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We report the properties of an A-site spinel magnet, CoAl2-xGaxO4, and analyze its anomalous, low-temperature magnetic behavior, which is derived from inherent, magnetically frustrated interactions. Rietveld analysis of the x-ray diffraction profile for CoAl2-xGaxO4revealed that the metallic ions were randomly distributed in the tetrahedral (A-) and octahedral (B-) sites in the cubic spinel structure. The inversion parameterηcould be controlled by varying the gallium (Ga) composition in the range 0.055 ⩽η⩽ 0.664. The composition-induced Néel-to-spin-glass (NSG) transition occurred between 0.05 ⩽η⩽ 0.08 and was verified by measurements of DC-AC susceptibilitiesχand thermoremanent magnetization (TRM) below the Néel transition temperatureTN. The relaxation rate and derivative with respect to temperature of TRM increased at bothTNand the spin glass (SG) transition temperatureTSG. The TRM decayed rapidly above and below these transitions. TRM was highly sensitive to macroscopic magnetic transitions that occurred in both the Néel and SG phases of CoAl2-xGaxO4. In the vicinity of the NSG boundary, there was a maximum of the TRM relaxation rate atTmax
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Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. INTRODUCTION: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. RESULTS: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. CONCLUSIONS: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. TRIAL REGISTRATION NUMBER: The present study is not registered.
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Conservadores de la Densidad Ósea , Demencia , Fracturas de Cadera , Osteoporosis , Médicos , Conservadores de la Densidad Ósea/efectos adversos , Femenino , Glucocorticoides/efectos adversos , Adhesión a Directriz , Humanos , Seguro de Salud , Japón/epidemiología , Masculino , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiologíaRESUMEN
AIMS: The aim of this study was to obtain cold-adapted denitrifying fungi that could be used for bioaugmentation in woodchip bioreactors to remove nitrate from agricultural subsurface drainage water. METHODS AND RESULTS: We isolated a total of 91 nitrate-reducing fungal strains belonging to Ascomycota and Mucoromycota from agricultural soil and a woodchip bioreactor under relatively cold conditions (5 and 15°C). When these strains were incubated with 15 N-labelled nitrate, 29 N2 was frequently produced, suggesting the occurrence of co-denitrification (microbially mediated nitrosation). Two strains also produced 30 N2 , indicating their ability to reduce N2 O. Of the 91 nitrate-reducing fungal strains, fungal nitrite reductase gene (nirK) and cytochrome P450 nitric oxide reductase gene (p450nor) were detected by PCR in 34 (37%) and 11 (12%) strains, respectively. Eight strains possessed both nirK and p450nor, further verifying their denitrification capability. In addition, most strains degraded cellulose under denitrification condition. CONCLUSIONS: Diverse nitrate-reducing fungi were isolated from soil and a woodchip bioreactor. These fungi reduced nitrate to gaseous N forms at relatively low temperatures. These cold-adapted, cellulose-degrading and nitrate-reducing fungi could support themselves and other denitrifiers in woodchip bioreactors. SIGNIFICANCE AND IMPACT OF THE STUDY: The cold-adapted, cellulose-degrading and nitrate-reducing fungi isolated in this study could be useful to enhance nitrate removal in woodchip bioreactors under low-temperature conditions.
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Celulosa/metabolismo , Desnitrificación , Hongos/enzimología , Hongos/genética , Nitratos/metabolismo , Óxidos de Nitrógeno/metabolismo , Nitrógeno/metabolismo , Agricultura , Biodegradación Ambiental , Reactores Biológicos/microbiología , Frío , ADN de Hongos/genética , Hongos/clasificación , Óxido Nítrico/metabolismo , Filogenia , ARN Ribosómico 18S/genética , ARN Ribosómico 28S/genética , Microbiología del Suelo , Agua/químicaRESUMEN
AIMS: This study was done to obtain denitrifiers that could be used for bioaugmentation in woodchip bioreactors to remove nitrate from agricultural subsurface drainage water. METHODS AND RESULTS: We isolated denitrifiers from four different bioreactors in Minnesota, and characterized the strains by measuring their denitrification rates and analysing their whole genomes. A total of 206 bacteria were isolated from woodchips and thick biofilms (bioslimes) that formed in the bioreactors, 76 of which were able to reduce nitrate at 15°C. Among those, nine potential denitrifying strains were identified, all of which were isolated from the woodchip samples. Although many nitrate-reducing strains were isolated from the bioslime samples, none were categorized as denitrifiers but instead as carrying out dissimilatory nitrate reduction to ammonium. CONCLUSIONS: Among the denitrifiers confirmed by 15 N stable isotope analysis and genome analysis, Cellulomonas cellasea strain WB94 and Microvirgula aerodenitrificans strain BE2.4 appear to be promising for bioreactor bioaugmentation due to their potential for both aerobic and anaerobic denitrification, and the ability of strain WB94 to degrade cellulose. SIGNIFICANCE AND IMPACT OF THE STUDY: Denitrifiers isolated in this study could be useful for bioaugmentation application to enhance nitrate removal in woodchip bioreactors.
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Agricultura/métodos , Reactores Biológicos/microbiología , Desnitrificación , Purificación del Agua/métodos , Madera/microbiología , Betaproteobacteria/aislamiento & purificación , Betaproteobacteria/metabolismo , Biodegradación Ambiental , Cellulomonas/aislamiento & purificación , Cellulomonas/metabolismo , Minnesota , Nitratos/aislamiento & purificación , Nitratos/metabolismo , Madera/metabolismoRESUMEN
We assessed whether a bone resorption marker, measured early in the menopause transition (MT), is associated with change in femoral neck size and strength during the MT. Higher levels of bone resorption were associated with slower increases in femoral neck size and faster decreases in femoral neck strength. PURPOSE: Composite indices of the femoral neck's ability to withstand compressive (compression strength index, CSI) and impact (impact strength index, ISI) forces integrate DXA-derived femoral neck width (FNW), bone mineral density (BMD), and body size. During the menopause transition (MT), FNW increases, and CSI and ISI decrease. This proof-of-concept study assessed whether a bone resorption marker, measured early in the MT, is associated with rates of change in FNW, CSI and ISI during the MT. METHODS: We used previously collected bone resorption marker (urine collagen type I N-telopeptide [U-NTX]) and femoral neck strength data from 696 participants from the Study of Women's Health Across the Nation (SWAN), a longitudinal study of the MT in a multi-ethnic cohort of community-dwelling women. RESULTS: Adjusted for MT stage (pre- vs. early perimenopause), age, body mass index (BMI), bone resorption marker collection time, and study site in multivariable linear regression, bone resorption in pre- and early perimenopause was not associated with transmenopausal decline rate in femoral neck BMD. However, each standard deviation (SD) increase in bone resorption level was associated with 0.2% per year slower increase in FNW (p = 0.03), and 0.3% per year faster declines in CSI (p = 0.02) and ISI (p = 0.01). When restricted to women in early perimenopause, the associations of bone resorption with change in FNW, CSI, and ISI were similar to those in the full sample. CONCLUSIONS: Measuring a bone resorption marker in pre- and early perimenopause may identify women who will experience the greatest loss in bone strength during the MT.
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Resorción Ósea/fisiopatología , Cuello Femoral/fisiopatología , Menopausia/fisiología , Adulto , Envejecimiento/fisiología , Envejecimiento/orina , Biomarcadores/orina , Fenómenos Biomecánicos/fisiología , Densidad Ósea/fisiología , Colágeno Tipo I/orina , Femenino , Cuello Femoral/patología , Humanos , Estudios Longitudinales , Menopausia/orina , Persona de Mediana Edad , Péptidos/orina , Valor Predictivo de las Pruebas , Pronóstico , Prueba de Estudio ConceptualRESUMEN
BACKGROUND: Macrophage phagocytosis constitutes an essential part of the host defence against microbes and the resolution of inflammation. Hyperglycaemia during sepsis is reported to reduce macrophage function, and thus, potentiate inflammatory deterioration. We investigated whether high-glucose concentrations augment lipopolysaccharide-induced reduction in macrophage phagocytosis via the endoplasmic stress-C/EBP homologous protein (CHOP) pathway using animal and laboratory investigations. METHODS: Peritoneal macrophages of artificially ventilated male Wistar rats, divided into four groups based on target blood glucose concentrations achieved by glucose administration with or without lipopolysaccharide, were obtained after 24 h. Human macrophages were also cultured in normal or high glucose with or without lipopolysaccharide exposure for 72 h. Changes in the phagocytic activity, intranuclear CHOP expression, and intracellular Akt phosphorylation status of macrophages were evaluated. These changes were also evaluated in human macrophages after genetic knock-down of CHOP by specific siRNA transfection or resolvin D2 treatment. RESULTS: Lipopolysaccharide impaired phagocytosis, increased intranuclear expression of CHOP, and inhibited Akt phosphorylation in both rat peritoneal and human macrophages. Hyperglycaemic glucose concentrations augmented these changes. Genetic knock-down of CHOP restored phagocytic ability and Akt phosphorylation in human macrophages. Furthermore, resolvin D2 co-incubation restored the inhibited phagocytosis and Akt phosphorylation along with the inhibition of intranuclear CHOP expression in human macrophages. CONCLUSIONS: These findings imply that controlling endoplasmic reticulum stress might provide new strategies for restoring reduced macrophage phagocytosis in sepsis-induced hyperglycaemia.
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Hiperglucemia/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/metabolismo , Fagocitosis/fisiología , Factor de Transcripción CHOP/metabolismo , Adulto , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/genética , Humanos , Masculino , Ratas , Ratas Wistar , Transducción de Señal , Factor de Transcripción CHOP/genéticaRESUMEN
Using the nationwide health insurance claims database, we found that the age-standardized hip fracture incidence rates in Japan indicated significant increase in males but no significant change in females during 2012-2015. The fracture risk in subjects aged 75-84 years indicated decrease in females but no change in males. INTRODUCTION: Nationwide registry data on hip fractures have not yet been established in Japan. Using the newly developed National Database of Health Insurance Claims (NDB), which covers the entire Japanese population, we investigated the incidence rates of hip fractures and the associated regional differences. We also assessed the frequency of osteoporosis prescriptions, bone turnover marker (BTM) level, and bone mineral density (BMD) measurements. METHODS: The annual numbers of hip fractures, osteoporosis prescriptions, and BTM level and BMD measurements by prefecture from 2012 to 2015 were obtained from NDB data. We calculated the standardized claims-data ratio (SCR) in each prefecture. RESULTS: The age-standardized incidence rates from 2012 to 2015 indicated no significant change in females and significant increase in males (p value for trend; 0.920, 0.002, respectively). The fracture risk decreased in females aged 75-84 years and indicated no increase in females aged 85-89 years during 2012-2015, while the fracture risk indicated no change in males aged 75-84 years and increased in males aged 85-89 years. The frequency of osteoporosis prescriptions, BTM level measurements, and BMD measurements in the general population in the corresponding period increased with statistical or marginal significance in females and males. West-east regional differences were observed in the incidence rates; the highest SCR values in the western prefectures were approximately double the lowest values in the eastern prefectures. CONCLUSIONS: The age-standardized hip fracture incidence rates indicated no significant change in females and significant increase in males in Japan from 2012 to 2015.
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Fracturas de Cadera/epidemiología , Fracturas Osteoporóticas/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/fisiología , Bases de Datos Factuales , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Fracturas de Cadera/fisiopatología , Fracturas de Cadera/prevención & control , Humanos , Incidencia , Japón/epidemiología , Masculino , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Fracturas Osteoporóticas/fisiopatología , Fracturas Osteoporóticas/prevención & control , Distribución por SexoAsunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Antígeno B7-H1/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Femenino , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacosRESUMEN
The extraction of mandibular third molars can lead to injury to the inferior alveolar nerve. Hence, it is important to assess the proximity of the root to the inferior alveolar canal before extraction. The classification system of Pell and Gregory and the Winter classification are commonly used to evaluate the positional relationship of the third molar based on radiographs. This retrospective study involving 105 mandibular third molars was performed to assess whether these systems reflect the proximity of the root to the canal (based on computed tomography images), and to identify risk factors for nerve injury. Regarding the prediction of computed tomography-verified canal invasion, the sensitivity, specificity, and positive and negative predictive values were high for each Pell and Gregory category when there was radiographic evidence. The mean distance of invasion was significantly greater in class III than in class I. However, there were no significant differences between the Winter inclination categories. The mean distance differed significantly between a horizontal inclination angle to the buccal side of >5° and an angle of ≤5°. Thus, a horizontal inclination angle >5° represents a novel risk factor for nerve injury.
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Mandíbula/cirugía , Nervio Mandibular/anatomía & histología , Tercer Molar/cirugía , Extracción Dental , Diente Impactado/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Nervio Mandibular/diagnóstico por imagen , Persona de Mediana Edad , Tercer Molar/diagnóstico por imagen , Radiografía Panorámica , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X , Diente Impactado/diagnóstico por imagen , Traumatismos del Nervio TrigéminoRESUMEN
OBJECTIVE: We recently reported that eating glutinous brown rice (GBR) for 1 day improved the whole-day glucose profile and postprandial plasma glucose level compared with eating white rice (WR) or standard brown rice. However, it was unknown whether eating GBR could maintain improvement of glycemic control for a longer period. Therefore, we evaluated the effect of GBR intake for 8 weeks on glycemic control in outpatients with diabetes mellitus. METHODS: This was an open-label randomized crossover study in outpatients with type 2 diabetes. Among the 18 subjects registered in this study, 2 were excluded from analysis. After a 1-week observation period while eating WR twice a day, the patients were randomly assigned to two groups. One group ate GBR as a staple food twice a day for 8 weeks and then switched to WR for the next 8 weeks, while the other group ate WR first and then switched to GBR. A mixed meal tolerance test was performed at baseline and after 8 and 16 weeks of dietary intervention to evaluate plasma glucose and serum C-peptide. RESULTS: None of the subjects failed to complete the study because of disliking the taste of GBR. Hemoglobin A1c (7.5-7.2%, P=0.014) and glycoalbumin (20.4-19.4%, P=0.029) both decreased significantly when the patients were eating GBR. Additionally, the 30-min postprandial plasma glucose level (194-172 mg dl-1, P=0.031) and the incremental area under the concentration vs time curve of serum C-peptide (31.3-22.1 ng min ml-1, P=0.023) during the mixed meal tolerance test were also decreased significantly by intake of GBR. In contrast, there were no changes of glycemic control during the WR period. CONCLUSIONS: We confirmed that GBR was well tolerated for 8 weeks and improved glycemic control in patients with type 2 diabetes.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/dietoterapia , Dieta , Alimentos , Oryza , Anciano , Péptido C/sangre , Estudios Cruzados , Diabetes Mellitus Tipo 2/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Escherichia coli is classified as a rod-shaped, Gram-negative bacterium in the family Enterobacteriaceae. The bacterium mainly inhabits the lower intestinal tract of warm-blooded animals, including humans, and is often discharged into the environment through faeces or wastewater effluent. The presence of E. coli in environmental waters has long been considered as an indicator of recent faecal pollution. However, numerous recent studies have reported that some specific strains of E. coli can survive for long periods of time, and potentially reproduce, in extraintestinal environments. This indicates that E. coli can be integrated into indigenous microbial communities in the environment. This naturalization phenomenon calls into question the reliability of E. coli as a faecal indicator bacterium (FIB). Recently, many studies reported that E. coli populations in the environment are affected by ambient environmental conditions affecting their long-term survival. Large-scale studies of population genetics revealed the diversity and complexity of E. coli strains in various environments, which are affected by multiple environmental factors. This review examines the current knowledge on the ecology of E. coli strains in various environments with regard to its role as a FIB and as a naturalized member of indigenous microbial communities. Special emphasis is given on the growth of pathogenic E. coli in the environment, and the population genetics of environmental members of the genus Escherichia. The impact of environmental E. coli on water quality and public health is also discussed.
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Escherichia coli/aislamiento & purificación , Agua Dulce/microbiología , Animales , Escherichia coli/clasificación , Escherichia coli/genética , Escherichia coli/fisiología , Infecciones por Escherichia coli/microbiología , Heces/microbiología , Humanos , Salud Pública , Contaminación del AguaRESUMEN
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant. Using a microarray, we selected candidate radiation sensitivity marker genes by choosing genes whose expression was consistent with a radiation-resistant or sensitive cell phenotype. RESULTS: Among candidate genes, cellular retinol binding protein 1 (CRBP1) was of particular interest because it was not only induced in HCT116 cells by tentative 10 Gy radiation treatments, but also its expression was increased in HCT116-derived radiation-resistant cells vs parental cells. Forced expression of CRBP1 decreased the viability of both HCT15 and DLD-1 cells in response to radiation therapy. We also confirmed that CRBP1 was epigenetically silenced by hypermethylation of its promoter DNA, and that the quantitative methylation value of CRBP1 significantly correlated with histological response in RC patients with NCRT (P=0.031). CONCLUSIONS: Our study identified CRBP1 as a radiation-sensitive predictor in RC.
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Biomarcadores de Tumor/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica/efectos de la radiación , Regiones Promotoras Genéticas/genética , Tolerancia a Radiación/genética , Neoplasias del Recto/genética , Proteínas Celulares de Unión al Retinol/genética , Western Blotting , Proliferación Celular , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Proteínas Celulares de Unión al Retinol/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
Methylation of cysteine dioxygenase type 1 (CDO1) gene, a tumor suppressor gene, has been studied in various cancers; however, there is no information regarding Barrett esophagus cancer. In this study, the clinical significance of CDO1 methylation in Barrett esophagus adenocarcinoma (BEA) was clarified. CDO1 gene promoter methylation was analyzed for DNA from the patient's specimens using quantitative methylation-specific polymerase chain reaction. Thirty-eight BEA patients who underwent resection were identified between 2000 and 2014. Hypermethylation of CDO1 gene was demonstrated to be frequently recognized even at early stage in BEA by quantitative methylation-specific polymerase chain reaction. In BEA, there is a robust prognostic difference between stage I and stage II/III/IV with regard to 5-year relapse-free survival (P = 0.0016) and 5-year overall survival (P = 0.0024), and the tumor size separated by 7 cm was also a prognostic factor. There was significant difference in CDO1 gene methylation according to the tumor size (P = 0.036). BEA patients with CDO1 gene methylation were shown marginally significantly poorer prognosis (P = 0.054) than otherwise patients. In conclusion, higher CDO1 gene methylation was seen in BEA at earlier stage than in squamous cell carcinoma, and it may account for aggressive phenotype of BEA.
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Adenocarcinoma/genética , Esófago de Barrett/genética , Cisteína-Dioxigenasa/genética , Metilación de ADN/genética , Neoplasias Esofágicas/genética , Predisposición Genética a la Enfermedad/epidemiología , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Esófago de Barrett/patología , Esófago de Barrett/cirugía , Transformación Celular Neoplásica/genética , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Esofagectomía/mortalidad , Esofagoscopía/métodos , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Estadísticas no Paramétricas , Análisis de SupervivenciaRESUMEN
BACKGROUND: The aim of the present study was to investigate whether the baseline impedance (BI) value is a useful parameter to evaluate the condition of the esophageal mucosa in neurologically impaired (NI) children undergoing multichannel intraluminal impedance pH measurements (pH/MII). METHODS: The retrospective study included 55 NI patients ≤15 years. The patients were divided into acid gastroesophageal reflux disease (GERD), non-acid GERD and GERD (-) groups. Furthermore, the patients in the acid GERD group were subdivided into erosive reflux disease (ERD) and non-erosive reflux disease (NERD) groups. pH/MII parameters and BI values (Z1-6) were compared among three groups or between two groups, respectively. A Spearman's correlation analysis was used for the correlation analysis of pH/MII parameters and BI values. A receiver operator characteristic curve analysis was used to evaluate the optimum cut-off values of BI to discriminate ERD patients. KEY RESULTS: The BI values of the proximal and the distal channels in ERD group were significantly lower than those in NERD group. The BI values of the distal channels demonstrated significant negative correlations with acid exposure related pH/MII parameters. The optimal cut off value of BI in the most distal channel was determined to be 1500 Ω. CONCLUSIONS & INFERENCES: The present study suggested that NI children with reflux esophagitis were likely to suffer mucosal damage up to the proximal esophagus and cut-off BI values may help estimate the presence of reflux esophagitis. Baseline impedance is a potent parameter, reflecting the esophageal mucosal damage in NI children who have difficulty in undergoing endoscopic examinations.
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Mucosa Esofágica/fisiopatología , Monitorización del pH Esofágico/métodos , Reflujo Gastroesofágico/diagnóstico , Enfermedades del Sistema Nervioso/complicaciones , Niño , Preescolar , Impedancia Eléctrica , Femenino , Reflujo Gastroesofágico/complicaciones , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Purpose: Thiamazole (MMI) is frequently used for the treatment of Graves' disease, but it occasionally induces agranulocytosis at the beginning of the treatment. To date, the predictive factors of recovery from MMI-induced agranulocytosis remain unclear. The primary aim of this study was to evaluate the predictive factor of the recovery time from MMI-induced agranulocytosis. Method: This was a retrospective cohort study performed in a university hospital and a thyroid hospital. We included 27 Japanese patients with Graves' disease with MMI-induced agranulocytosis diagnosed during follow-up. All patients were administrated recombinant human granulocyte colony-stimulating factor daily until they had a neutrophil count>1 000/µL, which was defined as recovery. The predictive factors associated with recovery time were estimated using multivariable regression analysis. Results: At the onset of agranulocytosis, the median administration period of MMI was 33 days, the average white blood cell count was 1 896/µL, and the median neutrophil count was 22/µL. The median recovery time was 4 days. Stepwise multivariate regression analysis identified the monocyte and basophil counts to be significant predictors of MMI-induced agranulocytosis. Conclusion: Patients with agranulocytosis and decreased monocyte and basophil counts at onset may recover late and require careful treatment.
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Agranulocitosis , Basófilos , Enfermedad de Graves , Metimazol , Monocitos , Neutrófilos , Recuperación de la Función/efectos de los fármacos , Adulto , Agranulocitosis/sangre , Agranulocitosis/inducido químicamente , Femenino , Enfermedad de Graves/sangre , Enfermedad de Graves/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Metimazol/administración & dosificación , Metimazol/efectos adversos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
The pH-dependent antigen binding antibody, termed a recycling antibody, has recently been reported as an attractive type of second-generation engineered therapeutic antibody. A recycling antibody can dissociate antigen in the acidic endosome, and thus bind to its antigen multiple times. As a consequence, a recycling antibody can neutralize large amounts of antigen in plasma. Because this approach relies on histidine residues to achieve pH-dependent antigen binding, which could limit the epitopes that can be targeted and affect the rate of antigen dissociation in the endosome, we explored an alternative approach for generating recycling antibodies. Since calcium ion concentration is known to be lower in endosome than in plasma, we hypothesized that an antibody with antigen-binding properties that are calcium-dependent could be used as recycling antibody. Here, we report a novel anti-interleukin-6 receptor (IL-6R) antibody, identified from a phage library that binds to IL-6R only in the presence of a calcium ion. Thermal dynamics and a crystal structure study revealed that the calcium ion binds to the heavy chain CDR3 region (HCDR3), which changes and possibly stabilizes the structure of HCDR3 to make it bind to antigen calcium dependently (PDB 5AZE). In vitro and in vivo studies confirmed that this calcium-dependent antigen-binding antibody can dissociate its antigen in the endosome and accelerate antigen clearance from plasma, making it a novel approach for generating recycling antibody.
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Antígenos , Calcio , Endosomas , Receptores de Interleucina-6 , Anticuerpos de Cadena Única , Antígenos/química , Antígenos/metabolismo , Calcio/química , Calcio/metabolismo , Línea Celular , Regiones Determinantes de Complementariedad/química , Regiones Determinantes de Complementariedad/metabolismo , Endosomas/química , Endosomas/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Receptores de Interleucina-6/química , Receptores de Interleucina-6/metabolismo , Anticuerpos de Cadena Única/química , Anticuerpos de Cadena Única/metabolismoAsunto(s)
Cardiomiopatías/patología , Enfermedad Injerto contra Huésped/patología , Leucemia Mieloide Aguda , Trasplante de Células Madre de Sangre Periférica , Aloinjertos , Cardiomiopatías/etiología , Enfermedad Crónica , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana EdadRESUMEN
Patients with adult growth hormone deficiency exhibit visceral fat accumulation, which gives rise to a cluster of metabolic disorders such as impaired glucose tolerance and dyslipidemia. Plasma growth hormone levels are lower in obese patients with metabolic syndrome than in healthy subjects. Here we examined the hypothesis that exogenous growth hormone administration regulates function of adipose tissue to improve glucose tolerance in diet-induced obese mice. Twelve-week-old obese male C57BL/6 J mice received bovine growth hormone daily for 6 weeks. In epididymal fat, growth hormone treatment antagonized diet-induced changes in the gene expression of adiponectin, leptin, and monocyte chemoattractant protein-1, and significantly increased the gene expression of interleukin-10 and CD206. Growth hormone also suppressed the accumulation of oxidative stress marker, thiobarbituric acid-reactive substances, in the epididymal fat and enhanced the gene expression of anti-oxidant enzymes. Moreover, growth hormone significantly restored glucose tolerance in obese mice. In cultured 3T3-L1 adipocytes, growth hormone prevented the decline in adiponectin gene expression in the presence of hydrogen peroxide. These results suggest that growth hormone administration ameliorates glucose intolerance in obese mice presumably by decreasing adipose mass, oxidative stress, and chronic inflammation in the visceral fat.
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Tejido Adiposo/efectos de los fármacos , Glucemia/metabolismo , Hormona del Crecimiento/administración & dosificación , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Adiponectina/genética , Adiponectina/metabolismo , Tejido Adiposo/inmunología , Tejido Adiposo/metabolismo , Animales , Bovinos , Intolerancia a la Glucosa/tratamiento farmacológico , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/inmunología , Intolerancia a la Glucosa/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Leptina/genética , Leptina/metabolismo , Masculino , Receptor de Manosa , Lectinas de Unión a Manosa/genética , Lectinas de Unión a Manosa/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/genética , Obesidad/inmunología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunologíaRESUMEN
UNLABELLED: Our objective was to examine associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Greater physical activity in each of the domains of sport, active living, home, and work was associated with higher peak femoral neck strength relative to load. INTRODUCTION: Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk. METHODS: Participants were 1,919 pre- and early perimenopausal women from the Study of Women's Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip dual-energy X-ray absorption scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations. RESULTS: Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, Study of Women's Health Across the Nation study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 (p < 0.05) to 0.20 (p < 0.0001). CONCLUSIONS: Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women.
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Envejecimiento/fisiología , Cuello Femoral/fisiología , Menopausia/fisiología , Actividad Motora/fisiología , Absorciometría de Fotón/métodos , Actividades Cotidianas , Adulto , Densidad Ósea/fisiología , Fuerza Compresiva/fisiología , Femenino , Encuestas Epidemiológicas , Humanos , Persona de Mediana Edad , Deportes/fisiología , Soporte de Peso/fisiología , Salud de la MujerRESUMEN
SUMMARY: Previous studies on the association between uric acid and bone mineral density yielded conflicting results. In this study, we demonstrated positive association between uric acid and lumbar spine bone mineral density in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism. INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of osteoporosis. Uric acid, a potent antioxidant substance, has been associated with bone mineral density but previous studies have yielded conflicting results. The objective of the study was to examine the association between serum uric acid and lumbar spine bone mineral density (BMD). METHODS: This was a retrospective analysis of medical records of 615 women, aged 45-75 years, who had lumbar spine BMD measurement by dual-energy X-ray absorptiometry as a part of health checkup from August 2011 to July 2012. RESULTS: Mean serum uric acid level was 4.7 mg/dL. Serum uric acid level was positively and significantly associated with lumbar spine BMD independent of age, body mass index, smoking, drinking, physical activity, years after menopause, diabetes mellitus, hypertension, serum calcium, estimated glomerular filtration rate, plasma C-reactive protein, and serum alkaline phosphatase (standardized beta = 0.078, p = 0.049). Uric acid rapidly increased until the age of 60 years, and then decelerated but continued to increase thereafter. The association between lumbar spine BMD and uric acid remained significantly positive after excluding women older than 60 years. CONCLUSION: The present study showed that higher uric acid levels were linearly associated with higher lumbar spine BMD in peri- and postmenopausal Japanese women. Further research is needed to elucidate the underlying mechanism of the association between uric acid and BMD.