Historical Southern Hemisphere biomass burning variability inferred from ice core carbon monoxide records.

Biomass burning plays an important role in climate-forcing and atmospheric chemistry. The drivers of fire activity over the past two centuries, however, are hotly debated and fueled by poor constraints on the magnitude and trends of preindustrial fire regimes. As a powerful tracer of biomass burning, reconstructions of paleoatmospheric carbon monoxide (CO) can provide valuable information on the evolution of fire activity across the preindustrial to industrial transition. Here too, however, significant disagreements between existing CO records currently allow for opposing fire histories. In this study, we reconstruct a continuous record of Antarctic ice core CO between 1821 and 1995 CE to overlap with direct atmospheric observations. Our record indicates that the Southern Hemisphere CO burden ([CO]) increased by 50% from a preindustrial mixing ratio of ca. 35 ppb to ca. 53 ppb by 1995 CE with more variability than allowed for by state-of-the-art chemistry-climate models, suggesting that historic CO dynamics have been not fully accounted for. Using a 6-troposphere box model, a 40 to 50% decrease in Southern Hemisphere biomass-burning emissions, coincident with unprecedented rates of early 20th century anthropogenic land-use change, is identified as a strong candidate for this mismatch.

Liver paired exchange U.S. single center experience - pairs, chains, and use of compatible pairs'.

BACKGROUND: In the United States, the discrepancy between organ availability and need has persisted despite changes in allocation, innovations in preservation, and policy initiatives. Living donor liver transplant (LDLT) remains an underutilized means of improving access to timely liver transplantation and decreasing waitlist mortality. Liver paired exchange (LPE) represents an opportunity to overcome LDLT pair incompatibility due to size, anatomy, or blood type. METHODS: LPE was adopted as a strategy to augment access to liver transplantation at our institution. Specific educational materials, consent forms, and selection processes were developed to facilitate LPE. RESULTS: From 2019 through October 2023, our center performed 11 LPEs, resulting in 23 LDLT pairs. The series included several types of LPE: those combining complementary incompatible pairs, the inclusion of compatible pairs to overcome incompatibility, and the use of altruistic non-directed donors to initiate chains. These exchanges facilitated transplantation for 23 recipients, including 1 pediatric patient. CONCLUSIONS: LPE improved access to liver transplantation at our institution. The ethical application of LPE includes tailored patient education, assessment and disclosure of exchange balance, mitigation of risk and maximization of benefit for donors and recipients.

Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial.

PURPOSE: The efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

Longitudinal analysis of blood pressure and lipids in childhood nephrotic syndrome.

BACKGROUND: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. METHODS: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. RESULTS: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. CONCLUSIONS: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.

Weighing your options-intragastric balloon versus semaglutide.

INTRODUCTION: Over half of Americans and up to 78% of US Veteran population meet criteria for obesity. Perioperatively placed intragastric balloon (IGB) can accelerate weight loss goals for safe surgical candidacy, however weight regain is common after removal. Glucagon-like peptide-1-receptor agonists (GLP1RA) may provide a more sustainable weight loss solution after surgery. We hypothesize that weight regain will be less at 1 year after initiation of GLP1RA than IGB placement in Veterans. METHODS: Retrospective review of prospective databases of perioperatively placed intragastric balloon cohort from 1/2019-1/2023 compared to patients who received initiatory GLP1RA from 6/2021-8/2022 at a VA Medical Center(VAMC). All patients were enrolled in the VAMC MOVE! multidisciplinary weight management program for a minimum of 12 weeks. Outcomes measured were patients' weights at 0, 3, 6, and 12 months and weight change for these intervals. Exclusion criteria included history of bariatric surgery and incomplete weight loss data. RESULTS: Two-hundred-twenty-three patients met inclusion criteria; 110 (49%) patients excluded. Mean age was 54 ± 11 years, the majority (78, 69%) were male, and the mean initial BMI was 37 ± 5.9 kg/m2. Seventeen (15%) patients underwent IGB placement and 96 (85%) patients received semaglutide. Weight (kg) change was measured at intervals: 0-3 months:- 11.8(- 17,- 9.5) IGB vs. - 5.1(- 7.4,- 2.3) semaglutide, p < 0.0001; 0-6 months:- 12.7(- 18.4,- 9.9) vs. - 9.4(- 12.6,- 6.1), p = 0.03; 3-6 months:- 0.5(- 2.3,2.3) vs. - 4.3(- 6.8,- 1.6), p < 0.0001; 6-12 months:3(0,7.3) vs. - 1.9(- 4.7,1), p = 0.0006. CONCLUSION: Weight loss occurs more rapidly in the first 6 months after intragastric balloon placement compared to semaglutide (- 12.7 vs. - 9.4 kg, p = 0.03). Despite ongoing attendance in a comprehensive weight loss program, weight regain is common after IGB removal by an average of 3 kg (23.6%) at 1 year. In contrast, patients on GLP1RA (semaglutide) continue to lose weight during this period. Further studies are needed to determine if optimal long-term outcomes may result from combination therapy with intragastric balloon and semaglutide.

Symptoms Associated With Exercise Intolerance and Resting Heart Rate Following Mild Traumatic Brain Injury.

OBJECTIVES: People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary aim to examine the relationship between symptom-based clinical profiles and recovery. METHODS: Prospective observational study of adults aged 18 to 65 years who had sustained mTBI within the previous 7 days. Symptoms were assessed using the Post-Concussion Symptom Scale, HR was measured at rest, and exercise tolerance was assessed using the Buffalo Concussion Bike Test. Symptom burden and symptom-based clinical profiles were examined with respect to exercise tolerance and resting HR. RESULTS: Data from 32 participants were assessed (mean age 36.5 ± 12.6 years, 41% female, 5.7 ± 1.1 days since injury). Symptom burden (number of symptoms and symptom severity) was significantly associated with exercise intolerance (P = .002 and P = .025, respectively). Physiological and vestibular-ocular clinical profile composite groups were associated with exercise tolerance (P = .001 and P = .014, respectively), with individuals who were exercise intolerant having a higher mean number of symptoms in each profile than those who were exercise tolerant. Mood-related and autonomic clinical profiles were associated with a higher resting HR (>80 bpm) (P = .048 and P = .028, respectively), suggesting altered autonomic response for participants with symptoms relating to this profile. After adjusting for age and mechanism of injury (sports- or non-sports-related), having a higher mood-related clinical profile was associated with persisting symptoms at 3 months postinjury (adjusted odds ratio = 2.08; 95% CI, 1.11-3.90; P = .013). CONCLUSION: Symptom-based clinical profiles, in conjunction with objective measures such as resting HR and exercise tolerance, are important components of clinical care for those having sustained mTBI. These results provide preliminary support for the concept that specific symptoms are indicative of autonomic dysfunction following mTBI.

Increased risk of attention-deficit/hyperactivity disorder in adolescents with high salivary levels of copper, manganese, and zinc.

Exposure to toxic heavy metals has been associated with the development of attention-deficit/hyperactivity disorder (ADHD). However, fewer studies have examined the associations between abnormal levels of essential trace metals and ADHD, and none have done so using saliva. We investigated whether salivary metals were associated with ADHD in adolescents aged 12 from the Family Life Project (FLP) using a nested case-control study design that included 110 adolescents who met diagnostic criteria for inattentive (ADHD-I), hyperactive-impulsive (ADHD-H), or combined type ADHD (ADHD-C) (cases) and 173 children who did not (controls). We used inductively coupled plasma optical emission spectrophotometry to measure chromium, copper, manganese, and zinc in saliva samples. We employed logistic regression models to examine associations between quartile levels of individual metals and ADHD outcomes by subtype. Salivary copper levels were significantly associated with increased odds of any ADHD diagnosis (OR = 3.31, 95% CI: 1.08-10.12; p = 0.04) and with increased odds of ADHD-C diagnosis (OR = 8.44, 95% CI: 1.58-45.12; p = 0.01). Salivary zinc levels were significantly associated with increased odds of ADHD-C diagnosis (OR = 4.06, 95% CI: 1.21-13.69; p = 0.02). Salivary manganese levels were also significantly associated with increased odds of ADHD-C diagnosis (OR = 5.43, 95% CI: 1.08-27.27, p = 0.04). This is the first study using saliva to assess metal exposure and provide a potential link between salivary levels of copper, manganese, and zinc and ADHD diagnoses in adolescents. Public health interventions focused on metal exposures might reduce ADHD incidence in low-income, minority communities.

Training in Cultural Competence for Mental Health Care: A Mixed-Methods Study of Students, Faculty, and Practitioners from India and USA.

Although the need to train clinicians to provide effective mental health care to individuals from diverse backgrounds has been recognized worldwide, a bulk of what we know about training in cultural competence (CC) is based on research conducted in the United States. Research on CC in mental health training from different world populations is needed due to the context-dependent nature of CC. Focusing on India and USA, two diverse countries that provide complementary contexts to examine CC, we explored graduate students', practicing clinicians', and faculty members' perspectives regarding CC training they received/provided and future training needs using mixed-methods. The data were collected using focus groups (n = 25 groups total: 15 in India, 11 in USA), and a survey (n = 800: 450 in India, 350 in USA). Our data highlight the salient social identities in these countries, and the corresponding constituents of CC training. Participants in India described a practical emphasis to their CC training (e.g., learning about CC through life experiences and clinical practice experiences) more so than through coursework, whereas participants in USA described varying levels of coursework related to CC along with practice. Participants in both countries considered enormity of CC as a challenge, while those in the US also identified CC training limited to a white, straight, male perspective, hesitancy in engaging with diversity topics, and limited time and competence of the faculty. Strengths of CC training in India and USA are mutually informative in generating recommendations for enhancing the training in both countries.

Novel Occupational Therapy Program (Step Up) to Facilitate the Transition from Early Intervention in Psychosis Services.

The purpose of this program evaluation was to examine preliminary outcomes associated with a novel stepdown program for clients of early intervention in psychosis services ("Step Up") that featured occupational therapy (OT) as a critical treatment component. Clients participated in Step Up for at least 6 months and were administered pre-post assessments of clinician-rated performance of daily living activities and self-perceived performance and satisfaction with daily occupational functioning. Paired samples Wilcoxon tests were used to compare outcomes across the two time points. Data from 23 participants of Step Up were analyzed. Clinician-rated performance of daily living (especially in the areas of money and time management and leisure engagement) and client-rated performance and satisfaction with daily occupational functioning improved significantly over time. Results demonstrate the promise of programs such as Step Up that capitalize on OT and promote functional outcomes during the transition from early intervention.

Heads up on concussion: Aboriginal and Torres Strait Islander peoples' knowledge and understanding of mild traumatic brain injury.

ISSUE ADDRESSED: Concussion awareness and knowledge among Aboriginal and Torres Strait Islander peoples residing in Perth, Western Australia and factors preventing presentation at a health service for assessment after such an injury. METHODS: Qualitative study with participants aged between 18 and 65 years. Recruitment was by Facebook advertising and snowball sampling. A semi-structured topic yarning guide was used to guide conversations through 1:1, multi-person or group yarns. Yarns were audio-recorded, transcribed and thematically analysed. RESULTS: Twenty-four participants were recruited. A good knowledge of modes of concussion injury was identified in these participants. However, they identified difficulty differentiating this injury from other injuries or medical conditions. Multiple factors contributed to a reluctance to seek assessment and further management of a potential concussion. Multiple strategies to enhance education and presentation for assessment were suggested by participants. CONCLUSIONS: Aboriginal and Torres Strait Islander-owned and led concussion education is the first step in enhancing understanding of this condition. Education must be coupled with improvements in the cultural safety of healthcare services, as without this, patients will continue to fail to present for assessment and management. SO WHAT?: It is recommended that concussion education focuses on the differentiation of concussion as a diagnosis from other injuries. Information regarding where and when to seek medical assessment is recommended, and this must be in a culturally safe environment. Typical recovery and potential sequelae must be explored, in programs led and devised by Aboriginal and Torres Strait Islander peoples engaged with the community for which the education is proposed.

Collaborative approaches in psychiatric rehabilitation: Innovations in practice.

OBJECTIVE: This special section is dedicated to collaborative approaches in psychiatric rehabilitation, which are rooted in foundational values such as service user involvement and self-determination. METHODS: Five articles featuring collaborative approaches are included and briefly reviewed here. RESULTS: These articles highlight innovations in collaborative approaches, addressing existing limitations in research and practice and advancing understanding of collaborative psychiatric care among diverse populations. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: They underscore the ongoing need for research and policy reform to promote more routine and widespread implementation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mapping neurodegeneration across the Huntington's disease spectrum: a five-year longitudinal analysis of plasma neurofilament light.

BACKGROUND: Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage. METHODS: 108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study. Individuals with the HD mutation were categorised separately by both HD-Integrated Staging System (HD-ISS) (Study 1) and PIN score-Approximated Staging System (PASS) (Study 2) criteria. Plasma NfL trajectories were examined using Mixed Linear Modeling (MLM); associations with symptom presentation were assessed using Spearman's rho correlations. FINDINGS: The MLM coefficients for disease stage (HD-ISS ß = 32.73, p < 0.0001; PASS ß = 33.00, p < 0.0001) and disease stage∗time (HD-ISS ß = 7.85, p = 0.004; PASS ß = 6.58, p = 0.0047) suggest these are significant contributors to plasma NfL levels. In addition, the plasma NfL rate of change varied significantly across time (HD-ISS ß = 3.14, p = 0.04; PASS ß = 2.94, p = 0.050). The annualised rate of change was 8.32% for HC; 10.55%, 12.75% and 15.62% for HD-ISS Stage ≤1, Stage 2, and Stage 3, respectively; and 12.13%, 10.46%, 10.33%, 17.52%, for PASS Stage 0, Stage 1, Stage 2, and Stage 3, respectively. Plasma NfL levels correlated with the Symbol Digit Modalities Test (SDMT) in HD-ISS Stage ≤1, and both SDMT and Total Motor Score in Stage 3 (ps < 0.01). INTERPRETATION: Our findings suggest that plasma NfL levels increase linearly across earlier disease stages, correlating with the cognitive SDMT measure. Thereafter, an increase or surge in plasma NfL levels, paired with correlations with both cognitive and motor measures, suggest a late acceleration in clinical and pathological progression. FUNDING: NIH (NS111655); the UCSD HDSA CoE; the UCSD ADRC (NIH-NIA P30 AG062429).

The Effect of Ophthalmic Antibiotics on Clinical Outcomes and Transmissibility of Conjunctivitis Associated with Haemophilus influenzae versus Other Pathogens: Secondary Analysis of a Randomized Controlled Trial.

Transmission rates among children with conjunctivitis were low and antibiotic use was not associated with reduced transmission. Policies recommending exclusion from daycare and school for conjunctivitis should be scrutinized as they may not reduce transmission and may increase unnecessary antibiotic use.

Deactivation and collective phasic muscular tuning for pointing direction: Insights from machine learning.

Arm movements in our daily lives have to be adjusted for several factors in response to the demands of the environment, for example, speed, direction or distance. Previous research has shown that arm movement kinematics is optimally tuned to take advantage of gravity effects and minimize muscle effort in various pointing directions and gravity contexts. Here we build upon these results and focus on muscular adjustments. We used Machine Learning to analyze the ensemble activities of multiple muscles recorded during pointing in various directions. The advantage of such a technique would be the observation of patterns in collective muscular activity that may not be noticed using univariate statistics. By providing an index of multimuscle activity, the Machine Learning (ML) analysis brought to light several features of tuning for pointing direction. In attempting to trace tuning curves, all comparisons were done with respects to pointing in the horizontal, gravity free plane. We demonstrated that tuning for direction does not take place in a uniform fashion but in a modular manner in which some muscle groups play a primary role. The antigravity muscles were more finely tuned to pointing direction than the gravity muscles. Of note, was their tuning during the first half of downward pointing. As the antigravity muscles were deactivated during this phase, it supported the idea that deactivation is not an on-off function but is tuned to pointing direction. Further support for the tuning of the negative portions of the phasic EMG was provided by the observation of progressively improving classification accuracies with increasing angular distance from the horizontal. We also demonstrated that the durations of these negative phases, without information on their amplitudes, is tuned to pointing directions. Overall, these results show that the motor system tunes muscle commands to exploit gravity effects and reduce muscular effort. It quantitatively demonstrates that phasic EMG negativity is an essential feature of muscle control. The ML analysis was done using Linear Discriminant analysis (LDA) and Support Vector Machines (SVM). The two led to the same conclusions concerning the movements being investigated, hence showing that the former, computationally inexpensive technique is a viable tool for regular investigation of motor control.

Occupational Therapy: A Potential Solution to the Behavioral Health Workforce Shortage.

Occupational therapy practitioners (OTPs) are clinically prepared to treat patients with behavioral health conditions. Yet, many state and national policies defining qualified behavioral health providers do not include occupational therapy. In this Open Forum, the authors argue that OTPs should be considered qualified to work as behavioral health professionals, especially given the severe behavioral health workforce shortage in the United States. The authors summarize policy barriers preventing OTPs from working on behavioral health teams and the evidence to support their presence. They also propose a policy and advocacy agenda to include and recognize OTPs as members of the behavioral health workforce.

Self-determination and self-efficacy as predictors of campus engagement among college students with serious mental illnesses.

OBJECTIVE: Campus engagement, including participation in student organizations and groups, is important for both academic and health outcomes. Yet, college students with serious mental illnesses demonstrate lower levels of campus engagement compared to peers without mental illnesses. To inform psychiatric rehabilitation approaches that might enhance this outcome, the purpose of this study was to test an integrated model of self-determination and self-efficacy theories to predict campus engagement within this student population. METHODS: Sixty-seven college students with serious mental illnesses completed measures assessing self-determination constructs (autonomy, competence, and relatedness), college self-efficacy, and campus engagement. Correlational and path analytic models examined relationships among these variables. RESULTS: Bivariate and multivariate analyses supported the interrelationships among the variables. Specifically, the theory-driven path model demonstrated that autonomy (but not competence or relatedness) was a significant predictor of college self-efficacy, which in turn was associated with campus engagement. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings particularly highlight the importance of autonomy and self-efficacy for promoting campus engagement among college students with serious mental illnesses. As such, they may be relevant targets for psychiatric rehabilitation interventions, such as supported education, that are designed to enhance student success. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A retrospective analysis of concussion and post-concussional syndrome diagnoses in Western Australian emergency departments.

OBJECTIVE(S): To determine the rate of concussion diagnoses per capita recorded in hospital emergency departments in Western Australia (WA) from 2002-2018 for ICD-10-AM concussion diagnoses S06.00-S06.05, and post-concussional syndrome (PCS) (F07.2). DESIGN, SETTING AND ANALYSIS: Retrospective analysis of hospital Emergency Department (ED) presentations and hospital admissions from all WA hospitals for all patients with an ICD-10-AM diagnosis code for concussion and post-concussional syndrome (PCS) over the period 2002-2018. Data pertaining to concussion and PCS presentations were extracted from the WA Department of Health Emergency Department Data Collection (EDDC). Total case numbers were aggregated by year (2002-2018) and regions of WA. MAIN OUTCOME MEASURES: The rates of diagnoses were calculated based on the population in the specific region and expressed as incidence rate per 100,000 person-years. The overall trends of diagnoses across the regions were analysed using negative binomial regression models and expressed as incidence rate ratio (IRR) with the corresponding 95 % CI, whilst adjusting for region. Tests for linearity were also performed. RESULTS: The rate of concussion diagnosis had significantly increased linearly over the years (p for trend: p < 0.001) whilst the rate of PCS diagnosis had significantly declined linearly over the same period (p for trend: p < 0.001). CONCLUSION: There was significant increase in all-cause ICD-10-AM concussion diagnoses in WA emergency departments. To further clarify the incidence and prevalence of all-cause concussion in Australia, investigation must focus on truly reflective S06.0 codes and include data linkage to primary care data. Conversely PCS ED presentations reduced; whether this relates to a change in where presentations occur for management of such a diagnosis, improved early intervention or an alternative explanation warrants further investigation.

Androgen receptor cofactors: A potential role in understanding prostate cancer.

Prostate cancer (PCa) is witnessing a concerning rise in incidence annually, with the androgen receptor (AR) emerging as a pivotal contributor to its growth and progression. Mounting evidence underscores the AR's ability to recruit cofactors, influencing downstream gene transcription and thereby fueling the proliferation and metastasis of PCa cells. Although, clinical strategies involving AR antagonists provide some relief, managing castration resistant prostate cancer (CRPC) remains a formidable challenge. Thus, the need of the hour lies in unearthing new drugs or therapeutic targets to effectively combat PCa. This review encapsulates the pivotal roles played by coactivators and corepressors of AR, notably androgen receptor-associated protein (ARA) and steroid receptor Coactivators (SRC) in PCa. Our data unveils how these cofactors intricately modulate histone modifications, cell cycling, SUMOylation, and apoptosis through their interactions with AR. Among the array of cofactors scrutinised, such as ARA70ß, ARA24, ARA160, ARA55, ARA54, PIAS1, PIAS3, SRC1, SRC2, SRC3, PCAF, p300/CBP, MED1, and CARM1, several exhibit upregulation in PCa. Conversely, other cofactors like ARA70α, PIASy, and NCoR/SMRT demonstrate downregulation. This duality underscores the complexity of AR cofactor dynamics in PCa. Based on our findings, we propose that manipulating cofactor regulation to modulate AR function holds promise as a novel therapeutic avenue against advanced PCa. This paradigm shift offers renewed hope in the quest for effective treatments in the face of CRPC's formidable challenges.

Awareness and understanding of concussion among Aboriginal Australians with high health literacy.

Aim: Indigenous Australians have higher rates of traumatic brain injury, with 74-90% of such injuries being concussion. This study explores concussion awareness and knowledge in Aboriginal Western Australians with high health literacy. Materials & methods: Participants, aged 18-65 years, engaged in research topic yarning, and thematic analysis of the qualitative data then undertaken. Results: There was awareness that direct head trauma can result in concussion, but a lack of differentiation between concussion and other head injuries. Knowledge was gained from sport, media or lived-experience. Symptom minimization and diversity of concussion symptoms prevented participants from seeking medical treatment. This was exacerbated by a mistrust of the medical system. Conclusion: Research findings highlight knowledge and service gaps where co-designed strategies can be targeted.

Despite higher injury rates in Indigenous Australians, literature relating to brain injuries such as concussion in these populations is lacking. This article provides information regarding awareness and knowledge of concussion in Aboriginal peoples with health or first responder experience. Through the process of yarning, 25 Aboriginal participants shared their awareness and knowledge of concussion. While there was good understanding of how concussion injury can occur, it was found that identification of concussion as a diagnosis is complex, and it is hard to differentiate from other conditions. Minimization of concussion symptoms was commonly reported, and multiple barriers to seeking healthcare after a potential concussion occurs were identified. Despite having health or first responder experience, participants reported their concussion knowledge was gained from community and televised sport, other aspects of media, and word of mouth. These results support the need for Indigenous Australian led and co-designed concussion education. They also support the need for further research in this space, targeting Indigenous Australian populations without high health literacy.

GPs' perspectives on diagnostic tests for children: a qualitative interview study.

BACKGROUND: Most healthcare contacts for children in the UK occur in general practice. Diagnostic tests can be beneficial in narrowing differential diagnoses; however, there is substantial variation in the use of tests for children in general practice. Unwarranted variation in testing can lead to variation in quality of care and may exacerbate health inequities. To our knowledge, no previous study has tried to understand why variation in testing exists for children in general practice. AIM: To explore GPs' perspectives on using diagnostic tests for children in primary care and the underlying drivers of variation. DESIGN AND SETTING: Qualitative study in which semi-structured interviews were conducted with GPs and trainee GPs in England. METHOD: Interviews were conducted with 18 GPs and two trainee GPs between April and June 2023. The interviews were transcribed and analysed using reflexive thematic analysis. RESULTS: GPs reflected that their approach to testing in children differed from their approach to testing in adults: their threshold to test was higher, and their threshold to refer to specialists was lower. GPs' perceptions of test utility varied, including objective testing for asthma. Perceived drivers of variation in testing were intrinsic (clinician-specific) factors relating to their risk tolerance and experience; and extrinsic factors, including disease prevalence, parental concern and expectations of health care, workforce changes leading to fragmentation in care, time constraints, and differences in guidelines. CONCLUSION: The findings of this study identify actionable issues for clinicians, researchers, and policymakers to address gaps in education, evidence, and guidance, reduce unwarranted differences in test use, and improve the quality of health care delivered to children in general practice.