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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 , Reologia , Viscosidade , Elasticidade , Alimentos , Fricção , Análise de Alimentos , Análise de Componente PrincipalRESUMO
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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Senescência Celular , Dioxinas , Phaeophyceae , Senescência Celular/efeitos dos fármacos , Animais , Suínos , Células Endoteliais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Floroglucinol/farmacologia , Floroglucinol/análogos & derivados , NanopartículasRESUMO
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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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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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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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 Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Receptores ErbB/genética , Custos de Cuidados de SaúdeRESUMO
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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Anticorpos Monoclonais Humanizados , Neoplasias do Endométrio , Quinolinas , Adulto , Feminino , Humanos , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Compostos de Fenilureia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
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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Despite recent therapeutic advances, the 5-year survival rate for adults with acute myeloid leukemia (AML) is poor and standard-of-care chemotherapy is associated with significant toxicity, highlighting the need for new therapeutic approaches. Recent work from our group and others established that the G protein-coupled estrogen receptor (GPER) is tumor suppressive in melanoma and other solid tumors. We performed a preliminary screen of human cancer cell lines from multiple malignancies and found that LNS8801, a synthetic pharmacologic agonist of GPER currently in early phase clinical trials, promoted apoptosis in human AML cells. Using human AML cell lines and primary cells, we show that LNS8801 inhibits human AML in preclinical in vitro models, while not affecting normal mononuclear cells. Although GPER is broadly expressed in normal and malignant myeloid cells, this cancer-specific LNS8801-induced inhibition appeared to be independent of GPER signaling. LNS8801 induced AML cell death primarily through a caspase-dependent apoptosis pathway. This was independent of secreted classical death receptor ligands, and instead required induction of reactive oxygen species (ROS) and activation of endoplasmic reticulum (ER) stress response pathways including IRE1α. These studies demonstrate a novel activity of LNS8801 in AML cells and show that targeting ER stress with LNS8801 may be a useful therapeutic approach for AML. Significance: Previous work demonstrated that LNS8801 inhibits cancer via GPER activation, especially in solid tumors. Here we show that LNS8801 inhibits AML via GPER-independent mechanisms that include ROS induction and ER activation.
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Endorribonucleases , Leucemia Mieloide Aguda , Adulto , Humanos , Espécies Reativas de Oxigênio , Proteínas Serina-Treonina Quinases , Leucemia Mieloide Aguda/tratamento farmacológico , Estrogênios , Estresse do Retículo EndoplasmáticoRESUMO
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.
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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 , Doença Pulmonar Obstrutiva Crônica , Idoso , Humanos , Feminino , Estados Unidos , Masculino , Fumarato de Formoterol , Glicopirrolato , Estudos Retrospectivos , Combinação de Medicamentos , Inaladores Dosimetrados , Medicare , Budesonida , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por InalaçãoRESUMO
Thermoelectric (TE) materials have been considered as a promising energy harvesting technology for sustainably providing power to electronic devices. In particular, organic-based TE materials that consist of conducting polymers and carbon nanofillers make a large variety of applications. In this work, we develop organic TE nanocomposites via successive spraying of intrinsically conductive polymers such as polyaniline (PANi) and poly(3,4-ethylenedioxy- thiophene):poly(styrenesulfonate) (PEDOT:PSS) and carbon nanofillers, and single-walled carbon nanotubes (SWNT). It is found that the growth rate of the layer-by-layer (LbL) thin films, which comprise a PANi/SWNT-PEDOT:PSS repeating sequence, made by the spraying method is greater than that of the same ones assembled by traditional dip coating. The surface structure of multilayer thin films constructed by the spraying approach show excellent coverage of highly networked individual and bundled SWNT, which is similarly to what is observed when carbon nanotubes-based LbL assemblies are formed by classic dipping. The multilayer thin films via the spray-assisted LbL process exhibit significantly improved TE performances. A 20-bilayer PANi/SWNT-PEDOT:PSS thin film (~90 nm thick) yields an electrical conductivity of 14.3 S/cm and Seebeck coefficient of 76 µV/K. These two values translate to a power factor of 8.2 µW/m·K2, which is 9 times as large as the same films fabricated by a classic immersion process. We believe that this LbL spraying method will open up many opportunities in developing multifunctional thin films for large-scaled industrial use due to rapid processing and the ease with which it is applied.
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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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The heterotrimeric flavin adenine dinucleotide dependent glucose dehydrogenase is a promising enzyme for direct electron transfer (DET) principle-based glucose sensors within continuous glucose monitoring systems. We elucidate the structure of the subunit interface of this enzyme by preparing heterotrimer complex protein crystals grown under a space microgravity environment. Based on the proposed structure, we introduce inter-subunit disulfide bonds between the small and electron transfer subunits (5 pairs), as well as the catalytic and the electron transfer subunits (9 pairs). Without compromising the enzyme's catalytic efficiency, a mutant enzyme harboring Pro205Cys in the catalytic subunit, Asp383Cys and Tyr349Cys in the electron transfer subunit, and Lys155Cys in the small subunit, is determined to be the most stable of the variants. The developed engineered enzyme demonstrate a higher catalytic activity and DET ability than the wild type. This mutant retains its full activity below 70 °C as well as after incubation at 75 °C for 15 min - much higher temperatures than the current gold standard enzyme, glucose oxidase, is capable of withstanding.
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Automonitorização da Glicemia , Glucose 1-Desidrogenase , Elétrons , GlicemiaRESUMO
Aim: To compare all-cause and epilepsy-specific pharmacy and total costs associated with initiation of eslicarbazepine acetate (ESL) or brivaracetam (BRV) among patients with focal seizures in long-term care (LTC) in the US. Methods: This retrospective analysis used data from IQVIA's New Data Warehouse. Results: 298 patients initiated ESL and 282 patients initiated BRV. Initiation of ESL versus BRV was associated with 33.3% lower all-cause pharmacy costs, 34.4% lower epilepsy-specific pharmacy costs, 21.3% lower all-cause total costs and 30.9% lower epilepsy-specific total costs (all p < 0.0001). Conclusion: Among patients with focal seizures in LTC in the US, initiation of ESL versus BRV was associated with significant reductions in all-cause and epilepsy-specific pharmacy and total costs compared with initiation of BRV.
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Anticonvulsivantes , Assistência de Longa Duração , Humanos , Estudos Retrospectivos , Anticonvulsivantes/uso terapêutico , Resultado do Tratamento , Convulsões/tratamento farmacológico , Convulsões/induzido quimicamenteRESUMO
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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Melanoma risk is 30 times higher in people with lightly pigmented skin versus darkly pigmented skin. Using primary human melanocytes representing the full human skin pigment continuum and preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity and susceptibility to malignant transformation, independent of melanin and ultraviolet exposure. These differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from darkly pigmented skin. We used both high-throughput pharmacologic and genetic in vivo CRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by inhibiting the muscarinic acetylcholine receptor M1 (CHRM1) signaling. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma.
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PURPOSE: This study aimed to develop the examination objectives based on nursing competency of the Korean Nursing Licensing Examination. METHODS: This is a validity study to develop the examination objectives based on nursing competency. Data were collected in December 2021. We reviewed the literature related to changing nurse roles and on the learning objectives for the Korea Medical Licensing Examination and other health personnel licensing examinations. Thereafter, we created a draft of the nursing problems list for examination objectives based on the literature review, and the content validity was evaluated by experts. A final draft of the examination objectives is presented and discussed. RESULTS: A total of 4 domains, 12 classes, and 85 nursing problems for the Korean Nursing Licensing Examination were developed. They included the essentials of objectives, related factors, evaluation goals, related activity statements, related clients, related settings, and specific outcomes. CONCLUSION: This study developed a draft of the examination objectives based on clinical competency that were related to the clinical situations of nurses and comprised appropriate test items for the licensing examination. Above results may be able to provide fundamental data for item development that reflects future nursing practices.
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Competência Clínica , Licenciamento em Enfermagem , Humanos , Licenciamento , República da CoreiaRESUMO
This study describes health-related quality of life (HRQoL) among older Medicare beneficiaries with hormone receptor-positive (HR+) early breast cancer (eBC). Women aged ≥65 years diagnosed with stage I-III HR+ eBC between 1997 and 2014 using the Surveillance, Epidemiology, and End Results Medicare Health Outcomes Survey Data Resource were included. HRQoL was measured using the Short Form Health Survey including physical/mental component summary (PCS/MCS) scores and subscales. Patient surveys ≤ 24 months post-diagnosis were matched to non-cancer controls. Mean differences in HRQoL were compared using analysis of covariance. Among 1880 HR+ eBC patients versus 5640 matched non-cancer controls, eBC patients surveyed ≤ 6 months post-diagnosis (n = 530) scored lower on component scores (PCS mean difference = 1.6 [95%CI: 0.6-2.6]; MCS mean difference = 2.0 [95%CI: 1.0-3.0]) and multiple subscales. Among women surveyed 19 to 24 months post-diagnosis (n = 402), mean differences in HRQoL were modest (PCS: 1.2 [95%CI: 0.1-2.4]; MCS: -1.5 [95%CI: -2.7 to -0.3]). Most differences in HRQoL following diagnosis of eBC did not indicate statistical significance or minimally important difference, emphasizing that preservation of HRQoL is an important and realistic goal among patients with eBC.
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A feedback field-effect transistor (FBFET) is a novel device that uses a positive feedback mechanism. FBFET has a high on-/off ratio and is expected to realize ideal switching characteristics through steep changes from off-state to on-state. In this paper, we propose and optimize FBFET devices with asymmetric source/drain doping concentrations. Additionally, we discuss the changes in electrical characteristics across various channel length and channel thickness conditions and compare them with those of FBFET with a symmetric source/drain. This shows that FBFET with an asymmetric source/drain has a higher on-/off ratio than FBFET with a symmetric source/drain.