Characterization of natural product inhibitors of quorum sensing in Pseudomonas aeruginosa reveals competitive inhibition of RhlR by ortho-vanillin.

Quorum sensing (QS) is a cell-cell signaling system that enables bacteria to coordinate population density-dependent changes in behavior. This chemical communication pathway is mediated by diffusible N-acyl L-homoserine lactone signals and cytoplasmic signal-responsive LuxR-type receptors in Gram-negative bacteria. As many common pathogenic bacteria use QS to regulate virulence, there is significant interest in disrupting QS as a potential therapeutic strategy. Prior studies have implicated the natural products salicylic acid, cinnamaldehyde and other related benzaldehyde derivatives as inhibitors of QS in the opportunistic pathogen Pseudomonas aeruginosa, yet we lack an understanding of the mechanisms by which these compounds function. Herein, we evaluate the activity of a set of benzaldehyde derivatives using heterologous reporters of the P. aeruginosa LasR and RhlR QS signal receptors. We find that most tested benzaldehyde derivatives can antagonize LasR or RhlR reporter activation at micromolar concentrations, although certain molecules also caused mild growth defects and nonspecific reporter antagonism. Notably, several compounds showed promising RhlR or LasR specific inhibitory activities over a range of concentrations below that causing toxicity. Ortho-Vanillin, a previously untested compound, was the most promising within this set. Competition experiments against the native ligands for LasR and RhlR revealed that ortho-vanillin can interact competitively with RhlR but not with LasR. Overall, these studies expand our understanding of benzaldehyde activities in the LasR and RhlR receptors and reveal potentially promising effects of ortho-vanillin as a small molecule QS modulator against RhlR.

Randomised Controlled Trial of a Customised Text Messaging and Activity Monitor Program for Lifestyle Improvement after Gestational Diabetes.

Gestational diabetes (GDM) is associated with a long-term risk of diabetes. We aimed to determine whether a text-messaging-based lifestyle support program would improve diabetes risk factors following GDM. Women with GDM were randomised following delivery to receive four text messages per week supporting a healthy lifestyle and parenting for 6 months, with feedback from an activity monitor (intervention), or to receive the activity monitor only (control). The primary outcome was a composite of weight, physical activity and dietary goals. There were 177 women randomised, with 88 intervention and 89 control participants. All the participants experienced COVID-19 lockdowns during the study. Six-month primary outcome data were obtained for 57 intervention participants and 56 controls. There were 7/57 (12%) intervention and 6/56 (11%) control participants who met the primary outcome (relative risk, 1.08; 95%CI, 0.63-1.85; p = 0.79). Two intervention participants met the dietary goals compared to none of the control participants (p = NS). The intervention participants were more likely to record >1000 steps/day (on 102 ± 59 vs. 81 ± 59 days, p = 0.03). When analysed monthly, this was not initially different but became significant 3-6 months post-partum. Interviews and surveys indicated that with the Intervention, healthier choices were made, but these were negatively impacted by COVID-19 restrictions. Participants found the messages motivational (74%) and the activity monitor useful (71%). In conclusion, no improvement in the diabetes risk factors occurred among the women receiving the text messaging intervention when affected by COVID-19 restrictions.

The socio-ecological determinants of help-seeking practices and healthcare access among young men: a systematic review.

Delayed engagement with health services is a key contributor to poorer health outcomes experienced by men. Patterns of health service usage which reduce the opportunity for disease prevention and health promotion appear to be especially prominent amongst young men. To identify the multiple and intersecting determinants of young men's help-seeking practices and health services usage, this review uses the social ecological model (SEM) to guide a critical synthesis of the literature on barriers and facilitators experienced by young men in accessing health services. A systematic review was conducted across five databases (MEDLINE, Embase, PsychINFO, CINAHL and Scopus). Included studies presented primary data regarding young men's (12-24 years) barriers and/or facilitators to seeking and accessing health care. Thirty-one studies (24 qualitative and 7 quantitative) underwent data extraction, quality appraisal and thematic analysis under the guiding framework of the SEM. Seven key themes were constructed, encapsulating the perceived barriers and facilitators to help-seeking and accessing health care experienced by young men, including masculine attitudes, health literacy, social pressure, service accessibility, economic factors, service characteristics and cultural attitudes. These findings highlight the complex interplay between the individual, interpersonal, organizational and societal factors impacting young men's healthcare engagement. They also illuminate avenues for multifaceted, context-specific interventions to enhance healthcare accessibility for this group, including addressing health literacy gaps, providing culturally sensitive care and reducing cost barriers.

Supporting Physical Activity Maintenance in Older Adults Following Supervised Group Exercise: A Mixed-Methods Study Among Culturally Diverse Older Adults.

Physical activity (PA) is important for prevention of falls and chronic disease in older adults. We aimed to examine the interrelated influences upon PA in culturally diverse older adults who completed a short-term exercise program, to inform maintenance strategies, using a mixed-methods design. Eighty-two past participants from the "Stepping On"© program were surveyed examining ongoing participation, social and cognitive determinants of PA, mental and physical functioning, and fear of falls. Semi-structured interviews were undertaken with 34 respondents regarding enablers and barriers, cultural factors, and preferences for PA. Data were collected in English, Chinese, Arabic, Punjabi, or Hindi. Cultural factors minimally affected PA participation. There was low perceived availability of PA opportunities. Health difficulties not only discouraged but also motivated participation. Social connection was a facilitator and could be used to support maintenance. Older adults may benefit from assistance in accessing PA opportunities and clinical guidance about the benefits of ongoing PA.

End on a positive note: an exploration of flourishing, identity, and career confidence in professional Australian footballers transitioning out of football.

This study explored professional male Australian rules football players leaving the Australian Football League (AFL), either from retirement or from deselected from their team. Identified athletes (n = 425) transitioning from the AFL competition from years 2019 to 2021 were invited to participate in an anonymous online survey with 60% completing the survey. Using scaled-response questions, responses were compared between groups across a number of areas including their experience of leaving, athlete identity, the influence of sport in their daily life, psychological flourishing, financial confidence, social relationships, and future career preparations. Results showed deselected players (n = 152), compared to retired players (n = 56), reported shorter career spans, and poorer perception of their club's handling of the transition process (p < 0.001). Compared to retired players, deselected players reported stronger identity attachment to sport, less confidence in their financial capabilities, and career outside football (all p < 0.05). Conversely retired players, compared to deselected players, showed stronger psychological flourishing. Correlations showed that retired players were more confidence in their finances, reported greater psychological flourishing, and lower attachment to an athletic identity (all p ≤ 0.05). The results of this study suggest that as deselected players expressed poorer perception of club's handling of the transition process the role of AFL club staff could improve the transition process in in preparation for life outside of professional sport.

Sport Participation for Academic Success: Evidence From the Longitudinal Study of Australian Children.

BACKGROUND: We aimed to identify long-term patterns of sport participation (overall, team, and individual sport) from childhood into adolescence, and to examine the association between these patterns and academic outcomes. METHODS: This cohort study used data from the Longitudinal Study of Australian Children in wave 3 (4-5 y) to wave 9 (20-21 y). The participants were a nationally representative sample of 4241 children. We conducted latent class analyses to identify sport participation trajectories and assessed the association between these trajectories and academic outcomes. RESULTS: Continued sport participation was associated with lower odds of being absent from school (OR = 0.44; 95% confidence intervals [CIs], 0.26 to 0.74), better performance on attention (B = -0.010; 95% CIs, -0.019 to -0.002) and working memory (B = -0.013; 95% CIs, -0.023 to -0.003), higher numeracy (B = 20.21; 95% CIs, 14.56 to 25.86) and literacy scores (B = 9.42; 95% CIs, 2.82 to 16.02), higher end of school academic performance (B = 3.28; 95% CIs, 1.47 to 5.09), and higher odds of studying at university (OR = 1.78; 95% CIs, 1.32 to 2.40). Team sport participation was associated with reduced absenteeism, better performance on attention and working memory, and being awarded the Higher School Certificate. Whereas individual sport participation was associated with higher literacy scores and end of school academic performance. CONCLUSIONS: Team and individual sport participation both benefit academic outcomes, but differently. Given the decline in sport participation during adolescence, these findings highlight the need to develop educational policies to establish an environment that promotes sport participation, which in turn could improve academic outcomes.

Blood-wall fluttering instability as a physiomarker of the progression of thoracic aortic aneurysms.

The diagnosis of aneurysms is informed by empirically tracking their size and growth rate. Here, by analysing the growth of aortic aneurysms from first principles via linear stability analysis of flow through an elastic blood vessel, we show that abnormal aortic dilatation is associated with a transition from stable flow to unstable aortic fluttering. This transition to instability can be described by the critical threshold for a dimensionless number that depends on blood pressure, the size of the aorta, and the shear stress and stiffness of the aortic wall. By analysing data from four-dimensional flow magnetic resonance imaging for 117 patients who had undergone cardiothoracic imaging and for 100 healthy volunteers, we show that the dimensionless number is a physiomarker for the growth of thoracic ascending aortic aneurysms and that it can be used to accurately discriminate abnormal versus natural growth. Further characterization of the transition to blood-wall fluttering instability may aid the understanding of the mechanisms underlying aneurysm progression in patients.

Teaching Basic Surgical Skills Using a More Frugal, Near-Peer, and Environmentally Sustainable Way: Mixed Methods Study.

BACKGROUND: The Royal College of Surgeons Basic Surgical Skills (BSS) course is ubiquitous among UK surgical trainees but is geographically limited and costly. The COVID-19 pandemic has reduced training quality. Surveys illustrate reduced logbook completion and increased trainee attrition. Local, peer-led teaching has been shown to be effective at increasing confidence in surgical skills in a cost-effective manner. Qualitative data on trainee well-being, recruitment, and retention are lacking. OBJECTIVE: This study aims to evaluate the impact of a novel program of weekly, lunchtime BSS sessions on both quantitative and qualitative factors. METHODS: A weekly, lunchtime BSS course was designed to achieve the outcomes of the Royal College of Surgeons BSS course over a 16-week period overlapping with 1 foundation doctor rotation. All health care workers at the study center were eligible to participate. The study was advertised via the weekly, trust-wide information email. Course sessions included knot tying, suturing, abscess incision and drainage, fracture fixation with application of plaster of Paris, joint aspirations and reductions, abdominal wall closure, and basic laparoscopic skills. The hospital canteen sourced unwanted pig skin from the local butcher for suturing sessions and pork belly for abscess and abdominal wall closure sessions. Out-of-date surgical equipment was used. This concurrent, nested, mixed methods study involved descriptive analysis of perceived improvement scores in each surgical skill before and after each session, over 4 iterations of the course (May 2021 to August 2022). After the sessions, students completed a voluntary web-based feedback form scoring presession and postsession confidence levels on a 5-point Likert scale. Qualitative thematic analysis of voluntary semistructured student interview transcripts was also performed to understand the impact of a free-to-attend, local, weekly, near-peer teaching course on perceived well-being, quality of training, and interest in a surgical career. Students consented to the use of feedback and interview data for this study. Ethics approval was requested but deemed not necessary by the study center's ethics committee. RESULTS: There were 64 responses. Confidence was significantly improved from 47% to 73% (95% CI 15%-27%; P<.001; t13=5.3117) across all surgical skills over 4 iterations. Among the 7 semistructured interviews, 100% (7/7) of the participants reported improved perceived well-being, value added to training, and positivity toward near-peer teaching and 71% (5/7) preferred local weekly teaching. Interest in a surgical career was unchanged. CONCLUSIONS: This course was feasible around clinical workloads, resourced locally at next to no cost, environmentally sustainable, and free to attend. The course offered junior doctors not only a weekly opportunity to learn but also to teach. Peer-led, decentralized surgical education increases confidence and has a positive effect on perceptions about well-being and training. We hope to disseminate this course, leading to reproduction in other centers, refinement, and wide implementation.

14 examples of how LLMs can transform materials science and chemistry: a reflection on a large language model hackathon.

Large-language models (LLMs) such as GPT-4 caught the interest of many scientists. Recent studies suggested that these models could be useful in chemistry and materials science. To explore these possibilities, we organized a hackathon. This article chronicles the projects built as part of this hackathon. Participants employed LLMs for various applications, including predicting properties of molecules and materials, designing novel interfaces for tools, extracting knowledge from unstructured data, and developing new educational applications. The diverse topics and the fact that working prototypes could be generated in less than two days highlight that LLMs will profoundly impact the future of our fields. The rich collection of ideas and projects also indicates that the applications of LLMs are not limited to materials science and chemistry but offer potential benefits to a wide range of scientific disciplines.

Engaging Australian men in disease prevention - priorities and opportunities from a national survey.

Objective and importance of the study: In Australia, preventable causes of morbidity and mortality are common among men. The National Men's Health Strategy 2021-2030 highlights the need to successfully engage men in disease prevention; hence, we aimed to examine the prevention priorities, attitudes and information sources reported by Australian men. STUDY TYPE: Population survey. METHODS: Men aged 18 years and over were recruited from the nationally representative Life in Australia panel. Participants completed an online survey that measured the prevention issues of greatest concern, attitudes to prevention behaviours and services, and the health information sources considered most useful. RESULTS: Among 1282 respondents, mental health issues, followed by those pertaining to chronic disease and relationships, were rated of highest concern. Weight management, physical activity, and fruit and vegetable consumption were most often considered as important for personal health. Being 65 years and older and having adequate health literacy were strongly associated with positive attitudes towards prevention practices. More than three-quarters of men rated their doctor as the most useful information source, followed by health websites, internet searching, and their partner. CONCLUSIONS: Psychological and social issues are of high concern to men, and their attitudes toward preventive behaviours and services often do not align with public health recommendations. Understanding the topics of greatest concern to men and their preferred sources of information can inform communication and engagement strategies to improve health-related practices among men.

Effects of customer relationship management (CRM) strategies and socio-cognitive constructs on the physical activity of individuals with arthritis over time.

BACKGROUND: Regular physical activity is important for arthritis self-management and could be promoted through tailoring community leisure and fitness centers' customer-relationship management (CRM) strategies. OBJECTIVES: This study investigates the influence of two CRM strategies on individuals with arthritis reaching or maintaining two moderate-to-vigorous physical activity (MVPA) thresholds (≥150 and ≥45 minutes/week) from baseline-to-12 months and 12-to-24 months as well as mean changes in total minutes/week of MVPA. It also explores time-dependent variations in the influence of socio-cognitive variables on MVPA outcomes. METHODS: Survey data from 374 participants with arthritis in a two-year randomized controlled trial (control versus two CRM strategies: IncentiveOnly and Incentive+Support) were used. Participants reported measures of physical activity participation, socio-cognitive decision-making, mental and physical wellbeing, friendship, community connectedness, sense of trust in others, and demographics. FINDINGS/DISCUSSION: Receiving the Incentive+Support CRM strategy (versus control) increased participants' likelihood of reaching/maintaining both physical activity thresholds from 12-to-24 months (≥150 MVPA minutes/week, p < .001; ≥45 MVPA minutes/week, p < .032) but not from baseline-to-12 months. However, receiving the IncentiveOnly CRM strategy (versus control) did not predict reaching/maintaining these thresholds. Importantly, socio-cognitive decision-making variables' influence on reaching/maintaining these MVPA thresholds varied over time, suggesting CRM strategies may require further tailoring based on time-specific profiles. Perhaps because of new facility induced excitement, the mean change in total MVPA minutes/week for the control group significantly increased (26.8 minute/week, p = .014, 95% CI [5.5, 48.0]) from baseline-to-12 months, but subsequently declined by 11.4 minute/week from 12-to-24 months (p = .296, 95% CI [-32.7, 9.9]). Mean changes in total MVPA minutes/week were non-significant for those receiving IncentiveOnly content but significant for those receiving Incentive+Support content: baseline-to-12 months (38.2 minute/week increase, p = .023, 95% CI [4.9, 71.4]) and baseline-to-24-months (45.9 minute/week increase, p = .007, 95% CI [12.7, 79.1]).

Improving Access to Cancer Clinical Trials for Patients From Culturally and Linguistically Diverse Backgrounds in Australia: A Survey of Clinical and Research Professionals.

PURPOSE: Patients with cancer from racial and ethnic minorities, referred to as culturally and linguistically diverse (CALD) in Australia, are significantly under-represented in cancer clinical trials. We performed a national survey of the Australian cancer clinical trials workforce to determine barriers and preferred solutions to address this inequity. METHODS: A 15-item online survey containing both closed- and open-ended purpose-designed questions was created using REDCap. The survey was emailed to members of the Clinical Oncology Society of Australia, Medical Oncology Group of Australia, and Australian cancer cooperative trial groups, and promoted via Twitter. Descriptive analyses summarized quantitative data, and free-text entries underwent thematic analysis with NVivo Version 12. RESULTS: Ninety one respondents completed the survey-with representation across Australia. Eighty-seven percent were directly involved in clinical trial recruitment. Sixty-eight percent were clinicians. Seventy-four percent of respondents did not collect routine data on CALD patient enrollment to cancer clinical trials. Communication (eg, lack of translated materials) and opportunity-related barriers (eg, exclusionary trial protocols) were the most frequently perceived barriers to recruitment. Additionally, qualitative analysis indicated that insufficient consultation time and difficulties accessing interpreters for patients with non-English language preference were significant barriers. Trial navigators and a generic cancer trial pamphlet available in multiple languages were judged the most likely solutions to improve recruitment. CONCLUSION: This study articulates the Australian clinical trials workforce's perspective on current barriers and potential solutions to the under-representation of patients from CALD backgrounds on cancer clinical trials. The insights and solutions from this survey provide steps toward achieving equity in Australian cancer clinical trials.

Harnessing citizen science in health promotion: perspectives of policy and practice stakeholders in Australia.

Citizen science is rapidly gaining momentum as a means of involving members of the public in research and decision-making in disease prevention and health promotion. However, citizen science projects have predominantly been led by academic researchers and there is limited understanding of how to support the application of citizen science approaches in policy and practice settings. This study aimed to understand the perceptions, motivations and early experiences of applying citizen science approaches in policy and practice settings. Semi-structured interviews were conducted with policy and practice stakeholders who were leading citizen science projects (project partners, n = 7), and their implementation partners (project implementers, n = 11). Participants viewed citizen science as an opportunity to access hard-to-reach data and to enhance engagement with community members to support policy and practice change. Barriers and facilitators of citizen science in policy and practice settings included navigating collaborative relationships, team capacity and resources available to deliver projects, recruitment and engagement of citizen scientists and ethical considerations in the design and implementation of citizen science projects. Findings support the feasibility and wider application of citizen science approaches in health promotion and are being used to inform the development of tools and resources to build capacity in these approaches in policy and practice settings.

Advancing loneliness and social isolation as global health challenges: taking three priority actions.

Loneliness and social isolation have been identified as critical global health issues in the aftermath of the coronavirus disease 2019 (COVID-19) crisis. While there is robust scientific evidence demonstrating the impact of loneliness and social isolation on health outcomes and mortality, there are fundamental issues to resolve so that health authorities, decision makers, and practitioners worldwide are informed and aligned with the latest evidence. Three priority actions are posited to achieve a wider and more substantial impact on loneliness and social isolation. They are 1) strengthening the evidence base; 2) adopting a whole-of-systems approach; 3) developing policy support for governments worldwide. These priority actions are essential to reduce the pervasive impact of loneliness and social isolation as social determinants of health.

A protocol for the Heart Matters stepped wedge cluster randomised trial: The effectiveness of heart attack education in regions at highest-risk.

Aim: To describe the Heart Matters (HM) trial which aims to evaluate the effectiveness of a community heart attack education intervention in high-risk areas in Victoria, Australia. These local government areas (LGAs) have high rates of acute coronary syndrome (ACS), out-of-hospital cardiac arrest (OHCA), cardiovascular risk factors, and low rates of emergency medical service (EMS) use for ACS. Methods: The trial follows a stepped-wedge cluster randomised design, with eight clusters (high-risk LGAs) randomly assigned to transition from control to intervention every four months. Two pairs of LGAs will transition simultaneously due to their proximity. The intervention consists of a heart attack education program delivered by trained HM Coordinators, with additional support from opportunistic media and a geo-targeted social media campaign. The primary outcome measure is the proportion of residents from the eight LGAs who present to emergency departments by EMS during an ACS event. Secondary outcomes include prehospital delay time, rates of OHCA and heart attack awareness. The primary and secondary outcomes will be analysed at the patient/participant level using mixed-effects logistic regression models. A detailed program evaluation is also being conducted. The trial was registered on August 9, 2021 (NCT04995900). Results: The intervention was implemented between February 2022 and March 2023, and outcome data will be collected from administrative databases, registries, and surveys. Primary trial data is expected to be locked for analysis by October 31st 2023, with a follow-up planned until March 31st 2024. Conclusion: The results from this trial will provide high-level evidence the effectiveness of a community education intervention targeting regions at highest-risk of ACS and low EMS use.

The prevalence of chronic and episodic loneliness and social isolation from a longitudinal survey.

Loneliness and social isolation, experienced more long-term, has been shown to increase mortality and lead to poorer health outcomes in specific cohorts. However, it is unclear what the prevalence of chronic loneliness and social isolation is, and which demographic groups are most at risk of reporting more chronic forms. A psychometrically validated classification system was used to identify people who met criteria for episodic and chronic loneliness and social isolation using the Household Income and Labour Dynamics in Australia (HILDA) survey waves 14-18. The prevalence of loneliness (overall 34%; 21% episodic, 13% chronic) far exceeded that of social isolation (overall 17%; 13% episodic, 4% chronic). There was consistency in the demographic characteristics (from age, sex, household type, income) of those who experienced loneliness and social isolation. However, people with a long-term health condition had an elevated risk of episodic loneliness (AOR 1.24, 95% CI 1.11-1.39) and a markedly higher risk of chronic loneliness (AOR 2.01, 95% CI 1.76-2.29), compared with those without a long-term health condition. Loneliness, both episodic and chronic subtypes, is more prevalent than social isolation. However, both chronic loneliness and social isolation remains neglected and poorly targeted within current practice and policy.

Oral health literacy, knowledge and perceptions in a socially and culturally diverse population: a mixed methods study.

BACKGROUND: Poor oral health literacy has been proposed as a causal factor in disparities in oral health outcomes. This study aims to investigate oral health literacy (OHL) in a socially and culturally diverse population of Australian adults visiting a public dental clinic in Western Sydney. METHODS: A mixed methods study where oral health literacy was assessed using the Health Literacy in Dentistry scale (HeLD-14) questionnaire and semi-structured interviews explored oral health related knowledge, perceptions and attitudes. Interviews were analysed using a thematic approach. RESULTS: A sample of 48 participants attending a public dental clinic in Western Sydney was recruited, with a mean age of 59.9 (SD16.2) years, 48% female, 50% born in Australia, 45% with high school or lower education, and 56% with low-medium OHL. A subgroup of 21 participants with a mean age of 68.1 (SD14.6) years, 40% female, 64% born in Australia, 56% with a high school or lower education, and 45% with low-medium OHL completed the interview. Three themes identified from the interviews included 1) attitudes and perceptions about oral health that highlighted a lack of agency and low prioritisation of oral health, 2) limited knowledge and education about the causes and consequences of poor oral health, including limited access to oral health education and finally 3) barriers and enablers to maintaining good oral health, with financial barriers being the main contributor to low OHL. CONCLUSIONS: Strategies aimed at redressing disparities in oral health status should include improving access to oral health information. The focus should be on the impact poor oral health has on general health with clear messages about prevention and treatment options in order to empower individuals to better manage their oral health.

Resilience, Generalized Self-Efficacy, and Mindfulness as Moderators of the Relationship Between Stress and Well-Being.

Heeding calls to examine multiple protective factors within single studies, this study tested whether resilience uniquely predicted higher life satisfaction and lower depression over the predictive ability of generalized self-efficacy (GSE) and mindfulness among 332 university students. A second purpose was to test whether resilience uniquely buffered the relationship between two forms of stress-cumulative stress from particular negative life events and general perceived stress-and both life satisfaction and depression over the buffering ability of GSE and mindfulness. In hierarchical multiple regressions, resilience uniquely predicted 3% of the variance in satisfaction with life and 1% of the variance in depression. GSE and mindfulness buffered the relationship between cumulative negative life event stress and depression. At higher levels of GSE and mindfulness, the relationship between cumulative negative life event stress and depression was weaker.