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Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing-Si herbal tea (JS), against H2O2-induced inflammation and cellular damage in HIG-82 synoviocytes. We found that JS did not show any significant alterations in cell viability at <188 µg/mL; however, a cytotoxic effect was observed at 188-1883 µg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)-degrading proteases MMP-13, ADAMTS-2, -8, and -17 were abnormally enhanced under H2O2-induced pathological oxidative stress (ROS) in HIG-82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose-dependent manner. Treatment with JS showed enhanced cell viability against H2O2-induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl-2 were increased, whereas MMP-13, ADAMTS-2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF-α treatment, respectively, in HIG-82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2-treated HIG-82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases.

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BACKGROUND: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. METHODS: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. RESULTS: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. CONCLUSION: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation.

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BACKGROUND AND AIMS: Diabetes is one of the major causes of cardiovascular disease (CVD). As high as 29 % of patients with diabetes develop atherosclerosis. Vascular Smooth Muscle Cells (VSMCs) are a key mediator in the pathogenesis of atherosclerosis, generating pro-inflammatory and proliferative characteristics in atherosclerotic lesions. METHODS: We used human atherosclerotic samples, developed diabetes-induced atherosclerotic mice, and generated loss of function and gain of function in Klotho human aortic smooth muscle cells to investigate the function of Klotho in atherosclerosis. RESULTS: We found that Klotho expression is decreased in smooth muscle actin-positive cells in patients with diabetes and atherosclerosis. Consistent with human data, we found that Apoe knockout mice with streptozotocin-induced diabetes fed on a high-fat diet showed decreased expression of Klotho in SMCs. Additionally, these mice showed increased expression of TGF-ß, MMP9, phosphorylation of ERK and Akt. Further, we utilized primary Human Aortic Smooth Muscle Cells (HASMCs) with d-glucose under dose-response and in time-dependent conditions to study the role of Klotho in these cells. Klotho gain of function and loss of function studies showed that Klotho inversely regulated the expression of atherosclerotic markers TGF-ß, MMP2, MMP9, and Fractalkine. Further, High Glucose (HG) induced Akt, and ERK1/2 phosphorylation were enhanced or mitigated by endogenous Klotho deficiency or its overexpression respectively. PI3K/Akt and MAPK/ERK inhibition partially abolished the HG-induced upregulation of TGF-ß, MMP2, MMP9, and Fractalkine. Additionally, Klotho knockdown increased the proliferation of HASMCs and enhanced α-SMA and TGF-ß expression. CONCLUSIONS: Taken together, these results indicate that local vascular Klotho is involved in diabetes-induced atherosclerosis, which is via PI3K/Akt and ERK1/2-dependent signaling pathways.

Asunto(s)

Aterosclerosis , Diabetes Mellitus Experimental , Glucuronidasa , Proteínas Klotho , Ratones Noqueados para ApoE , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteínas Klotho/metabolismo , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Glucuronidasa/metabolismo , Glucuronidasa/genética , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Masculino , Transducción de Señal , Células Cultivadas , Aorta/patología , Aorta/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/enzimología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proliferación Celular

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INTRODUCTION: As patients nowadays tend to have multiple diseases and complex medical histories, our aim was to identify high-quality, non-instrumental dysphagia screening tools used for the detection of adult dysphagia cases in all disease categories in acute-care settings. METHOD: A literature search was conducted in five databases from each database's earliest inception to 31 July 2021 and guided by five keywords: 'dysphagia', 'deglutition', 'screening', 'test' and 'measure'. Without limiting the search in any specific disease category, reviewers assessed original studies and identified tools if they had been validated against instrumental evaluations and if they had been designed as a pass-fail procedure to screen whether dysphagia is absent or present. We further excluded any tool if it was (1) for pediatric focus, or (2) a patient self-report questionnaire. All final tool candidates underwent a methodological quality appraisal using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). RESULT: Out of 195 studies with 165 tools identified, 20 tool candidates underwent QUADAS-2 review. We found six high-quality, non-instrumental screening tools for detecting adult dysphagia cases in acute-care settings, including the Yale Swallow Protocol, Gugging Swallowing Screen, Toronto Bedside Swallowing Screening Test (both English and Portuguese versions), Sapienza Global Bedside Evaluation of Swallowing and Two-Step Thickened Water Test. These high-quality tools were developed primarily for patients with stroke. Only Yale Swallow Protocol was originally tested for heterogeneous populations with stroke, multiple sclerosis, traumatic brain injury, oesophageal surgery, neurosurgery and head-and-neck cancer. CONCLUSIONS: The results highlight the gap in the unavailability of high-quality dysphagia screening tool in several emerged high-risk populations including elderly inpatients, or patients following endotracheal extubation. Further research is needed to determine whether these six tools can be effectively applied across different high-risk populations in acute-care settings to screen for cases finding.

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The antibiotic heliomycin (resistomycin), which is generated from Streptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+ which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, our in vitro and in vivo findings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.

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Neoplasias de la Boca , Compuestos Policíclicos , Sirtuina 1 , Humanos , Animales , Ratones , Sirtuina 1/metabolismo , Línea Celular Tumoral , NAD/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Simulación del Acoplamiento Molecular , Apoptosis , Neoplasias de la Boca/tratamiento farmacológico

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Colorectal cancer is the most common cancer that affects both sexes and has a poor prognosis due to aggressiveness and chemoresistance. Essential oils isolated from Calocedrus formosana (CF-EOs) have been shown to demonstrate anti-termite, antifungal, anti-mosquito, and anti-microbial activities. However, the anticancer effects of CF-EOs are not yet fully understood. Therefore, the present study aimed to explore the molecular mechanism underlying CF-EOs-mediated anti-proliferative activity in colon cancer cells. Here, cell impedance measurements showed that CF-EOs inhibit proliferation in colon cancer cells with wild-type or mutant p53. Flow cytometry revealed that CF-EOs at 20, 50 µg/mL significantly induced ROS generation and autophagy in both HCT116 p53-wt and HCT116 p53-null cell lines, whereas pretreatment with the ROS scavenger N-acetyl cysteine (NAC) markedly attenuated these changes. CF-EOs also induced apoptosis at 50 µg/mL in both lines, as determined by flow cytometry. Protein analysis showed that CF-EOs markedly induced apoptosis markers, including Trail, cleaved caspase-3, cleaved caspase-9, and cleaved PARP, as well as autophagy markers, such as the levels of ULK1, Atg5, Atg6, Atg7, and the conversion of LC3-I to LC3-II. CF-EOs were further found to inhibit the activity and expression of the NAD+-dependent deacetylase SIRT1 to increase the levels of acetylated p53 (Ac-p53) in p53-wt cells and acetylated c-Myc (Ac-c-Myc) in p53-null cells, ultimately inducing apoptosis in both lines. Interestingly, suppression of SIRT1 by CF-EOs enhanced the acetylation of ULK1, which in turn prompted ROS-dependent autophagy in colon cancer cells. The induction of apoptosis and autophagy by CF-EOs suggests that they may have potential as a promising new approach for treating cancer. Collectively, our results suggest that essential oils isolated from Calocedrus formosana act as a promising anticancer agent against colon cancer cells by targeting SIRT1 to induce ROS-mediated autophagy and apoptosis.

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Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting approximately 1% of the global population, with a higher prevalence in women than in men. Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of RA. Anethole, a prominent compound derived from fennel (Foeniculum vulgare), possesses a spectrum of therapeutic properties, including anti-arthritic, anti-inflammatory, antioxidant, and tumor-suppressive effects. However, its specific impact on RA remains underexplored. This study sought to uncover the potential therapeutic value of anethole in treating RA by employing an H2 O2 -induced inflammation model with HIG-82 synovial cells. Our results demonstrated that exposure to H2 O2 induced the inflammation and apoptosis in these cells. Remarkably, anethole treatment effectively countered these inflammatory and apoptotic processes triggered by H2 O2 . Moreover, we identified the aquaporin 1 (AQP1) and protein kinase A (PKA) pathway as critical regulators of inflammation and apoptosis. H2 O2 stimulation led to an increase in the AQP1 expression and a decrease in p-PKA-C, contributing to cartilage degradation. Conversely, anethole not only downregulated the AQP1 expression but also activated the PKA pathway, effectively suppressing cell inflammation and apoptosis. Furthermore, anethole also inhibited the enzymes responsible for cartilage degradation. In summary, our findings highlight the potential of anethole as a therapeutic agent for mitigating H2 O2 -induced inflammation and apoptosis in synovial cells, offering promising prospects for future RA treatments.

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Artritis Reumatoide , Sinoviocitos , Masculino , Humanos , Femenino , Sinoviocitos/metabolismo , Acuaporina 1 , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Inflamación/patología , Artritis Reumatoide/metabolismo , Fibroblastos/metabolismo , Células Cultivadas , Proliferación Celular

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Parenting programs are the most common intervention for preventing the lethal form of child maltreatment, abusive head trauma (AHT). However, certain results of the effects of these programs have not yet been compared across studies. A systematic review with meta-analysis is warranted to quantitively synthesize the available evidence to identify effective elements and strategies of the programs for preventing AHT. This review aims to estimate AHT preventive parenting programs' pooled effect on the reduction of AHT incidence, the improvement of parental knowledge, and the increased use of safe strategies in response to infants' inconsolable crying. Studies published in English and Mandarin were searched and retained if they were randomized control trials (RCTs) or with a quasi-experimental design, included an AHT preventive parenting program, and provided data that quantified targeted outcomes. Eighteen studies were included in this review. AHT preventive parenting programs had a pooled effect on improving parents' knowledge and increasing the use of safe coping strategies in response to inconsolable crying but not on the incidence of AHT and parents' emotional self-regulation. Subgroup analyses showed that the intervention effects were mostly present across study designs or measurements and emerged in the reduction of AHT incidence compared with historical controls. The findings suggest that AHT preventive parenting programs enhance parenting knowledge and skills to provide safe care for infants. Further efforts to evaluate AHT parenting programs on the reduction of AHT incidence are necessary for decision-making on allocating and disseminating interventions.

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Maltrato a los Niños , Traumatismos Craneocerebrales , Síndrome del Bebé Sacudido , Lactante , Niño , Humanos , Síndrome del Bebé Sacudido/prevención & control , Responsabilidad Parental , Maltrato a los Niños/prevención & control , Maltrato a los Niños/psicología , Padres/psicología , Traumatismos Craneocerebrales/epidemiología , Traumatismos Craneocerebrales/prevención & control

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CPT-11 is one of the drugs employed in colorectal cancer treatment and has faced challenges in the form of resistance. The insulin-like growth factor 1 receptor is a tyrosine kinase receptor that mediates cancer cell survival and drug resistance. It is frequently overexpressed in colorectal cancer and has previously been identified as a microRNA target. MicroRNAs are non-coding RNA molecules that regulate gene function by suppressing messenger RNA translation. Studies have demonstrated that natural compounds can regulate microRNA function and their target genes. Therefore, combining natural compounds with existing cancer drugs can enhance the therapeutic efficacy. We investigated a natural compound, Aloin, for the potential sensitization of colorectal cancer to CPT-11. We used western blot, MTT cell viability assay, flow cytometry, and microRNA/gene knockdown and overexpression experiments, as well as an in vivo mouse model. Our investigation revealed that combining Aloin with CPT-11 exerts an enhanced anti-tumor effect in colorectal cancer. This combination reduced cell viability and induced apoptosis, both in vivo and in vitro. Furthermore, this combination upregulated miRNA-133b, while downregulating the IGF1R and its downstream MEK/ERK, and PI3K/AKT/mTOR pathways. Our findings suggests that CPT-11 and Aloin are potential combination treatment partners against colorectal cancer. MicroRNA-133b may serve as a co-therapeutic target with IGF1R against colorectal cancer, which might overcome the existing treatment limitations.

Asunto(s)

Neoplasias Colorrectales , MicroARNs , Animales , Ratones , Irinotecán/farmacología , Irinotecán/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Fosfatidilinositol 3-Quinasas/metabolismo , Sistema de Señalización de MAP Quinasas , Proliferación Celular , Serina-Treonina Quinasas TOR/metabolismo , MicroARNs/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Línea Celular Tumoral

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BACKGROUND: The resumption of oral feeding and free from pneumonia are important therapeutic goals for critically ill patients who have been successfully extubated after prolonged (≥ 48 h) endotracheal intubation. We aimed to examine whether a swallowing and oral-care (SOC) program provided to critically ill patients extubated from prolonged mechanical ventilation improves their oral-feeding resumption and reduces 30-day pneumonia incidence. METHODS: In this randomized, open-label, controlled trial, participants were consecutively enrolled and randomized to receive the SOC program or usual care. The interventions comprised three protocols: oral-motor exercise, sensory stimulation and lubrication, and safe-swallowing education. Beginning on the day following patient extubation, an SOC nurse provided the three-protocol care for seven consecutive days or until death or hospital discharge. With independent outcome assessors, oral-feeding resumption (yes, no) corresponded to level 6 or level 7 on the Functional Oral Intake Scale (censored seven days postextubation) along with radiographically documented pneumonia (yes, no; censored 30 days postextubation), abstracted from participants' electronic medical records were coded. RESULTS: We analyzed 145 randomized participants (SOC group = 72, control group = 73). The SOC group received, on average, 6.2 days of intervention (14.8 min daily) with no reported adverse events. By day 7, 37/72 (51.4%) of the SOC participants had resumed oral feeding vs. 24/73 (32.9%) of the control participants. Pneumonia occurred in 11/72 (15.3%) of the SOC participants and in 26/73 (35.6%) of the control participants. Independent of age and intubation longer than 6 days, SOC participants were likelier than their control counterparts to resume oral feeding (adjusted hazard ratio, 2.35; 95% CI 1.38-4.01) and had lower odds of developing pneumonia (adjusted odds ratio, 0.28; 95% CI 0.12-0.65). CONCLUSIONS: The SOC program effectively improved patients' odds that oral feeding would resume and the 30-day pneumonia incidence would decline. The program might advance dysphagia care provided to critically ill patients extubated from prolonged mechanical ventilation. TRIAL REGISTRATION: NCT03284892, registered on September 15, 2017.

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Trastornos de Deglución , Neumonía , Humanos , Deglución , Extubación Traqueal/efectos adversos , Enfermedad Crítica/terapia , Neumonía/prevención & control

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The angular displacement sensor is a digital angular displacement measurement device that integrates optics, mechanics, and electronics. It has important applications in communication, servo control, aerospace, and other fields. Although conventional angular displacement sensors can achieve extremely high measurement accuracy and resolution, they cannot be integrated because complex signal processing circuitry is required at the photoelectric receiver, which limits their suitability for robotics and automotive applications. The design of a fully integrated line array angular displacement-sensing chip is presented for the first time using a combination of pseudo-random and incremental code channel designs. Based on the charge redistribution principle, a fully differential 12-bit, 1 MSPS sampling rate successive approximation analog-to-digital converter (SAR ADC) is designed for quantization and subdivision of the incremental code channel output signal. The design is verified with a 0.35 µm CMOS process and the area of the overall system is 3.5 × 1.8 mm2. The fully integrated design of the detector array and readout circuit is realized for the angular displacement sensing.

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Object tracking is a fundamental task in computer vision. Recent years, most of the tracking algorithms are based on deep networks. Trackers with deeper backbones are computationally expensive and can hardly meet the real-time requirements on edge platforms. Lightweight networks are widely used to tackle this issue, but the features extracted by a lightweight backbone are inadequate for discriminating the object from the background in complex scenarios, especially for small objects tracking task. In this paper, we adopted a lightweight backbone and extracted features from multiple levels. A hierarchical feature fusion transformer (HFFT) was designed to mine the interdependencies of multi-level features in a novel model-SiamHFFT. Therefore, our tracker can exploit comprehensive feature representations in an end-to-end manner, and the proposed model is capable of handling small target tracking in complex scenarios on a CPU at a rate of 29 FPS. Comprehensive experimental results on UAV123, UAV123@10fps, LaSOT, VOT2020, and GOT-10k benchmarks with multiple trackers demonstrate the effectiveness and efficiency of SiamHFFT. In particular, our SiamHFFT achieves good performance both in accuracy and speed, which has practical implications in terms of improving small object tracking performance in the real world.

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BACKGROUND: Hypertension is a severe public health risk factor worldwide. Elevated angiotensin II (Ang II) produced by the renin-angiotensin-aldosterone system can lead to hypertension and its complications. METHOD: In this study, we addressed the cardiac-injury effects of Ang II and investigated the signaling mechanism induced by Ang II. Both H9c2 cardiomyoblast cells and neonatal rat cardiomyocytes were exposed to Ang II to observe hypertension-related cardiac apoptosis. RESULTS: The results of western blotting revealed that Ang II significantly attenuated the IGF1R-PI3K-AKT pathway via the Ang II-AT1 receptor axis and phosphatase and tensin homolog expression. Furthermore, real-time PCR showed that Ang II also activated miR-320-3p transcription to repress the PI3K-Akt pathway. In the heart tissue of spontaneously hypertensive rats, activation of the IGF1R survival pathway was also reduced compared with that in Wistar-Kyoto rats, especially in aged spontaneously hypertensive rats. CONCLUSION: Hence, we speculate that the Ang II-AT1 receptor axis induces both phosphatase and tensin homolog and miR-320-3p expression to downregulate the IGF1R-PI3K-AKT survival pathway and cause cell apoptosis in the heart.

Asunto(s)

Hipertensión , MicroARNs , Ratas , Animales , Angiotensina II/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Tensinas/metabolismo , Ratas Endogámicas SHR , Monoéster Fosfórico Hidrolasas/metabolismo , Monoéster Fosfórico Hidrolasas/farmacología , Ratas Endogámicas WKY , Apoptosis , Miocitos Cardíacos/metabolismo , Hipertensión/metabolismo , MicroARNs/metabolismo

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BACKGROUND: Nursing students with master degrees have the strong potential to serve as future leaders in medical teams. Implementing a well-developed and integrated educational program for nursing leadership at the master's level can strengthen the leadership of advanced practice nurses and promote a positive nursing practice environment. PURPOSE: To develop a leadership integrated educational program for master's nursing students and conduct a preliminary evaluation of the effectiveness of this program in cultivating leadership competencies in these students. METHODS: Phase 1: A modified Delphi survey conducted on 14 experts with clinical or academic backgrounds was used to identify the teaching objectives and strategies of the leadership integrated educational program. Phase 2: These teaching objectives and strategies were embedded into nine compulsory courses within a current training program for master's nursing students at a national university. The core elements of the leadership integrated educational program were incorporated into each compulsory course. The objectives of each compulsory course directly reflected the objectives of the integrated program. The leadership integrated educational program was implemented for one academic year, and its effectiveness was evaluated using a quasi-experimental test with a single group pre- and post-test design. A self-developed, 10-item "Master Nursing Student's Leadership Competence Scale" covering four core elements was applied to measure the self-reported leadership competencies of the participants. A paired sample t-test was applied to analyze the differences in leadership competencies between pre- and post-intervention. RESULTS: A consensus on the teaching objectives and strategies of the leadership integrated educational program was achieved in the first round of the Delphi survey. The overarching teaching objective of the leadership integrated educational program was to "lead the healthcare team with the leadership and competencies, and demonstrate the advanced nursing practice skills for improving quality of care." In addition, the four core elements under the overarching goal, i.e., personal characteristics, leading people, business management, and vision building, were proposed. Forty-eight master's nursing students participated in this study. The results showed the average total score of leadership competency was 42.33 ± 12.16 (potential range: 10 - 70), indicating that the participants had a middle level of leadership competency prior to program participation. After participating in the Leadership Integrated Educational Program for one academic year, the average total score for leadership competency increased to 51.27 ± 9.74, indicating that the participants still had a middle level of leadership competency. Nevertheless, the 8.94 increase in the post-intervention score was statistically significant (p < .01). Moreover, the scores for each subscale (personal characteristics, leading people, business management, and vision building) had all increased significantly increased from 13.52 to 15.71, 12.65 to 15.35, 8.15 to 10.31, and 8.02 to 9.90, respectively (p < .01). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: This study offers proactive recommendations for reforming master's degree programs in nursing. The proposed multidisciplinary-expert-informed leadership integrated educational program may be used to strengthen leadership competencies in this student population. Furthermore, the findings provide a benchmark for developing an effective nursing leadership integrated educational program that may be incorporated into domestic master's degree programs.

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Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Liderazgo , Investigación en Educación de Enfermería , Taiwán

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Lung cancer is the major cause of cancer associated mortality. Mutations in EGFR have been implicated in lung cancer pathogenesis. Gefitinib (GF) is a RTKI (receptor tyrosine kinase inhibitor) first-choice drug for EGFR mutated advanced lung cancer. However, drug toxicity and cancer cell resistance lead to treatment failure. Consequently, new therapeutic strategies are urgently required. Therefore, this study was aimed at identifying tumor suppressive compounds that can synergistically improve Gefitinib chemosensitivity in the lung cancer treatment. Medicinal plants offer a vast platform for the development of novel anticancer agents. Daidzein (DZ) is an isoflavone compound extracted from soy plants and has been shown to possess many medicinal benefits. The anticancer potential of GF and DZ combination treatment was investigated using MTT, western blot, fluorescent microscopy imaging, flow cytometry and nude mice tumor xenograft techniques. Our results demonstrate that DZ synergistically induces c-Jun nuclear translocation through ROS/ASK1/JNK and downregulates EGFR-STAT/AKT/ERK pathways to activate apoptosis and a G0/G1 phase cell cycle blockade. In in-vivo, the combination treatment significantly suppressed A549 lung cancer cells tumor xenograft growth without noticeable toxicity. Daidzein supplements with current chemotherapeutic agents may well be an alternative strategy to improve the treatment efficacy of lung adenocarcinoma.

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Adenocarcinoma del Pulmón , Antineoplásicos , Isoflavonas , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Apoptosis , Línea Celular Tumoral , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Gefitinib/farmacología , Gefitinib/uso terapéutico , Humanos , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Neoplasias Pulmonares/genética , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno

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Calreticulin (CRT) is located in the endoplasmic reticulum (ER), it helps proteins fold correctly inside the ER, and acts as a modulator of Ca2+ homeostasis. Aberrant expression of CRT is implicated in several cancer types, qualifying CRT as a potential therapeutic target. However, it remains unclear how CRT affects specific oncogenic pathways. In this study, we used histone deacetylase inhibitors (HDACis) to establish drug-resistant liver cancer cells and further analyzed the molecular mechanism of development of drug resistance in those cells. The 2D gel electrophoresis and RT-PCR data showed that CRT was downregulated in HDACis-resistant cells by comparing with HA22T parental cells. We previously elucidated the development of drug-resistance in HCC cells via activation of PP1-eIF2α pathway, but not via ER stress pathway. Here, we show that thapsigargin induced ER stress through mechanism other than ER stress downstream protein GRP78-PERK to regulate CRT expression in HDACis-R cells. Moreover, the expression level of CRT was not the main cause of apoptosis in HDACis-resistant cells. Mechanistic studies identified the apoptosis factors in the nucleus-the HDACis-mediated overexpression of CRT, CRT translocation to the cell nucleus, and reduced CaM/CaMKII/CREB pathway-that led to chemosensitivity in HDACis-R HCC cells.

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Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptosis/fisiología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Núcleo Celular/metabolismo , Estrés del Retículo Endoplásmico , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Transducción de Señal

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Background: Tissue-engineered vascular grafts (TEVGs) have the potential to advance the surgical management of infants and children requiring congenital heart surgery by creating functional vascular conduits with growth capacity. Methods: Herein, we used an integrative computational-experimental approach to elucidate the natural history of neovessel formation in a large animal preclinical model; combining an in vitro accelerated degradation study with mechanical testing, large animal implantation studies with in vivo imaging and histology, and data-informed computational growth and remodeling models. Results: Our findings demonstrate that the structural integrity of the polymeric scaffold is lost over the first 26 weeks in vivo, while polymeric fragments persist for up to 52 weeks. Our models predict that early neotissue accumulation is driven primarily by inflammatory processes in response to the implanted polymeric scaffold, but that turnover becomes progressively mechano-mediated as the scaffold degrades. Using a lamb model, we confirm that early neotissue formation results primarily from the foreign body reaction induced by the scaffold, resulting in an early period of dynamic remodeling characterized by transient TEVG narrowing. As the scaffold degrades, mechano-mediated neotissue remodeling becomes dominant around 26 weeks. After the scaffold degrades completely, the resulting neovessel undergoes growth and remodeling that mimicks native vessel behavior, including biological growth capacity, further supported by fluid-structure interaction simulations providing detailed hemodynamic and wall stress information. Conclusions: These findings provide insights into TEVG remodeling, and have important implications for clinical use and future development of TEVGs for children with congenital heart disease.

RESUMEN

BACKGROUND: Abusive head trauma (AHT) is a serious health problem that results the highest mortality among children who are maltreated. Many AHT survivors suffer from long-term sequelae and require medical treatment. However, the knowledge of AHT-attributable health services utilization and costs at national level are limited. OBJECTIVE: To estimate health services utilization and costs attributable to AHT among children aged 0-4 years in Taiwan. PARTICIPANTS AND SETTING: Sixty-three fatal and 664 survival AHT cases were identified using Taiwan national population database between 2003 and 2015. A total of 2656 non-AHT children were exactly 4:1 matched to the survival cases based on their birth year, gender, the calendar year of the index date, insured location, and health insurance premium (social economic status indicator). METHODS: Health services utilization and costs were calculated on an annual basis for 3 years after the index date. AHT-attributable health services utilization and costs during 3-year follow-up period was evaluated by regression models. RESULTS: AHT diagnosis was positively associated with inpatient admissions, length of stay, emergency room (ER) visits, and outpatient visits. AHT-attributable medical costs were 1.64-17.27 times, 1.25-5.22 times, and 1.77-2.36 times greater for inpatient, ER, and outpatient during 3-year period than matched controls, respectively. Fatal AHT cases had higher inpatient utilization and greater medical costs than AHT survivors. CONCLUSIONS: Children with AHT had greater health services utilization and higher costs for years. Strategies to reduce the burden of AHT on health care system are imperative.

Asunto(s)

Maltrato a los Niños , Traumatismos Craneocerebrales , Niño , Estudios de Cohortes , Traumatismos Craneocerebrales/diagnóstico , Utilización de Instalaciones y Servicios , Humanos , Lactante , Estudios Retrospectivos , Taiwán/epidemiología

RESUMEN

AIMS: To appraise the current instruments available for measuring the nursing work environment and re-examine the definition and construct of the nursing work environment. BACKGROUND: A psychometrically sound instrument is fundamental to understanding and improving the nursing work environment. The nursing work environment is a complex construct, and its definition remains inconclusive. None of the instruments available is considered as the gold standard. EVALUATION: A comprehensive searching was undertaken in August 2021 in six databases according to PRISMA. The COSMIN and modified GRADE were applied to assess the methodological quality and measurement properties of the instruments. Instruments were categorized into three levels. The definition and construct of nursing work environment were revisited. KEY ISSUES: Forty-one studies (19 instruments) were included. One, fourteen, and four instruments are respectively appraised as A-, B- and C-level recommendation. Definition and eight labels of nursing work environment are identified. CONCLUSION: This paper provides recommendations for selecting a proper instrument for the nursing work environment. IMPLICATIONS FOR NURSING MANAGEMENT: This study helps nurse managers to select instruments and understand the construct of the nursing work environment. The eight labels can be used as a reference for tailoring policy aimed at creating a favourable nursing work environment.

Asunto(s)

Enfermeras Administradoras , Humanos , Psicometría , Reproducibilidad de los Resultados

RESUMEN

AIM: The aim of the study was to identify baccalaureate nursing leadership objectives and evaluate their effectiveness when embedded into an undergraduate nursing curriculum. BACKGROUND: The objectives of nursing leadership competencies cannot be met in one semester but must be gradually developed over successive courses. METHOD: A list of learning objectives for leadership competence was generated and reviewed by 12 experts using the Delphi method. The consensuses objectives were embedded into a four-year nursing baccalaureate curriculum in Taiwan. Nursing students (N = 120) who participated in the courses evaluated the embedded objectives of leadership competency introduced in their undergraduate nursing program. Leadership competence was improved among students on nine items (t = 2.282 to 5.741, p = .001 to .030) of the Nursing Leadership Competence Assessment Scale for Undergraduate Nursing Students. CONCLUSION: The results can serve as a reference for universities seeking to promote nursing leadership education.

Asunto(s)

Bachillerato en Enfermería , Educación en Enfermería , Estudiantes de Enfermería , Competencia Clínica , Curriculum , Humanos , Liderazgo