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We prospectively examined associations between mobility in neighborhood opportunity and early childhood recurrent wheezing/asthma. Downward mobility was associated with developing asthma, but not recurrent wheezing, though associations were attenuated after adjusting for family-level socioeconomic status. Elucidating how neighborhoods impact asthma may inform asthma equity initiatives in early childhood.
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Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.
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COVID-19 , SARS-CoV-2 , Telemedicina , Humanos , COVID-19/epidemiología , Taiwán/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pandemias , Glucemia/análisis , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Satisfacción del Paciente , Control Glucémico/métodos , Oftalmopatías/diagnóstico , Adulto , Hemoglobina Glucada/análisis , Automonitorización de la Glucosa Sanguínea/métodos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/sangre , Tamizaje Masivo/métodosRESUMEN
This study developed an eco-friendly method to synthesize 3-arylisoquinoline from 2-alkynylbenzaldehydes using Nafion® NR50 as an acidic catalyst and hexamethyldisilazane (HMDS) as a nitrogen source. The reaction proceeded via a 6-exo-dig cyclization under microwave irradiation, giving the corresponding isoquinolines in excellent yields. The advantages of this protocol include: (1) the use of recyclable acid catalysts, (2) transition-metal-free catalysis, and (3) the effective formation of the target product. These features make this methodology a promising approach for the sustainable and efficient synthesis of 3-arylisoquinoline. Some structures were also confirmed by single-crystal X-ray diffraction analysis.
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OBJECTIVES: To assess the association between age of juice introduction and child anthropometry after the American Academy of Pediatrics changed their guidelines in 2017 to recommend delaying juice introduction until at least 12 months of age (previously 6 months), citing concerns of weight gain. STUDY DESIGN: Upstate KIDS is a prospective birth cohort with follow-up through 9 years of age. Juice introduction was assessed on parental questionnaires at 4-18 months and categorized as <6, 6-<12, and ≥12 months. Child height and weight were recorded at 2-3 and 7-9 years of age. Weight-, height-, and body mass index (BMI)-for-age and sex z scores were calculated using the Centers for Disease Control and Prevention reference. Overweight/obese and obese status were categorized as BMI-for-age z score ≥85th and ≥95th percentiles. Controlling for sociodemographic characteristics and parental BMI, we assessed the associations of age of juice introduction with child anthropometry. RESULTS: Prevalence of childhood obesity was 16.4% at 2-3 (n = 1713) and 22.8% at 7-9 years of age (n = 1283). Juice introduction at <6 vs ≥12 months was associated with higher weight-for-age z score at 2-3 years of age (mean difference = 0.21; 95% CI 0.04-0.37). At 7-9 years of age, juice introduction at <6 vs ≥12 months was related to higher BMI-for-age (0.38; 0.12-0.64) and weight-for-age z scores (0.27; 0.06-0.49). Risk of developing overweight/obesity and obesity was 1.54 (0.99-2.38) and 2.17 (1.11-4.23) times higher among children with juice introduced at <6 months. No associations were found with juice introduced at 6-<12 vs ≥12 months. CONCLUSIONS: Risk of developing overweight/obesity or obesity is higher among children introduced to juice before 6 months of age compared with ≥12 months.
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Sobrepeso , Obesidad Infantil , Antropometría , Índice de Masa Corporal , Niño , Preescolar , Humanos , Lactante , Sobrepeso/epidemiología , Obesidad Infantil/epidemiología , Obesidad Infantil/etiología , Estudios ProspectivosRESUMEN
STUDY QUESTION: Are children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions? SUMMARY ANSWER: Infertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy. WHAT IS KNOWN ALREADY: Asthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments. STUDY DESIGN, SIZE, DURATION: Upstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (â¼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, â¼20%), or no treatment (â¼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI). LIMITATIONS, REASONS FOR CAUTION: Childhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association. WIDER IMPLICATIONS OF THE FINDINGS: Though future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.
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Asma , Fármacos para la Fertilidad , Infertilidad , Asma/complicaciones , Asma/epidemiología , Niño , Preescolar , Femenino , Humanos , Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Maternal obesity may affect offspring asthma and atopic disease risk by altering fetal immune system development. However, few studies evaluate gestational weight gain (GWG). OBJECTIVE: To evaluate relationships between maternal body mass index (BMI), GWG, and persistent wheeze, eczema, allergy, and asthma risk in offspring through middle childhood. METHODS: A total of 5939 children from Upstate KIDS, a population-based longitudinal cohort of children born in upstate New York (2008-2019) were included in the analysis. Persistent wheeze or asthma, eczema, and allergy were maternally reported at multiple study time points throughout early and middle childhood. Poisson regression models with robust SEs were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for offspring atopic outcomes by maternal prepregnancy BMI and GWG. RESULTS: Prepregnancy BMI was associated with increased risk of persistent wheeze by 3 years of age even after adjustments for maternal atopy (class I obesity: aRR, 1.58; 95% CI, 1.13-2.20; class II or III obesity: aRR, 1.69; 95% CI, 1.22-2.35). Associations with reported asthma in middle childhood did not reach statistical significance. Furthermore, no associations were found between prepregnancy BMI and atopic outcomes in either early or middle childhood. GWG was not associated with higher risk of early childhood persistent wheeze or middle childhood asthma. CONCLUSION: Maternal prepregnancy BMI was associated with increased risk of offspring wheeze, whereas excessive GWG was generally not associated with childhood asthma or atopy.
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Asma , Eccema , Ganancia de Peso Gestacional , Hipersensibilidad , Obesidad Materna , Asma/epidemiología , Índice de Masa Corporal , Niño , Preescolar , Eccema/epidemiología , Femenino , Humanos , Obesidad/epidemiología , Embarazo , Ruidos Respiratorios , Factores de Riesgo , Aumento de PesoRESUMEN
Background: Home blood pressure telemonitoring (BPT) has been shown to improve blood pressure control. A community-based BPT program (the Health+ program) was launched in 2015 in an urban area around a medical center. Objectives: To examine the impact of the BPT program on the use of medical resources. Methods: We conducted a retrospective propensity-score (PS)-matched observational cohort study using the National Health Insurance Research Database (NHIRD) 2013-2016 in Taiwan. A total of 9,546 adults with a high risk of cardiovascular disease participated in the integrated BPT program, and 19,082 PS-matched controls were identified from the NHIRD. The primary and secondary outcome measures were changes in 1-year emergency department visit rate, hospitalization rate, duration of hospital stay, and healthcare costs. Results: The number of emergency department visits in the Health+ group significantly reduced (0.8 to 0.6 per year vs. 0.8 to 0.9 per year, p < 0.0001) along with a significant decrease in hospitalization rate (43.7% to 21.3% vs. 42.7% to 35.3%, p < 0.001). The duration of hospital stay was also lower in the Health+ group (4.3 to 3.3 days vs. 5.3 to 6.5 days, p < 0.0001). The annual healthcare costs decreased more in the Health+ group (USD 1642 to 1169 vs. 1466 to 1393 per year, p < 0.001), compared with the controls. Subgroup analysis of the Health+ group revealed that the improvements in outcomes were significantly greater among those who were younger and had fewer comorbidities, especially without diabetes or hypertension. Conclusions: A community-based integrated BPT program may improve patients' health outcomes and reduce healthcare costs.
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BACKGROUND: The American Academy of Pediatrics recommends that if parents choose to introduce juice, they wait until ≥12 months, citing concerns of obesity and dental caries. OBJECTIVES: We sought to identify correlates of early juice introduction (<6 months) and determine whether early introduction establishes a pattern of sugary beverage intake in childhood. METHODS: Upstate KIDS is a prospective birth cohort study with follow-up through 7 years (n = 4989). The age of juice introduction was assessed from responses on periodic questionnaires from 4-18 months and categorized as <6, 6 to <12, and ≥12 months. Sociodemographic information was reported using vital records or maternal questionnaires. At 24, 30, and 36 months and 7 years, mothers reported their child's regular juice, soda, water, and milk intakes. The analysis was restricted to singletons and 1 randomly selected twin from each pair with information on juice introduction (n = 4067). We assessed associations of sociodemographic correlates with juice introduction using Cox proportional hazard models. The relations of juice introduction with beverage intake were evaluated using Poisson or logistic regression for adjusted risk ratios (aRR) or ORs, adjusting for sociodemographic covariates and total beverage intake. RESULTS: Of the mothers, 25% and 74% introduced juice prior to 6 and 12 months, respectively. Younger maternal age; black or Hispanic race/ethnicity; lower educational attainment; Special Supplemental Nutrition Program for Women, Infants, and Children participation (yes); smoking during pregnancy; a higher pre-pregnancy BMI; a lower household income; and living in a townhouse/condominium or mobile home were associated with earlier juice introduction. Earlier juice introduction was related to a higher childhood juice intake, any soda intake, and lower water intake, holding total beverage intake constant [aRR, 1.5 (95% CI: 1.3-1.7; P-trend < 0.0001); adjusted OR 1.6 (95% CI: 1.0-2.4; P-trend = 0.01); aRR 0.9 (95% CI: 0.8-0.9; P-trend < 0.0001), respectively]. CONCLUSIONS: Markers of lower socioeconomic status are strongly associated with earlier juice introduction, which, in turn, relates to sugary beverage intake in childhood, potentially replacing water.
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Caries Dental , Bebidas , Bebidas Gaseosas , Niño , Estudios de Cohortes , Femenino , Humanos , Lactante , Estudios ProspectivosRESUMEN
Liver disorders are a major health concern. Saikosaponin-d (SSd) is an effective active ingredient extracted from Bupleurum falcatum, a traditional Chinese medicinal plant, with anti-inflammatory and antioxidant properties. However, its hepatoprotective properties and underlying mechanisms are unknown. We investigated the effects and underlying mechanisms of SSd treatment for thioacetamide (TAA)-induced liver injury and high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in male C57BL/6 mice. The SSd group showed significantly higher food intake, body weight, and hepatic antioxidative enzymes (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) and lower hepatic cyclooxygenase-2 (COX-2), serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and fibroblast growth factor-21 (FGF21) compared with controls, as well as reduced expression of inflammation-related genes (nuclear factor kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)) messenger RNA (mRNA). In NAFLD mice, SSd reduced serum ALT, AST, triglycerides, fatty acid-binding protein 4 (FABP4) and sterol regulatory element-binding protein 1 (SREBP1) mRNA, and endoplasmic reticulum (ER)-stress-related proteins (phosphorylated eukaryotic initiation factor 2α subunit (p-eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). SSd has a hepatoprotective effect in liver injury by suppressing inflammatory responses and acting as an antioxidant.
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Antiinflamatorios no Esteroideos/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Alanina Transaminasa/análisis , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Aspartato Aminotransferasas/análisis , Catalasa/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/inducido químicamente , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Saponinas/uso terapéutico , Superóxido Dismutasa/análisis , Tioacetamida/toxicidadRESUMEN
Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1ß, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor ß (TGF-ß), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Sirolimus/análogos & derivados , Células A549 , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Citocinas/sangre , Citocinas/metabolismo , Receptores ErbB/metabolismo , Fluorouracilo/administración & dosificación , Humanos , Receptores de Hialuranos/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones Endogámicos BALB C , FN-kappa B/genética , FN-kappa B/metabolismo , Sirolimus/administración & dosificación , Sirolimus/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Clozapine is widely employed in the treatment of schizophrenia. Compared with that of atypical first-generation antipsychotics, atypical second-generation antipsychotics such as clozapine have less severe side effects and may positively affect obesity and blood glucose level. However, no systematic study of clozapine's adverse metabolic effects-such as changes in kidney and liver function, body weight, glucose and triglyceride levels, and retinopathy-was conducted. This research investigated how clozapine affects weight, the bodily distribution of chromium, liver damage, fatty liver scores, glucose homeostasis, renal impairment, and retinopathy in mice fed a high fat diet (HFD). We discovered that obese mice treated with clozapine gained more weight and had greater kidney, liver, and retroperitoneal and epididymal fat pad masses; higher daily food efficiency; higher serum or hepatic triglyceride, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine levels; and higher hepatic lipid regulation marker expression than did the HFD-fed control mice. Furthermore, the clozapine group mice exhibited insulin resistance, poorer insulin sensitivity, greater glucose intolerance, and less Akt phosphorylation; their GLUT4 expression was lower, they had renal damage, more reactive oxygen species, and IL-1 expression, and, finally, their levels of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and catalase) were lower. Moreover, clozapine reduced the thickness of retinal cell layers and increased iNOS and NF-κB expression; a net negative chromium balance occurred because more chromium was excreted through urine, and this influenced chromium mobilization, which did not help overcome the hyperglycemia. Our clozapine group had considerably higher fatty liver scores, which was supported by the findings of lowered adiponectin protein levels and increased FASN protein, PNPLA3 protein, FABP4 mRNA, and SREBP1 mRNA levels. We conclude that clozapine can worsen nonalcoholic fatty liver disease, diabetes, and kidney and retinal injury. Therefore, long-term administration of clozapine warrants higher attention.
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Cromo/deficiencia , Clozapina/farmacología , Intolerancia a la Glucosa/metabolismo , Enfermedades Renales/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/metabolismo , Enfermedades de la Retina/metabolismo , Adipocitos/metabolismo , Animales , Biomarcadores , Pesos y Medidas Corporales , Modelos Animales de Enfermedad , Proteínas de Unión a Ácidos Grasos/genética , Técnica del Anticuerpo Fluorescente , Expresión Génica , Regulación de la Expresión Génica , Inmunohistoquímica , Insulina/metabolismo , Enfermedades Renales/etiología , Hígado/metabolismo , Ratones , Ratones Obesos , Óxido Nítrico Sintasa de Tipo II , Enfermedad del Hígado Graso no Alcohólico/etiología , Obesidad/complicaciones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Enfermedades de la Retina/etiología , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
Risperidone, a second-generation antipsychotic drug used for schizophrenia treatment with less-severe side effects, has recently been applied in major depressive disorder treatment. The mechanism underlying risperidone-associated metabolic disturbances and liver and renal adverse effects warrants further exploration. This research explores how risperidone influences weight, glucose homeostasis, fatty liver scores, liver damage, and renal impairment in high-fat diet (HFD)-administered C57BL6/J mice. Compared with HFD control mice, risperidone-treated obese mice exhibited increases in body, liver, kidney, and retroperitoneal and epididymal fat pad weights, daily food efficiency, serum triglyceride, blood urea nitrogen, creatinine, hepatic triglyceride, and aspartate aminotransferase, and alanine aminotransferase levels, and hepatic fatty acid regulation marker expression. They also exhibited increased insulin resistance and glucose intolerance but decreased serum insulin levels, Akt phosphorylation, and glucose transporter 4 expression. Moreover, their fatty liver score and liver damage demonstrated considerable increases, corresponding to increases in sterol regulatory element-binding protein 1 mRNA, fatty acid-binding protein 4 mRNA, and patatin-like phospholipid domain containing protein 3 expression. Finally, these mice demonstrated renal impairment, associated with decreases in glutathione peroxidase, superoxide dismutase, and catalase levels. In conclusion, long-term administration of risperidone may exacerbate diabetes syndrome, nonalcoholic fatty liver disease, and kidney injury.
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Intolerancia a la Glucosa/metabolismo , Insulina/sangre , Enfermedad del Hígado Graso no Alcohólico/enzimología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Risperidona/farmacología , Adipocitos/citología , Adipocitos/efectos de los fármacos , Adiponectina/metabolismo , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Proteínas de Unión al ADN/metabolismo , Ácido Graso Sintasas/sangre , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Glutatión Peroxidasa/metabolismo , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Fosfolipasas A2 Calcio-Independiente/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Superóxido Dismutasa-1/metabolismo , Factores de Transcripción/metabolismo , Triglicéridos/sangreRESUMEN
Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1ß, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor ß (TGF-ß), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Fluorouracilo/administración & dosificación , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.
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Antiinflamatorios , Antioxidantes , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Hígado/efectos de los fármacos , Polisacáridos , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Citocinas/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Polisacáridos/administración & dosificación , Polisacáridos/farmacología , Tioacetamida/toxicidadRESUMEN
OBJECTIVES: To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN: Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS: Compared with children of mothers with a BMI of <25, children whose mothers had BMI 25-30, 30-35, and ≥35 kg/m2 had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS: Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.
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Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Peso Corporal , Padre , Madres , Obesidad , Problema de Conducta , Adulto , Índice de Masa Corporal , Niño , Femenino , Humanos , Masculino , Obesidad/epidemiología , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The proportion of registered nurses (RNs) with employment in health-related positions before their initial RN education has increased in the past two decades. Previous research found that prior health-related employment is positively associated with RN workforce supply, potentially due to the wage differences based on different career paths. This study's objective is to test the hypotheses that prior health-related employment is associated with differences in starting wages and with different rates of wage growth for experience as an RN. METHODS: We conducted a cross-sectional analysis using the 2008 National Sample Survey of Registered Nurses (NSSRN) linked with county-level variables from the Area Health Resource File. We estimated a Heckman model where the second-stage equation's outcome variable was the logarithm of the RN hourly wage, accounting for the self-selection of working or not working as an RN (i.e., the first-stage equation's outcome variable). Key covariates included interaction terms between years of experience, experience squared, and six categories of prior health-related employment (manager, LPN/LVN, allied health, nursing aide, clerk, and all other healthcare positions). Additional covariates included demographics, weekly working hours, marital status, highest nursing degree, and county-level variables (e.g., unemployment rate). We estimated the marginal effect of experience on wage for each type of prior health-related employment, conducting separate analyses for RNs whose initial education was a Bachelor of Science in Nursing (BSN) (unweighted N = 10,345/weighted N = 945,429), RNs whose initial education was an Associate degree (unweighted N = 13,791/weighted N = 1,296,809), and total population combining the former groups (unweighted N = 24,136/weighted N = 2,242,238). RESULTS: Prior health-related employment was associated with higher wages, with the strongest wage differences among BSN-educated RNs. Among BSN-educated RNs, previous employment as a health care manager, LPN/LVN, or nursing aide produced statistically higher starting wages ($1.72-$3.86 per hour; $3400-$7700 per year; p = 0.006-0.08). However, experience-based wage growth was lower for BSN-educated RNs previously employed as allied health workers, LPN/LVNs, or nursing aides. Among Associate degree-educated RNs, wage difference was not observed except for higher initial wage for RNs with previous employment as LPN/LVNs. CONCLUSIONS: Prior employment in health-related positions was associated with both starting salary and experience-based wage growth among BSN-educated RNs. The higher wage return for those with a BSN may motivate non-RN healthcare workers to seek a BSN in their transition to RN jobs, which could help advancement toward the 80 % BSN workforce recommended by the U.S. Institute of Medicine.
Asunto(s)
Enfermeras y Enfermeros/economía , Salarios y Beneficios , Estudios Transversales , Empleo , Femenino , Personal de Salud/estadística & datos numéricos , Humanos , Masculino , Factores Socioeconómicos , Estados UnidosRESUMEN
Registered nurses (RN) who held prior health-related employment in occupations other than licensed practical or vocational nursing (LPN/LVN) are reported to have increased rapidly in the past decades. Researchers examined whether prior health-related employment affects RN workforce supply. A cross-sectional bivariate probit model using the 2008 National Sample Survey of Registered Nurses was esti- mated. Prior health-related employment in relatively lower-wage occupations, such as allied health, clerk, or nursing aide, was positively associated with working s an RN. ~>Prior health-related employ- ment in relatively higher-wage categories, such as a health care manager or LPN/LVN, was positively associated with working full-time as an RN. Policy implications are to promote an expanded career ladder program and a nursing school admission policy that targets non-RN health care workers with an interest in becoming RNs.
Asunto(s)
Empleo/estadística & datos numéricos , Enfermeras y Enfermeros/provisión & distribución , Ocupaciones/estadística & datos numéricos , Adulto , Estudios Transversales , Demografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salarios y Beneficios , Estados UnidosRESUMEN
The fermented marine alga Porphyra dentata suspension was tested for its fibrinolytic and immune-enhancing activities. An isolated Bacillus subtilis N2 strain was selected for its fibrinolytic activity on fibrin plates. After investigating the effects of biomass amounts of P. dentata powder in water, various additives including sugars, nitrogen-containing substances, lipids and minerals, and cultural conditions of temperature and agitation in flask, the highest fibrinolytic activity in the cultural filtrate was obtained by cultivating N2 strain in 3% (w/v) P. dentata powder suspension containing 1% peanut oil at 37 °C, 150 rpm for 48 h. A fermentor system was further established using the same medium with controlled pH value of 7.0 at 37 °C, 150 rpm, 2.0 vvm for 48 h for the best fibrinolytic activity. The fermented product also showed its immune-enhancing activity by increasing cell proliferation and stimulating the secretion of IL-1ß, IL-6, and TNF-α in J774.1 cells.
Asunto(s)
Bacillus subtilis/metabolismo , Fermentación , Fibrinolíticos/metabolismo , Inmunomodulación/efectos de los fármacos , Porphyra/metabolismo , Animales , Línea Celular , Proliferación Celular , Manipulación de Alimentos , Concentración de Iones de Hidrógeno , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Suspensiones , TemperaturaRESUMEN
BACKGROUND: Lower neighborhood opportunity, measured by the Child Opportunity Index [COI], is associated with increased pediatric morbidity, but is less frequently used to examine longitudinal well child care. We aimed to evaluate associations between the COI and well child visit [WCV] attendance from birth - <36 months of age. METHODS: The Upstate KIDS population-based birth cohort includes children born 2008-2010 in New York state. The exposure, 2010 census tract COI (very low [VL] to very high [VH]), was linked to children's geocoded residential address at birth. The outcome was attended WCVs from birth - <36 months of age. Parents reported WCVs and their child's corresponding age on questionnaires every 4-6 months. These data were applied to appropriate age ranges for recommended WCVs to determine attendance. Associations were modeled longitudinally as odds of attending visits and as mean differences in proportions of WCVs by COI. RESULTS: Among 4650 children, 21% (n = 977) experienced VL or low COI. Children experiencing VL (adjusted OR [aOR] 0.68, 95% CI 0.61, 0.76), low (aOR 0.81, 95% CI 0.73, 0.90), and moderate COI (aOR 0.88, 95% CI 0.81, 0.96), compared to VH COI, had decreased odds of attending any WCV. The estimated, adjusted mean proportions of WCV attendance were lower among children experiencing VL (0.45, P < .01), low (0.53, P = .02), moderate (0.53, P = .05), and high (0.54, P = .03) compared to VH COI (0.56). CONCLUSIONS: Lower COI at birth was associated with decreased WCV attendance throughout early childhood. Reducing barriers to health care access for children experiencing lower COI may advance equitable well child care.
RESUMEN
Early infant growth trajectories have been linked to obesity risk. The aim of this study was to examine early infant feeding practices in association with anthropometric measures and risk of overweight/obesity in childhood. A total of 2492 children from Upstate KIDS, a population-based longitudinal cohort, were included for the analysis. Parents reported breastfeeding and complementary food introduction from 4 to 12 months on questionnaires. Weight and height were reported at 2-3 years of age and during later follow-up at 7-9 years of age. Age and sex z-scores were calculated. Linear mixed models were conducted, adjusting for maternal and child sociodemographic factors. Approximately 54% of infants were formula-fed at <5 months of age. Compared to those formula-fed, BMI- (adjusted B, -0.23; 95% CI: -0.42, -0.05) and weight-for-age z-scores (adjusted B, -0.16; -0.28, -0.03) were lower for those exclusively breastfed. Infants breastfed for ≥12 months had a lower risk of being overweight (aRR, 0.33; 0.18, 0.59) at 2-3 years, relative to formula-fed infants. Compared to introduction at <5 months, the introduction of fruits and vegetables between 5 and 8 months was associated with lower risk of obesity at 7-9 years (aRR, 0.45; 0.22, 0.93). The type and duration of breastfeeding and delayed introduction of certain complementary foods was associated with lower childhood BMI.