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Aim: Describe treatment and dosing patterns of lenvatinib and pembrolizumab combination therapy (lenva+pembro) among endometrial cancer (EC) patients in US clinical practice. Materials & methods: Retrospective cohort study among adults with EC initiating lenva+pembro in second line (2L) or third line and later (≥3L) between 17 September 2019 and 30 June 2021. Results: 110 patients initiated lenva+pembro in 2L and 135 patients in ≥3L. Majority of patients initiated lenva+pembro at label-recommended starting doses/interval. Less than half changed lenvatinib dose over time. At median follow-up of 7.3 and 8.7 months, median (95% CI) duration of therapy was 5.1 (4.7-6.1) and 5.8 (4.2-7.3) months for patients in 2L and ≥3L, respectively. Conclusion: Lenva+pembro was mostly initiated at label-recommended dose.
This study looked at details of lenvatinib and pembrolizumab combination treatment among patients with endometrial cancer (EC) in the USA. Specifically, these patients had received prior chemotherapy or hormone therapy before starting lenvatinib and pembrolizumab. Most patients started lenvatinib and pembrolizumab at the dose recommended by the product label and received the next pembrolizumab injection within the recommended timeframe. Over time, more than half of the patients did not change the dose of lenvatinib, and most patients had the same dose of pembrolizumab. On average, patients were treated with lenvatinib and pembrolizumab for 56 months. This study showed that in general, patients were taking lenvatinib and pembrolizumab for treatment of EC as recommended by product labels.
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Anticuerpos Monoclonales Humanizados , Neoplasias Endometriales , Quinolinas , Adulto , Femenino , Humanos , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Compuestos de Fenilurea , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Enzymes are molecules that catalyze reactions critical to life. These catalysts are often studied in bulk water, where the influence of water volume on reactivity is neglected. Here, we demonstrate rate enhancement of up to two orders of magnitude for enzymes trapped in submicrometer water nanodroplets suspended in 1,2-dichloroethane. When single nanodroplets irreversibly adsorb onto an ultramicroelectrode surface, enzymatic activity is apparent in the amperometric current-time trace if the ultramicroelectrode generates the enzyme cofactor. Nanodroplet volume is easily accessible by integrating the current-time response and using Faraday's Law. The single nanodroplet technique allows us to plot the enzyme's activity as a function of nanodroplet size, revealing a strong inverse relationship. Finite element simulations confirm our experimental results and offer insights into parameters influencing single nanodroplet enzymology. These results provide a framework to profoundly influence the understanding of chemical reactivity at the nanoscale.
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Electroquímica , Glucosa Deshidrogenasas/metabolismo , Nanopartículas/química , Agua/química , Electrodos , Flavina-Adenina DinucleótidoRESUMEN
AIM: To assess the effectiveness of the Clinical Nurse Educator Support Project and offer valuable insights for supporting nursing education. BACKGROUND: Allocating clinical nursing educators is crucial for supporting novice nurses' transition into the clinical setting and improving their performance. INTRODUCTION: In 2019, the Ministry of Health and Welfare in South Korea implemented the Clinical Nurse Educator Support Project, which involves governmental financial support for the employment of clinical nurse educators. METHODS: This study employed a repeated cross-sectional design to assess the project outcomes. Following the framework of the Kirkpatrick Evaluation Model, secondary data from annual self-program evaluation reports were analyzed to assess program satisfaction, clinical adaptation, and turnover rates of novice nurses. The "Strengthening the Reporting of Observational Studies in Epidemiology checklist" guided the reporting of the study. RESULTS: The project played a pivotal role in enhancing the quality of nursing education. Novice nurses' program satisfaction and clinical adaptation consistently remained high or exhibited an increase. The project led to a decrease in turnover rate among novice nurses, while the coronavirus 2019 pandemic resulted in increased turnover rates due to limited clinical practice opportunities for nursing students. CONCLUSION: Government support for clinical nurse educators has positively impacted the institutionalization of nursing education. The pressing need is to prioritize not only the enhancement of nursing education quality and the improvement of nurses' working conditions but also the development of healthcare policies and programs to effectively respond to unforeseen challenges and crises. IMPLICATIONS FOR NURSING POLICY: Government and healthcare institutions must collaborate to strengthen clinical education, crucial for novice nurses' clinical adaptation. Prioritizing the improvement of nursing education quality and nurses' working conditions is essential. Continuous research and evaluation of the Clinical Nurse Educator Support Project is imperative to assess its impact and make necessary adjustments.
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BACKGROUND: Critical reflection is an effective learning strategy that enhances clinical nurses' reflective practice and professionalism. Therefore, training programs for nurse educators should be implemented so that critical reflection can be applied to nursing education. This study aimed to investigate the effects of a critical reflection competency program for clinical nurse educators on improving critical thinking disposition, nursing reflection competency, and teaching efficacy. METHODS: A pilot study was conducted using a pre- and post-test control-group design. Participants were clinical nurse educators recruited using a convenience sampling method. The program was conducted once a week for 90 min, with a total of four sessions. The effectiveness of the developed program was verified by analyzing pre- and post-test results of 26 participants in the intervention group and 27 participants in the control group, respectively. The chi-square test, independent t-test, Mann-Whitney U test, and analysis of covariance with age as a covariate were conducted. RESULTS: The critical thinking disposition and teaching efficacy of the intervention group improved after the program, and the differences between the control and intervention groups were statistically significant (F = 14.751, p < 0.001; F = 11.047, p < 0.001). There was no significant difference in the change in nursing reflection competency between the two groups (F = 2.674, p = 0.108). CONCLUSION: The critical reflection competency program was effective in improving the critical thinking disposition and teaching efficacy of nurse educators. Therefore, it is necessary to implement the developed program for nurse educators to effectively utilize critical reflection in nursing education.
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Women with hormone receptor (HR)-positive early-stage breast cancer (BC) have five-year survival rates of > 90% but remain at serious risk for developing distant metastases beyond five years from diagnosis. This retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) registries to examine associations between distant recurrence-free interval (DRFI) and risk of BC-specific mortality following distant relapse. The analysis includes 1,057 women with second primary stage IV BC who were initially diagnosed with AJCC stages I-III HR-positive BC between1990 and 2016. Overall, 65% of women had a preceding DRFI of ≥ 5 years. Five-year BC-specific survival following development of distant recurrence was 52% for women with DRFI ≥ 5 years compared to 31% in women with DRFI of < 5 years. In multivariable analyses, risks of cancer-specific mortality following distant recurrence were lower in women with DRFI of 5 years or more (subdistribution hazard ratio = 0.72, 95% CI 0.58-0.89, p = 0.002). The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients who develop a distant recurrence of disease.
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Neoplasias de la Mama , Neoplasias Primarias Secundarias , Neoplasias de la Mama/epidemiología , Femenino , Humanos , Masculino , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
This study designs a simple current controller employing deep symbolic regression (DSR) in a surface-mounted permanent magnet synchronous machine (SPMSM). A novel DSR-based optimal current control scheme is proposed, which after proper training and fitting, generates an analytical dynamic numerical expression that characterizes the data. This creates an understandable model and has the potential to estimate data that have not been seen before. The goal of this study was to overcome the traditional linear proportional-integral (PI) current controller because the performance of the PI is highly dependent on the system model. Moreover, the outer speed control loop gains are tuned using the cuckoo search algorithm, which yields optimal gain values. To demonstrate the efficacy of the proposed design, we apply the control design to different test cases, that is varied speed and load conditions, as well as sinusoidal speed reference, and compare the results with those of a traditional vector control design. Compared with traditional control approaches, we deduce that the DSR-based control design could be extrapolated far beyond the training dataset, laying the foundation for the use of deep learning techniques in power conversion applications.
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The purpose of this study was to examine nurse staffing in comprehensive nursing care units in Korea and examine the corresponding nurse outcomes, including intent to leave, job satisfaction, and occupational injuries. A total of 356 nurses working in comprehensive nursing care units at eight small-medium sized Korean hospitals participated in this cross-sectional study. In the day, evening, and night shifts, nurse staffing ranged from 9.00 to 24.82, 9.04 to 24.26, and 9.02 to 25.80, respectively. The nurse staffing on each shift did not have a significant impact on nurses' intent to leave, job satisfaction, and occupational injuries. However, workload had a strong relationship with intent to leave and job satisfaction. Voluntary overtime was related to occupational injuries. These findings demonstrate that workload is an important factor for intent to leave and job satisfaction among nurses working in comprehensive nursing care units. Improvements of the work environment, as well as rearrangement of nurse workload to account for patient acuity and nursing needs, are required for the future expansion of comprehensive nursing care services.
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Intención , Satisfacción en el Trabajo , Traumatismos Ocupacionales/psicología , Admisión y Programación de Personal/normas , Adulto , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Traumatismos Ocupacionales/epidemiología , Admisión y Programación de Personal/estadística & datos numéricos , Psicometría/instrumentación , Psicometría/métodos , República de Corea/epidemiología , Encuestas y CuestionariosRESUMEN
The centrosome serves as a major microtubule-organizing center (MTOC). The Cdc6 protein is a component of the pre-replicative complex and a licensing factor for the initiation of chromosome replication and localizes to centrosomes during the S and G2 phases of the cfell cycle of human cells. This cell cycle-dependent localization of Cdc6 to the centrosome motivated us to investigate whether Cdc6 negatively regulates MTOC activity and to determine the integral proteins that comprise the pericentriolar material (PCM). Time-lapse live-cell imaging of microtubule regrowth revealed that Cdc6 depletion increased microtubule nucleation at the centrosomes and that expression of Cdc6 in Cdc6-depleted cells reversed this effect. This increase and decrease in microtubule nucleation correlated with the centrosomal intensities of PCM proteins such as γ-tubulin, pericentrin, CDK5 regulatory subunit-associated protein 2 (CDK5RAP2), and centrosomal protein 192 (Cep192). The regulation of microtubule nucleation and the recruitment of PCM proteins to the centrosome required Cdc6 ATPase activity, as well as a centrosomal localization of Cdc6. These results suggest a novel function for Cdc6 in coordinating centrosome assembly and function.
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Proteínas de Ciclo Celular/metabolismo , Centrosoma/metabolismo , Centro Organizador de los Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Sustitución de Aminoácidos , Antígenos/metabolismo , Biomarcadores/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Centrosoma/química , Proteínas Cromosómicas no Histona/metabolismo , Eliminación de Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Microscopía Fluorescente , Centro Organizador de los Microtúbulos/química , Mutagénesis Sitio-Dirigida , Mutación , Proteínas del Tejido Nervioso/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/química , Proteínas Nucleares/genética , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Transporte de Proteínas , Interferencia de ARN , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Imagen de Lapso de Tiempo , Tubulina (Proteína)/metabolismoRESUMEN
Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.
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Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/patología , Dieta Alta en Grasa/efectos adversos , Kéfir , Obesidad/inducido químicamente , Obesidad/patología , Adipocitos/efectos de los fármacos , Adipocitos/patología , Adipogénesis/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Tamaño de la Célula , Epidídimo , Lípidos/sangre , Lipogénesis/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/sangre , Obesidad/metabolismoRESUMEN
A total of 400, one day-old commercial broiler chicks were divided into five diet groups (negative control, positive control group with 55 ppm Zn-bacitracin, 15 ppm ß-glucan, 30 ppm ß-glucan, and 60 ppm ß-glucan) and fed for six weeks. Ten broilers were allotted to each of 40 floor pens. Eight floor pens were randomly assigned to one of the 5 diets. Each diet was fed to the broilers for 6 weeks with free access to water and diet. The survival rate, growth rate, feed efficiency, and feed conversion rate of the broilers were calculated. At the end of the feeding trial, the birds were slaughtered, breast muscles deboned, and quality parameters of the breast meat during storage were determined. The high level of dietary ß-glucan (60 ppm) showed better feed conversion ratio and survival rate than the negative control. The survival rate of 60 ppm ß-glucan-treated group was the same as that of the antibiotic-treated group, which showed the highest survival rate among the treatments. There was no significant difference in carcass yield, water holding capacity, pH, color, and 2-thiobarbituric acid reactive substances values of chicken breast meat among the 5 treatment groups. Supplementation of 60 ppm ß-glucan to broiler diet improved the survival rate and feed conversion rate of broilers to the same level as 55 ppm Zn-bacitracin group. The result indicated that use of ß-glucan (60 ppm) can be a potential alternative to antibiotics to improve the survival and performance of broilers. However, dietary ß-glucan showed no effects on the quality parameters of chicken breast meat.
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Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1), the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.
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Inflamación/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Phaeophyceae/química , Polifenoles/farmacología , Animales , Colesterol 7-alfa-Hidroxilasa/genética , Citocinas/genética , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/patología , Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Polifenoles/aislamiento & purificación , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Once-monthly paliperidone palmitate (PP1M) is a long-acting injectable antipsychotic approved for the treatment of schizophrenia and schizoaffective disorder (SCA) in adults. OBJECTIVE: To assess treatment patterns and schizophrenia/SCA-related hospitalization following payer rejection, patient reversal, or payment of an initial PP1M claim. METHODS: This was a retrospective cohort study using the IQVIA Formulary Impact Analyzer database linked to the Medical Claims, Hospital Charge Detail Master, and Experian consumer databases. Patients with schizophrenia/SCA and ≥1 PP1M pharmacy claim from January 1, 2018, to February 28, 2022, were identified and stratified into 3 cohorts based on the transaction status of the initial PP1M claim (index date): rejected (payer not approved), reversed (payer approved, patient abandoned), and paid (payer approved, patient filled). Patient characteristics during the 12 months before the index date, subsequent treatment patterns, and schizophrenia/SCA-related hospitalization for patients with >6 months of follow-up were assessed by cohort. RESULTS: The rejected, reversed, and paid cohorts included 1,260, 1,046, and 1,686 patients, respectively. Across these cohorts, the mean ages ranged between 39.2 and 44.5 years; more than half were male (50.8%-51.6%) and White (50.6%-58.3%); 19.8%-24.6% of patients had a Quan-Charlson Comorbidity Index score of ≥2. Rates of prior atypical oral and long-acting injectable antipsychotic use ranged between 76.4%-80.3% and 7.8%-12.7%, respectively. Among patients with ≥6 months of follow-up, 52.2% in the rejected and 53.1% in the reversed cohorts had a subsequent paid PP1M claim during the study period; the median (quartile 1-quartile 3) time to the first paid PP1M claim was 22 (5-74) days for rejection and 11 (1-41) days for reversal. In the rejected and reversed cohorts, 10.2% (n = 111) and 9.8% (n = 90) of patients, respectively, did not receive any paid claim for an antipsychotic after the initial PP1M rejection/reversal. The prevalence of schizophrenia/SCA-related hospitalization during follow-up was similar between patients with a paid (7.4%) and rejected PP1M claim (7.0%; P = 0.689) but higher among patients with a reversed claim (10.8%; P = 0.004). After adjusting for confounders, patients in the reversed cohort were 39% more likely to have a schizophrenia/SCA-related hospitalization than those in the paid cohort (odds ratio = 1.39; 95% CI = 1.03-1.87). CONCLUSIONS: Payer rejection and patient reversal of initial PP1M claims is a form of primary nonadherence and may influence patient trajectory. Data from this study suggest that patient reversal of PP1M may lead to an increased risk of schizophrenia/SCA-related hospitalizations, potentially caused by missed or delayed treatment. Policy initiatives that remove barriers to primary adherence or fulfillment may help improve patients' clinical outcomes.
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Antipsicóticos , Preparaciones de Acción Retardada , Hospitalización , Palmitato de Paliperidona , Trastornos Psicóticos , Esquizofrenia , Humanos , Palmitato de Paliperidona/administración & dosificación , Palmitato de Paliperidona/economía , Palmitato de Paliperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/economía , Masculino , Antipsicóticos/economía , Antipsicóticos/administración & dosificación , Antipsicóticos/uso terapéutico , Femenino , Estudios Retrospectivos , Adulto , Hospitalización/estadística & datos numéricos , Hospitalización/economía , Persona de Mediana Edad , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/economía , Adulto Joven , Inyecciones , Estudios de CohortesRESUMEN
AIMS: This study described treatment patterns, healthcare resource utilization (HRU) and costs among advanced or metastatic non-small cell lung cancer (a/mNSCLC) patients with different epidermal growth factor receptor (EGFR) mutation types. MATERIALS AND METHODS: This retrospective study leveraged NeoGenomics NeoNucleus linked with IQVIA PharMetrics Plus between 01 January 2016 to 30 April 2021 (study period). Patients with evidence of a/mNSCLC between 01 July 2016 to 31 March 2021 (selection window) with EGFR test results indicating exon 19 deletion (exon19del), exon 21 L858R (L858R), or exon 20 insertion (exon20i) mutations were included; date of first observed evidence of a/mNSCLC was the index date. Treatment patterns, all-cause HRU and costs during ≥1 month follow-up were reported for each cohort (exon19del, L858R, and exon20i). RESULTS: A total of 106 exon19del, 75 L858R, and 13 exon20i patients met the study criteria. The prevalence of hospitalization was highest in the exon20i cohort (76.9%), followed by L858R (62.7%) and exon19del (55.7%) cohorts. A higher proportion of patients had evidence of hospice/end-of-life care in the exon20i (30.8%) and L858R (29.3%) cohorts relative to the exon19del cohort (22.6%). The exon20i cohort had higher median total healthcare costs per patient per month ($27,069) relative to exon19del ($17,482) and L858R ($17,763). EGFR tyrosine kinase inhibitors (TKI) were the most frequently observed treatment type for exon19del and L858R cohorts, while chemotherapy was the most observed treatment in exon20i cohort. LIMITATIONS: The sample size for the study cohorts was small, thus no statistical comparisons were conducted. CONCLUSIONS: This is one of the first real-world studies to describe HRU and costs among a/mNSCLC patients by specific EGFR mutation type. HRU and costs varied between EGFR mutation types and were highest among exon20i cohort, potentially reflecting higher disease burden and unmet need among patients with this mutation.
Patients with non-small cell lung cancer (NSCLC) in an advanced or metastatic stage (a/mNSCLC) where cancer has spread to other parts of the body have high chance of dying within five years. Treatment and management of a/mNSCLC also incurs significant healthcare resource utilization (HRU) and costs. Patients with a/mNSCLC may have their epidermal growth factor receptor (EGFR) gene mutated with different variations. Our study described what a/mNSCLC patients were treated with, their HRU and healthcare costs separately for the following three types of EGFR mutations: exon 19 deletion (exon19del), exon 21 L858R (L858R), or exon 20 insertion (exon20i). Our study found that patients with exon19del or L858R mutation were commonly treated with EGFR tyrosine kinase inhibitors (TKIs), while exon20i patients were mostly treated with chemotherapy due to lack of targeted treatment for exon20i during the time when the study was conducted. HRU and healthcare costs were highest for patients with exon20i, which shows that patients with exon20i face high burden and have a need for new treatment options.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Mutación , Receptores ErbB/genética , Costos de la Atención en SaludRESUMEN
Nanoplastics (NPs), plastic particles ranging from 1 to 100 nm are ubiquitous environmental pollutants infiltrating ecosystems. Their small size and widespread use in various products raise concerns for human health, particularly their association with cardiovascular diseases (CVD). NPs can enter the human body through multiple routes, causing oxidative stress, and leading to the senescence and dysfunction of endothelial cells (ECs). Although there are potential natural compounds for treating CVD, there is limited research on preventing CVD induced by NPs. This study investigates the efficacy of Ecklonia cava extract (ECE) in preventing NPs-induced premature vascular senescence and dysfunction. Exposure of porcine coronary arteries (PCAs) and porcine coronary ECs to NPs, either alone or in combination with ECE, demonstrated that ECE mitigates senescence-associated ß-galactosidase (SA-ß-gal) activity induced by NPs, thus preventing premature endothelial senescence. ECE also improved NPs-induced vascular dysfunction. The identified active ingredient in Ecklonia cava, 2,7'-Phloroglucinol-6,6'-bieckol (PHB), a phlorotannin, proved to be pivotal in these protective effects. PHB treatment ameliorated SA-ß-gal activity, reduced oxidative stress, restored cell proliferation, and decreased the expression of cell cycle regulatory proteins such as p53, p21, p16, and angiotensin type 1 receptor (AT1), well known triggers for EC senescence. Moreover, PHB also improved NPs-induced vascular dysfunction by upregulating endothelial nitric oxide synthase (eNOS) expression and restoring endothelium-dependent vasorelaxation. In conclusion, Ecklonia cava and its active ingredient, PHB, exhibit potential as therapeutic agents against NPs-induced premature EC senescence and dysfunction, indicating a protective effect against environmental pollutants-induced CVDs associated with vascular dysfunction.
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Senescencia Celular , Dioxinas , Phaeophyceae , Senescencia Celular/efectos de los fármacos , Animales , Porcinos , Células Endoteliales/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Floroglucinol/farmacología , Floroglucinol/análogos & derivados , NanopartículasRESUMEN
The tribological properties of 19 commercial food products, grouped into six categories (yogurt, dressings, spreads, porridges, emulsified sauces, and syrups) were investigated in relation to their rheological (dynamic oscillatory shear test) and nutritional properties (fat, carbohydrate, and protein). A tribological system (a glass ball and three polydimethylsiloxane pins) generated the extended Stribeck curve, monitoring friction factors (f) over an extended range of sliding speed (v) (10-8 to 100 m/s). Tribological parameters (f, v) at four inflection points dividing the frictional regimes (X1, breakaway point between the static and kinetic regimes; X1-X2, boundary; X2-X3, mixed; X3-X4, hydrodynamic regimes) and the slope between X3 and X4 (s) were subjected to principal component analysis and hierarchical clustering on principal components, using rheological and nutritional parameters as quantitative supplementary variables. Tribological patterns were predominantly influenced by viscosity, viscoelasticity, yield stress, fat content, and the presence of particles (e.g., sugar, proteins, and fibers) and pasting materials (e.g., starches and modified starches). The 19 tribological patterns were classified into 3 clusters: low f and s for fat- and/or viscoelastic-dominant foods (Cluster 1), low f and high s for food emulsions and/or those with low extent of shear-thinning (Cluster 2), and high f at the boundary regime either for the most viscous foods or for those in the presence of particulates (Cluster 3). These results suggest that the compositional and rheological properties have a more profound impact on the classification of complex tribological patterns than the categories of food products.
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Valor Nutritivo , Reología , Viscosidad , Elasticidad , Alimentos , Fricción , Análisis de los Alimentos , Análisis de Componente PrincipalRESUMEN
In an effort to reduce the flammability of synthetic polymeric materials such as cotton fabrics and polyurethane foam (PUF), hybrid nanocoatings are prepared by layer-by-layer assembly. Multilayered nanocomposites of a cationic polyelectrolyte, poly(diallyldimethylammonium chloride) (PDDA), are paired with two kinds of clay nanoplatelets, montmorillonite (MMT) and vermiculite (VMT). The physical properties such as thickness and mass and thermal behaviors in clay-based nanocoatings with and without incorporation of tris buffer are compared to assess the effectiveness of amine salts on flame retardant (FR) performances. A PDDA-tris/VMT-MMT system, in which tris buffer is introduced into the cationic PDDA aqueous solution, produces a thicker and heavier coating. Three different systems, including PDDA/MMT, PDDA/VMT-MMT, and PDDA-tris/VMT-MMT, result in conformal coating, retaining the weave structure of the fabrics after being exposed to a vertical and horizontal flame test, while the uncoated sample is completely burned out. The synergistic effects of dual clay-based hybrid nanocoatings are greatly improved by adding amine salts. Cone calorimetry reveals that the PDDA-tris/VMT-MMT-coated PUF eliminates a second peak heat release rate and significantly reduces other FR performances, compared to those obtained from the clay-based multilayer films with no amine salts added. Ten bilayers of PDDA-tris/VMT-MMT (≈250 nm thick) maintain the shape of foam after exposure to a butane torch flame for 12 s. As for practical use of these nanocomposites in real fire disasters, spray-assisted PDDA-tris/VMT-MMT multilayers on woods exhibit high resistance over flammability. Improved fire resistance in PDDA-tris/VMT-MMT is believed to be due to the enhanced char yield through the addition of tris buffer that promotes the deposition of more clay particles while retaining a highly ordered deposition of a densely packed nanobrick wall structure. This work demonstrates the ability to impart significant fire resistance to synthetic polymer materials in a fully renewable nanocoating that uses environmentally benign chemistry.
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BACKGROUND: Kefir, a traditional fermented milk composed of microbial symbionts, is reported to have various health benefits such as anti-tumour, anti-inflammatory, anti-neoplastic and pro-digestive effects. In this study, to elucidate the effects of kefir on adipocyte differentiation and lipid accumulation, three fractions were prepared from kefir culture broth. The inhibitory effects of kefir liquid culture broth fraction (Fr-1), soluble fraction (Fr-2) and insoluble fraction (Fr-3), prepared by sonication of kefir solid culture broth, on adipocyte differentiation in 3T3-L1 preadipocytes were examined. RESULTS: Fr-3 (0.1 mg mL(-1)) significantly decreased lipid accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity by 60 and 68% respectively without affecting cell viability. In addition, Fr-3 treatment down-regulated the mRNA expression of adipogenic transcription factors including C/EBPα (32%), PPARγ (46%) and SREBP-1c (34%) during adipocyte differentiation compared with untreated control cells. The mRNA expression of adipocyte-specific genes (aP2, FAS and ACC) was also clearly decreased. CONCLUSION: The results suggest that the insoluble fraction of kefir (Fr-3) mediates anti-adipogenic effects through the inhibition of adipocyte differentiation, partly via suppression of the C/EBPα-, SREBP-1c- and PPARγ-dependent pathways.
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Adipocitos/citología , Adipogénesis/genética , Diferenciación Celular/fisiología , Productos Lácteos Cultivados/fisiología , Factores de Transcripción/genética , Células 3T3-L1 , Animales , Proteína alfa Potenciadora de Unión a CCAAT/antagonistas & inhibidores , Proteína alfa Potenciadora de Unión a CCAAT/genética , Productos Lácteos Cultivados/química , Regulación hacia Abajo , Glicerolfosfato Deshidrogenasa/antagonistas & inhibidores , Ratones , PPAR gamma/antagonistas & inhibidores , PPAR gamma/genética , ARN Mensajero/genética , Solubilidad , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/antagonistas & inhibidores , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genéticaRESUMEN
BACKGROUND: Docking the scope and instruments through a multi-channel trocar has enabled reduced-port robotic distal gastrectomy (RRDG) for gastric cancer. To facilitate lymphadenectomy over the anatomical hindrances during RRDG, we recently introduced the Vessel Sealer Extend® (VSE) (Intuitive Surgical, Sunnyvale, CA, USA), a bipolar vessel-sealing device (BVSD) with an articulating jaw. METHODS: From May 2020 to August 2023, we performed RRDG to treat T1 gastric cancer. One endoscope arm and three instrument arms of the da Vinci® Xi Surgical System (Intuitive Surgical) were used. During the lymphadenectomy, the endoscope and VSE (Intuitive Surgical) were docked through a multi-channel trocar established on a trans-umbilical incision. Two Cardiere forceps were docked through cannulas established on each flank. A trans-umbilical lymphadenectomy using an articulating BVSD (TULAB) was then performed. RESULTS: A total of 42 patients underwent planned RRDG with the TULAB technique. The number of retrieved lymph nodes did not differ between the patients who underwent RRDG and those who underwent conventional laparoscopic distal gastrectomies (CLDG) (p = 0.362). There was no statistically significant difference in postoperative complications between the RRDG and CLDG group (p = 0.189). The mean time to first semi-fluid diet was shorter in the patients who underwent RRDG than CLDG (p = 0.030), and the incidence of postoperative ileus was lower in the RRDG group than the CLDG group (0% and 9.9%, respectively, p = 0.034). CONCLUSIONS: Despite use of fewer ports, RRDG with TULAB had similar outcomes to CLDG in terms of the incidence of postoperative morbidity and the number of harvested lymph nodes. Furthermore, by reducing the number of incisions, the incidence of the intra-abdominal adhesions can potentially be lowered when RRDG is used.
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INTRODUCTION: A twice-daily single inhaler triple therapy consisting of budesonide/glycopyrrolate/formoterol fumarate (BGF) was approved by the US Food and Drug Administration (FDA) in July 2020 as a maintenance treatment for patients with chronic obstructive pulmonary disease (COPD). The objective of this AURA study is to describe patient characteristics, exacerbation and treatment history, and healthcare resource utilization (HCRU) before BGF initiation to better inform treatment decisions for prescribers. METHODS: This retrospective cohort study leveraged data of all payer types from IQVIA's Longitudinal Prescription Data (LRx) linked to Medical Data (Dx). Patients with COPD who had ⩾1 LRx claim for BGF between 1 October 2020 and 30 September 2021 were included. The date of first BGF claim was the index date. Patient demographic and clinical characteristics, history of COPD exacerbation or related event, treatment history, and HCRU were assessed during the 12 months before index (baseline). RESULTS: We identified 30,339 patients with COPD initiating BGF (mean age: 68.2 years; 57.1% female; 67.6% Medicare). Unspecified COPD (J44.9; 74.0%) was the most commonly coded COPD phenotype. The most prevalent respiratory conditions/symptoms were dyspnea (50.8%), lower respiratory tract infection (25.3%), and sleep apnea (19.0%). Uncomplicated hypertension (58.8%), dyslipidemia (43.9%), cardiovascular disease (41.4%), and heart failure (19.9%) were the most prevalent nonrespiratory conditions. During the 12-month baseline, 57.9% of patients had evidence of a COPD exacerbation or related event, and 14.9% had ⩾1 COPD-related emergency department (ED) visit; 21.0% of patients had evidence of prior triple therapy use, while 54.3% had ⩾1 oral corticosteroid (OCS) fill. Among OCS users, 29.9% had cumulative exposures >1000 mg [median [Q1-Q3] exposure: 520 (260-1183) mg]. CONCLUSION: This real-world data analysis indicates that BGF is being initiated in patients with COPD experiencing symptoms and exacerbations despite current therapy, and among patients who have various chronic comorbidities, most often cardiopulmonary-related.
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Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Humanos , Femenino , Estados Unidos , Masculino , Fumarato de Formoterol , Glicopirrolato , Estudios Retrospectivos , Combinación de Medicamentos , Inhaladores de Dosis Medida , Medicare , Budesonida , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por InhalaciónRESUMEN
This study was performed to investigate the effects of bitter melon extract (BME) on glucose metabolism, insulin resistance, and various metabolic parameters of participants with prediabetes. A 12-week randomized placebo-controlled clinical study was conducted with prediabetic patients. A total of 76 participants were randomly assigned to initiate the study. In the final analysis, 33 and 32 subjects were included in the BME and placebo groups, respectively. Results showed that 75 g oral glucose tolerance test (OGTT) blood glucose level decreased in BME group after 12 weeks. The glucose level after 30 min of glucose ingestion decreased significantly. The glucagon level in the BME group after 12 weeks significantly decreased 120 min after 75 g OGTT. These results suggested that bitter melon exhibits glucose-lowering effects through suppression of glucagon levels in people with prediabetes.