RESUMEN
Synaptic plasticity is crucial as it dynamically molds the strength and connectivity of neural circuits, influencing learning, memory, and the development of neurological disorders. Metformin, a widely prescribed anti-diabetic medication, has been shown to readily cross the blood-brain barrier (BBB) and the placenta. However, its prolonged impact on neuronal morphology and functions remains underexplored. In this study, we investigated the influence of metformin on dendrite development and synaptic plasticity in embryonic brains and primary rat cortical neurons. Our findings reveal a negative modulation of dendrite development by metformin, as evidenced by altered dendritic arborization, impaired dendritic spine morphology and disruptions in synaptic plasticity, suggesting a potential link between metformin exposure and aberrations in neuronal connectivity. In addition, we extend our insights to the impact of maternal metformin exposure on embryonic brains, revealing a significant inhibition of dendrite development in E18.5 rat brains. In conclusion, this study adds to the expanding knowledge base on the non-metabolic effects of metformin, emphasizing the significance of assessing its potential influence on both neuronal structure and function. There is an urgent need for further investigations into the enduring impact of prolonged metformin administration on the structural and functional aspects of neurons.
Asunto(s)
Plasticidad Neuronal , Neuronas , Embarazo , Femenino , Ratas , Animales , Plasticidad Neuronal/fisiología , Aprendizaje , Barrera Hematoencefálica , DendritasRESUMEN
While T-cell-mediated immune responses in solid tumors have been well-established and have driven major therapeutic advances, our understanding of B-cell biology in cancer is comparatively less developed. A total of 60 lung cancer patients were included, of which 53% were diagnosed at an early stage while 47% were diagnosed at an advanced stage. Flow cytometry was used to analyze the proportion of T and B cells in all blood samples, and the levels of human serum cytokines were also assessed. Compared to the control group, cancer patients showed lower frequencies of IgD+CD27+ marginal B cells and CD32+ B cells, and higher frequencies of T cells with lower CD8+ T cells and higher central memory and naïve CD4+ T cells. Additionally, advanced-stage cancer patients exhibited higher levels of cytokines, a higher proportion of effector memory CD8+ T cells, and a lower frequency of CD27+CD28+CD4+/CD8+ T cells. Linear regression analysis revealed significant correlations between cancer stage and the frequency of B and T cell subsets, leukocyte count, and cytokine levels. Survival analysis demonstrated that patients with higher frequency of class-switched B cells had a worse prognosis, while patients with higher frequency of CD8+ effector T cells and lower frequency of CD4+57+ T cells appeared to have a better survival rate. These findings provide valuable insight into the immunological changes that occur during lung cancer progression and have the potential to inform the development of new immunotherapeutic strategies.
RESUMEN
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on global health and economies, resulting in millions of infections and deaths. This retrospective cohort study aimed to investigate the effect of antifibrotic agents (nintedanib and pirfenidone) on 1-year mortality in COVID-19 patients with acute respiratory failure. METHODS: Data from 61 healthcare organizations in the TriNetX database were analyzed. Adult patients with COVID-19 and acute respiratory failure were included. Patients with a pre-existing diagnosis of idiopathic pulmonary fibrosis before their COVID-19 diagnosis were excluded. The study population was divided into an antifibrotic group and a control group. Propensity score matching was used to compare outcomes, and hazard ratios (HR) for 1-year mortality were calculated. RESULTS: The antifibrotic group exhibited a significantly lower 1-year mortality rate compared to the control group. The survival probability at the end of the study was 84.42% in the antifibrotic group and 69.87% in the control group. The Log-Rank test yielded a p-value of less than 0.001. The hazard ratio was 0.434 (95% CI: 0.264-0.712), indicating a significant reduction in 1-year mortality in the antifibrotic group. Subgroup analysis demonstrated significantly improved 1-year survival in patients receiving nintedanib treatment and during periods when the Wuhan strain was predominant. DISCUSSION: This study is the first to demonstrate a survival benefit of antifibrotic agents in COVID-19 patients with acute respiratory failure. Further research and clinical trials are needed to confirm the efficacy of these antifibrotic agents in the context of COVID-19 and acute respiratory failure.
Asunto(s)
COVID-19 , Fibrosis Pulmonar Idiopática , Insuficiencia Respiratoria , Adulto , Humanos , Antifibróticos , Estudios Retrospectivos , Prueba de COVID-19 , Fibrosis Pulmonar Idiopática/complicaciones , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/diagnóstico , Insuficiencia Respiratoria/tratamiento farmacológico , Piridonas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND CONTEXT: Postoperative pain control following spine surgery can be difficult. The Enhanced Recovery After Surgery (ERAS) programs use multimodal approaches to manage postoperative pain. While an erector spinae plane block (ESPB) is commonly utilized, the ideal distance for injection from the incision, referred to as the ES (ESPB to mid-surgical level) distance, remains undetermined. PURPOSE: We evaluated the impact of varying ES distances for ESPB on Numerical Rating Scale (NRS) measures of postoperative pain within the ERAS protocol. STUDY DESIGN/SETTING: Retrospective observational study. PATIENT SAMPLE: Adult patients who underwent elective lumbar spine fusion surgery. OUTCOME MEASURES: Primary outcome measures include the comparative postoperative NRS scores across groups at immediate (T1), 24 (T2), 48 (T3), and 72 (T4) hours postsurgery. For secondary outcomes, a propensity matching analysis compared these outcomes between the ERAS and non-ERAS groups, with opioid-related recovery metrics also assessed. METHODS: All included patients were assigned to one of three ERAS groups according to the ES distance: Group 1 (G1, ES > 3 segments), Group 2 (G2, ES = 2-3 segments), and Group 3 (G3, ES<2 segments). Each patient underwent a bilateral ultrasound-guided ESPB with 60 mL of diluted ropivacaine or bupivacaine. RESULTS: Patients within the ERAS cohort reported mild pain (NRS < 3), with no significant NRS variation across G1 to G3 at any time. Sixty-five patients were matched across ERAS and non-ERAS groups. The ERAS group exhibited significantly lower NRS scores from T1 to T3 than the non-ERAS group. Total morphine consumption during hospitalization was 26.7 mg for ERAS and 41.5 mg for non-ERAS patients. The ERAS group resumed water and food intake sooner and had less postoperative nausea and vomiting. CONCLUSIONS: ESPBs can be effectively administered at or near the mid-surgical level to the low thoracic region for lumbar spine surgeries. Given challenges with sonovisualization, a lumbar ESPB may be preferred to minimize the risk of inadvertent pleural injury.
Asunto(s)
Recuperación Mejorada Después de la Cirugía , Vértebras Lumbares , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Masculino , Femenino , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Persona de Mediana Edad , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Anciano , Fusión Vertebral/métodos , Fusión Vertebral/efectos adversos , Músculos Paraespinales/inervación , Adulto , Dimensión del Dolor , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/administración & dosificación , Resultado del Tratamiento , Manejo del Dolor/métodosRESUMEN
BACKGROUND/AIM: Bladder cancer remains a significant global health concern, necessitating a deeper understanding of the molecular mechanisms underlying its progression. Cyclin-Dependent Kinase 5 (CDK5) has recently emerged as a potential player in bladder cancer pathogenesis. This study investigated the involvement of CDK5 in bladder cancer, emphasizing its potential as a therapeutic target. MATERIALS AND METHODS: The expression levels of CDK5 and p35 (CDK5 regulatory protein) and their roles in the tumor grade and malignancy of patient samples were evaluated using western blot analysis and immunohistochemistry. In addition, tumor cancer genome atlas (TCGA) was utilized to evaluate survival rate in patients with bladder cancer. We further confirmed the role of CDK5 with in vitro experiments using western blot analysis, immunocytochemistry, cell culture-based proliferation and migration assays. RESULTS: Higher CDK5 and p35 were associated with a higher tumor grade and poor survival rate in patients with bladder cancer. To confirm the role of CDK5 in vitro, we over-expressed CDK5 in bladder cancer cells. The results showed that the over-expression of CDK5 enhanced bladder cancer cell proliferation and migration. In addition, CDK5 inhibition by a pan-CDK inhibitor, Roscovitine (RV), significantly reduced proliferation of bladder cancer cells. Indeed, the migration and adhesion of bladder cancer cells were inhibited by RV treatment. CONCLUSION: CDK5 might play important roles in bladder cancer progression and be a potential diagnostic and therapeutic target in the near future.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Proliferación Celular , Quinasa 5 Dependiente de la Ciclina/genética , Quinasa 5 Dependiente de la Ciclina/metabolismo , Roscovitina , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
AIM: The purpose of this study was to evaluate the effectiveness of ECMO care board games facilitated teaching approach (ECMO care board games) in enhancing ECMO care knowledge, clinical reasoning and learning engagement among intensive care unit (ICU) nurses. BACKGROUND: ECMO is a highly complex, relatively low-incidence, high-risk clinical life support device system used in the intensive care unit (ICU). Its usage has increased nearly tenfold over the past 30 years. Traditionally, ECMO education has been delivered through classroom teaching, which has demonstrated limited effectiveness in promoting nurses' learning engagement, clinical reasoning competency and confidence. The literature suggests that well-designed board games can enhance learning engagement, stimulate higher-level thinking and improve the effectiveness and confidence of nurses' learning. DESIGN: A quasi-experimental study two-group repeated measure design. METHODS: A purposive sample of 73 ICU nurses from two campuses of one medical center was recruited (37 in the experimental group and 36 in the control group). The experimental group received ECMO care training through ECMO care board games facilitated teaching approach, whereas the control group completed the training through a traditional teaching approach. Instruments used for data collection include a demographic information sheet, ECMO Care Knowledge Scale, Clinical Reasoning Scale (Huang et al., 2023) and Learning Engagement Scale (Ciou , 2020). Both groups completed a pre-test before the training, a post-test one week after the training and a second post-test three weeks after the training. RESULTS: Prior to the intervention, there were no significant differences between the two groups in ECMO care knowledge and learning engagement. However, there was a significant difference in clinical reasoning. One week after the intervention, the experimental group demonstrated significantly higher scores in ECMO care knowledge, clinical reasoning and learning engagement than the control group (p <0.01). Three weeks after the intervention, the experimental group showed significantly higher scores in ECMO care knowledge, clinical reasoning and learning engagement (p <0.001). CONCLUSIONS: The content for ECMO care is complex and difficult. Board games can enhance ECMO care knowledge, clinical reasoning and learning engagement. This teaching strategy may be applied to learning challenging subjects in the future to improve learning effectiveness. The clinical reasoning framework is conducive to guiding nurses' learning. In future continuing education, board games designed based on the clinical reasoning framework and tailored to the focus of in-service education can effectively enhance nurses' learning effectiveness.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Humanos , Oxigenación por Membrana Extracorpórea/educación , Unidades de Cuidados Intensivos , Aprendizaje , Competencia Clínica , EscolaridadRESUMEN
PURPOSE: The Blood First Assay Screening Trial (BFAST) is a prospective study using next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) in treatment-naïve advanced/metastatic non-small-cell lung cancer (NSCLC). We compared liquid biopsy to tissue testing and analyzed genomic alterations in Taiwanese patients with NSCLC using the BFAST database. MATERIALS AND METHODS: A total of 269 patients underwent FoundationOne Liquid Companion Diagnostic (F1LCDx) assay at the National Taiwan University Hospital, of whom 264 underwent tissue-based genetic testing also. We analyzed the actionable mutations and the concordance between tissue-based genetic testing, which was limited to EGFR, ALK, ROS1, and BRAF, in a real-life clinical setting and blood-based NGS in the clinical trial. Additionally, we analyzed the co-occurring genomic alterations from the blood-based ctDNA assay. RESULTS: A total of 76.2% patients showed actionable mutations. Standard tissue testing did not detect known driver alterations in about 22.7% of the patients (sensitivity, 70.24%). Liquid NGS detected additional mutations (RET, KRAS, MET, and ErbB2) in 14% of the patients, which went undetected by the standard-of-care testing. The complementary use of ctDNA NGS increased the detection rate by 42%. The F1LCDx assay had a sensitivity of 83.41%. Lower tumor and metastasis stages predicted nondetected blood-based NGS ctDNA results. Common co-occurring mutations in the blood-based NGS ctDNA assay were TP53, DNMT3A, TET2, PIK3CA, CTNNB1, and RB1. Among the patients with EGFR-mutated NSCLC, TET2 co-occurring alterations correlated with shorter progression-free survival of EGFR tyrosine kinase inhibitor treatment. CONCLUSION: NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , ADN Tumoral Circulante , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , ADN Tumoral Circulante/genética , Estudios Prospectivos , Proteínas Tirosina Quinasas , Taiwán , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas , Genómica , Receptores ErbB/genéticaRESUMEN
Response surface models (RSMs) are a new trend in modern anesthesia. RSMs have demonstrated significant applicability in the field of anesthesia. However, the comparative analysis between RSMs and logistic regression (LR) in different surgeries remains relatively limited in the current literature. We hypothesized that using a total intravenous anesthesia (TIVA) technique with the response surface model (RSM) and logistic regression (LR) would predict the emergence from anesthesia in patients undergoing video-assisted thoracotomy surgery (VATS). This study aimed to prove that LR, like the RSM, can be used to improve patient safety and achieve enhanced recovery after surgery (ERAS). This was a prospective, observational study with data reanalysis. Twenty-nine patients (American Society of Anesthesiologists (ASA) class II and III) who underwent VATS for elective pulmonary or mediastinal surgery under TIVA were enrolled. We monitored the emergence from anesthesia, and the precise time point of regained response (RR) was noted. The influence of varying concentrations was examined and incorporated into both the RSM and LR. The receiver operating characteristic (ROC) curve area for Greco and LR models was 0.979 (confidence interval: 0.987 to 0.990) and 0.989 (confidence interval: 0.989 to 0.990), respectively. The two models had no significant differences in predicting the probability of regaining response. In conclusion, the LR model was effective and can be applied to patients undergoing VATS or other procedures of similar modalities. Furthermore, the RSM is significantly more sophisticated and has an accuracy similar to that of the LR model; however, the LR model is more accessible. Therefore, the LR model is a simpler tool for predicting arousal in patients undergoing VATS under TIVA with Remifentanil and Propofol.
RESUMEN
Patients with knee osteoarthritis (KOA) might have gait deviations, but few previous studies have discussed gait compensatory movements of the proximal and distal parts of muscle groups related to KOA. The study aimed to measure lumbar and hip movements during gait test and collect muscle activities of the lower extremities. Thirty-four participants with KOA and 28 healthy participants aged over 50 years were recruited for this study. Lumbar and hip motions during walking test were measured using inertial measurement units. Four muscle groups of the lower extremity (erector spinae, gluteus maximus, quadriceps muscle, and gastrocnemius) activities in gait were collected using surface EMGs. KOA patients used an 2.12∘anterior inclined lumbar spine (p = 0.007) and 22.94∘ flexed hip (p = 0.001) in gait compared to healthy participants. The KOA patients had a small hip movement range 30.19∘(p = 0.001) and a higher asymmetric stance time ratio 0.39 (p = 0.006). Patients with KOA showed decreased erector spinae and gluteus maximus muscle activation and increased activation of the quadriceps and gastrocnemius muscles during gait. In conclusion, patients with KOA used a hyperlordotic lumbar and hip flexed strategy, which overactivates distal extensor muscles through the whole gait and might cause overstress on the lower extremity joints.
Asunto(s)
Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Persona de Mediana Edad , Osteoartritis de la Rodilla/complicaciones , Articulación de la Cadera/fisiología , Marcha/fisiología , Músculo Esquelético/fisiología , Nalgas , Articulación de la Rodilla , Fenómenos Biomecánicos , Osteoartritis de la Cadera/complicacionesRESUMEN
Pulmonary auscultation is essential for detecting abnormal lung sounds during physical assessments, but its reliability depends on the operator. Machine learning (ML) models offer an alternative by automatically classifying lung sounds. ML models require substantial data, and public databases aim to address this limitation. This systematic review compares characteristics, diagnostic accuracy, concerns, and data sources of existing models in the literature. Papers published from five major databases between 1990 and 2022 were assessed. Quality assessment was accomplished with a modified QUADAS-2 tool. The review encompassed 62 studies utilizing ML models and public-access databases for lung sound classification. Artificial neural networks (ANN) and support vector machines (SVM) were frequently employed in the ML classifiers. The accuracy ranged from 49.43% to 100% for discriminating abnormal sound types and 69.40% to 99.62% for disease class classification. Seventeen public databases were identified, with the ICBHI 2017 database being the most used (66%). The majority of studies exhibited a high risk of bias and concerns related to patient selection and reference standards. Summarizing, ML models can effectively classify abnormal lung sounds using publicly available data sources. Nevertheless, inconsistent reporting and methodologies pose limitations to advancing the field, and therefore, public databases should adhere to standardized recording and labeling procedures.
RESUMEN
INTRODUCTION: This study aimed to report the incidence of anterior mid-portion capsular tears identified during arthroscopic Bankart repair (ABR), the clinical outcomes of repairing this combined lesion, and to evaluate the associated bone defects. METHODS: We retrospectively reviewed the records of patients undergoing ABR between January 2014 and December 2017. Data from patients with capsular tears identified during ABR were included and analyzed. Age, number of dislocations, repair technique, follow-up results, and X-rays were reviewed. The size of the glenoid defect and Hill-Sachs lesion were reviewed via magnetic resonance imaging or magnetic resonance arthrography (MRA). RESULTS: Records of 95 patients undergoing ABR during the study period were reviewed, and nine were included. The overall incidence of capsular tears was 9.5% and the mean age at surgery was 45.3 ± 14.3 years. All cases had > 3 dislocations before treatment. All patients had labral lesions, and one had a glenoid defect. Hill-Sachs lesions were observed in eight patients. Seven patients underwent MRA examination, and all seven showed axillary pouch disruption. Over 3.9 ± 1.1 years of follow-up, there was no instability recurrence, and Rowe scores improved from 42.2 to 96.7 (p < 0.001). CONCLUSIONS: There was no recurrent shoulder instability after combined arthroscopic repair of capsular and Bankart lesions. There were Rowe score improvements over at least three years of follow-up. Although our case number was small, we found that mid-portion capsular tear occurred in patients over 30 years with multiple recurrent dislocations, with or without small glenoid bone defects, and with axillary pouch disruption on MRA images.
Asunto(s)
Lesiones de Bankart , Luxaciones Articulares , Inestabilidad de la Articulación , Luxación del Hombro , Articulación del Hombro , Humanos , Adulto , Persona de Mediana Edad , Luxación del Hombro/diagnóstico por imagen , Luxación del Hombro/etiología , Luxación del Hombro/cirugía , Hombro , Lesiones de Bankart/cirugía , Articulación del Hombro/cirugía , Inestabilidad de la Articulación/cirugía , Estudios Retrospectivos , Luxaciones Articulares/complicaciones , Artroscopía/métodos , RecurrenciaRESUMEN
BACKGROUND: Evidence of associations between psychological symptoms and tumor necrosis factor (TNF)-α level is scant, as is evidence on sex differences in associations for children and adolescents with obesity. This study examined sex differences in associations between psychological symptoms (self-concept, anxiety, depression, anger, and disruptive behavior) and TNF-α level in Taiwanese children and adolescents with healthy weight, overweight, or obesity. METHODS: In 2010, 564 first, fourth, and seventh graders-comprising 250 children with overweight or obesity (44.3 %), 330 adolescents (58.5 %), and 303 males (53.7 %)-underwent a health examination and blood sampling and completed a questionnaire. RESULTS: A significantly higher TNF-α level was found in children and adolescents with healthy weight than in those with overweight or obesity (median: 14.5 vs. 4.1 (pg/mL); p < 0.001). In multiple linear regression models, anxiety was significantly positively associated with TNF-α level in female participants with healthy weight (ß = 0.11 per 10 increments in anxiety, 95 % confidence interval = 0.01-0.22). LIMITATIONS: Given the cross-sectional nature of the study, no inferences of causal relationships among TNF-α level, obesity, and psychological symptoms could be made. CONCLUSIONS: The findings enrich the literature on the TNF-α-psychological symptom association. Sex differences were found in children and adolescents without obesity rather than in those without obesity, and a higher TNF-α level was associated with increased anxiety in girls without obesity. The role of sex differences in the complex associations among psychological symptoms, TNF-α level, and overweight or obesity requires further investigation.
Asunto(s)
Sobrepeso , Factor de Necrosis Tumoral alfa , Humanos , Niño , Adolescente , Femenino , Masculino , Sobrepeso/psicología , Estudios Transversales , Caracteres Sexuales , Taiwán/epidemiología , Obesidad/epidemiología , Índice de Masa CorporalRESUMEN
The pupil constricts in response to an increase in global luminance level, commonly referred to as the pupil light reflex. Recent research has shown that these reflex responses are modulated by high-level cognition. There is larger pupil constriction evoked by a bright stimulus when the stimulus location spatially overlaps with the locus of attention, and these effects have been extended to saccade planning and working memory (here referred to as pupil local-luminance modulation). Although research in monkeys has further elucidated a central role of the frontal eye field (FEF) and superior colliculus in the pupil local-luminance modulation, their roles remain to be established in humans. Through applying continuous theta-burst transcranial magnetic stimulation over the right FEF (and vertex) to inhibit its activity, we investigated the role of the FEF in human pupil local-luminance responses. Pupil light reflex responses were transiently evoked by a bright patch stimulus presented during the delay period in the visual- and memory-delay tasks. In the visual-delay task, larger pupil constriction was observed when the patch location was spatially aligned with the target location in both stimulation conditions. More interestingly, after FEF stimulation, larger pupil constriction was obtained when the patch was presented in the contralateral, compared to the ipsilateral visual field of the stimulation. In contrast, FEF stimulation effects were absence in the memory-delay task. Linear mixed model results further found that stimulation condition, patch location consistency, and visual field significantly modulated observed pupil constriction responses. Together, our results constitute the first evidence of FEF modulation in human pupil local-luminance responses.
RESUMEN
We report on carbon monoxide desorption and oxidation induced by 400 nm femtosecond laser excitation on the O/Ru(0001) surface probed by time-resolved x-ray absorption spectroscopy (TR-XAS) at the carbon K-edge. The experiments were performed under constant background pressures of CO (6 × 10-8 Torr) and O2 (3 × 10-8 Torr). Under these conditions, we detect two transient CO species with narrow 2π* peaks, suggesting little 2π* interaction with the surface. Based on polarization measurements, we find that these two species have opposing orientations: (1) CO favoring a more perpendicular orientation and (2) CO favoring a more parallel orientation with respect to the surface. We also directly detect gas-phase CO2 using a mass spectrometer and observe weak signatures of bent adsorbed CO2 at slightly higher x-ray energies than the 2π* region. These results are compared to previously reported TR-XAS results at the O K-edge, where the CO background pressure was three times lower (2 × 10-8 Torr) while maintaining the same O2 pressure. At the lower CO pressure, in the CO 2π* region, we observed adsorbed CO and a distribution of OC-O bond lengths close to the CO oxidation transition state, with little indication of gas-like CO. The shift toward "gas-like" CO species may be explained by the higher CO exposure, which blocks O adsorption, decreasing O coverage and increasing CO coverage. These effects decrease the CO desorption barrier through dipole-dipole interaction while simultaneously increasing the CO oxidation barrier.
RESUMEN
Pharmacodynamic models have described the interactions between anesthetics. Applying the models to clinical practice is still problematic due to inherent limitations: 1. modeling conditions are different from practice. 2. One model can only describe one endpoint. To tackle these, we propose a new method of model validation for recovery and intraprocedural sedation adequacy with a three-drug pharmacodynamic model using six published clinical studies that contain midazolam, opioid, and propofol. Mean drug dose, intraprocedural sedation level, procedure, and recovery time are extracted from each study. Simulated drug regimens are designed to best approximate study conditions. A published deep sedation model is used for simulation. Model-predicted recovery time and intraprocedural sedation scores are compared with the original clinical study outcomes. The model successfully predicted recovery times in eight out of nine regimens. Lower doses of midazolam are associated with faster recovery. Model prediction of intraprocedural sedation level was compatible with the clinical studies in five out of seven regimens. The three-drug pharmacodynamic model describes the course of gastrointestinal endoscopy sedations from clinical studies well. Model predictions are consistent with the results from clinical studies. The approach implies that large scale validation can be performed repeatedly.
RESUMEN
Purpose: Inadequate inhaler technique and nonadherence to therapy are associated with poorer clinical outcomes in chronic obstructive pulmonary disease (COPD). Shared decision-making (SDM), based on clinical evidence, patient goals and preferences, improves quality of care. This study aims to investigate the initial patients' choices of inhaler devices in patients with newly-diagnosed COPD after an SDM process. Patients and Methods: We conducted a prospective, observational, multi-center study in four hospitals in Taiwan from December 2019 to July 2021. All treatment-naïve patients with newly-diagnosed COPD who were able to use three different inhalers of dual bronchodilators (Respimat®, Ellipta®, and Breezhaler®) in the outpatient setting were enrolled. After an SDM process, every patient was prescribed with one inhaler chosen by him- or herself. Errors of using inhalers were recorded after prescription of the inhaler, and at the follow-up visit a month later. The patients' adherence, satisfaction score, and willingness to keep the initially chosen inhaler were investigated. Results: In 109 enrolled patients, 43, 45, and 21 patients chose Respimat®, Ellipta®, and Breezhaler®, respectively. Patients chose different inhalers had similar rates of critical error on both visits, while the rates greatly decrease on the follow-up visit, no matter which inhaler devices they chose initially. The majority of patients had good adherence (use as the prescription daily, n = 79, 82%), satisfaction (satisfaction score ≥4, n = 70, 73%), and strong willingness to keep the initial inhaler (n = 89, 93%) on the follow-up visit regardless of disease severity and their comorbidities. Conclusion: SDM might facilitate inhaler choosing, reduce inhaler errors (versus baseline) with good adherence, satisfaction and strong willingness to keep the initial inhaler in patients with newly-diagnosed COPD.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Broncodilatadores/efectos adversos , Inhaladores de Polvo Seco , Diseño de Equipo , Humanos , Masculino , Nebulizadores y Vaporizadores , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológicoRESUMEN
Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.
Asunto(s)
Apoptosis , Neoplasias de la Próstata , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , Extractos Vegetales/farmacología , Polyporales , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismoRESUMEN
Carbide formation on iron-based catalysts is an integral and, arguably, the most important part of the Fischer-Tropsch synthesis process, converting CO and H2 into synthetic fuels and numerous valuable chemicals. Here, we report an in situ surface-sensitive study of the effect of pressure, temperature, time, and gas feed composition on the growth dynamics of two distinct iron-carbon phases with the octahedral and trigonal prismatic coordination of carbon sites on an Fe(110) single crystal acting as a model catalyst. Using a combination of state-of-the-art X-ray photoelectron spectroscopy at an unprecedentedly high pressure, high-energy surface X-ray diffraction, mass spectrometry, and theoretical calculations, we reveal the details of iron surface carburization and product formation under semirealistic conditions. We provide a detailed insight into the state of the catalyst's surface in relation to the reaction.
RESUMEN
This study investigates an association between obesity and cardiorespiratory fitness concerning their potential effects on cognitive flexibility in young adults from behavioral and neuroelectrical perspectives. Eligible young adults (N = 140, 18-25 years) were assigned into one of four groups, according to their status of obesity (i.e., body mass index) and cardiorespiratory fitness levels (i.e., estimated maximal oxygen uptake), namely, normal weight with high cardiorespiratory fitness (NH), obese with high cardiorespiratory fitness (OH), normal weight with low cardiorespiratory fitness (NL), and obese with low cardiorespiratory fitness (OL). The task-switching test was utilized, and its induced endogenous (P3) and exogenous (N1) event-related potential components were recorded. Concerning behavioral indices, the NH demonstrated superior behavioral performance across global switching and local switching of the task-switching test compared to individuals with lower cardiorespiratory fitness and obesity (i.e., NL, OH, and OL). Additionally, the OH demonstrated better performance than the OL during the heterogeneous condition. For neuroelectrical indices, the NH had larger mean P3 amplitudes during global and local switching than the other three groups. A larger N1 amplitude was also observed in the NH during local switching than in the OH group. The findings suggest that cardiorespiratory fitness has beneficial effects on cognitive flexibility, attentional resource allocation, and sensory evaluation in young adults. Furthermore, our research provided novel evidence showing that cardiorespiratory fitness might potentially alleviate the adverse effects of obesity on cognitive flexibility in young adults.
RESUMEN
The active chemical state of zinc (Zn) in a zinc-copper (Zn-Cu) catalyst during carbon dioxide/carbon monoxide (CO2/CO) hydrogenation has been debated to be Zn oxide (ZnO) nanoparticles, metallic Zn, or a Zn-Cu surface alloy. We used x-ray photoelectron spectroscopy at 180 to 500 millibar to probe the nature of Zn and reaction intermediates during CO2/CO hydrogenation over Zn/ZnO/Cu(211), where the temperature is sufficiently high for the reaction to rapidly turn over, thus creating an almost adsorbate-free surface. Tuning of the grazing incidence angle makes it possible to achieve either surface or bulk sensitivity. Hydrogenation of CO2 gives preference to ZnO in the form of clusters or nanoparticles, whereas in pure CO a surface Zn-Cu alloy becomes more prominent. The results reveal a specific role of CO in the formation of the Zn-Cu surface alloy as an active phase that facilitates efficient CO2 methanol synthesis.