RESUMO
BACKGROUND: Associated factors for frailty development according to age group remain unclear. OBJECTIVES: To identify frailty score trajectories among community-dwelling older Japanese individuals and examine their associated factors. DESIGN: 13-year longitudinal study. SETTING: Kusatsu Town in Gunma Prefecture, Japan. PARTICIPANTS: 1706 older adults aged ≥ 65 years who completed an annual frailty assessment at least once between 2007 and 2019. MEASUREMENTS: Frailty status was determined using an index based on the Fried frailty phenotype criteria. Potential associated factors for frailty trajectory included physical, biological, lifestyle-related, and psychological factors, as well as comorbidities. RESULTS: We identified five trajectory patterns in the frailty score from age of 65 to 90 years -individuals who were robust (Group 1, 10.5%) as well as individuals with late-onset frailty (Group 2, 16.1%), middle-onset frailty (Group 3, 25.6% and Group 4, 35.2%), and early-onset frailty (Group 5, 12.7%). Compared with the other groups, the early-onset group showed a higher prevalence of cerebrovascular diseases, bone and joint diseases, poor nutrition, sarcopenia, hospitalization, low cognitive function, and smoking at the end of follow-up. Associated factors in the middle-onset group largely overlapped with those of the early-onset group. The late-onset frailty group tended to have a higher association with heart disease and bone and joint diseases compared with the robust group. CONCLUSION: Our findings from a 13-year longitudinal study identified five frailty trajectory patterns and seven associated factors for frailty trajectory. Proposed effective population-based frailty prevention strategies in each age group may contribute to effective strategies to extend healthy life expectancy in aging, aged, and super-aged communities.
Assuntos
Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Vida Independente , Humanos , Idoso , Masculino , Feminino , Japão/epidemiologia , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Idoso de 80 Anos ou mais , Estudos Longitudinais , Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Vida Independente/estatística & dados numéricos , Comorbidade , Fatores de Risco , Prevalência , População do Leste AsiáticoRESUMO
OBJECTIVES: To examine whether eating status and dietary variety were associated with functional disability during a 5-year follow-up analysis of older adults living in a Japanese metropolitan area. DESIGN: A 5-year follow-up study. SETTING: Ota City, Tokyo, Japan. PARTICIPANTS: A total of 10,308 community-dwelling non-disabled adults aged 65-84 years. MEASUREMENTS: Eating status was assessed using a self-reported questionnaire. Dietary variety was assessed using the dietary variety score (DVS). Based on the responses, participants were classified according to eating alone or together and DVS categories (low: 0-3; high: 4-10). Functional disability incidence was prospectively identified using the long-term care insurance system's nationally unified database. Multilevel survival analyses calculated the adjusted hazard ratio (HR) and 95% confidence interval (CI) for incident functional disability. RESULTS: During a 5-year follow-up, 1,991 (19.3%) individuals had functional disabilities. Eating status or DVS were not independently associated with incident functional disability. However, interaction terms between eating status and DVS were associated with functional disability; HR (95% CI) for eating together and low DVS was 1.00 (0.90-1.11), eating alone and high DVS was 0.95 (0.77-1.17), and eating alone and low DVS was 1.20 (1.02-1.42), compared to those with eating together and high DVS. CONCLUSION: Older adults should avoid eating alone or increase dietary variety to prevent functional disability. This can be ensured by providing an environment of eating together or food provision services for eating a variety of foods in the community.
Assuntos
Dieta , Pessoas com Deficiência , Idoso , Seguimentos , Alimentos , Humanos , Vida Independente , Japão/epidemiologiaRESUMO
OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.
OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.
Assuntos
Eriodictyon/química , Cor de Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adulto , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Eriodictyon/classificação , Feminino , Humanos , Técnicas In Vitro , Queratinócitos/efeitos da radiação , Masculino , Melaninas/biossíntese , Melaninas/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/metabolismo , Pele/efeitos dos fármacos , Especificidade da EspécieAssuntos
Placenta Acreta/diagnóstico por imagem , Placenta Prévia/diagnóstico por imagem , Placenta/irrigação sanguínea , Cesárea , Feminino , Humanos , Placenta/diagnóstico por imagem , Placenta Acreta/patologia , Placenta Prévia/patologia , Gravidez , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-NatalAssuntos
Retardo do Crescimento Fetal/diagnóstico por imagem , Placenta/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Placenta/irrigação sanguínea , Placenta/patologia , Gravidez , Trimestres da Gravidez , Ultrassonografia Doppler em CoresAssuntos
Ecocardiografia Quadridimensional/métodos , Coração Fetal/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Coração Fetal/anormalidades , Idade Gestacional , Humanos , Imageamento Tridimensional , Gravidez , Ultrassonografia Pré-NatalAssuntos
Doenças Fetais/diagnóstico por imagem , Hemangioma/diagnóstico por imagem , Imageamento Tridimensional/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia Pré-Natal/instrumentação , Adulto , Cesárea , Feminino , Hemangioma/embriologia , Humanos , Recém-Nascido , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/embriologia , Imageamento por Ressonância Magnética , Gravidez , Tomografia Computadorizada por Raios X , Ultrassonografia Doppler em CoresRESUMO
BACKGROUND: Multiple studies have noted an association between hepatitis C and psoriasis, but it is not known whether psoriasis is a result of treatment modalities for hepatitis C or a result of hepatitis C alone. OBJECTIVE: To examine the relationship between psoriasis and hepatitis C by measuring the expression of cathelicidin, TLR9 and IFNγ in psoriatic lesional and non-lesional skin in HCV-positive and negative psoriatic patients. METHODS: Two 2 mm punch biopsies of lesional and non-lesional skin in 10 patients who were HCV-negative psoriatics and seven HCV-positive psoriatics were used to measure cathelicidin, TLR9 and IFNγ mRNA expression by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). RESULTS: The mRNA levels of cathelicidin, TLR9 and IFNγ were significantly higher in both non-lesional and lesional skin of HCV-positive patients with psoriasis as compared to HCV-negative psoriatic patients. Additionally, the IFNγ level in lesional skin of HCV-positive psoriatic patients was higher than the IFNγ level seen in non-lesional skin of those same patients. CONCLUSION: These findings suggest that HCV infection upregulates these inflammatory cytokines, possibly increasing susceptibility to developing psoriasis.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Hepatite C/genética , Interferon gama/genética , Psoríase/genética , RNA Mensageiro/metabolismo , Receptor Toll-Like 9/genética , Adulto , Feminino , Expressão Gênica , Hepatite C/complicações , Hepatite C/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/complicações , Psoríase/metabolismo , Pele/metabolismo , CatelicidinasRESUMO
BACKGROUND: Although the serum adiponectin level is inversely correlated to body mass index and closely associated with obesity and related diseases, neither the impact of weight loss on the adiponectin level nor other factors that might influence the adiponectin level during weight loss intervention are well documented. OBJECTIVE: The objective of the study is to assess the change in the serum adiponectin level during weight loss intervention and to determine if sleep parameters affect the serum adiponectin level. METHODS: Ninety women with overweight or obesity aged 25 to 65 years completed a 7-month cognitive behavioural therapy based weight loss intervention that included dieting, exercise and stress management. Serum adiponectin level, body fat percent, symptoms of depression and anxiety and objective sleep parameters, assessed by actigraphy, were measured at baseline and at the end of the intervention. RESULTS: The serum adiponectin level was significantly increased after the weight loss intervention (P < 0.001). In a multiple regression analysis, the change of the adiponectin level was positively associated with the magnitude of body fat loss (ß = -0.317, P < 0.001) and an increase of sleep minutes (ß = 0.210, P = 0.043). CONCLUSION: An increase in objective sleep duration was related to a significantly increased serum adiponectin level independently of the change of body fat during the weight loss intervention.
RESUMO
Pharmacokinetic parameters were summarized in clinical bioequivalence studies in Japan to confirm the validity for the use of parameters obtained from the clinical studies. Pharmacokinetic parameters, including maximum plasma/serum concentrations (Cmax), area under the plasma/serum drug concentration-time curve (AUC), time to achieve Cmax (Tmax), and half life (t1/2), of the standard products (original drugs) after oral administration of antimicrobials, including respiratory quinolones, cephalosporins, macrolides, and penicillin-based antibiotics were investigated by use of interview forms and/or package inserts from the generic products and the relationship among the pharmacokinetic parameters such as Cmax, AUC, Tmax, and t1/2 were estimated. In all the studies, the standard and generic products were administrated orally to healthy fasting subjects. Although there was more than a 1.5-fold difference in the Cmax and AUC0-24 h, but not in the Tmax and t1/2 values for levofloxacin tablets and cefacrol tablets, these parameters for other antibiotics were similar in various studies. The obtained results suggested that the parameters obtained from recent bioequivalence studies would be useful in identifying pharmacokinetic behavior of the original drugs, especially early time release; however, the pharmacokinetic results obtained from the recently conducted bioequivalence studies may be superior to those obtained from studies conducted in the past.
Assuntos
Antibacterianos/farmacocinética , Medicamentos Genéricos/farmacocinética , Equivalência Terapêutica , Animais , Antibacterianos/uso terapêutico , Medicamentos Genéricos/uso terapêutico , Meia-Vida , HumanosAssuntos
Imageamento Tridimensional/métodos , Tumor de Krukenberg/diagnóstico por imagem , Segunda Neoplasia Primária/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Idoso , Neoplasias da Mama/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Histerectomia , Tumor de Krukenberg/cirurgia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/cirurgia , Neoplasias Ovarianas/cirurgiaAssuntos
Falso Aneurisma/diagnóstico por imagem , Complicações Cardiovasculares na Gravidez/diagnóstico por imagem , Artéria Uterina , Adulto , Falso Aneurisma/diagnóstico , Cesárea , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-NatalAssuntos
Atresia Intestinal/diagnóstico por imagem , Jejuno/anormalidades , Ultrassonografia Pré-Natal , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Atresia Intestinal/diagnóstico , Jejuno/diagnóstico por imagem , Masculino , Gravidez , Terceiro Trimestre da Gravidez , Adulto JovemRESUMO
BACKGROUND: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers. METHODS: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry. RESULTS: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. CONCLUSIONS: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
Assuntos
Neoplasias Colorretais/genética , Genes Supressores de Tumor , Proteínas Mitocondriais/fisiologia , Sirtuínas/fisiologia , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Progressão da Doença , Glutamina/metabolismo , Células HCT116 , Células HT29 , Humanos , Invasividade Neoplásica , Prognóstico , Células Tumorais CultivadasRESUMO
Islet autotransplantation following total pancreatectomy differs from allograft transplantation with respect to the requirement of biliary reconstruction. Although it is known that careful consideration should be given to postoperative cholestatic liver injury after biliary reconstruction, its direct effects on transplanted islets have not been completely elucidated. In this study, we developed a murine model of postoperative cholestatic liver injury after biliary reconstruction with islet autotransplantation that involved syngeneic intraportal islet transplantation into chemically induced diabetic mice and common bile duct ligation. We assessed the viability and function of the transplanted islets. The impaired viability of transplanted islets and increased blood glucose levels indicated restoration of the diabetic state after common bile duct ligation in this murine model. Furthermore, impaired islet viability and function occurred earlier in the transplanted islets than in the surrounding liver tissues, which was consistent with the faster and higher expression of oxidative stress markers in the transplanted islets. Transplanted islets may be more vulnerable to oxidative stress caused by cholestatic liver injury than the surrounding liver tissue. Therefore, patients should be intensively managed after total pancreatectomy with islet autotransplantation to preserve viability and function of the transplanted islets.
Assuntos
Sistema Biliar/fisiopatologia , Colestase/prevenção & controle , Ilhotas Pancreáticas/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse OxidativoRESUMO
BACKGROUND: A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. PATIENTS AND METHODS: Patients were randomly assigned to receive FOLFIRI plus bevacizumab 5 or 10 mg/kg in 2-week cycles until disease progression. The primary end point was progression-free survival (PFS), and secondary end points included overall survival (OS), time to treatment failure (TTF), and safety. RESULTS: Three hundred and eighty-seven patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n = 181 and 10 mg/kg, n = 188). Safety was evaluated in 365 patients (5 mg/kg, n = 180 and 10 mg/kg, n = 185). The median PFS was 6.1 versus 6.4 months (hazard ratio, 0.95; 95% confidence interval [CI] 0.75-1.21; P = 0.676), and median TTF was 5.2 versus 5.2 months (hazard ratio, 1.01; 95% CI 0.81-1.25; P = 0.967), respectively, for the bevacizumab 5 and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. CONCLUSION: Bevacizumab 10 mg/kg plus FOLFIRI as the second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. CLINICAL TRIAL IDENTIFIER: UMIN000002557.