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OBJECTIVES: This study investigates how 24-hour movement behaviors (physical activity, sedentary time, sleep) relate to cognitive performance in older adults. METHODS: 213 adults (aged 65+) wore accelerometers to track activity. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Isotemporal substitution analysis examined how replacing one behavior with another affected cognition. RESULTS: Increased light physical activity was linked to better cognitive function, whereas longer sleep had a negative impact. Replacing 30 min of sedentary behavior or sleep with light physical activity improved orientation, attention, language, and short-term memory. Substituting moderate-to-vigorous physical activity did not have the same cognitive benefit. CONCLUSION: Encouraging older adults to replace sedentary time or excess sleep with light physical activity could support cognitive health and potentially help prevent dementia. These findings have implications for public health strategies promoting cognitive well-being in aging populations.
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PURPOSE: This study investigated whether weekend catch-up sleep was related to a decreased risk of cognitive dysfunction in older Taiwanese adults by using self-reported diaries and objective accelerometer measurements. METHODS: This cross-sectional study enrolled participants who were aged ≥ 65 years and had the capability to walk independently from a medical center in Taipei City, Taiwan, between September 2020 and December 2022. Self-reported sleep diaries and tri-axial accelerometers were used to record and measure sleep-related data for 7 consecutive nights. Weekend catch-up sleep was defined as the mean of weekend sleep time minus the mean of weekdays sleep time. Mini-Mental State Examination (MMSE) was evaluated the risk of cognitive dysfunction. The association between weekend catch-up sleep and the MMSE score was examined using a binary logistic regression model. RESULTS: A total of 215 older adults (53.0% female; 80.5 ± 7.1 years old; 11.6% at risk of cognitive dysfunction) were included. In the adjusted model (adjusted for sex, education level, moderate-to-vigorous physical activity and total accelerometer wear time), both the self-reported sleep diaries (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.09-0.69, P = 0.007) and the accelerometer data (OR = 0.27, 95% CI = 0.10-0.70, P = 0.007) indicated that weekend catch-up sleep could decrease the risk of cognitive dysfunction by 73-74%. CONCLUSION: The study findings suggest that there is an association between weekend catch-up sleep and lower risk for cognitive decline. The causal relationship between weekend catch-up sleep and cognitive function in older adults should be further investigated in a study with longitudinal design.
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INTRODUCTION: The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥ 18 years. METHODS: In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. RESULTS: During 22 March 2021-13 December 2021, 77,468 adults were enrolled; 59.0 % were female and 77.8 % were aged 18-49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18-49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3 %) than among men (7.0 %). CONCLUSIONS: Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the V-Watch survey were mild and of short duration.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Masculino , Humanos , Femenino , Vacunas contra la COVID-19/efectos adversos , Vacuna nCoV-2019 mRNA-1273 , Vacuna BNT162 , ChAdOx1 nCoV-19 , Taiwán/epidemiología , COVID-19/prevención & control , Vacunación/efectos adversosRESUMEN
An electroluminescent quantum-dot light-emitting diode (QLED) device and a micro QLED device array with a top-emitting structure were demonstrated in this study. The QLED device was fabricated in the normal structure of [ITO/Ag/ITO anode]/PEDOT:PSS/PVK/QDs/[ZnO nanoparticles]/Ag/MoO3, in which the semi-transparent MoO3-capped Ag cathode and the reflective ITO/metal/ITO (IMI) anode were designed to form an optical microcavity. Compared with conventional bottom-emitting QLED, the microcavity-based top-emitting QLED possessed enhanced optical properties, e.g., ~500% luminance, ~300% current efficiency, and a narrower bandwidth. A 1.49 inch micro QLED panel with 86,400 top-emitting QLED devices in two different sizes (17 × 78 µm2 and 74 × 40.5 µm2) on a low-temperature polysilicon (LTPS) backplane was also fabricated, demonstrating the top-emitting QLED with microcavity as a promising structure in future micro display applications.
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Aim: High-flow nasal cannulas (HFNCs) show potential in the application of positive pressure, improving gas exchange, and decreasing work of breathing in patients with acute respiratory distress. The aims of this study were to elucidate the indications for HFNC therapy in children of all ages and diagnoses, and to evaluate the efficacy and risk factors for failure of HFNC therapy in children with acute respiratory distress with hypoxia in a pediatric intensive care unit. Methods: We conducted this retrospective cohort study at a tertiary pediatric intensive care unit between January 1, 2018 and December 31, 2020. All children, from 1 month to 18 years of age, with acute respiratory distress with hypoxia and HFNC therapy were eligible. The clinical data were reviewed. Results: One hundred and two children met the eligibility criteria for the study, of whom 57 (55.9%) were male, and the mean age was 7.00 6.79 years. Seventy-eight (76.5%) of the children had underlying disorders. The most common indications for the use of HFNC therapy were pneumonia (40, 39.2%), sepsis-related respiratory distress (17, 16.7%), and bronchiolitis (16, 15.7%). The failure rate was 15.7% (16 of 102 children). Higher initial and maximum fraction of inspiration O2 levels and lower initial and lowest SpO2/FiO2 (S/F) ratio were early and possible signs of failure requiring escalation of respiratory support. Conclusion: In our population, we found that HFNC therapy could be initiated as the first-line therapy for various etiologies of acute respiratory distress with hypoxia in a pediatric intensive care unit and for all age groups.
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Many visualizations, including word clouds, cartographic labels, and word trees, encode data within the sizes of fonts. While font size can be an intuitive dimension for the viewer, using it as an encoding can introduce factors that may bias the perception of the underlying values. Viewers might conflate the size of a word's font with a word's length, the number of letters it contains, or with the larger or smaller heights of particular characters ('o' versus 'p' versus 'b'). We present a collection of empirical studies showing that such factors-which are irrelevant to the encoded values-can indeed influence comparative judgements of font size, though less than conventional wisdom might suggest. We highlight the largest potential biases, and describe a strategy to mitigate them.
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BACKGROUND: Mechanical ventilation is a life-saving procedure for patients with acute respiratory failure, although it may cause pulmonary vascular inflammation and leakage, leading to ventilator-induced lung injury (VILI). Ly6C+high monocytes are involved in the pathogenesis of VILI. In this study, we investigated whether pulmonary infiltrated Ly6C+high monocytes produce vascular endothelial growth factor (VEGF) and contribute to VILI. METHODS: A clinically relevant two-hit mouse model of VILI, with intravenous lipopolysaccharide (LPS, 20 ng/mouse) immediately before high tidal volume (HTV, 20 mL/kg) ventilation (LPS+HTV), was established. Blood gas and respiratory mechanics were measured to ensure the development of VILI. Flow cytometry and histopathological analyses revealed pulmonary infiltration of leukocytes subsets. Clodronate liposomes were intravenously injected to deplete pulmonary monocytes. In vitro endothelial cell permeability assay with sorted Ly6C+high monocytes condition media assessed the role of Ly6C+high monocytes in vascular permeability. RESULTS: LPS+HTV significantly increased total proteins, TNF-α, IL-6, vascular endothelial growth factor (VEGF) and mononuclear cells in the bronchoalveolar lavage fluid (BALF). Pulmonary Ly6C+high monocytes (SSClowCD11b+F4/80+Ly6C+high), but not Ly6C+low monocytes (SSClowCD11b+F4/80+Ly6C+low), were significantly elevated starting at 4 hr. Clodronate liposomes were able to significantly reduce pulmonary Ly6C+high monocytes, and VEGF and total protein in BALF, and restore PaO2/FiO2. There was a strong correlation between pulmonary Ly6C+high monocytes and BALF VEGF (R2 = 0.8791, p<0.001). Moreover, sorted Ly6C+high monocytes were able to produce VEGF, resulting in an increased permeability of endothelial cell monolayer in an in vitro endothelial cell permeability assay. CONCLUSION: VEGF produced by pulmonary infiltrated Ly6C+high monocytes regulates vasculature permeability in a two-hit model of HTV-induced lung injury. Ly6C+high monocytes play an important role in the pathogenesis of VILI.
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Antígenos Ly/metabolismo , Monocitos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Animales , Análisis de los Gases de la Sangre , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Células Endoteliales/citología , Células Endoteliales/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/toxicidad , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/citología , Monocitos/efectos de los fármacos , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Análisis de Regresión , Respiración Artificial/efectos adversos , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismoRESUMEN
This study was undertaken to determine whether there was an association between fine particle matter (PM(2.5)) levels and daily outpatient department visits (OPD) for headaches in Taipei, Taiwan. Daily OPD visits for headaches and ambient air pollution data for Taipei were obtained for the period 2006-2011. The relative risk of visits for OPD headaches was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased OPD visits for headaches were significantly associated with levels of PM(2.5) both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 10-14%) and 3% (95% CI = 1-5%) elevation in OPD visits for headaches, respectively. In the two-pollutant models, PM(2.5) remained significant after inclusion of sulfur dioxide (SO2) or ozone (O3) on both warm and cool days. This study provides evidence that higher levels of PM(2.5) increase the risk of OPD visits for headaches in Taipei, Taiwan.
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Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Enfermedades Ambientales/inducido químicamente , Cefalea/inducido químicamente , Modelos Biológicos , Material Particulado/toxicidad , Salud Urbana , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Bases de Datos Factuales , Enfermedades Ambientales/epidemiología , Enfermedades Ambientales/terapia , Monitoreo del Ambiente , Cefalea/epidemiología , Cefalea/terapia , Hospitales Urbanos , Humanos , Programas Nacionales de Salud , Servicio Ambulatorio en Hospital , Oxidantes Fotoquímicos/análisis , Oxidantes Fotoquímicos/toxicidad , Ozono/análisis , Ozono/toxicidad , Material Particulado/análisis , Riesgo , Estaciones del Año , Dióxido de Azufre/análisis , Dióxido de Azufre/toxicidad , Taiwán/epidemiologíaRESUMEN
This study was undertaken to determine whether there was an association between fine particles (PM2.5) levels and hospital admissions for cardiovascular diseases (CVD) in Kaohsiung, Taiwan. Hospital admissions for CVD (including ischemic heart disease [IHD], stroke, congestive heart failure [CHF], and arrhythmias) and ambient air pollution data for Kaohsiung were obtained for the period from 2006-2010. The relative risk of hospital admissions for CVD was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), elevated number of admissions for CVD were significantly associated with higher PM2.5 levels only on cool days (<25°C), with an interquartile range rise associated with a 47% (95% CI = 39-56%), 48% (95% CI = 40-56%), 47% (95% CI = 34-61%), and 51% (95% CI = 34-70%) increase in IHD, stroke, CHF, and arrhythmias admissions, respectively. No significant associations between PM2.5 and hospital admissions for CVD were observed on warm days. In the two-pollutant models, PM2.5 levels remained significant even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM2.5 enhance the risk of hospital admissions for CVD in Kaohsiung, Taiwan.
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Enfermedades Cardiovasculares/epidemiología , Hospitalización/estadística & datos numéricos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Monóxido de Carbono/análisis , Enfermedades Cardiovasculares/inducido químicamente , Ciudades , Estudios Cruzados , Humanos , Modelos Logísticos , Dióxido de Nitrógeno/análisis , Ozono/análisis , Factores de Riesgo , Dióxido de Azufre/análisis , Taiwán/epidemiología , Factores de Tiempo , Clima TropicalRESUMEN
This study investigates whether exposure to allergen elicits insulin resistance as a result of adipose tissue inflammation. Male C57BL/6 mice were challenged with ovalbumin (OVA) allergen for 12 weeks, and blood and adipose tissue samples were collected at 24h after the last challenge. Levels of adhesion molecules, fasting insulin, fasting glucose, and adipokines in the blood were analyzed, and fasting homeostasis model assessment was applied to determine insulin resistance (HOMA-IR). The expression of pro- and anti-inflammatory genes in dissected adipose tissues was analyzed by real-time RT-PCR. Our results showed that OVA exposure increased insulin resistance as well as resistin and E-selectin, but reduced adiponectin in the serum. Resistin level was significantly correlated with HOMA-IR. Moreover, in adipose tissues of OVA-challenged mice, the pro-inflammatory M1 genes were more abundant while the anti-inflammatory M2 genes were less than those of PBS-treated mice. The expressional changes of both M1 and M2 genes were significantly associated with serum levels of adiponectin, resistin, and E-selectin. Hematoxylin and eosin (HE) and immunohistochemistry (IHC) stain also showed that there was more obvious inflammation in OVA-challenged mice. In conclusion, the current study suggests the relationship between allergen-elicited adipose tissue inflammation and circulating inflammatory molecules, which are possible mediators for the development of insulin resistance. Therefore, we propose that allergen exposure might be one risk factor for insulin resistance.
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Tejido Adiposo/inmunología , Alérgenos/inmunología , Exposición a Riesgos Ambientales , Hipersensibilidad/inmunología , Inflamación/inmunología , Adiponectina/sangre , Animales , Selectina E/metabolismo , Humanos , Resistencia a la Insulina/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Resistina/metabolismoRESUMEN
This study was undertaken to determine whether there was a correlation between fine particle (PM2.5) levels and hospital admissions for hemorrhagic stroke (HS) in Taipei, Taiwan. Hospital admissions for HS and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single-pollutant model (without adjustment for other pollutants), increased HS admissions were significantly associated with PM2.5 levels both on warm days (>23°C) and cool days (<23°C), with an interquartile range rise associated with a 12% (95% CI = 7-18%) and 4% (95% CI = 0-8%) elevation in admissions for HS, respectively. In the two-pollutant models, PM2.5 remained significantly high after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for HS.
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Exposición a Riesgos Ambientales/efectos adversos , Trastornos Hemorrágicos/epidemiología , Hospitalización/estadística & datos numéricos , Material Particulado/toxicidad , Accidente Cerebrovascular/epidemiología , Contaminación del Aire/análisis , Estudios Cruzados , Trastornos Hemorrágicos/inducido químicamente , Humanos , Modelos Logísticos , Ozono/análisis , Tamaño de la Partícula , Factores de Riesgo , Accidente Cerebrovascular/inducido químicamente , Dióxido de Azufre/análisis , Taiwán/epidemiologíaRESUMEN
This study was undertaken to determine whether there was an association between PM2.5 levels and daily mortality in Taipei, Taiwan, the largest metropolitan city with a subtropical climate. Daily mortality, air pollution, and weather data for Taipei were obtained for the period from 2006-2008. The relative risk of daily mortality was estimated using a time-stratified case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single pollutant model, PM2.5 showed association with total mortality both on warm (>23 °C) and cool days (<23 °C). There is no indication of an association between PM2.5 and risk of death due to respiratory diseases both on warm and cool days. PM2.5 had effects on the risk of death from cardiovascular diseases only on cool days. In the two-pollutant models, PM2.5 remained effects on the risk of mortality for all cause and cardiovascular disease after the inclusion of SO2 and O3 both on warm and cool days. This study provides evidence that short-term exposure to PM2.5 increased the risk of death for all cause and cardiovascular disease.
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Enfermedades Cardiovasculares/mortalidad , Exposición a Riesgos Ambientales , Material Particulado/toxicidad , Enfermedades Respiratorias/mortalidad , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/inducido químicamente , Ciudades/epidemiología , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Enfermedades Respiratorias/inducido químicamente , Riesgo , Estaciones del Año , Taiwán/epidemiología , Salud Urbana , Tiempo (Meteorología)RESUMEN
BACKGROUND: Hypokalemia and hypertension are common manifestations of preclinical cardiovascular conditions that have a predictive value for cardiovascular morbidity and mortality. Cardiac hypertrophy, an important risk factor in heart failure, is attributed to long-term hypokalemia and hypertension. Sesame oil is rich in nutrients and possesses potent antihypertensive activities. METHODS: We investigated the therapeutic potential of sesame oil using a hypertensive model created by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/mL/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats. Sesame oil was administered by oral gavage (0.5 or 1 mL/kg/d for 7 days) after 4 weeks of DOCA/salt treatment. Systolic blood pressure (SBP) and diastolic blood pressure (DBP), electrocardiography (ECG), and K(+) and Mg(2+) levels were assessed 24 hours after the last dose of sesame oil. Heart tissue was collected for histologic analysis. RESULTS: Sesame oil effectively reduced the SBP/DBP and ECG abnormalities and increased the serum levels of K(+) and Mg(2+) while limiting the urinary excretion of K(+) in DOCA/salt-induced hypertensive rats. In addition, sesame oil decreased the heart mass, the thickness of the left ventricle, and the diameter of cardiomyocytes, indicating the regression of left ventricular hypertrophy in the hypertensive rats. CONCLUSION: We demonstrate that sesame oil therapeutically ameliorates cardiac hypertrophy by regulating hypokalemia in hypertensive rats.
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Cardiomegalia/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Hipopotasemia/tratamiento farmacológico , Aceite de Sésamo/uso terapéutico , Animales , Presión Sanguínea , Modelos Animales de Enfermedad , Electrocardiografía , Magnesio/sangre , Masculino , Potasio/sangre , Ratas , Ratas Sprague-Dawley , Cloruro de Sodio/administración & dosificación , Cloruro de Sodio/análisisRESUMEN
We undertook this study to investigate whether there is an association between atmospheric fine particles (PM2.5) levels and inpatient admissions for chronic obstructive pulmonary disease (COPD) in Taipei, Taiwan. Data on inpatient admissions for COPD and ambient on air pollution levels in Taipei were obtained for years 2006 to 2010. We estimated the relative risk of inpatient admissions for COPD using a case-crossover design with the following control variables: weather measures, day of the week, seasonality, and long-term time trends. For the single-pollutant model (not controlling for other atmospheric pollutants), COPD admissions were significantly and positively associated with higher PM2.5 levels during both warm days (>23 °C) and cool days (<23 °C), with an interquartile range increase of 12% (95% CI = 8-16%) and 3% (95% CI = 0-7%) in COPD admissions, respectively. In the two-pollutant models, PM2.5 remained significant even controlling for SO2 or O3 on both warm and cool days. Taken as a whole, our study demonstrates that higher levels of PM2.5 may increase the risk of inpatient admissions for COPD.
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Contaminantes Atmosféricos/toxicidad , Hospitalización , Material Particulado/toxicidad , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Cruzados , Humanos , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Estaciones del Año , Taiwán , Tiempo (Meteorología)RESUMEN
This study investigates whether allergen exposure elevates the risk of diabetes or cardiovascular diseases using acute OVA (Ovalbumin) allergen exposure model. We hypothesize that exposure to allergen can induce adipose tissue inflammation and affect adiponectin levels. An intranasal challenge with OVA male C57BL/6 mice was performed at dose of 6.25, 12.5, 25, 50 and 100µg, and compared to which challenge with PBS (phosphate buffered saline). Results showed that acute OVA exposure did not only cause airway inflammation in study mice, but also decreased serum adiponectin levels with a dose-response effect. When examining the gonadal adipose tissues, there was no significantly difference of adiponectin mRNA in OVA challenged mice compared to those PBS challenged, but lower inguinal adiponectin mRNA expression was found compared to those PBS-challenged, and had a good relationship with the serum adiponectin. Inguinal adipose tissues of OVA challenged mice, had significantly lower adipose tissue weight, and higher TNF-α expression without statistical significance. Our data indicate that acute OVA exposure appears to affect the characteristics of adipose tissues, and change the adiponectin levels in serum and adipose tissues. Allergen exposure may be considered a potential risk factor for presenting diabetes or cardiovascular diseases.
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Adiponectina/inmunología , Tejido Adiposo/inmunología , Hiperreactividad Bronquial/inmunología , Inflamación/inmunología , Ovalbúmina/inmunología , Adiponectina/genética , Animales , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN/química , ARN/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
We compared the enhancement effect between a newly synthesized tissue-specific contrast agent, [Gd-DOTA-FPßG], and a commercially available agent, [Gd(DOTA)](-), in a murine model of liver tumor using a clinical magnetic resonance imaging scanner. The colon cancer cell lines with and without ß-glucuronidase (ßG) expression were implanted into the liver of mice. Self-synthesized gadolinium-based magnetic resonance contrast agent, [Gd(DOTA-FPßG)], was administered to measure enhancement on magnetic resonance images using a commercially available agent, [Gd(DOTA)](-), as control in a clinical 3.0 tesla (T) magnetic resonance scanner. In vivo fluorescence imaging and histopathology of the liver were also performed to compare and correlate with the magnetic resonance studies. The in vivo fluorescence imaging failed to depict a sufficiently intense signal for liver or liver tumor of mice without exposure of the liver following an incision on the abdominal wall. The tissue-specific magnetic resonance agent, [Gd(DOTA-FPßG)], caused significantly stronger enhancement in tumors expressing ßG (CT26/mßG-eB7) than in tumors not expressing ßG (CT26) (p < 0.05). In the magnetic resonance imaging studies using control agent [Gd(DOTA)](-), the tumors with and without ßG expression depicted no significant difference in enhancement on the T1-weighted images. The [Gd(DOTA-FPßG)] also provided significantly more contrast uptake in the CT26/mßG-eB7 tumor than in the normal liver parenchyma, whereas the [Gd(DOTA)](-) did not. This study confirms that better contrast enhancement can be readily detected in vivo by the use of a tissue-specific magnetic resonance contrast agent to target tumor cells with specific biomarkers in a clinical magnetic resonance imaging scanner.
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Medios de Contraste , Complejos de Coordinación , Glucuronatos , Compuestos Heterocíclicos , Neoplasias Hepáticas Experimentales/patología , Compuestos Organometálicos , Animales , Línea Celular Tumoral , Medios de Contraste/farmacocinética , Complejos de Coordinación/farmacocinética , Glucuronatos/farmacocinética , Compuestos Heterocíclicos/farmacocinética , Hígado/metabolismo , Hígado/patología , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Imagen Óptica , Compuestos Organometálicos/farmacocinéticaRESUMEN
This study was undertaken to determine whether there was a correlation between fine particles (PM2.5) levels and hospital admissions for myocardial infarction (MI) in Taipei, Taiwan. Hospital admissions for MI and ambient air pollution data for Taipei were obtained for the period 2006-2010. The relative risk of hospital admissions for MI was estimated using a casecrossover approach, controlling for weather variables, day of the week, seasonality, and longterm time trends. For the single-pollutant model (without adjustment for other pollutants), increased numbers of MI admissions were significantly associated with higher PM2.5 levels both on warm days (>23°C) and on cool days (<23°C). This was accompanied by an interquartile range elevation correlated with a 10% (95% CI = 6-15%) and 5% (95% CI = 1-9%) rise in number of MI admissions, respectively. In the two-pollutant models, PM2.5 remained significant after inclusion of SO2 or O3 on both warm and cool days. This study provides evidence that higher levels of PM2.5 increase the risk of hospital admissions for MI.
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Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Hospitalización/estadística & datos numéricos , Infarto del Miocardio/epidemiología , Material Particulado/efectos adversos , Clima Tropical , Femenino , Humanos , Masculino , Infarto del Miocardio/etiología , Taiwán/epidemiología , Salud UrbanaRESUMEN
BACKGROUND: Sinusoidal obstruction syndrome (SOS) occurs in patients undergoing hematopoietic cell transplantation and chemotherapy. The chemotherapeutic drugs oxaliplatin and cyclophosphamide cause SOS. Sesame oil is a nutrient-rich antioxidant popular in alternative medicine. It contains sesamin, sesamol, and sesamolin, all of which contribute to its antioxidant property. The authors investigated the protective effect of prophylactic sesame oil against monocrotaline-induced SOS in rats. METHODS: Male Sprague-Dawley rats were gavaged with a single dose of sesame oil (0.5, 1, 2, or 4 mL/kg). One hour later, those rats were gavaged with monocrotaline (90 mg/kg) to induce SOS. Control rats were treated with saline only. Aspartate transaminase, alanine transaminase, laminin, collagen, myeloperoxidase, nitrate content, lipid peroxidation, glutathione levels, matrix metalloproteinase (MMP)-9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were assessed 48 hours after the monocrotaline gavage. RESULTS: All tested parameters except TIMP-1, laminin, collagen, and glutathione were higher in monocrotaline-treated rats than in saline-only-treated control rats. In sesame oil-treated rats, all tested parameters except TIMP-1, laminin, collagen, and glutathione were significantly attenuated compared with monocrotaline-only-treated rats. Sesame oil downregulated MMP-9 expression but upregulated TIMP-1 expression in monocrotaline-only-treated rats. In addition, a histological analysis of liver tissue samples showed that sesame oil showed significant protection. CONCLUSION: A single prophylactic dose of sesame oil protects against SOS by downregulating MMP-9 expression, upregulating TIMP-1 expression, and inhibiting oxidative stress.
Asunto(s)
Antioxidantes/uso terapéutico , Enfermedad Veno-Oclusiva Hepática/prevención & control , Metaloproteinasa 9 de la Matriz/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Aceite de Sésamo/uso terapéutico , Sesamum/química , Animales , Antioxidantes/farmacología , Enfermedad Veno-Oclusiva Hepática/metabolismo , Enfermedad Veno-Oclusiva Hepática/patología , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Monocrotalina , Ratas , Ratas Sprague-Dawley , Aceite de Sésamo/farmacología , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
ß-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FPßGu)]) for molecular imaging of ß-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a ß-glucuronidase substrate (ß-d-glucopyranuronic acid). The binding association constant (KA) of [Gd(DOTA-FPßGu)] is 7.42 × 10(2), which is significantly lower than that of a commercially available MS-325 (KA = 3.0 × 10(4)) RIME contrast agent. The low KA value of [Gd(DOTA-FPßGu)] is due to the pendant ß-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPßGu)] can be used for detection of ß-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FPßGu)] was elucidated by LC-MS. The kinetics of ß-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPßGu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, kcat = 3.76 × 10(3), and kcat/Km = 2.72 × 10(3) M(-1) s(-1). The low Km value indicates high affinity of ß-glucuronidase for [Gd(DOTA-FPßGu)] at physiological pH. Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPßGu)] changes in response to the concentration of ß-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FPßGu)] showed significant change in MR image signal in the presence of ß-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of ß-glucuronidase.
Asunto(s)
Antineoplásicos/farmacología , Medios de Contraste/farmacología , Gadolinio , Glucuronidasa/metabolismo , Neoplasias Experimentales/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/síntesis química , Medios de Contraste/química , Relación Dosis-Respuesta a Droga , Activación Enzimática , Gadolinio/química , Ligandos , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Neoplasias Experimentales/enzimología , Neoplasias Experimentales/patología , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Relación Estructura-Actividad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of development of kidney cancer and (2) determine whether hardness levels in drinking water modify the effects of TTHM on risk of kidney cancer induction. A matched case-control study was used to investigate the relationship between the risk of death attributed to kidney cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from 1998 through 2007 were obtained. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels and levels of hardness in drinking water were also collected. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and hardness exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77-1.25) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. However, evidence of an interaction was noted between the use of soft water and drinking water TTHM concentrations. Increased knowledge of the interaction between hardness and TTHM levels in reducing risk of kidney cancer development will aid in public policy decision and establishing standards to prevent disease occurrence.