Enterovirus-A71 exploits RAB11 to recruit chaperones for virus morphogenesis.

BACKGROUND: Enterovirus 71 (EV-A71) causes Hand, Foot and Mouth Disease (HFMD) in children and has been associated with neurological complications. The molecular mechanisms involved in EV-A71 pathogenesis have remained elusive. METHODS: A siRNA screen in EV-A71 infected-motor neurons was performed targeting 112 genes involved in intracellular membrane trafficking, followed by validation of the top four hits using deconvoluted siRNA. Downstream approaches including viral entry by-pass, intracellular viral genome quantification by qPCR, Western blot analyses, and Luciferase reporter assays allowed determine the stage of the infection cycle the top candidate, RAB11A was involved in. Proximity ligation assay, co-immunoprecipitation and multiplex confocal imaging were employed to study interactions between viral components and RAB11A. Dominant negative and constitutively active RAB11A constructs were used to determine the importance of the protein's GTPase activity during EV-A71 infection. Mass spectrometry and protein interaction analyses were employed for the identification of RAB11A's host interacting partners during infection. RESULTS: Small GTPase RAB11A was identified as a novel pro-viral host factor during EV-A71 infection. RAB11A and RAB11B isoforms were interchangeably exploited by strains from major EV-A71 genogroups and by Coxsackievirus A16, another major causative agent of HFMD. We showed that RAB11A was not involved in viral entry, IRES-mediated protein translation, viral genome replication, and virus exit. RAB11A co-localized with replication organelles where it interacted with structural and non-structural viral components. Over-expression of dominant negative (S25N; GDP-bound) and constitutively active (Q70L; GTP-bound) RAB11A mutants had no effect on EV-A71 infection outcome, ruling out RAB11A's involvement in intracellular trafficking of viral or host components. Instead, decreased ratio of intracellular mature viral particles to viral RNA copies and increased VP0:VP2 ratio in siRAB11-treated cells supported a role in provirion maturation hallmarked by VP0 cleavage into VP2 and VP4. Finally, chaperones, not trafficking and transporter proteins, were found to be RAB11A's top interacting partners during EV-A71 infection. Among which, CCT8 subunit from the chaperone complex TRiC/CCT was further validated and shown to interact with viral structural proteins specifically, representing yet another novel pro-viral host factor during EV-A71 infection. CONCLUSIONS: This study describes a novel, unconventional role for RAB11A during viral infection where it participates in the complex process of virus morphogenesis by recruiting essential chaperone proteins.

Motivations and experiences of patients with advanced cancer participating in Phase 1 clinical trials: A qualitative study.

BACKGROUND: Persons with advanced cancer may participate in Phase 1 clinical trials - first-in-human trials that are conducted with the main objectives of safety and dosing. The motivations for participation are not well understood and may include hope for cure. AIM: To explore the perspectives of persons with advanced cancer in order to understand the motivations for participating in Phase 1 clinical trials, experiences while being on trial and views on palliative care provision. DESIGN: Qualitative study with a constructivist stance, using thematic analysis based upon the grounded theory approach. SETTING/PARTICIPANTS: 20 persons with advanced cancer who were participating in a Phase 1 clinical trial. RESULTS: Many participants described how Phase 1 clinical trial participation was their last hope, as they were cognisant of their advanced disease. Information-seeking needs differed - some needed comprehensive information while others relied on the doctor's recommendation. Participants experienced varied negative and positive physical and psycho-emotional concerns, and needed to draw on multiple sources of support such as family, friends and healthcare professionals. Some could list potential benefits of palliative care but felt they did not require it yet. The overarching theme was hope and positive thinking as a way of coping. CONCLUSIONS: The concepts of hope as a way of coping and the supportive presence of healthcare professionals could be weaved into a future model of palliative care to improve the illness journey for patients considering Phase 1 clinical trial participation and other persons with advanced cancer.

Is telehealth an effective and feasible option for improving falls-related outcomes in community-dwelling adults with neurological conditions? A systematic review and meta-analysis.

OBJECTIVE: To determine the effectiveness of telehealth interventions in reducing community falls risk or rates compared to equivalent in-person interventions in adults with neurological conditions. DATA SOURCES: Eight electronic databases, trial registries and search engines were searched for the concepts 'falls', 'neurological conditions', and 'telehealth', limited to English language, from inception until August 2022. REVIEW METHODS: Search for original research where the intervention was delivered via synchronous videoconferencing with the aim of reducing falls and falls-related outcomes. Screening and risk of bias assessment were completed by two independent researchers. Outcome data included falls rates, falls-related outcomes, safety, feasibility, and acceptability. Risk of bias was assessed using the ROB-2 and ROBINS-I tools. Quality of evidence was rated with the grading of recommendations, assessment, development and evaluation (GRADE) approach. RESULTS: Seventeen studies with 581 participants were included; six were randomised controlled trials. Risk of bias ranged from low to high. Only one study (n = 76) reported falls and did not find differences between telehealth and in-person physiotherapy. There was low-quality evidence that telehealth interventions improve balance outcomes more than face-to-face interventions (pooled between-group mean difference 2.48 Berg Balance Scale units, 95%CI 0.77 to 4.20). Fear of falling was not different between intervention delivery modes. CONCLUSION: Findings suggest that telehealth delivered falls prevention interventions are safe, feasible and acceptable in community-dwelling adults with neurological conditions, however, data related to effectiveness in reducing falls is limited. Low-quality evidence suggests that telehealth may deliver similar or better outcomes for standing balance in this population.PROSPERO Registration: (CRD42021240167).

Genome-wide association study of primary dysmenorrhea in the Taiwan Biobank validates associations near the NGF and IL1 gene loci.

Using the Taiwan Biobank, we aimed to identify traits and genetic variations that could predispose Han Chinese women to primary dysmenorrhea. Cases of primary dysmenorrhea included those who self-reported "frequent dysmenorrhea" in a dysmenorrhea-related Taiwan Biobank questionnaire, and those who have been diagnosed with severe dysmenorrhea by a physician. Controls were those without self-reported dysmenorrhea. Customized Axiom-Taiwan Biobank Array Plates were used to perform whole-genome genotyping, PLINK was used to perform association tests, and HaploReg was used to conduct functional annotations of SNPs and bioinformatic analyses. The GWAS analysis included 1186 cases and 24,020 controls. We identified 53 SNPs that achieved genome-wide significance (P < 5 × 10-8, which clustered in 2 regions. The first SNP cluster was on chromosome 1, and included 24 high LD (R2 > 0.88) variants around the NGF gene (lowest P value of 3.83 × 10-13 for rs2982742). Most SNPs occurred within NGF introns, and were predicted to alter regulatory binding motifs. The second SNP cluster was on chromosome 2, including 7 high LD (R2 > 0.94) variants around the IL1A and IL1B loci (lowest P value of 7.43 × 10-10 for rs11676014) and 22 SNPs that did not reach significance after conditional analysis. Most of these SNPs resided within IL1A and IL1B introns, while 2 SNPs may be in the promoter histone marks or promoter flanking regions of IL1B. To conclude, data from this study suggest that NGF, IL1A, and IL1B may be involved in the pathogenesis of primary dysmenorrhea in the Han Chinese in Taiwan.

Gender differences in health protective behaviours and its implications for COVID-19 pandemic in Taiwan: a population-based study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored. METHODS: We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2019 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors. RESULTS: A total of 1,990 participants (median age = 45·92 years, 49% were women) were included. Significant gender disparities (p < .001) were observed. The risk perception of pandemic (OR = 1·28, 95% CI [1·21 - 1·35], p < .001), older age (OR = 1·06, 95% CI [1·05 - 1·07], p < .001), female gender (OR = 1·18, 95% CI [1·09-1·27], p < .001), higher education (OR = 1·10, 95% CI [1·06 - 1·13], p < .001), and larger family size (OR = 1·09, 95% CI [1·06 - 1·15], p < .001) were positively associated with health protective behaviors. The risk perception of pandemic (OR = 1·25, 95% CI [1·15 - 1·36]), higher education (OR = 1·07, 95% CI [1·02 - 1·13], p < .05), being married (OR = 1·17, 95% CI [1·01-1·36, p < .05), and larger family size (OR = 1·33, 95% CI [1·25 - 1·42], p < .001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR = 0·85, 95% CI [0·75 - 0·90], p < ·01) and to comply with contact-tracing (OR = 0·95, 95% CI [0·90 - 1·00], p < .05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR = 0·77, 95% CI [0·66 - 0·90], p < .001). CONCLUSION: This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics.

Janus Particle Preparation through UV-Induced Partial Photodegradation of Spin-Coated Particle Films.

Janus particles contain two or more chemical properties typically on opposing faces. With various property combinations possible, there are several potential applications, such as surfactants and drug delivery. However, scaling up the particle production process at reasonable cost is a limiting factor, and the method reported here aims to circumvent this issue. The process is based on a top-down destructive strategy that consists of two steps. Photocatalytic titanium dioxide particles prefunctionalized with a surface coating were assembled as particle films via spin-coating on a substrate. The particle films were placed directly under an ultraviolet light source, which induced the photodegradation of the surface coating only on the particle surfaces exposed to the light. The generated Janus particles were amphiphobic-amphiphilic in character. The Janus particles had a theoretical Janus balance close to ideal and remained attached at a hexane/water interface after disruption. They were able to make Pickering emulsions of water in silicone oil with a low energy input. The reported method may be easily scaled up to facilitate the production of gram-scale yields. The use of UV is clean and efficient and can be applied to semiconductor particles with surface coatings that are susceptible to photodegradation, making this method highly versatile.

Targeting Glycolysis in Macrophages Confers Protection Against Pancreatic Ductal Adenocarcinoma.

Inflammation in the tumor microenvironment has been shown to promote disease progression in pancreatic ductal adenocarcinoma (PDAC); however, the role of macrophage metabolism in promoting inflammation is unclear. Using an orthotopic mouse model of PDAC, we demonstrate that macrophages from tumor-bearing mice exhibit elevated glycolysis. Macrophage-specific deletion of Glucose Transporter 1 (GLUT1) significantly reduced tumor burden, which was accompanied by increased Natural Killer and CD8+ T cell activity and suppression of the NLRP3-IL1ß inflammasome axis. Administration of mice with a GLUT1-specific inhibitor reduced tumor burden, comparable with gemcitabine, the current standard-of-care. In addition, we observe that intra-tumoral macrophages from human PDAC patients exhibit a pronounced glycolytic signature, which reliably predicts poor survival. Our data support a key role for macrophage metabolism in tumor immunity, which could be exploited to improve patient outcomes.

Improved protein A resin for antibody capture in a continuous countercurrent tangential chromatography system.

Continuous countercurrent tangential chromatography (CCTC) enables steady-state continuous bioprocessing with low-pressure operation and high productivity. CCTC has been applied to initial capture of monoclonal antibodies (mAb) from clarified cell culture harvest and postcapture polishing of mAb; however, these studies were performed with commercial chromatography resins designed for conventional column chromatography. In this study, a small particle size prototype agarose resin (20-25 µm) with lower cross-linking was co-developed with industrial partner Purolite and tested with CCTC. Due to increased binding capacity and faster kinetics, the resulting CCTC process showed more than a 2X increase in productivity, and a 2X reduction in buffer consumption over commercial protein A resins used in previous CCTC studies, as well as more than a 10X productivity increase versus conventional column operation. Single-pass tangential flow filtration was integrated with the CCTC system, enabling simple control of eluate concentration. A scale-up exercise was conducted to provide a quantitative comparison of CCTC and batch column chromatography. These results clearly demonstrate opportunities for using otherwise unpackable soft small particle size resins with CCTC as the core of a continuous bioprocessing platform.

Extended high cut-off haemodialysis for myeloma cast nephropathy in Auckland, 2008-2012.

Myeloma cast nephropathy contributes to high morbidity and early mortality associated with the development of end-stage renal disease. Treatment with extended high cut-off haemodialysis coupled with novel anti-myeloma therapies enables significant reduction of serum-free light chains and has been shown to improve renal outcomes. In this case series, medical records of 6 patients who received high cut-off haemodialysis for biopsy-proven cast nephropathy were retrospectively reviewed. Patients received a total of 344 hours of high cut-off haemodialysis and concurrent chemotherapy. Only 50% became dialysis independent following treatment. One patient who achieved sustained remission remained dialysis dependent. The added benefit of high cut-off haemodialysis in the light of novel anti-myeloma therapies requires further evaluation.

Utility of overnight oximetry indices in the evaluation of children with snoring and suspected obstructive sleep apnea.

STUDY OBJECTIVES: Optimal cutoff values of oximetry indices that differentiate obstructive sleep apnea (OSA) from primary snoring (PS) is not well established. Our study aimed to assess the utility of overnight oximetry indices in differentiating PS from OSA and assessing OSA severity, compared to polysomnography (PSG), in children with suspected OSA. METHODS: This was a retrospective study of children (1-18 years) with snoring who underwent PSG. Patients with Down syndrome, craniofacial anomalies, known genetic syndromes, neuromuscular conditions and central apnea index ≥ 5 were excluded. Demographic data, PSG variables and oximetry indices (e.g. oxygen desaturation index [ODI3, defined as number of ≥ 3% desaturation episodes/hour of artifact free recording time and SpO2 nadir]) were collected. RESULTS: Of 1,203 children (mean age 9.1±3.9 years, 67.7% males), 91.8% (847/923) ≤ 12 years and 84.3% (236/280) > 12 years had OSA. Optimal cutoff of ODI3 for differentiating PS from OSA was 2.4 [Se: 78.8% (75.9%-81.6%), Sp: 80.5% (69.9%-88.7%)] in ≤ 12 years and 3.6 [Se: 71.1% (64.8%-76.8%), Sp: 91.1% (78.8%-97.5%)] in > 12 years. The optimal cutoff of ODI3 for differentiating PS from mild, moderate and severe OSA categories were 2.0 [Se: 70.1% (65.3%-74.5%), Sp: 70.1% (58.6%-80.0%)]; 3.7 [Se: 82.3% (76.6%-87.1%), Sp: 94.8% (87.2%-98.6%)] and 4.3 [Se: 99.1% (96.8%-99.9%), Sp: 98.7% (93.0%-100.0%)] in ≤ 12 years; and 1.9 [Se: 78.8% (75.9%-81.6%), Sp: 80.5% (69.9%-88.7%)]; 4.1 [Se: 85.4% (72.2%-93.9%), Sp: 91.1% (78.8%-97.5%)] and 6.9 [Se: 98.4% (91.2%-100.0%), Sp: 97.8% (88.2%-99.9%)] in > 12 years, respectively. CONCLUSIONS: This study provides optimal cutoff values for ODI3 in differentiating PS from OSA and assessing OSA severity in children. As oximetry is cheaper and widely available, ODI3 has the potential to be incorporated into cost-effective clinical decision-making algorithms, especially in resource limited settings.

Facilitators and barriers to implementation of a patient and staff reported measure for screening of palliative concerns of patients with heart failure: a qualitative analysis using the Consolidated Framework for Implementation Research.

Background: Screening patients with patient-reported outcome measures allows identification of palliative care concerns. The Integrated Palliative Care Outcome Scale (IPOS) was developed in the United Kingdom for this purpose. Tools developed in another setting might not be readily usable locally. We previously evaluated the validity and reliability of the IPOS in our cardiology setting. However, it remains uncertain what factors would influence the subsequent implementation of IPOS for routine screening of patients with advanced heart failure in future practice. Objectives: This study aimed to identify the factors that could affect the IPOS implementation for patients with advanced heart failure. Design: This was a qualitative study conducted at the National Heart Centre Singapore. Methods: Patients with advanced heart failure who participated in our previous IPOS validation study were purposively recruited for semi-structured interviews. Healthcare workers caring for these patients and involved in the testing of the IPOS tool were also invited for interviews. The interviews were analyzed thematically and mapped to the Consolidated Framework for Implementation Research (CFIR). Results: Our analysis identified six potential facilitators and six potential barriers to implementation across five major domains of the CFIR (intervention characteristics, inner setting, outer setting, individual characteristics, and process). Facilitators include: (i) perception of utility, (ii) perception of minimal complexity, (iii) perception of relatability, (iv) conducive culture, (v) dedicated resources, and (vi) advocates for implementation. Barriers include: (i) need for adaptation, (ii) mindsets/role strains, (iii) resource constraints, (iv) cultural concerns, (v) individual needs, and (vi) change process. Conclusion: Institutions could focus on cultivating appropriate perceptions and conducive cultures, providing dedicated resources for implementation and introducing facilitators to advocate for implementation. Adaptation of IPOS to suit workflows and individual needs, consideration of change processes, and systemic changes to alleviate cultural, resource, and staff role strains would improve IPOS uptake during actual implementation in clinical services. Trial registration: Not applicable.

Deciding to Live (or Not) With a Left Ventricular Assist Device-a Thematic Analysis Exploring Factors Influencing the Decision-Making Process in Advanced Heart Failure Patients in Singapore.

Background: It is often difficult for patients with advanced heart failure (HF) to decide whether to live with a left ventricular assist device (LVAD) or not. Little is known about their decisional needs prior to LVAD implantation and if these needs were met in the Asian cultural setting. Aims: We aimed to explore the influences, concerns, and needs surrounding the decision-making process of the LVAD implantation among multi-ethnic Asian patients with HF. Methods: Semi-structured interviews with HF patients and caregivers were conducted, based upon the grounded theory approach. Participants were purposively recruited from the inpatient and outpatient setting of the National Heart Centre Singapore. Results: A total of 31 patients and 11 caregivers participated. Mindsets that shaped decision-making ranged from "having no choice," "being reflective," "taking a gamble," and "fighting on." Instead of making a sole decision, many patients reported that decisions were shared with the family or medical team. Current LVAD patients who acted as patient ambassadors were also strong influences. Spiritual support was pivotal to decision-making for some participants. Goals influencing decision-making including protecting the family and life prolongation improving quality of life. Values held close included sanctity of life, trusting in a higher power, believing in pre-destination or karma, and preserving family harmony. Participants had concerns about cost, employment, and health outcomes. Conclusions: Asian LVAD patients and caregivers had culturally specific mindsets, goals, and values and concerns around decision-making. Our findings have implications for the design of interventions and supportive care models.

Serum levels of copeptin predict adverse outcomes and improve risk prediction of TRISS and MGAP scores in patients with multiple trauma: A single-center prospective cohort study.

BACKGROUND: Multiple trauma deserves early prognostication and stratification. Copeptin, a precursor of vasopressin, is produced in response to stress. We examined the association between serum levels of copeptin and mortality risk in patients with multiple trauma. We aimed to also enhance the previously established Trauma-Related Injury Severity Score (TRISS) and Mechanism, GCS, Age, and Arterial Pressure (MGAP) score with the additional consideration of copeptin levels. METHODS: This single-center prospective cohort study enrolled patients who presented to the emergency department with potential major injuries. The serum levels of copeptin were measured, and the correlation to clinical severity in terms of 30-day mortality and requirement of intensive care management was analyzed. By combining copeptin levels with TRISS or MGAP, comparison between performance of the original models with the copeptin-enhanced models was performed via discrimination, calibration, and reclassification analyses. RESULTS: There was a significant increase in copeptin levels in patients who died within 30 days (median 644.4 pg/L, interquartile range [472.5, 785.9]) or were admitted to intensive care units (233.8 pg/L, [105.7, 366.4]), compared with those who survived (37.49 pg/L, [17.88, 77.68]). Adding the natural log of copeptin levels to the established TRISS and MGAP models improved the AUC of TRISS from 0.89 to 0.96, and that of MGAP from 0.82 to 0.95. Both calibrations as measured by Brier's scores and reclassification as measured by net reclassification improvement or integrated discrimination improvement demonstrated significant improvements. A Web-based calculator was built to generate predicted mortality rates of various models for convenient clinical use. CONCLUSION: Admission serum copeptin levels were correlated with clinical severity in multiple trauma. Coupling copeptin with preexisting trauma severity scores improved prediction accuracy. Copeptin shows promise as a novel biomarker for the prediction of trauma outcome. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Genome-phenome wide association study of broadly defined headache.

Until recently, most genetic studies of headache have been conducted on participants with European ancestry. We therefore conducted a large-scale genome-wide association study of self-reported headache in individuals of East Asian ancestry (specifically those who were identified as Han Chinese). In this study, 108 855 participants were enrolled, including 12 026 headache cases from the Taiwan Biobank. For broadly defined headache phenotype, we identified a locus on Chromosome 17, with the lead single-nucleotide polymorphism rs8072917 (odds ratio 1.08, P = 4.49 × 10-8), mapped to two protein-coding genes RNF213 and ENDOV. For severe headache phenotype, we found a strong association on Chromosome 8, with the lead single-nucleotide polymorphism rs13272202 (odds ratio 1.30, P = 1.02 × 10-9), mapped to gene RP11-1101K5.1. We then conducted a conditional analysis and a statistical fine-mapping of the broadly defined headache-associated loci and identified a single credible set of loci with rs8072917 supporting that this lead variant was the true causal variant on RNF213 gene region. RNF213 replicated the result of previous studies and played important roles in the biological mechanism of broadly defined headache. On the basis of the previous results found in the Taiwan Biobank, we conducted phenome-wide association studies for the lead variants using data from the UK Biobank and found that the causal variant (single-nucleotide polymorphism rs8072917) was associated with muscle symptoms, cellulitis and abscess of face and neck, and cardiogenic shock. Our findings foster the genetic architecture of headache in individuals of East Asian ancestry. Our study can be replicated using genomic data linked to electronic health records from a variety of countries, therefore affecting a wide range of ethnicities globally. Our genome-phenome association study may facilitate the development of new genetic tests and novel drug mechanisms.

Expanding the anti-flaviviral arsenal: Discovery of a baicalein-derived Compound with potent activity against DENV and ZIKV.

With approximately 3.8 billion people at risk of infection in tropical and sub-tropical regions, Dengue ranks among the top ten threats worldwide. Despite the potential for severe disease manifestation and the economic burden it places on endemic countries, there is a lack of approved antiviral agents to effectively treat the infection. Flavonoids, including baicalein, have garnered attention for their antimicrobial properties. In this study, we took a rational and iterative approach to develop a series of baicalein derivatives with improved antiviral activity against Dengue virus (DENV). Compound 11064 emerged as a promising lead candidate, exhibiting antiviral activity against the four DENV serotypes and representative strains of Zika virus (ZIKV) in vitro, with attractive selectivity indices. Mechanistic studies revealed that Compound 11064 did not prevent DENV attachment at the cell surface, nor viral RNA synthesis and viral protein translation. Instead, the drug was found to impair the post-receptor binding entry steps (endocytosis and/or uncoating), as well as the late stage of DENV infection cycle, including virus assembly/maturation and/or exocytosis. The inability to raise DENV resistant mutants, combined with significant antiviral activity against an unrelated RNA virus (Enterovirus-A71) suggested that Compound 11064 targets the host rather than a viral protein, further supporting its broad-spectrum antiviral potential. Overall, Compound 11064 represents a promising antiviral candidate for the treatment of Dengue and Zika.

Flow in contemporary musicians: Individual differences in flow proneness, anxiety, and emotional intelligence.

Flow is a highly focussed state of consciousness that is rewarding, fulfilling, and sought after by many, especially musicians. It is characterised by exceptional levels of concentration, loss of self-consciousness, and competent control over one's actions. Several personality and non-cognitive traits have been positively linked with flow proneness, such as emotional intelligence; however, anxiety is thought to be the antithesis of flow, yet the relationship between trait anxiety and flow proneness in musicians is not adequately characterised. This study investigated the individual differences in flow proneness in contemporary musicians (N = 664), focusing on the interaction of trait anxiety and emotional intelligence. We identified a significant negative correlation between trait anxiety and flow. Emotional intelligence was positively correlated with flow proneness and negatively with trait anxiety. Moderation analysis revealed a difference in the relationship between trait anxiety and flow depending on the level of emotional intelligence; there was no correlation in those with low emotional intelligence, whereas a strong negative relationship was found in those with high emotional intelligence. Finally, hierarchical regression indicated that musical training was the most substantial predictor of all the tested variables and that trait anxiety did not add any predictive power on top of the known predictors. Altogether, this study provided new insights into the possible disruption of flow proneness linked to high anxiety and low emotional intelligence in contemporary musicians.

Validity and Reliability of the Integrated Palliative Care Outcome Scale in Asian Heart Failure Patients.

Background: The Integrated Palliative Care Outcome Scale (IPOS) was developed in the United Kingdom for health assessment in advanced illness. Objectives: To evaluate the validity and reliability of a culturally adapted IPOS (both patient and staff versions) for heart failure (HF). Design/Setting: We recruited HF patients and staff from a tertiary hospital in Singapore. We collected patient IPOS, New York Heart Association (NYHA) status, Edmonton Symptom Assessment System (ESAS) and Minnesota Living with Heart Failure (MLHF) scores at baseline, and patient IPOS at follow-up. Each baseline patient IPOS was matched with a staff IPOS. Measurements: Pearson correlation coefficient (r) between ESAS, MLHF, and patient IPOS was calculated to assess construct validity. The two-sample T-test assessed difference in patient and staff IPOS scores across NYHA status and care settings for known-group validity. Internal consistency of patient and staff IPOS was assessed using Cronbach's alpha (α). Intraclass correlation coefficient (ICC) was used to assess test-retest reliability of patient IPOS and inter-rater reliability between patient and staff IPOS. Results: Ninety-one patients and 12 staff participated. There was strong convergent validity of total patient IPOS with MLHF (r = 0.78) and ESAS (r = 0.81). There were statistically significant differences in total IPOS across care settings (patient-IPOS: 8.05, staff-IPOS 13.61) and NYHA (patient-IPOS: 7.52, staff-IPOS 12.71).There was high internal consistency of total patient (α = 0.83) and staff IPOS (α = 0.88) and high test-retest reliability of patient IPOS (ICC 0.81). Inter-rater reliability (ICC) ranged between 0.82 and 0.91. Conclusion: The IPOS was valid and reliable for HF patients in Singapore.

A Scoping Review of Flow Research.

Flow is a gratifying state of deep involvement and absorption that individuals report when facing a challenging activity and they perceive adequate abilities to cope with it (EFRN, 2014). The flow concept was introduced by Csikszentmihalyi in 1975, and interest in flow research is growing. However, to our best knowledge, no scoping review exists that takes a systematic look at studies on flow which were published between the years 2000 and 2016. Overall, 252 studies have been included in this review. Our review (1) provides a framework to cluster flow research, (2) gives a systematic overview about existing studies and their findings, and (3) provides an overview about implications for future research. The provided framework consists of three levels of flow research. In the first "Individual" level are the categories for personality, motivation, physiology, emotion, cognition, and behavior. The second "Contextual" level contains the categories for contextual and interindividual factors and the third "Cultural" level contains cultural factors that relate to flow. Using our framework, we systematically present the findings for each category. While flow research has made progress in understanding flow, in the future, more experimental and longitudinal studies are needed to gain deeper insights into the causal structure of flow and its antecedents and consequences.

Gender Differences in Health Protective Behaviors During the COVID-19 Pandemic in Taiwan: An Empirical Study.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored. METHODS: We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2014 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors. RESULTS: A total of 1,990 participants (median age 45.92 years, 49% women) were included. Significant gender disparities (p<0.001) were observed. The risk perception of pandemic (OR=1.28, 95% CI=1.21-1.35, p<0.001), older age (1.06, 95%=1.05-1.07, p<0.001), female gender (OR = 1.18, 95% CI = 1.09□1.27, p<0.001), higher education (OR=1.10, 95% CI=1.06-1.13, p<0.001), and larger family size (OR=1.09, 95% CI=1.06-1.15, p<0.001) were positively associated with health protective behaviors. The risk perception of pandemic (OR=1.25, 95% CI=1.15-1.36), higher education (OR=1.07, 95% CI=1.02-1.13, p<0.05), being married (OR=1.17, 95% CI=1.01-1.36, p<0.05), and larger family size (OR=1.33, 95% CI=1.25-1.42, p<0.001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR=0.85, 95% CI=0.75-0.90, p<0.01) and to comply with contact-tracing (OR=0.95, 95% CI=0.90-1.00, p<0.05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR=0.77, 95% CI=0.66-0.90, p<0.001). CONCLUSION: This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics.

Lived Experiences and Long-Term Challenges and Needs of Asian Left Ventricular Assist Device Caregivers.

Background: Caregivers are essential for improved outcomes in patients living with left ventricular assist device (LVAD). There is a paucity of research on a long-term LVAD caregivers' experiences and burdens. Objectives: The aim of this study was to explore long-term challenges and needs of LVAD caregivers in the Asian health care setting. Design: We conducted semistructured interviews with caregivers of patients who were currently or previously living with the LVAD. Settings/Subjects: Caregivers were recruited from the National Heart Centre Singapore. Measurements: Interviews were conducted in English and Chinese. All interviews were transcribed verbatim and analyzed based on grounded theory. Chinese interviews were translated to English before transcription. Results: A multiethnic and multireligious sample of 11 caregivers participated. Median caregiving duration was 45 months. Caregivers described long-term challenges that were multifaceted. Misaligned patient expectations, stigmatization and limited social resources within the family and society affected caregivers' coping. Existing gender roles and spiritual and cultural influences shaped how caregivers appraised, made meaning of caregiving, and assessed support. Long-term caregivers' needs included learning from role models, shifting perspectives, enhancing communication between patient and caregivers, advocacy efforts, and holistic medical care. Conclusions: Gender roles as well as cultural and spiritual influences affected coping and access to support in long-term Asian LVAD caregivers. Future interventions should consider culturally relevant approaches to improve well-being and quality of life of caregivers.