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Abstract Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (βCAC = − 0.14, P = 0.23; βcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.

Abstract Objectives Aortic pathologies often present with elevated inflammatory biomarkers due to the nature of the disease. Open aortic surgery causes significant trauma to the body due to often mandatory ischemic periods, long cardiopulmonary bypass times and polytransfusion. We aim to determine postoperative trends on inflammation biomarkers for different aortic pathologies and type of surgery in different segments of the aorta. Methods Retrospective review of prospectively collected data of 193 consecutive patients who underwent aortic surgery in our centre between 2017 and 2021, grouped according to the type of aortic intervention: (1) Type A aortic dissection (AD) repair with ascending aorta/hemiarch replacement, (2) Aortic root replacement (ARR), (3) Aortic arch + Frozen elephant trunk (FET), (4) Descending thoracic aorta (DTA)/Thoraco-Abdominal aortic repair (TAA). Primary outcomes were daily values of white blood cells (WBC) and C-Reactive Protein (CRP) during the first 15 postoperative days. Results All groups had a similar inflammatory peak in the first 2–4 days (WBC 12-15 × 109 c/L). AD and FET groups show similar trends with WBC and CRP peaks on days 2 and 10. The ARR group didn’t experience the 2nd peak as most patients were already discharged. DTA/TAA patients experienced a more prolonged inflammatory response, reaching a plateau by day 5–10. AD group shows the highest WBC levels and the DTA/TAAA group the highest CRP levels. CRP levels remain elevated (100–200 mg/L) in all groups after 15 postoperative days. Conclusions Inflammatory biomarkers show different postoperative trends depending on the clinical presentation and complexity of the aortic procedure performed. Further understanding of the inflammatory response to different aortic pathologies and surgical procedures will permit reduction on the liberal use of antibiotics that this cohort of patients are usually exposed to. An earlier version of the data included in this manuscript was presented as Oral Abstract in the UK Society of Cardiothoracic Surgery Annual meeting in 2021

Abstract: Introduction: Despite recent advancements in sports medicine and sports psychiatry, a lack of clarity remains in understanding the pathogenesis and etiology of Overtraining Syndrome (OTS). Early research on endurance athletes in high volume/intensity cycles of training described a condition of “staleness”, which could be detected using psychometric assessments on mood. Associated with both physical and psychological symptoms, “staleness” was found to be dose responsive and tended to abate with a reduction in training. Subsequent study of OTS has not revealed reliable or reproducible measurements for ascertaining or treating the condition. Methods: We reviewed historical literature discussing “staleness”, summarizing its theoretical trajectory in academic domains, and comparing this with more recent work that emphasizes the physiological parameters of OTS. We also consider the sociocultural context surrounding these terminological shifts. Results: Though the term “staleness” has fallen out of favor, past work into this topic may have relevance in attempts to define, diagnose, and treat OTS. Further, sports psychiatry may be in a unique position to revisit the literature and emphasize the utility of psychometric assessment in screening, as well as underlining the importance of maintaining mental health among high performing athletes. Conclusion: Research and psychometric assessments designed to discuss “staleness” still remain relevant, particularly in sports psychiatry, and may deserve to be revisited as well as expanded.

This case report describes the therapeutic trajectory of a 47-year-old male ultra football fan from Switzerland, who was diagnosed and treated for attention-deficit/hyperactivity disorder, together with comorbid alcohol misuse and insomnia. Prior to this episode of care, the patient exhibited symptoms of impulsivity and inattention and persistent patterns of harmful alcohol consumption, recurrently participating in football-related violence. A multimodal approach involving psychotherapy and psychopharmacology yielded notable improvements in symptom management. To date, the patient has shown improved psychosocial functioning, reporting a significant reduction in alcohol use and the cessation of all aggressive acts. Consequently, this case provides insights into the relationship between attention-deficit/hyperactivity disorder and football-related violence, underlining the potential for tailored mental health interventions to enhance overall quality of life.

Throughout history, armed conflicts have profoundly affected individuals and societies, with recent events in Ukraine, the Middle East, and beyond bringing into sharp focus the severe mental health and humanitarian consequences of geopolitical crises. Such situations often result in mass fatalities, destruction, displacement, forced migration, and other critical life events. Amid these scenarios, the adverse outcomes for mental health and well-being in both the short and long term must be emphasized. As a conceivable example of the latter, the proposed concept of intergenerational trauma could have far-reaching implications. In particular, in certain regions, civilians have repeatedly experienced instances of violence and may have continually been exposed to critical life events and traumatic stress. In this context, the consequences of these events for individual well-being and global mental health will likely be registered for years to come. Accordingly, urgent help and actions to address the mental health burdens within contemporary conflicts should be accentuated in humanitarian, political, and diplomatic interventions. Equally, health policies must adopt a long-term approach to support initiatives under the purview of global and public mental health objectives.

Since its inception, social media has brought about numerous benefits, including higher levels of social connectedness, potential positive interactions, and greater access to information. Nonetheless, the excessive use of social media can lead to negative health outcomes, such as social anxiety, depression, low self-esteem, reduced sleep quality, and higher perceived stress. It has been argued that boredom and loneliness may be mediating factors between social media misuse and negative mental health effects, above all among youth and adolescents. Likewise, exposure to graphic imagery or misinformation on social media may also have deleterious implications for mental health. Taken together, this suggests a need for targeted studies on the relationship between social media and mental health, as well as the development of educational interventions for adolescents to share knowledge about the safe use of such tools. Mental health professionals should be adequately trained in identifying risk factors and treating the negative health outcomes that may result from social media. Specific strategies and guidelines should be adopted by social media companies aligned with international evidence from health agencies and experts in e-mental health.

Abstract: Introduction: Cycling can confer public mental health advantages for diverse populations, attenuating stressors and strengthening prosocial engagement. Conversely, competitive conditions in high-performance domains may entail prominent psychiatric risk factors that require bespoke interventions. In other sports, certain national federations have introduced mental health schemes for various target populations. However, the extent to which comparable approaches have been adopted across cycling remains unclear. Methods: We sought to gain broader insights into whether European cycling federations (ECFs) have implemented dedicated programmes around mental health, focussing on N=51 ECFs affiliated with the international regulator, the Union Cycliste Internationale. Initially, a search was conducted of ECF websites. Where apposite materials were unavailable, ECFs were contacted via email and phone. Results: 62% of total ECFs (N=32) were captured in the results. Findings were analysed and coded to three categories, namely: “ECF-level literature or initiatives”, “No ECF-level literature or initiatives”, and “No response”. Based on our interpretation, of these N=32 ECFs, n=7 (22%) highlighted literature and strategies either on their website or during contact phases. The remaining n=25 (78%) ECFs noted no official policies or initiatives. Conclusion: Across included ECFs, there appears to be limited consideration about developing mental health schemes, potentially conditioned by resource constraints or disparate organisational priorities and regulations. For those ECFs with relevant programmes, the majority focussed on high-performance contexts, with less attention towards the relationship between cycling and mental health in broader demographics. Accordingly, evidence from different associations and sports could guide effective, tailored approaches.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is prevalent amongst offenders, increasing risks for aggressive and delinquent behaviors. Since ADHD and its symptoms can persist into adulthood, accurately diagnosing and maintaining diagnoses in offenders is crucial to ensure appropriate treatment and reduce recidivism.MethodsThis study employed a retrospective longitudinal design to investigate ADHD amongst adult offenders with a confirmed diagnosis of ADHD during childhood or adolescence at a Swiss forensic outpatient clinic between 2008 and 2021. N = 181 patient files were reviewed, including forensic expert witness assessments and treatment reports. We charted the adulthood trajectory of patients with a confirmed childhood/adolescence ADHD diagnosis, examining the course of their diagnoses.ResultsOf 181 patients, evidence indicated that 12 (7%) had an ADHD diagnosis in childhood/adolescence. In 1 (8%) of these 12 cases, the diagnosis was maintained throughout the observation period. For 4 patients (33%), a diagnosis was given in the first forensic psychiatric expert witness assessment in adulthood but subsequently dropped. In another 4 cases (33%), the diagnosis was dropped in adulthood but later re-assigned, whereas in 3 cases (25%), the diagnosis was discontinued throughout the observation period. In 50% of cases with a diagnostic change, the discontinuation of an adult ADHD diagnosis coincided with a newly diagnosed personality disorder (or vice versa).ConclusionsOur findings highlighted considerable inconsistencies in the assignment of adult ADHD diagnoses amongst offenders. Whilst ADHD remission in adulthood occurs, the diagnostic variability in our results warrants detailed scrutiny. One possibility is that ADHD has similar fluctuations to conditions like depression, as argued elsewhere. Equally, diagnoses may become “lost”, meaning they are not given even when applicable and replaced by other diagnoses. Additionally, residual symptoms may remain but beyond the diagnostic threshold. This is significant because untreated ADHD can increase re-offending risks and adverse health outcomes.

IntroductionWith ultramarathon attracting burgeoning interest, evidence has emerged about doping behaviors. However, currently, research into the anti-doping policy landscape and the adoption of testing and athlete surveillance is limited, including the applicability of rubric from the World Anti-Doping Agency (WADA) and National Anti-Doping Organizations (NADOs). Consequently, it remains unclear if anti-doping provisions have been developed and enforced in ultramarathon, which is a timely consideration given growth in the sport.MethodsThis study gathered perspectives on anti-doping and testing procedures from ultramarathon race organizers (UMROs). To that end, a sample of n = 35 prominent competitions was compiled using web materials and community engagement, encompassing elite and amateur entrants, diverse course designs, and prize money opportunities. Data-gathering was conducted across two phases between November and December 2023, with an initial review of UMRO web resources. Subsequently, UMROs were contacted via email to validate or ascertain their anti-doping and testing policies. Insights from UMRO respondents were reviewed and coded. UMROs who did not reply were excluded from the analysis.ResultsBased on this methodology, the positions of n = 17 UMROs were captured, covering 159 ultramarathon races and approximately 96,500 annual participants. Of these, n = 8 UMROs did not have a self-developed policy and their rubric was pursuant to external authorities like WADA and NADOs. n = 4 had created a specific proprietary policy, which often incorporated WADO or NADO materials. The remaining n = 5 UMROs reported no anti-doping controls were in place at the time of the study. There was also notable heterogeneity in testing and surveillance, ranging from rigorous procedures to an absence of protocols. Interestingly, none of the included UMROs explicitly reported that they had enacted anti-doping measures against athletes.DiscussionVarious determinants could inform these regulatory inconsistencies across UMROs, such as financial constraints, infrastructural and logistical barriers, cultural factors, and the lack of a unifying international federation in ultramarathon. Given the disparate approaches identified in our results, greater cooperation and education may be necessary to enhance understanding about the implications of doping and advance cohesive frameworks. This should involve collaborations with WADA and NADOs to promote best-practices and evidence-based exchanges within the community.

IntroductionDiabetes is associated with an increased risk of stroke. In many cases, a diabetes diagnosis may predate a stroke; however, diabetes is often diagnosed during the hospital admission following a stroke. To explore the experiences of stroke survivors as they cope with a new diabetes diagnosis, particularly regarding developing an effective strategy for managing the disease.MethodsA qualitative grounded theory approach was used that employed focus group interviews with participants, including clinicians and stroke survivors, to develop a holistic understanding of primary and secondary stroke care services and the experiences of those accessing them.ResultsClinicians believed they were not optimally equipped to manage diabetes as a condition. They believed more emphasis should be placed on self-management, which would be better managed by lifestyle changes than medication alone. Conversely, stroke survivors with diabetes experienced an additional burden associated with the diagnoses but relied on clinicians to manage their diabetes and believed the clinicians were failing if they were unwilling or unable to achieve this.DiscussionThe research highlights the tensions between stroke survivors and healthcare professionals. Stroke survivors relied on the healthcare teams to provide the optimal treatment when they had recently undergone a significant health event where they had experienced a stroke and received a diabetes diagnosis. However, the healthcare teams, while recognizing the importance of a holistic and comprehensive treatment package, struggled to provide it due to resource limitations. To optimize post-stroke diabetes self-management education, a strategic framework that prioritizes patient empowerment and interdisciplinary collaboration is paramount. Tailoring educational interventions to align with individual patient profiles—considering their unique health status, personal preferences, and cultural context—is essential for fostering self-efficacy. Such a strategy not only empowers patients to take an active role in managing their diabetes post-stroke but also contributes to superior health outcomes and an elevated standard of living.

Weight-related issues can be prevalent in elite-level sports, especially in men’s road cycling, where riders may exhibit harmful behaviours, with potentially adverse outcomes for mental and physical health. This study investigated Body Mass Index (BMI) values amongst the top five finishers in the three Grand Tours and the five Monuments races between 1994 and 2023 to assess longitudinal patterns. Publicly available height and weight figures were sourced from ProCyclingStats and BMI scores were calculated for n = 154 and n = 255 individual athletes for the Grand Tours and Monuments, respectively. Two analyses were conducted with correlations and ANOVAs: the first included the BMIs of all top-five finishes and the second focussed on the BMIs of new top-five entrants. The results from both analyses revealed consistent mean BMI decreases over the years and larger effect sizes were apparent in the Grand Tours compared to the Monuments. Although lower BMIs are associated with certain performance advantages, these declining trajectories suggest a need for enhanced awareness in the cycling community and possible regulatory measures and educational programmes to promote the sustainable wellbeing of riders. This may be particularly pertinent given the wider evidence of unhealthy weight-related attitudes and behaviours throughout the sport.

Historically, bicycle riding connoted freedom, independence, and enhanced mental and physical wellbeing for women. Persevering through criticism and moral panic, female cyclists have been competitive since the late 19th century—many earning substantial prize money and prestige. Unfortunately, this progress was not linear in its trajectory and contemporary professional women's cycling continues to be pervaded by structural and cultural challenges, which can have deleterious effects on athlete mental health. Notably, socioeconomic pressures endure, like unstable employment terms, limited team support, and role conflicts. Furthermore, sexual harassment, body shaming, and manipulation may characterize women's experiences with their coaches and teams. Sizable investment gaps between men's and women's teams and competitions often underpin these scenarios of disadvantage. Alongside hindering the development of women's cycling, these adverse circumstances may induce psychosocial risk factors. Within this context, by highlighting sport-specific and sex-specific considerations, the emerging subdiscipline of sports psychiatry can be valuable for protecting and promoting athlete welfare in women's cycling. Raising awareness about extant symptoms, vulnerabilities, contributing behaviours, and systemic issues, can bolster efforts to develop better conditions and care equivalence. To that end, this perspective article draws upon anecdotal and scholarly evidence to provide an overview of psychiatric concerns in women's professional cycling. This informs recommended strategies to improve mental health and advance equality within the sport, which should involve actions from several stakeholders, such as athletes, teams, and governing bodies.

Abstract: Introduction: The popularity of ultra-endurance cycling is increasing. Amongst race participants, sleep deprivation and periods of intermittent or acutely short sleep are common. Scientific research has typically focussed on the physiological or competitive performance based impact of these sleep-related paradigms. However, there is limited evidence about the mental health effects of sleep patterns in ultra-endurance cycling, despite established links between sleep deprivation and psychiatric and psychological issues. Methods: We conducted a narrative review synthesising extant empirical literature about sleep deprivation in ultra-endurance cycling. Results: Based on our search criteria, seven papers were identified discussing sleep patterns in ultra-endurance races. Each of these indicate that sleep deprivation is a prominent aspect of ultra-endurance competitions, with varying implications for riders. Discussion: Using these findings, we highlight the possible mental health consequences of sleep deprivation in these races, with reference to general scientific literature and other ultra-endurance sports. We also advocate for increased knowledge exchanges, regulatory emphasis, and additional research. Conclusion: Sleep deprivation and extreme sleep patterns are a substantial issue in elite-level cycling competitions, raising potential mental health concerns. More attention to this topic is necessary amongst organisers, participants, researchers, and community-level platforms, like the Global Cycling Network.

We study the coupling of hydrodynamics and reactions in simulations of the double-detonation model for Type Ia supernovae. When assessing the convergence of simulations, the focus is usually on spatial resolution; however, the method of coupling the physics together as well as the tolerances used in integrating a reaction network also play an important role. In this paper, we explore how the choices made in both coupling and integrating the reaction portion of a simulation (operator/Strang splitting versus the simplified spectral deferred corrections method we introduced previously) influences the accuracy, efficiency, and nucleosynthesis of simulations of double detonations. We find no need to limit reaction rates or reduce the simulation time step to the reaction timescale. The entire simulation methodology used here is GPU-accelerated and made freely available as part of the Castro simulation code.

IntroductionInterest in ultra endurance sport (UES) is increasing, with relevant events growing in popularity. However, these activities may encompass more complex characteristics and demands that do not correspond to scientifically validated correlations between physical activity and improved health. It is unknown whether high volume training for UES can have adverse implications, although certain sociocultural aspects of western society, such as an emphasis on autonomy and self-directed success, may encourage participation as a representation of personal achievement. As media depictions of UES can be highly influential, we aimed to explore prominent messages to better comprehend the values and aspirations of established and aspiring ultra endurance athletes (UEA).MethodsUsing qualitative, conventional content analysis techniques, we evaluated n = 15 popular YouTube videos on various UES to synthesize the most common themes. A YouTube search was conducted, and videos were selected based on sport and relevance. Subsequently, videos were analyzed and coded to discern the most frequently repeated themes.ResultsFive recurring themes were identified: discussion of the mental aspects of UES participation; the adoption of folk-tale storytelling; dietary habits of UEA; a focus on pain and suffering; the use of words associated with mental illness as a colloquial descriptor of UES/UEA.DiscussionYouTube depictions of UES participation appear to accentuate suffering and co-occurring phenomena as attractive qualities. These resonate with sociocultural ideologies in western contexts, which emphasize fitness and personal success, but appear inconsistent with evidence around potentially adverse health-related implications of UES.ConclusionDiscrepancies between popular portrayals of UES and scientific evidence suggest a need for greater community education and information sharing about sport-specific risk factors for physical and mental health conditions and appropriate training protocols. Further research is also required to better define the relationship between motivations for UES participation and overall health using interdisciplinary approaches.

Background: Healthcare policy is an important societal concern in Switzerland, often dominating the national agenda. In other countries, studies have explored the influence of physicians in public office on healthcare policies, but little is known about the representation of medical doctors in Switzerland's political structures, despite ongoing health-related debates. Methods: In January 2023, we examined the proportion of registered doctors currently serving in Swiss governmental branches: the executive (the Federal Council) and the legislative (the Council of States and the National Council, together the United Federal Assembly). We used publicly available information to demarcate Federal, State, and National Councillors with professional medical backgrounds. We subsequently verified physician registrations using the Federal Office of Public Health’s “Register of Medical Professionals” (MedReg) Results: Six physicians registered in MedReg were identified across the Federal Council and the United Federal Assembly in 2023, equivalent to 2.37% of the total number of Councillors in these chambers. This corresponds to 14.20% of members in the Federal Council (the executive chamber) and 2.03% of members in the United Federal Assembly (the legislative chamber). Conclusions: Rates of physicians sitting in Switzerland’s Federal Council and United Federal Assembly are higher than general population trends for doctors per person. Nonetheless, physicians in Swiss legislative positions are proportionally lower than comparative data from the United States. We highlight how existing professional frameworks may already ensure medical doctors are sufficiently participating in Swiss healthcare debates outside of formal roles. We also suggest that more international evidence is needed to determine the benefits of physicians serving in public office.

Abstract. Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) in elite-level cycling is an overlooked area of clinical enquiry. Whilst former riders have raised awareness about ADHD, there is scant evidence about pharmacotherapeutic treatment levels of this disorder. This is a pertinent concern amidst contemporaneous anti-doping contexts, as common medicines for ADHD are prohibited during active competition by the World Anti-Doping Agency and thus require a Therapeutic Use Exemption (TUE). Methods: We conducted a preliminary investigation into pharmacotherapeutic treatment rates of ADHD in elite-level riders. We gathered secondary, publicly-available data about cyclists in the Registered Testing Pool (RTP) from the professional body, the Union Cycliste International (UCI), in 2020 and 2021. We then compared this with the total TUEs for prohibited medications granted on behalf of the UCI during this timeframe. Results: 1,265 elite-level riders were included in the RTP sample in 2020, as compared to 10 TUEs. 1,234 elite-level riders were included in the 2021 RTP sample, as compared to 10 TUEs. Discussion: Based on these data, we estimate that ADHD may be undertreated in this cohort of elite-level cyclists per general trends. We highlight the adverse mental health effects of medicinal undertreatment for ADHD and its implications for the sport. We also hypothesise potential reasons for this, including stigmatisation, negative conceptions of doping allegations, and possible medicolegal consequences. Conclusion: ADHD in elite-level cycling has received little coverage, especially in relation to treatment rates. Detailed research examining this issue and awareness campaigns are required to protect the mental health of elite-level riders.

Background: Healthcare policy is an important societal concern in Switzerland, often dominating the national agenda. In other countries, studies have explored the influence of physicians in public office on healthcare policies, but little is known about the representation of medical doctors in Switzerland's political structures, despite ongoing health-related debates. Methods: In January 2023, we examined the proportion of registered doctors currently serving in Swiss governmental branches: the executive (the Federal Council) and the legislative (the Council of States and the National Council, together the United Federal Assembly). We used publicly available information to demarcate Federal, State, and National Councillors with professional medical backgrounds. We subsequently verified physician registrations using the Federal Office of Public Health’s “Register of Medical Professionals” (MedReg) Results: Six physicians registered in MedReg were identified across the Federal Council and the United Federal Assembly in 2023, equivalent to 2.37% of the total number of Councillors in these chambers. This corresponds to 14.20% of members in the Federal Council (the executive chamber) and 2.03% of members in the United Federal Assembly (the legislative chamber). Conclusions: Rates of physicians sitting in Switzerland’s Federal Council and United Federal Assembly are higher than general population trends for doctors per person. Nonetheless, physicians in Swiss legislative positions are proportionally lower than comparative data from the United States. We highlight how existing professional frameworks may already ensure medical doctors are sufficiently participating in Swiss healthcare debates outside of formal roles. We also suggest that more international evidence is needed to determine the benefits of physicians serving in public office.

Pancreatic cancer remains a formidable challenge due to limited treatment options and its aggressive nature. In recent years, the naturally occurring anticancer compound juglone has emerged as a potential therapeutic candidate, showing promising results in inhibiting tumor growth and inducing cancer cell apoptosis. However, concerns over its toxicity have hampered juglone’s clinical application. To address this issue, we have explored the use of polymeric micelles as a delivery system for juglone in pancreatic cancer treatment. These micelles, formulated using Poloxamer 407 and D-α-Tocopherol polyethylene glycol 1000 succinate, offer an innovative solution to enhance juglone’s therapeutic potential while minimizing toxicity. In-vitro studies have demonstrated that micelle-formulated juglone (JM) effectively decreases proliferation and migration and increases apoptosis in pancreatic cancer cell lines. Importantly, in-vivo, JM exhibited no toxicity, allowing for increased dosing frequency compared to free drug administration. In mice, JM significantly reduced tumor growth in subcutaneous xenograft and orthotopic pancreatic cancer models. Beyond its direct antitumor effects, JM treatment also influenced the tumor microenvironment. In immunocompetent mice, JM increased immune cell infiltration and decreased stromal deposition and activation markers, suggesting an immunomodulatory role. To understand JM’s mechanism of action, we conducted RNA sequencing and subsequent differential expression analysis on tumors that were treated with JM. The administration of JM treatment reduced the expression levels of the oncogenic protein MYC, thereby emphasizing its potential as a focused, therapeutic intervention. In conclusion, the polymeric micelles-mediated delivery of juglone holds excellent promise in pancreatic cancer therapy. This approach offers improved drug delivery, reduced toxicity, and enhanced therapeutic efficacy.

There has been a growing interest around the broader effects of psychopathic traits, particularly in relation to deviant behaviors and the notion of so-called “successful psychopathy”. As significant sociocultural touchstones, sporting events are often characterized by competitiveness and a sense of prestige. However, there has been limited attention towards psychopathic traits across recreational, amateur, and elite sports. Accordingly, we conducted a narrative review synthesizing primary observations on this topic, searching keywords in Scopus, APA PsychNet, and PubMed. Twenty-four academic papers were included in our results, which we thematized around demographic groups, namely: athletes and sport-adjacent non-athletes (i.e., coaches and spectators). Based on empirical findings from the reviewed papers, psychopathic traits could have medicolegal and forensic implications in relation to substance use, aggression, and violence. These could intersect with wider issues around doping, cheating, foul play, and have adverse outcomes for fellow participants, team dynamics, and spectators. Interestingly, our review also indicates that psychopathic traits may have correlations with determination and achievement in sport, echoing developing ideas around “successful psychopathy” in other domains. As such, increased awareness from all stakeholders and further multidisciplinary exchanges are vital to better understand the effects of psychopathic traits in sporting frameworks and their wider consequences.

Abstract Background and Purpose The use of patient reported outcomes measures (PROMs) may offer utility that are important for stroke survivors. This study assessed the PROMIS-10, which contains Mental health (MH) and Physical Health (PH) domains, with an additional five stroke specific questions. The aim of this study was to evaluate the association between the MH and PH measures following a stroke and pre-existing health conditions. Methods A multicentre prospective cohort study at 19 hospital sites across England and Wales during 2019 was conducted. The association between each PROMIS-10 domain and demographic and health conditions were calculated using a multilevel multivariable linear and present the adjusted mean difference (aMD). Results The study enrolled 549 stroke survivors within 14 days of the index event, 232 were women (42.3%) and with a mean age of 72.7 years (SD = 12.9, range 25 to 97). The MH domain was scored as poor in 3.9% of participants, and very good or excellent in almost a half (48.4%). In contrast the PH domain was scored as poor in 39.9%, compared to very good or excellent in 8.5%. The MH domain was associated with pre-existing diabetes (aMD = − 2.01; 95%CI -3.91, − 0.12; p = 0.04), previous stroke (aMD = − 3.62; 95%CI -5.86, − 1.39; p = 0.001), age (aMD = 0.07; 95%CI: 0.01, 0.14; p = 0.037), and female sex (aMD = 1.91; 95%CI 0.28, 3.54; p = 0.022). The PH domain was found to be associated with sex (female) (aMD = 2.09; 95%CI 0.54, 3.65; p = 0.008) and previous stroke (aMD = − 3.05; 95%CI -5.17, − 0.93; p = 0.005). Conclusions Almost half of stroke survivors reported poor PH using a PROM with less reporting poor MH. age, and sex were associated with both MH and PH domains, and additionally pre-exising diabetes and stroke were associated with poorer MH. Clinical management offers an opportunity to investigate and intervene to prevent long term poorer health in stroke survivors.

Abstract Background Fifty years after its introduction, the American Psychiatric Association’s (APA) Goldwater Rule remains contentious, prohibiting member-psychiatrists from providing mental health commentary on individuals they have not treated and where they lack consent. Whilst its resonance extends beyond the United States, there is limited awareness about the Goldwater Rule’s applicability elsewhere, notably within Europe. Methods In 2022, we investigated whether the European Psychiatric Association’s (EPA) forty-four National Psychiatric Association Members (NPAs) had similar guidelines to the Goldwater Rule or comparable ethical positions around media and public commentary. We initially searched NPA websites and subsequently contacted NPAs via email and phone. Findings were coded to four categories: “NPA-level rules or position”, “No NPA-level rules orposition but noted country-level rules”, “No NPA-level rules or position and did not note country-level rules”, and “No response”. Results n=27 NPAs had relevant web materials or replied to our correspondence (61.3% of total NPAs). From these 27, based on our interpretation, n=6 (22.2%) had rules or positions, n=6 (22.2%) indicated that country-level rules existed, and n=15 (55.5%) did not have applicable NPA-level or country-level regulations. Conclusions A sizeable proportion of NPAs included in our study have not yet formally developed or considered ethical issues addressed by the Goldwater Rule and psychiatric commentary on an individual’s psychopathology. Accordingly, the EPA could consider broader discussions about this, accounting for national traditions and sociocultural aspects of clinical practice. These could integrate the advantages and disadvantages of the APA’s rubric towards an evolved ethical debate.

Abstract Background An RFA lesion quality indicator, Surpoint Tag Index® (TI) incorporates key factors: power, time, and contact force, impacting lesion quality. TI accurately estimates lesion depth in animal studies. However, the relationship between TI and in‐vivo atrial wall thickness in patients exhibiting bidirectional block remains unknown. Objective To describe the relationship between atrial wall thickness and TI in CTI exhibiting bidirectional block. Methods Data from 492 RFA lesions from 25 patients undergoing PVI and CTI ablations in SR with point‐by‐point RF lesions (30 min. Results In lesions exhibiting bidirectional block, the thinnest (1–2 mm; 5% lesions) and thickest (8–10 mm; 6% lesions) portions of the CTI correlated with the lowest (429 ± 75) and highest (516 ± 64) TI. The bulk of thickness (2–6 mm; 80%) correlated with a TI of 455 ± 72 (p = 0.001). There was a weak but positive correlation between TI and CTI thickness (r = 0.2; p ≤ 0.01). Examined in sectors, the anterior 1/3rd CTI was the thickest (4.8 ± 1.9 mm) but correlated with a similar TI value (479 ± 75 vs. 471 ± 70; p = 0.34) as the thinner middle 1/3rd (3.8 ± 1.7 mm; p ≤ 0.0001). Conclusion A mean TI value of 455 correlates with bidirectional block across the bulk of CTI with lower and higher values needed for the thinner and thicker portions, respectively. Tissue composition, aside from wall thickness, influences TI values for the creation of the bidirectional block.

Lung cancer remains the leading cause of cancer deaths in the United Kingdom. For locally advanced disease, multimodality treatment is recommended, which includes a combination of chemotherapy, radiotherapy, surgery and, more recently immunotherapy. Options depend on the resectability of the cancer and there has been debate about the optimal treatment strategy: surgery may be planned to follow chemoradiotherapy (CRT), be offered for residual disease after CRT, or given as salvage therapy for patients treated with CRT who have later relapse of their disease. We conducted a retrospective analysis of all patients who underwent CRT and surgical resection under a single surgical team and performed a descriptive study after dividing the patients into these three groups. For the planned trimodality group, 30-day mortality this was 7% (n = 1) and 1-year survival was 78.6%; the residual disease group had a 30-day mortality rate of 0% and 1-year survival of 81.3%; for the salvage group, the figures were 0% and 62.5%, respectively. The median overall survival of the study population was 35.8 months. Median overall survival in the trimodality group was 35.4 months (20.1–51.7 interquartile range IQR), for the residual group was 34.2 months (18.5–61.0 IQR). and for the salvage group was 35.8 months (32.4–52.7 IQR).)

Introduction: Although research suggests that exercise benefits mental health, psychiatric disorders have been acknowledged in the ultra-endurance-athlete population. At present, the mental-health consequences of high-volume training associated with ultra-endurance sports are not well understood. Methods: We conducted a narrative review summarizing primary observations about mental disorders per ICD-11 criteria in ultra-endurance athletes using a keyword search in Scopus and PubMed. Results: We identified 25 papers discussing ICD-11-classified psychiatric disorders such as depression, anxiety, eating disorders, attention-deficit/hyperactivity disorder, and schizophrenia in ultra-endurance athletes. Discussion: Although evidence is limited, available papers indicate that there is a sizable incidence of mental-health issues and composite psychopathological vulnerabilities in this community. We contend that ultra-endurance athletes may represent a different, though similar, demographic than elite and/or professional athletes, as they often engage in high-volume training with similarly high motivation. This can have regulatory implications, which we also highlight. Conclusion: Mental illness in ultra-endurance athletes is an underrepresented topic in sports medicine, though psychiatric disorders may be especially prevalent in this population. Further inquiry is necessary to inform athletes and healthcare practitioners about the possible mental-health implications associated with participation in ultra-endurance sports.

Sexual reproduction is a complex process that contributes to differences between the sexes and divergence between species. From a male's perspective, sexual selection can optimize reproductive success by acting on the variance in mating success (pre-insemination selection) as well as the variance in fertilization success (post-insemination selection). The balance between pre- and post-insemination selection has not yet been investigated using a strong hypothesis-testing framework that directly quantifies the effects of post-insemination selection on the evolution of reproductive success. Here we use experimental evolution of a uniquely engineered genetic system that allows sperm production to be turned off and on in obligate male-female populations of Caenorhabditis elegans. We show that enhanced post-insemination competition increases the efficacy of selection and surpasses pre-insemination sexual selection in driving a polygenic response in male reproductive success. We find that after 10 selective events occurring over 30 generations post-insemination selection increased male reproductive success by an average of 5- to 7-fold. Contrary to expectation, enhanced pre-insemination competition hindered selection and slowed the rate of evolution. Furthermore, we found that post-insemination selection resulted in a strong polygenic response at the whole-genome level. Our results demonstrate that post-insemination sexual selection plays a critical role in the rapid optimization of male reproductive fitness. Therefore, explicit consideration should be given to post-insemination dynamics when considering the population effects of sexual selection.

Abstract Background Recovery following a stroke is a long and ongoing process. Post-stroke follow-up after leaving the hospital is recommended. Methods for follow-up patients include face-to-face, via the telephone, post or online (internet). However, there is a debate which method is preferred by patients. This study aimed to determine whether telephone interview, online questionnaire and postal questionnaire were as acceptable as face-to-face follow-up. Methods In a blinded, UK-wide, multi-centre, Zelen’s designed, 4-arm (postal, online, telephone, compared to face-to-face), pragmatic non-inferiority randomised controlled trial of the mode of administration, stroke survivors were randomised to postal, online, telephone and face-to-face assessment, in an equal ratio (1:1:1:1). The primary outcome was the proportion of participants that responded to the three allocation groups, compared to the face-to-face group. Subgroup analyses for age, aphasia and type and severity of stroke were carried out. A non-inferiority margin of 0.025 was used, and Holm-Bonferroni multiplicity adjustment was made. Results Of the 2074 eligible patients randomised, 55% were male (1142/2074), with an average age of 73.0 years old (SD = 13.2). Of those randomised, 22% (116/525), 9% (47/515) and 20% (101/513) responded in postal, online and telephone, respectively, compared to 17% (89/521) in the face-to-face group. The reduction in the online response rate compared to face-to-face was found to be both inferior and not non-inferior and estimated as an 8% reduction (95% CI 3.9 to 12.0%; p

Abstract Background The discovery that voltage-gated calcium channel genes such as CACNA1C are part of the aetiology of psychiatric disorders has rekindled interest in the therapeutic potential of L-type calcium channel (LTCC) antagonists. These drugs, licensed to treat hypertension and angina, have previously been used in bipolar disorder, but without clear results. Neither is much known about the broader effects of these drugs on the brain and behaviour. Methods The Oxford study of Calcium channel Antagonism, Cognition, Mood instability and Sleep (OxCaMS) is a high-intensity randomised, double-blind, placebo-controlled experimental medicine study on the effect of the LTCC antagonist nicardipine in healthy young adults with mood instability. An array of cognitive, psychiatric, circadian, physiological, biochemical and neuroimaging (functional magnetic resonance imaging and magnetoencephalography) parameters are measured during a 4-week period, with randomisation to drug or placebo on day 14. We are interested in whether nicardipine affects the stability of these measures, as well as its overall effects. Participants are genotyped for the CACNA1C risk polymorphism rs1006737. Discussion The results will clarify the potential of LTCC antagonists for repurposing or modification for use in psychiatric disorders in which cognition, mood and sleep are affected. Trial registration ISRCTN, ISRCTN33631053. Retrospectively registered on 8 June 2018 (applied 17 May 2018).