Long-term safety and efficacy of the anti-tissue factor pathway inhibitor marstacimab in participants with severe haemophilia: Phase II study results.

Marstacimab, an investigational human monoclonal antibody targeting tissue factor pathway inhibitor, demonstrated safety and efficacy in preventing bleeding episodes in patients with haemophilia. This multicentre, open-label study investigated safety, tolerability, and efficacy of long-term weekly prophylactic marstacimab treatment in participants with severe haemophilia A and B, with or without inhibitors. Adult participants were enrolled from a previous phase Ib/II study or de novo and assigned to one of two subcutaneous (SC) marstacimab doses: once-weekly 300 mg or a 300-mg loading dose followed by once-weekly 150-mg doses, for up to 365 days. Study end-points included safety assessments and annualised bleeding rates (ABRs). Of 20 enrolled participants, 18 completed the study. Overall, 70% of participants had treatment-emergent adverse events, including injection site reactions, injection site haematoma, and haemarthrosis. No treatment-related serious adverse events or thrombotic events occurred. Across all dose cohorts, mean and median on-study ABRs ranged from 0 to 3.6 and 0 to 2.5 bleeding episodes/participant/year respectively, demonstrating comparable efficacy to that observed in the short-term parent study. No treatment-induced anti-drug antibodies were detected. Once-weekly SC marstacimab prophylaxis was well tolerated, with an acceptable safety profile, and maintained long-term efficacy up to 365 days. (Clinicaltrials.gov identifier, NCT03363321).

Factors affecting academic burnout of nursing students according to clinical practice experience.

BACKGROUND: Academic burnout has a negative effect on learning outcomes of nursing students. Factors affecting academic burnout may differ depending on whether or not they have experience in clinical practice and identifying these differences would be necessary to seek for strategies to lower academic burnout of nursing students. This study aimed to determine the effects of stress, depression, and anxiety on academic burnout according to the clinical practice experience of nursing students. METHODS: Data were collected from 171 female nursing students in South Korea. Self-report questionnaires from 83 participants without clinical practice experience and 88 with clinical practice experience were analyzed using descriptive statistics, χ2-tests, analysis of variance, t-test, Spearman correlation coefficient, and stepwise multiple regression. RESULTS: Academic burnout was positively correlated to stress (r = .52, p < .001), anxiety (r = .50, p < .001) and depression (r = .44, p < .001). In those students with no clinical practice experience, anxiety and depression explained for academic burnout by 44%, and those students with clinical practice experience, stress and major satisfaction explained for 33% of academic burnout. CONCLUSIONS: Universities and clinical institutions should establish a cooperative system to reduce stress, depression and anxiety and increase major satisfaction.

Solid-state colorimetric polydiacetylene liposome biosensor sensitized by gold nanoparticles.

Polydiacetylene (PDA), a conjugated polymer, has attracted attention for realization of a label-free real-time colorimetric biosensor because it exhibits large and rapid colorimetric responses upon the binding of biomolecules. This is due to the conformational distortion of its conjugated backbone. However, solid-state PDA biosensors for point-of-care diagnosis remain unexplored. We describe a highly sensitive solid-state biosensor based on PDA liposomes. We employed gold nanoparticles (AuNPs) on PDA liposomes as the molecular-binding-signal sensitizer, which provides additional conformational distortion in the backbone structure of PDA by exerting steric repulsion to the attached biomolecules. To prove the concept, AuNPs and a thrombin-binding-aptamer were individually functionalized on PDA liposomes, which were attached to a substrate for the detection of thrombin. We found that the sensitivity was enhanced 2.5 times in the presence of AuNPs compared with the case without AuNPs. Because the steric repulsion of the AuNPs is target-independent, we believe that our solid-state biosensor provides a path toward advanced solid-state biosensors.

Nanoparticle Linker-Controlled Molecular Wire Devices Based on Double Molecular Monolayers.

Highly conductive molecular wires are an important component for realizing molecular electronic devices and have to be explored in terms of interactions between molecules and electrodes in their molecular junctions. Here, new molecular wire junctions are reported to enhance charge transport through gold nanoparticle (AuNP)-linked double self-assembled monolayers (SAMs) of cobalt (II) bis-terpyridine molecules (e.g., Co(II)(tpyphS)2 ). Electrical characteristics of the double-SAM devices are explored in terms of the existence of AuNP. The AuNP linker in the Co(II)(tpyphS)2 -AuNP-Co(II)(tpyphS)2 junction acts as an electronic contact that is transparent to electrons. The weak temperature dependency of the AuNP-linked molecular junctions strongly indicates sequential tunneling conduction through the highest occupied molecular orbitals (HOMOs) of Co(II)(tpyphS)2 molecules. The electrochemical characteristics of the AuNP-Co(II)(tpyphS)2 SAMs reveal fast electron transfer through molecules linked by AuNP. Density functional theory calculations reveal that the molecular HOMO levels are dominantly affected by the formation of junctions. The intermolecular charge transport, controlled by the AuNP linker, can provide a rational design for molecular connection that achieves a reliable electrical connectivity of molecular electronic components for construction of molecular electronic circuits.

Anti-Diabetic Effects of Acankoreagenin from the Leaves of Acanthopanax Gracilistylus Herb in RIN-m5F Cells via Suppression of NF-κB Activation.

Diabetes mellitus is a chronic degenerative disease that causes long-term complications and represents a serious public health problem. In this manuscript, acankoreagenin isolated from the leaves of Acanthopanax gracilistylus (LAG) is thought to possess excellent anti-diabetic properties. In vitro, anti-diabetic activities were assessed based on the inhibitory activities with α-glucosidase (IC50 13.01 µM), α-amylase (IC50 30.81 µM), and PTP1B (IC50 16.39 µM). Acankoreagenin showed better anti-diabetic effects. Then, an investigation was performed to analyze the insulin secretion effects of the insulin-secreting cell line in RIN-m5F cells. It was found that acankoreagenin could increase the insulin release in RIN-m5F cells. It was also found that acankoreagenin reduced NO production, activity of caspase-3, and the reactive oxygen species levels in the cells injured by processing of cytokines. In western blotting, inactivation of NF-κB signaling was confirmed. Acankoreagenin (20 µM) showed a higher I-κBα expression and lower NF-κB expression than the control group and showed a better expression than the positive control L-NAME (1 mM) (p < 0.05). This study demonstrates the anti-diabetic effects of acankoreagenin in vitro and suggests acankoreagenin might offer therapeutic potential for treating diabetes mellitus.

Functional Molecular Junctions Derived from Double Self-Assembled Monolayers.

Information processing using molecular junctions is becoming more important as devices are miniaturized to the nanoscale. Herein, we report functional molecular junctions derived from double self-assembled monolayers (SAMs) intercalated between soft graphene electrodes. Newly assembled molecular junctions are fabricated by placing a molecular SAM/(top) electrode on another molecular SAM/(bottom) electrode by using a contact-assembly technique. Double SAMs can provide tunneling conjugation across the van der Waals gap between the terminals of each monolayer and exhibit new electrical functions. Robust contact-assembled molecular junctions can act as platforms for the development of equivalent contact molecular junctions between top and bottom electrodes, which can be applied independently to different kinds of molecules to enhance either the structural complexity or the assembly properties of molecules.

Factors Affecting the Field Adaptation of Early-Stage Nurses in South Korea.

Supporting early-stage nurses to adapt to the field and become proficient in nursing is important to improve the quality of patient care. This study aimed to determine the effects of the nursing work environment, nursing practice readiness, and optimism on the field adaptation of early-stage nurses. A descriptive survey was conducted among 209 early-stage nurses with ≤3 years of work experience at hospitals. The collected data were analyzed using descriptive statistics, the t-test, ANOVA, Pearson's correlation coefficients, and regression analysis with the SPSS Program. The participating nurses' mean field adaptation score was 2.90 ± 0.40 (total score = 5) and a significant positive correlation was found between nursing work environment (r = 0.61, p < 0.001), nursing practice readiness (r = 0.41, p < 0.001), and optimism (r = 0.26, p < 0.001). The regression analysis revealed that the nursing work environment (ß = 0.38, p < 0.001), job satisfaction (ß = 0.33, p < 0.001), nursing practice readiness (ß = 0.24, p < 0.001), and turnover intention (ß = 0.17, p = 0.001) significantly affect the field adaptation of early stage nurses; the explanatory power was 56.1% (F = 27.55, p < 0.001). The results suggest that to facilitate the field adaptation of early-stage nurses, the nursing work environment, job satisfaction, and nursing practice readiness should be improved. Improvement in the nursing work environment and the development of additional training for field adaptation would enhance the ability of early-stage nurses to adapt to the field and, consequently, improve the quality of nursing care.

A double-blind, randomized, placebo-controlled study assessing the efficacy and tolerability of desvenlafaxine 10 and 50 mg/day in adult outpatients with major depressive disorder.

BACKGROUND: In an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder. METHODS: Adult outpatients with DSM-IV-defined major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HAM-D(17)) total score ≥20 were randomly assigned to receive placebo or desvenlafaxine (10 or 50 mg/day) after a 6- to 14-day single-blind placebo lead-in period in an 8-week, phase 3, fixed-dose trial. The primary efficacy measure was change from baseline in the HAM-D(17) score analyzed using analysis of covariance. Efficacy analyses were conducted with the intent-to-treat population, using the last observation carried forward. RESULTS: The intent-to-treat population included 673 patients. Change from baseline to final evaluation in adjusted HAM-D(17) total scores was not significantly different comparing desvenlafaxine 10 mg/day (-9.28) and desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42). There were no differences among treatment groups in the rates of treatment response or remission. Discontinuations due to adverse events occurred in 1.8%, 0.9%, and 1.8% of patients in the placebo and desvenlafaxine 10- and 50-mg/day groups, respectively. Overall rates of treatment-emergent adverse events with both doses were similar to placebo. CONCLUSIONS: Both doses of desvenlafaxine failed to separate from placebo. However, in a companion study reported separately, desvenlafaxine 50 mg, but not 25 mg, separated from placebo. Taken together, these studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. CLINICALTRIALS.GOV IDENTIFIER: NCT00863798 http://clinicaltrials.gov/ct2/show/NCT00863798?term=00863798&rank=1.

Can commonly used hydrazine produce n-type graphene?

A simple chemical method to obtain bulk quantities of N-doped, reduced graphene oxide (rGO) sheets (see figure) as an n-type semiconductor through the treatment of as-prepared GO sheets with the commonly used reducing reagent hydrazine, followed by rapid thermal annealing (RTA) is described.

Effect of Stress on Quality of Life of Shift Nurses in Tertiary General Hospital: The Mediating Effect of Mindfulness.

The purpose of this study was to examine the mediating effects of mindfulness on the relationships between stress and quality of life among shift nurses. A descriptive cross-sectional survey design was conducted using purposive sampling of 206 shift nurses in a tertiary general hospital in Korea. Data were analyzed with descriptive statistics, Pearson correlation and multiple regression analysis using SPSS/WIN 26.0 program. There were significant correlations among stress, mindfulness and quality of life. The quality of life had a positive correlation with mindfulness (r = 0.52, p < 0.001) and a negative correlation with stress among nurses. Mindfulness acts as a mediator in explaining relationship between stress and quality of life. This study provide evidence for the role of mindfulness in the relationship between stress and quality of life in shift nurses. Mindfulness appears to be a protective factor against nurses' stress. If mindfulness-based interventions are developed and applied to improve the quality of life of shift nurses based on this study, it can help reduce their stress and improve the quality of life, which could ultimately improve the quality of nursing care for patients.

Factors Affecting the Quality of Work Life of Nurses at Tertiary General Hospitals in the Context of the COVID-19 Pandemic.

The prolonged coronavirus disease 2019 (COVID-19) pandemic has caused an overload of work for nurses and resulted in high levels of stress. Improving the quality of work life may be a useful mediator for these demands. The purpose of this study was to identify factors affecting work stress, turnover intention, mindfulness, and quality of work life in nurses working in tertiary general hospitals. The participants of this study were 207 female nurses working in tertiary general hospitals with more than six months of clinical experience. Data were collected using an online Google survey. Data were analyzed using the SPSS/WIN 26.0 program. The mean score for the quality of work life was 3.81 ± 0.53 out of six points. The quality of work life was negatively correlated with job stress (r = −0.36, p < 0.001) and turnover intention (r = −0.45, p < 0.001) and positively correlated with mindfulness (r = 0.35, p < 0.001). Factors affecting quality of work life were work satisfaction (ß = 0.27, p = 0.004), job stress (ß = −0.23, p < 0.001), and turnover intention (ß = −0.18, p = 0.016). As a result, positive factors such as work satisfaction had stronger effects than negative factors. Thus, it would be necessary to seek strategies such as improving compensation for nurses, enhancing teamwork, or establishing a support system for managers, superiors, and colleagues.

Effect of Sleep Quality and Depression on Married Female Nurses' Work-Family Conflict.

Married female nurses experience work-family conflict (WFC) as they manage excessive work and various working-hour types while rearing children and tending household chores, and as a result, they continuously constantly deliberate over quitting their job or moving to a different workplace. Married nurses were found to have shorter sleep duration and sleep latency compared to single nurses, and high job stress not only hinders their family life but also causes sleep problems. Depression is a classic negative emotion experienced by married working women who must manage both work and family. This study aims to examine WFC in married female nurses and investigate its predictors, namely depression and sleep quality. A total of 229 married female nurses completed a Google questionnaire link consisting of the Work-Family Conflict Scale, Sleep-Quality Scale, and the Center for Epidemiologic Studies Depression Scale (CES-D). Data were analyzed by descriptive statistics, t-test, ANOVA, LSD post hoc test, Pearson's correlation coefficients, and multiple regression using the SPSS/WIN 26.0 program. The average WFC score was 4.84 ± 1.12 (range 1-7); WFC showed a statistical difference according to a stage of the lifecycle (F = 7.12, p = 0.001) and perceived health (F = 12.01, p < 0.001). WFC was low among those in the non-parenthood stage of the lifecycle (ß = -0.26, p < 0.001), those with good (ß = -0.18, p = 0.011) or moderate perceived health (ß = -0.15, p = 0.023), and those without turnover intention (ß = -0.13, p = 0.016). On the other hand, WFC was high among those who were extremely dissatisfied with their job (ß = 0.16, p = 0.008) and those who had a high level of depression (ß = 0.22, p = 0.002); these variables explained 20.2% of WFC (F = 7.663, p < 0.001). Based on these results, subsequent studies should develop and implement coping programs that help reduce WFC and improve depression and sleep quality in married female nurses.

Initial Clinical Practicum Stress among Nursing Students: A Cross-Sectional Study on Coping Styles.

Nursing students experience various stressors during their initial clinical practicum. As these stressors negatively affect learning and performance, coping strategies are essential. Therefore, this research study explored the relationship between coping styles and stress levels using a cross-sectional study with a convenience sample of 184 nursing students. Clinical practicum stress and coping styles were assessed via electronic questionnaires, and the data were analyzed using descriptive statistics, t-tests, and variance analyses. The highest score for clinical practice stress was for the practical education environment and practical work burden. The total stress score differed significantly according to coping style (t = -2.36, p = 0.020), and the total stress score of the passive coping group was higher. Among the sub-categories of stress, the scores of the education environment (t = -2.68, p = 0.008) and having undesirable role models (t = -2.14, p = 0.034) were significantly higher in the passive coping group. Although practical work burden was the highest stress factor in the active coping style group, the stress on the environment was highest in the passive coping group. The findings show that professors and clinical educators should recognize the various coping styles and incorporate different teaching methods in the clinical setting.

The effects of multiple doses of rolofylline on the single-dose pharmacokinetics of midazolam in healthy subjects.

Rolofylline is a potent, selective adenosine A1 receptor antagonist that was under development for the treatment of patients with acute decompensated heart failure and renal function impairment. This was a phase I, randomized, open-label, 2-period, fixed-sequence study in 19 healthy adult volunteers to examine the effect of multiple intravenous rolofylline doses on the single-dose pharmacokinetics of midazolam, a sensitive CYP3A4 substrate. In period 1, subjects received a single oral dose of midazolam 7.5 mg on day 1. In period 2, subjects received 30 mg, 4-hour infusions of rolofylline (intended clinical dose and duration) once daily for 4 consecutive days; midazolam 7.5 mg was coadministered on day 4. The geometric mean ratios and 90% confidence intervals for AUC0-infinity and Cmax of midazolam in the presence/absence of rolofylline were 1.20 (1.12-1.29) and 1.17 (1.03-1.32), respectively. The apparent terminal half-life (t1/2) for midazolam was similar in the presence/absence of rolofylline (4.31 and 4.27 hours, respectively). The geometric mean ratios (90% confidence intervals) for AUC0-infinity and Cmax of 1'-hydroxymidazolam in the presence/absence of rolofylline were 1.04 (0.96-1.13) and 0.98 (0.84-1.14), respectively. The t1/2 for 1'-hydroxymidazolam was slightly higher in the presence relative to absence of rolofylline (4.24 and 3.17 hours, respectively). Multiple doses of intravenous rolofylline 30 mg for 4 days were generally well tolerated and did not result in clinically important inhibition of CYP3A4 as indicated by little or no change in the pharmacokinetics of midazolam.

Effects of the organizational culture type, job satisfaction, and job stress on nurses' happiness: A cross-sectional study of the long-term care hospitals of South Korea.

AIM: It was aimed to explore the effects of the long-term-care (LTC) hospital-nurse organizational culture type, job satisfaction, and job stress on nurses' happiness. METHODS: Included were 226 participants who were randomly selected among the nurses who were working in 17 LTC hospitals with ≥100 beds, located in five cities in South Korea. A multiple regression analysis was carried out in order to examine the factors affecting the happiness of the nurses. RESULTS: The happiness of the LTC hospital nurses was not high. Regarding the factors affecting their happiness, a higher feeling of happiness was evident when the estimation of their subjective health status was healthier, when they were in an organization with hierarchy-oriented culture properties, when they expressed a higher job satisfaction regarding autonomy, and when the number of task requests was lower. Among these factors, autonomy-based job satisfaction exerts the greatest effect. CONCLUSION: Based on these results, the development of personal health improvement programs for nurses' happiness should be required. In addition, hospitals need to be stably operated and managed to ensure organizational safety and the nurse managers should encourage the nurses to carry out their tasks with autonomy.

Artemisia princeps Inhibits Growth, Biofilm Formation, and Virulence Factor Expression of Streptococcus mutans.

This study was designed to determine whether the ethanol extract of Artemisia princeps could inhibit the cariogenic activity of Streptococcus mutans. The increase in acid production and biofilm formation by S. mutans were evaluated. The expression levels of virulence factor genes were determined by performing the real-time polymerase chain reaction (PCR). The bactericidal effect was tested by confocal laser scanning microscopy. The A. princeps extract was observed to inhibit the growth of S. mutans at concentrations >0.05 mg/mL (P < .05). After using the safranin staining method, we found that the A. princeps extract had an inhibitory effect against biofilm formation at a concentration of >0.05 mg/mL. These experimental results were similar to that observed with the scanning electron microscopy. The results of the confocal microscopy revealed that the A. princeps extract at high concentrations of 0.4-3.2 mg/mL showed a bactericidal effect in a concentration-dependent manner. According to the results of the real-time PCR analysis, it was observed that the A. princeps extract inhibited the expression of virulence factor genes. These results suggest that A. princeps may inhibit the cariogenic activity of S. mutans, and may be useful as an anticariogenic agent.

Characteristics of nursing students with high levels of academic resilience: A cross-sectional study.

BACKGROUND: Academic resilience is an important characteristic that helps nursing students, who must engage in intensive learning and clinical practice, to overcome academic stress and adapt to their school and the clinical field. OBJECTIVES: To determine the characteristics of nursing students with high academic resilience. DESIGN: This study used a cross-sectional design. SETTING: Three universities in South Korea. SUBJECTS: We recruited a convenience sample of 254 nursing students. METHODS: Academic resilience, general characteristics, clinical practice stress, clinical practice satisfaction, and social-affective capability were assessed via self-reported questionnaires. The collected data were analyzed using descriptive statistics, chi-squared test, and analysis of variance with Tukey's post hoc test. RESULTS: The mean academic resilience score was 3.79. A greater proportion of respondents with high levels of academic resilience had good interpersonal relationships (χ2 = 35.175, p < .001), high academic grades (χ2 = 30.968, p < .001), a role model (χ2 = 9.770, p = .033), and high satisfaction with their major (χ2 = 20.214, p = .001). Significant differences in the subscale scores for clinical practice stress, including burden of clinical tasks (F = 4.727, p = .010), conflict of interpersonal relations (F = 4.889, p = .008), and conflict with patients (F = 7.023, p = .001), were found among the academic resilience groups. We also observed differences in the subscale scores of clinical practice satisfaction, including practice content (F = 4.894, p = .008) and practice environment (F = 8.301, p < .001). Respondents in the high resilience group had higher social-affective capability scores than did those with lower resilience (F = 43.994, p < .001). CONCLUSION: Based on our results, students with high academic resilience are more likely to continue their studies and benefit from programs that strengthen their social-affective capability. We therefore propose that nursing school curriculum focus on enhancing social-affective capability.

FeIn2S4 Nanocrystals: A Ternary Metal Chalcogenide Material for Ambipolar Field-Effect Transistors.

An ambipolar channel layer material is required to realize the potential benefits of ambipolar complementary metal-oxide-semiconductor field-effect transistors, namely their compact and efficient nature, reduced reverse power dissipation, and possible applicability to highly integrated circuits. Here, a ternary metal chalcogenide nanocrystal material, FeIn2S4, is introduced as a solution-processable ambipolar channel material for field-effect transistors (FETs). The highest occupied molecular orbital and the lowest unoccupied molecular orbital of the FeIn2S4 nanocrystals are determined to be -5.2 and -3.75 eV, respectively, based upon cyclic voltammetry, X-ray photoelectron spectroscopy, and diffraction reflectance spectroscopy analyses. An ambipolar FeIn2S4 FET is successfully fabricated with Au electrodes (EF = -5.1 eV), showing both electron mobility (14.96 cm2 V-1 s-1) and hole mobility (9.15 cm2 V-1 s-1) in a single channel layer, with an on/off current ratio of 105. This suggests that FeIn2S4 nanocrystals may be a promising alternative semiconducting material for next-generation integrated circuit development.