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Background: The switching/sucrose non-fermentable (SWI/SNF) Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A (SMARCA) member 2 and member 4 (SMARCA2/4) are paralogs and act as the key enzymatic subunits in the SWI/SNF complex for chromatin remodeling. However, the role of SMARCA2/4 in DNA damage response remains unclear. Methods: Laser microirradiation assays were performed to examine the key domains of SMARCA2/4 for the relocation of the SWI/SNF complex to DNA lesions. To examine the key factors that mediate the recruitment of SMARCA2/4, the relocation of SMARCA2/4 to DNA lesions was examined in HeLa cells treated with inhibitors of Ataxia-telangiectasia-mutated (ATM), Ataxia telangiectasia and Rad3-related protein (ATR), CREB-binding protein (CBP) and its homologue p300 (p300/CBP), or Poly (ADP-ribose) polymerase (PARP) 1/2 as well as in H2AX-deficient HeLa cells. Moreover, by concomitantly suppressing SMARCA2/4 with the small molecule inhibitor FHD286 or Compound 14, the function of SMARCA2/4 in Radiation sensitive 51 (RAD51) foci formation and homologous recombination repair was examined. Finally, using a colony formation assay, the synergistic effect of PARP inhibitors and SMARCA2/4 inhibitors on the suppression of tumor cell growth was examined. Results: We show that SMARCA2/4 relocate to DNA lesions in response to DNA damage, which requires their ATPase activities. Moreover, these ATPase activities are also required for the relocation of other subunits in the SWI/SNF complex to DNA lesions. Interestingly, the relocation of SMARCA2/4 is independent of γH2AX, ATM, ATR, p300/CBP, or PARP1/2, indicating that it may directly recognize DNA lesions as a DNA damage sensor. Lacking SMARCA2/4 prolongs the retention of γH2AX, Ring Finger Protein 8 (RNF8) and Breast cancer susceptibility gene 1 (BRCA1) at DNA lesions and impairs RAD51-dependent homologous recombination repair. Furthermore, the treatment of an SMARCA2/4 inhibitor sensitizes tumor cells to PARP inhibitor treatment. Conclusions: This study reveals SMARCA2/4 as a DNA damage repair factor for double-strand break repair.

Abstract Background Interprofessional education (IPE) has the potential to shape students’ collaboration perception and interprofessional identity but remains understudied. This study aims to understand the effects of the IPE program as a contextual trigger to promote collaboration perception change and interprofessional identity formation among healthcare professional students. Methods Using concurrent triangulation mixed-methods, we examined the relationship between collaboration perception and interprofessional identity change among health profession students (N = 263), and explored their perspectives on how their IPE experiences influenced their perception and identity. Participants completed the Interdisciplinary Education Perception Scale and Extended Professional Identity Scale and responded to open-ended questions before and after the IPE intervention. Pearson’s correlation, t-tests, regression (quantitative), and thematic analysis (qualitative) were conducted. Results Teams with initially lower collaboration perception (M = 3.59) and lower interprofessional identity (M = 3.59) showed a significant increase in collaboration perception (M = 3.76, t = 2.63; p = .02) and interprofessional identity (M = 3.97, t = 4.86; p

Abstract Real‐world data (RWD) and real‐world evidence (RWE) are increasingly used to support regulatory decision making, but regulatory agencies and stakeholders may apply different definitions for RWD and use different criteria to determine when analysis of such data are considered RWE in decisions on drug approvals. To explore this issue, we reviewed two prominent publications that operationalized the definitions of RWD and RWE when describing the use of RWE in drug approvals by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Both publications considered noninterventional (observational) studies, RWD as a comparator arm for a single‐arm trial, product‐related literature reviews, and RWD to support clinical trial implementation (e.g., to identify potential participants) as generating RWE. In contrast, inconsistencies were identified regarding types of data sources and study designs that were considered as not generating RWE. For example, a lack of agreement existed regarding whether RWE is generated when RWD describe therapeutic contexts or are used in phase I/II interventional trials, open‐label extension studies, or pharmacovigilance activities. These discrepancies highlight opportunities to develop a consistent understanding of the role of RWE in regulatory decision making for drug approvals among regulatory agencies and stakeholders.

Abstract Background Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients’ lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient’s perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety. Methods A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient’s MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes. Discussion This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice. Trial registration This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.gov NCT04979546 . Registered on July 28, 2021.

Abstract Background Volunteers have been a valuable resource in supporting people with dementia and their caregivers in the community. However, factors such as misconceptions, negative attitudes towards dementia, and a lack of motivation might impact the quality of volunteer care. The present paper aims to examine the effect of training and service provision on the knowledge and attitudes of volunteers towards dementia and the association between knowledge and attitudes with the levels of motivation to volunteer. Methods The present study is part of an effectiveness-implementation cluster randomized clinical hybrid trial using a music-with-movement intervention to promote the well-being of people with dementia and their informal caregivers. Volunteers were recruited to receive training to support the delivery of the intervention. Training and enrichment workshops were offered to volunteers during the one-year project. Before and after their training and service, the recruited volunteers were asked to complete the following assessments: Dementia Attitudes Scale, and the Alzheimer’s Disease Knowledge Scale. The levels of motivation to volunteer was measured with Volunteer Functions Inventory at baseline. Wilcoxon signed-rank test and multiple regression test were applied for statistical analyses. Results A total of 107 volunteers were recruited, and 81 of them completed a mean period of 47.32 weeks of training and service. Significant improvements in their total score on the Alzheimer’s Disease Knowledge Scale (p = .009) and Dementia Attitudes Scale (p

Abstract Background The prevalence of fatigue and sleep disturbances is high in stroke populations. Sleep quality can be targeted by interventions to alleviate fatigue following a stroke. This study aimed to determine the prevalence of fatigue and poor sleep quality, and to quantify the contribution of sleep quality to fatigue following a stroke, in chronic (≥1 year) stroke survivors. Methods A cross-sectional design was adopted. A total of 112 stroke survivors (mean age ± standard deviation [year], 64.18 ± 5.77) at 6.08 ± 4.80 years post-stroke completed this study. All participants were assessed using the Fatigue Assessment Scale, the Pittsburgh Sleep Quality Index, the Visual Analogue Scale-Pain, the Fugl-Meyer Assessment of the upper and lower extremities, the 5-Time Sit-To-Stand Test, the Epworth Sleepiness Scale, the Frenchay Activities Index, the Life-Space Assessment, the Community Integration Measure, and the Multidimensional Scale of Perceived Social Support. Pearson and partial correlation coefficients were used to examine the correlation between fatigue and other variables. A multiple linear regression (the forced entry method) was performed to quantify the independent contribution of sleep quality to prediction of fatigue. Results Of the 112 participants, 52.7% reported experiencing fatigue and 64.3% reported poor sleep quality. Sleep quality could independently account for 5.9% of the variance in fatigue scores after a stroke. Conclusions There is a high prevalence of fatigue and poor sleep quality in Chinese stroke survivors. Sleep quality is an independent predictor of fatigue in those living in the community who have survived a stroke for a year or longer.

Introduction: : Lack of health literacy for smoking nurses has worsened image of nursing services. The role of leader can be a support in increasing behavior change of nurses who smoke. The aimed to find out health literacy of smokers in nursing staff through interpersonal role of the head of the room by intervention based on Peplau’s model. Methods: A quasi-experimental research with a pre-and post-control group design, using modification questionnaire of knowledge and behavior. The target population was nurses living in Singkawang who smoke in a hospital. Sample was 35 respondents for each group (controlling group and intervention group) using purposive sampling. Dependent variable is health literacy among nurses who smoke and independent variable is intervention based on Peplau’s model. Intervention is in the form of a guide module consisting of strengthening health literacy (health awareness, self-reflection, cognitive competence and behavioral interpersonal relationships in the head of the room) and will be implemented to nurses who smoke. Analysis data for bivariate used paired t – test and for multivariate used the McNemar test. Results: The research showed that the difference before and after intervention was 2.23 (p = 0.001) and control group was 8.00 with a default value of 0.870 deviation. The results showed a significant increase in health literacy in nurse smokers through the role of interpersonal head nurse (p=0.001). Conclusion:Role of head of room in interpersonal relationship with Peplau’s model affects the health literacy of nursing staff who smoke.

Clinical assessment of pupil appearance and pupillary light reflex (PLR) may inform us the integrity of the autonomic nervous system (ANS). Current clinical pupil assessment is limited to qualitative examination, and relies on clinical judgment. Infrared (IR) video pupillography combined with image processing software offer the possibility of recording quantitative parameters. In this study we describe an IR video pupillography set-up intended for human and animal testing. As part of the validation, resting pupil diameter was measured in human subjects using the NeurOptics? (Irvine, CA, USA) pupillometer, to compare against that measured by our IR video pupillography set-up, and PLR was assessed in guinea pigs. The set-up consisted of a smart phone with a light emitting diode (LED) strobe light (0.2 s light ON, 5 s light OFF cycles) as the stimulus and an IR camera to record pupil kinetics. The consensual response was recorded, and the video recording was processed using a custom MATLAB program. The parameters assessed were resting pupil diameter (D1), constriction velocity (CV), percentage constriction ratio, re-dilation velocity (DV) and percentage re-dilation ratio. We report that the IR video pupillography set-up provided comparable results as the NeurOptics? pupillometer in human subjects, and was able to detect larger resting pupil size in juvenile male guinea pigs compared to juvenile female guinea pigs. At juvenile age, male guinea pigs also had stronger pupil kinetics for both pupil constriction and dilation. Furthermore, our IR video pupillography set-up was able to detect an age-specific increase in pupil diameter (female guinea pigs only) and reduction in CV (male and female guinea pigs) as animals developed from juvenile (3 months) to adult age (7 months). This technique demonstrated accurate and quantitative assessment of pupil parameters, and may provide the foundation for further development of an integrated system useful for clinical applications. [ABSTRACT FROM AUTHOR]

Abstract Aim To validate the 4‐ and 7‐point Chinese Non‐pharmacological Therapy Experience Scales and test the psychometric properties of the scales on persons with intellectual disability. Design A validation study. Methods Sixty‐seven persons with intellectual disability were recruited from six hostels or centres for persons with intellectual disability in Hong Kong. A total of 1,163 and 1,161 observations were collected by the trained observers with the 4‐point and 7‐point scales, respectively. The floor and ceiling effects, inter‐rater reliability, internal consistency, responsiveness of both scales and the scale equivalence were examined. Results The Cronbach's α of the 4‐ and 7‐point scales was .762 and .797, respectively. The correlation between the two scales was 0.906. The inter‐rater reliability of the 4‐ and 7‐point scales was 0.774 and 0.835, respectively. Neither scale had the floor or ceiling effects. The effect size of the 7‐point scale was consistently higher than that of the 4‐point scale.

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[This corrects the article DOI: 10.1371/journal.pone.0181780.].

INTRODUCTION:Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). MATERIALS AND METHODS:English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. RESULTS:Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. CONCLUSIONS:A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.