal range but are not considered disease-related, the thresholds of physicians' findings can vary to some extent, therefore it is necessary to define a new evaluation method and quantify it. The implementation of such methods is difficult and expensive in terms of time and labor. In this study, a total of 83,005 chest X-ray images were used to diagnose the common findings of pleural thickening and scoliosis. A novel method for quantitatively evaluating the probability that a physician would judge the images to have these findings was established. The proposed method successfully quantified the variation in physicians' findings using a deep learning model trained only on binary annotation data. It was also demonstrated that the developed method could be applied to both transfer learning using convolutional neural networks for general image analysis and a newly learned deep learning model based on vector quantization variational autoencoders with high correlations ranging from 0.89 to 0.97.

17.
Intern Med ; 63(4): 565-569, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-37380455

RESUMEN

Human immunodeficiency virus (HIV)-associated neuropathy is a common complication of HIV infection and has several clinical subtypes. HIV-associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating neuropathy whose clinical features are known to differ from those of CIDP in the HIV-uninfected population. We herein report a case of CIDP in an HIV-infected patient who was finally diagnosed with anti-neurofascin 155 (NF155) antibody-positive neuropathy. The clinical features, including clinical findings and therapeutic responses, were typical of paranodal antibody-mediated neuropathy. To our knowledge, this is the first case of anti-NF155 antibody-associated neuropathy in an HIV-infected patient.


Asunto(s)
Infecciones por VIH , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/complicaciones , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , VIH , Infecciones por VIH/complicaciones , Autoanticuerpos , Moléculas de Adhesión Celular/uso terapéutico , Factores de Crecimiento Nervioso
18.
Artículo en Inglés | MEDLINE | ID: mdl-36900877

RESUMEN

BACKGROUND: In our previous study, international university students showed a significantly higher dental caries morbidity rate than domestic students. On the other hand, the periodontal health status of international university students has not been clarified yet. In this study, we compared the periodontal health status of international and domestic university students in Japan. METHODS: We conducted a retrospective review of the clinical data of the university students that visited a dental clinic in the division for health service promotion at a university in Tokyo for screening between April 2017 and March 2019. Bleeding on probing (BOP), calculus deposition and probing pocket depth (PPD) were investigated. RESULTS: The records of 231 university students (79 international and 152 domestic university students) were analyzed; 84.8% of international students were from Asian countries (n = 67). The international university students showed a higher percentage of BOP than domestic students (49.4% and 34.2%, respectively: p < 0.05) and they showed more extensive calculus deposition (calculus grading score [CGS]) than domestic university students (1.68 and 1.43, respectively: p < 0.01), despite no significant difference in PPD. CONCLUSIONS: The current study shows that international university students have poorer periodontal health than domestic students in Japan, even though the result might include many uncertainties and possible biases. To prevent severe periodontitis in the future, regular checkups and thorough oral health care are essential for the university students, especially those from foreign countries.


Asunto(s)
Caries Dental , Humanos , Japón , Universidades , Estudiantes , Estado de Salud
19.
Sci Rep ; 13(1): 9607, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37311763

RESUMEN

Several clinical trials have shown that the humoral response produced by anti-spike antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines gradually declines. The kinetics, durability and influence of epidemiological and clinical factors on cellular immunity have not been fully elucidated. We analyzed cellular immune responses elicited by BNT162b2 mRNA vaccines in 321 health care workers using whole blood interferon-gamma (IFN-γ) release assays. IFN-γ, induced by CD4 + and CD8 + T cells stimulated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike epitopes (Ag2), levels were highest at 3 weeks after the second vaccination (6 W) and decreased by 37.4% at 3 months (4 M) and 60.0% at 6 months (7 M), the decline of which seemed slower than that of anti-spike antibody levels. Multiple regression analysis revealed that the levels of IFN-γ induced by Ag2 at 7 M were significantly correlated with age, dyslipidemia, focal adverse reactions to full vaccination, lymphocyte and monocyte counts in whole blood, Ag2 levels before the second vaccination, and Ag2 levels at 6 W. We clarified the dynamics and predictive factors for the long-lasting effects of cellular immune responses. The results emphasize the need for a booster vaccine from the perspective of SARS-CoV-2 vaccine-elicited cellular immunity.


Asunto(s)
Vacuna BNT162 , COVID-19 , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Inmunidad Celular , Interferón gamma , ARN Mensajero/genética
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