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Objective: Midkine (MK) is a member of a small protein family that includes pleiotrophin. MK levels are elevated in obese patients and have a pro-arthrogenic effect through various pathophysiological processes including vascular inflammation and atherogenesis. This study aimed to investigate the association between serum MK levels and several atherosclerotic risk factors in patients with type 2 diabetes mellitus (T2DM)., Methodology: Ninety subjects were enrolled in this study, comprising 60 T2DM patients and 30 age-matched healthy subjects (HS). The patients were categorized into two groups based on dyslipidemia: group 1 consisted of 30 patients with dyslipidemia, while group 2 included 30 patients without dyslipidemia. Laboratory tests were conducted using routine assays at the National Diabetes Center. MK levels were analyzed using enzyme-linked immunosorbent assay (ELISA)., Results: MK levels were significantly higher in patients with dyslipidemia compared to those without dyslipidemia and HS ( P  ≤ 0.0001). A significant negative correlation was observed between MK levels and the atherogenic index of plasma (AIP), Castelli's risk index-1 (CRI-I), and Castelli's risk index-2 (CRI-II) ( r  = - 0.489, p  = 0.005; r  = - 0.465, p  = 0.008; r  = - 0.421, p  = 0.018, respectively) in patients with dyslipidemia. Furthermore, a significant positive correlation was found between MK levels and HDL-C ( r  = 0.524, p  = 0.002) in patients without dyslipidemia. MK, AIP, and CRI-I were identified as predictors of atherosclerosis in DM patients, with MK indicating very good discriminate power (AUC = 0.805) in identifying T2DM patients with dyslipidemia at a cut-off value of ≤ 4.457 ng/ml., Conclusion: These findings suggest that MK could be considered a predictive biomarker for dyslipidemia associated with DM. MK levels correlate significantly with atherogenic risk factors, indicating its potential as a sensitive risk predictor for atherosclerosis in patients with T2DM., Competing Interests: Conflict of interestThe authors affirm that no conflict of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A wide range of animals, including a number of bird, fish, mammal and reptile species, show sex differences in cognitive tests. Hardly anything is known, however, about whether and how sex-specific non-cognitive factors (e.g. response to novelty) affect the expression of cognition in the wild. We used a series of learning and problem-solving tasks in wild breeding skuas, a species in which females are the larger sex (female-biased sexual size dimorphism). We also evaluated the birds' response to novelty (novel objects) before and after the tasks were administered. Both sexes performed equally well in learning ( Discrimination-learning task ) and re-learning ( Reversal-learning task ) food associations with colour and spatial cues, but female skuas outperformed males in problem-solving tasks ( String-pulling task , Box-opening task ). Females were also less neophobic than males: they were faster at accepting a food reward in novel situations. Better female performance may not imply higher cognition per se . Sex-specific size differences may translate into less or more neophobic behavioural types, which, in turn, predict females' problem-solving success and response to novelty. Species with female-biased sexual dimorphism may present a useful model to assess the interactions between sex, non-cognitive factors and cognition in the wild.

Purpose: Enhanced histological detection of clinically significant prostate cancer is the goal of the prebiopsy imaging pathway. Risk stratification at a prebiopsy meeting can facilitate optimization of lesion targeting. We aimed to evaluate the feasibility of cognitive registration, freehand transperineal prostate biopsy in a biopsy-naïve population following biparametric MRI for the detection of clinically significant disease (International Society of Urological Pathology Grade Group ≥2)., Materials and Methods: A consecutive series of biopsy-naïve men, prospectively recorded between July 2018 and March 2023, were risk-stratified at our prebiopsy meeting following biparametric MRI to undergo either target-only biopsy or target with systematic biopsy. Biopsies were routinely performed under local anesthesia and without antibiotic prophylaxis in the outpatient setting. Overall prostate cancer and clinically significant prostate cancer detection were primary outcomes., Results: Of 1251 biopsies, prostate cancer was detected in 84% and clinically significant disease in 70.6%. Prostate cancer and clinically significant disease were detected in 86.2% and 76.5% of target-only biopsies, respectively, and in 78.7% and 56.3% of target with systematic biopsies. Postbiopsy complication rate was 0.7%., Conclusions: Prebiopsy biparametric MRI with risk stratification at a prebiopsy meeting in the setting of cognitive targeting and freehand transperineal prostate biopsy yielded a high detection of prostate cancer that is comparable to other studies. These data support the use of cognitive registration, freehand transperineal prostate biopsy as safe, feasible, and cost-effective.

Objectives: The lack of Indigenous health care data in Canada makes it challenging to plan health care services and inform Indigenous leadership on the health care needs of their respective Nations and communities. Several Canadian health care organizations have implemented a voluntary Indigenous identifier of patients within their electronic medical records. This study examines facilitators and barriers to implementing such a voluntary self-reported Indigenous identifier, from the perspective of key stakeholders who work at four Canadian health providers where an Indigenous identifier has been implemented., Methods: The four Canadian sites comprise three hospitals and one health authority. At each site, key stakeholders participated in semi-structured qualitative interviews. Interviews were transcribed and coded. Relevant documents that were publicly available or provided by each site were reviewed., Results: There were four primary findings. First, for the introduction of an Indigenous identifier to be successful there must be pre-existing strong and trusting relationships between Indigenous communities and health care organizations. Second, health care organizations must provide training for those who ask clientele to self-identify as Indigenous, to overcome issues such as any patient backlash. Third, for the relationship between Indigenous people and health organizations to flourish, data governance must be Indigenous-led. Finally, the collection of Indigenous identifier data can enhance Indigenous health care services and health care service planning and delivery., Conclusions: Due to the ongoing distrust of government and health care services among Indigenous peoples and communities, special considerations are required prior to the implementation of an Indigenous identifier. Of primary importance is how health care organizations can contribute to Indigenous data governance and minimize potential harms associated with the collection of such data. The findings of this study can be used to guide other health care sites and Indigenous leaders aspiring for more robust health data by implementing voluntary Indigenous identity data collection., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Conflict of interest: none declared.

Background: The incidence of obesity in patients with inflammatory bowel disease (IBD) is increasing and there are limited data on the impact of obesity on perianal fistulas in Crohn's disease (CD)., Aims: We aim to examine the relationship between obesity and the prevalence and complications of Crohn's perianal fistulas., Methods: We conducted a cross-sectional study of CD patients treated at a tertiary care center from 2012 to 2022. Obesity was defined as maximum BMI > 30 kg/m 2 and further subdivided into 5 BMI categories. The prevalence of perianal fistulas was defined by any history of perianal fistula. The complications of perianal fistulas were measured by five variables including complex fistulas, history of perianal fistula surgery, number of perianal surgeries, history of fecal diversion, and median time to first anal surgery., Results: In all, 704 patients with CD were included; 31.1% were obese. There was no significant association between obesity and prevalence of perianal fistulas (p = 0.719), complex fistulas (p = 0.144), history of perianal surgery (p = 0.146), ≥ 1 perianal surgeries (p = 0.220), fecal diversion (p = 0.705), or median time to first perianal surgery (p = 0.192). Increasing BMI category was not associated with the prevalence of perianal fistulas (p = 0.944), complex fistulas (p = 0.089), perianal surgery (p = 0.583), ≥ 1 perianal surgeries (p = 0.114), fecal diversion (p = 0.542), or median time to first perianal surgery (p = 0.486). When comparing those with perianal fistulas to those without, there was no significant difference in rates of obesity (p = 0.876)., Conclusion: There was no association between obesity and the prevalence and complications of Crohn's perianal fistulas., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: Cardiac rehabilitation (CR) under-attendance presents a global challenge. The Queensland Cardiac Outcomes Registry is a comprehensive clinical registry that routinely collects point-of-care CR data. We aimed to determine whether demographic, clinical, psychosocial, and behavioural characteristics of the population vary between those who (i) declined, (ii) commenced but did not complete, and (iii) completed CR., Methods: The cohort comprised 33,055 patients referred to one of 56 Queensland CR services extracted from the Queensland Cardiac Outcomes Registry (2020-2022). Bivariate and multivariable logistic regression analyses were used to identify factors associated with CR non-attendance and non-completion., Results: Over the study period, 12,152 patients (37%) declined CR, 11,621 (35%) initiated but did not complete CR, and 9,282 (28%) completed CR. Significant predictors of CR non-attendance were aged ≥75 years (adjusted odds ratio [aOR] 1.51; 95% confidence interval [CI] 1.42-1.61), Indigenous status (aOR 1.65; 95% CI 1.50-1.81), living regionally (aOR 1.76; 95% CI 1.65-1.87) or remotely (aOR 2.33; 95% CI 1.92-2.82), and having arrhythmia (aOR 2.38; 95% CI 2.07-2.73), heart failure (aOR 1.54; 95% CI 1.37-1.74), non-ST-elevation myocardial infarction (aOR 1.30; 95% CI 1.21-1.40) or unstable angina (aOR 1.24; 95% CI 1.1.13-1.37). Significant predictors of CR non-completion were age <55 years (aOR 1.55; 95% CI 1.37-1.75), Indigenous status (aOR 1.60; 95% CI 1.29-1.98), living regionally (aOR 1.29; 95% CI 1.12-1.48), obesity (aOR 1.14; 95% CI 1.01-1.28), being a current (aOR 1.97; 95% CI 1.70-2.27) or former smoker (aOR:1.22, 95% CI 1.11-1.33) and having low social support (aOR 1.58; 95% CI 1.24-2.02)., Conclusion: As one of the largest studies of CR participation to date, these findings can now be applied to develop targeted, co-designed initiatives to enhance CR participation, especially among First Nations populations, smokers, those with limited social support, people living regionally/remotely, patients with arrhythmia and heart failure, and those in varying age groups., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Persistent organic pollutants (POPs) are halogenated contaminants found globally. Cetaceans are impacted by these pollutants, and nowadays, it is essential to understand their presence to mitigate their impacts. This study aimed to establish baseline levels of POPs in the blubber of Commerson's dolphins (Cephalorhynchus commersonii) within the Subantarctic ecosystem. A wide range of POPs concentrations were measured among individuals: ΣPCBs from 289.5 to 15264 ng g -1 lw and ΣDDTs from 540.4 to 17657 ng g -1 lw. Levels of HCB and mirex ranged from 48 to 1703.7 ng g -1 lw and 5.1-1917.4 ng g -1 lw, respectively. The predominant POPs were mid-to high molecular weight PCBs (hexa-PCBs), consistent with other findings in cetaceans of the southern hemisphere. The mean ratio of ΣDDT/ΣPCB was 0.44, with p,p'-DDE/ΣDDT at 0.56, indicating p,p'-DDE as the dominant DDT isomer. Furthermore, differences in POP concentrations were observed based on sexual maturity, with mature males exhibiting higher levels of ƩPCBs, HCB, ƩDDT, and mirex. Age and total body length of animals were strongly correlated with POP concentrations. Our study provides valuable insights into the pollutant status of POPs in the Subantarctic population of Commerson's dolphins inhabiting the southernmost coastal regions of South America., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity in patients with fibromyalgia (FM). This multi-group randomized clinical trial compared home-based active tDCS (HB-a-tDCS) on the left dorsolateral prefrontal cortex (l-DLPFC) or home-based sham tDCS (HB-s-tDCS), and HB-a-tDCS or HB-s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies., Methods: We included 48 women with FM, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of HB-a-tDCS 2mA or HB-s-tDCS, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC)., Results: In the EC condition, comparing pre to post-treatment, the HB-a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t = -3.542, p = .048). The l-DLPFC HB-a-tDCS compared to HB-s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t = -4.000, p = .017). In the EO condition, the l-DLPFC HB-a-tDCS compared to M1 HB-s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t = -4.059, p = .048). Regression analysis demonstrated that the HB-a-tDCS effect on the l-DLPFC was positively correlated with sleep quality. On the other hand, the HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing., Conclusions: These results show that HB-a-tDCS affects the neural connectivity between parts of the brain that control pain's emotional and attentional aspects, which are most noticeable at lower EEG frequencies in a rest state. This effect on neural oscillations could serve as a neural marker associated with its efficacy in alleviating fibromyalgia symptoms., Clinical Trial Registration: identifier [NCT03843203]., Competing Interests: WC, National Council for Scientific and Technological Development - (CNPq), Brazil, ILST reported grants from National Council for Scientific and Technological Development, and Fundación de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduct of the study and PRSS grants from National Council for Scientific and Technological Development during the conduct of the study. PRSS reported grants from Financiadora de Estudos e Projetos during the conduct of the study; in addition, WC, ILST, PRSS had a patent for BR 20 2015 016450 0 licensed to Quark Medical. The tDCS device used in this study was developed and patented by PRSS, DPSJ, ILST, and WC, and these authors received royalties from Quark Medical (patent for BR 20 2015 016450 0 licensed to Quark Medical). DPSJ reported grants from Financiadora de Estudos e Projetos during the conduct of the study. No other competing interests were reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lopes Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Two million Americans have type 1 diabetes (T1DM). Innovative treatments have standardized insulin delivery and improved outcomes for patients, but patients' access to such technologies depends on social determinants of health, including insurance coverage, proper diagnosis, and appropriate patient supports. Prior estimates of US prevalence, incidence, and patient characteristics have relied on data from select regions and younger ages and miss important determinants. Objectives: This study sought to use large, nationally representative healthcare claims data sets to holistically estimate the size of the current US population with T1DM and investigate geographic nuances in prevalence and incidence, patient demographics, insurance coverage, and device use. This work also aimed to project T1DM population growth over the next 10 years. Methods: We used administrative claims from 4 sources to identify prevalent and incident T1DM patients in the US, as well as various demographic and insurance characteristics of the patient population. We combined this data with information from national population growth projections and literature to construct an actuarial model to project growth of the T1DM population based on current trends and scenarios for 2024, 2029, and 2033. Results: We estimated 2.07 million T1DM patients nationally across all insurance coverages in our 2024 baseline model year: 1.79 million adults (≥20 years) and 0.28 million children. This represents a US T1DM prevalence rate of 617 per 100 000 and an incidence rate of 0.016%. By 2033, we project the US population with T1DM will grow by about 10%, reaching approximately 2.29 million patients. Discussion: Our results showed important differences in T1DM prevalence and incidence across regions, payers, and ethnic groups. This suggests studies based on more geographically concentrated data may miss important variation in prevalence and incidence across regions. It also indicates T1DM prevalence tends to vary by income, consistent with several international studies. Conclusions: Accurate projections of T1DM population growth are critical to ensure appropriate healthcare coverage and reimbursement for treatments. Our work supports future policy and research efforts with 2024, 2029, and 2033 projections of demographics and insurance coverage for people with T1DM., Competing Interests: The authors are employees of Milliman, Inc., an international healthcare consulting and actuarial firm, and Breakthrough T1D, a global type 1 diabetes patient advocacy and research organization.

Breast cancer (BC) is one of the most significant neoplasms globally due to its high incidence and mortality, particularly among females. As a highly heterogeneous pathology, biomarkers are essential for characterizing specific tumors. Currently, several biological processes are well-described in the context of this neoplasm, such as alterations in BRCA1/2, HER, and pathways involving estrogen and progesterone hormone receptors. These studies have enabled the use of these findings as more precise methods for diagnosis, prognosis, and treatment. However, beyond patients who do not exhibit these classic markers, some individuals within the same risk group respond differently to treatment. Therefore, the search for biological markers that can improve diagnosis, aid in stratification, or serve as therapeutic targets is continuous and urgent. Genetic signatures have led to molecular tests currently used in clinical practice, though certain limitations persist. Understanding genetic and epigenetic mechanisms facilitates the identification of potential biomarkers. Biomarker targets must undergo experimental and clinical trials on samples of significant size before reaching clinical utility. In this review, we compile the classical markers and describe the potential use of other markers associated with the biological processes of this neoplasm., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Upper airway obstruction (UAO) management in children, particularly those with associated anatomical mid-face structural differences, poses a significant challenge. This study describes using a nasopharyngeal airway (NPA) in managing infants with severe upper airway obstruction., Methods: Infants discharged home from Queensland Children's Hospital with an NPA in situ for the management of upper airway obstruction were retrospectively evaluated for clinical and demographic parameters, underlying diagnoses and respiratory support, including NPA insertion details and comorbidities., Results: Sixty-seven children (24 male) were included with a median age at NPA insertion of 24 (IQR 7-59) days and a median duration of NPA use of 229.1 (IQR 151.50-297.75) days. Fifty-two (77.6%) had Pierre Robin sequence. Other diagnoses included CHARGE syndrome, Treacher Collins syndrome, Stickler syndrome, Crouzon syndrome, Bohring-Opitz syndrome, isolated cleft palate, Beckwith-Wiedemann syndrome, Chromosome 3 deletion and VACTERL association. Four infants required tracheostomy, and no complications related to NPA use were reported. Those with oximetry and polysomnography data showed improving indices following NPA insertion [pre NPA median (IQR) SpO 2 : 95.9% (94.73-97.73), AHI: 51.40 (44.50-69.45), OAHI 65.9 (56.45-73.35) and TcCO 2 (mmHg) 65.70 (61.95-67.30) vs. post-NPA median (IQR) SpO 2 : 97.1% (96.19-97.9), AHI: 12.20 (11.25-24.35), OAHI 10.20 (6.12-5.62) and TcCO 2 (mmHg) 52.40 (47.90-58.40)]., Conclusion: Our findings highlight the effectiveness and safety of NPA as a noninvasive management option for severe upper airway obstruction in children, particularly in those with anatomical midface structural differences. Further research and larger studies are warranted to confirm these findings and optimise management strategies for these patients., (© 2024 John Wiley & Sons A/S.)

Importance: Most youths receiving palliative care undergo many surgical interventions over their lifetimes. The intended purposes of interventions in the context of goals of care are not commonly articulated., Objective: To describe the goals and purposes of surgical intervention in youths receiving palliative care and propose a framework discussing intervention using goal-oriented language., Design, Setting, and Participants: This retrospective cohort analysis was conducted among a subset of patients enrolled between April 2017 and March 2021 in a prospective multicenter cohort study of youths receiving palliative care (the Pediatric Palliative Care Research Network's Shared Data and Research [SHARE] Study). Patients younger than 30 years receiving palliative care services were eligible for inclusion in SHARE, and all enrolled at Boston Children's Hospital/Dana Farber Cancer Institute, a SHARE site, were included in this study. Goals and purposes of all surgical interventions from the time of diagnosis through the present were abstracted from patient records. A goal and purpose framework was generated using a hybrid deductive-inductive approach based on established goals-of-care frameworks and the clinical context of surgical interventions. Data were analyzed in September 2023., Main Outcomes and Measures: Primary outcomes included goals and purposes of surgical interventions performed in the study population., Results: Among 197 youths receiving palliative care (mean [SD] age at palliative care start, 8.01 [7.53] years; 108 male [54.8%]; 6 Asian [3.0%], 12 Black [6.1%], 129 White [65.5%], and 16 with >1 race [8.1%]; 27 Hispanic [13.7%] and 142 not Hispanic [72.1%]), almost all individuals (189 youths [95.9%]) underwent at least 1 surgical intervention (mean [SD] 17.5 [16.3] interventions; median [IQR] 13 [5-22] interventions). Of 3331 surgical interventions, there were 878 interventions (26.5%) conducted with the goal of life extension, 1229 interventions (37.1%) conducted for life enhancement, and 79 interventions (2.4%) conducted for both goals; the remaining 1130 interventions (34.1%) held neither goal. Most interventions were performed with the purpose of diagnosis (1092 interventions [32.9%]) or cure and repair (1055 interventions [31.8%]), with fewer performed for the purpose of placing or maintaining assistive technology (696 interventions [21.0%]) or for supportive (434 interventions [13.1%]) or temporizing (39 interventions [1.2%]) purposes. Patients with cardiovascular disease and cancers constituted approximately half (592 patients [56.1%]) of those undergoing curative or repair interventions, whereas youths with neurologic or genetic conditions constituted approximately half (244 patients [56.2%]) of those undergoing supportive interventions., Conclusions and Relevance: In this cohort study, nearly all youths underwent surgical intervention, and the purposes of intervention differed by serious illness type. These findings suggest that conversations centered on a proposed framework concerning goals and purposes of surgical intervention may facilitate goal-concordant, high-quality care for youths with serious illness.

Problem: Intrauterine infection is one of the most jeopardizing conditions associated with adverse outcomes, including preterm birth; however, multiple tolerance mechanisms operate at the maternal-fetal interface to avoid the rejection of the fetus. Among the factors that maintain the uterus as an immunoprivileged site, Galectin-1 (Gal-1), an immunomodulatory glycan-binding protein secreted by the maternal-fetal unit, is pivotal in promoting immune cell homeostasis. This work aimed to evaluate the role of Gal-1 during a lipopolysaccharide (LPS)-induced-inflammatory milieu., Method of Study: Using an ex vivo culture with two independent compartments, human fetal membranes at term were pretreated with 40 and 80 ng/mL of Gal-1, then to reproduce an intraamniotic inflammation, the fetal side of membranes was stimulated with 500 ng/mL of LPS for 24 h. The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP1), macrophage inflammatory protein (MIP1) α, regulated upon activation normal T cell expressed and secreted (RANTES), and matrix metalloproteinase (MMP)-9 were measured in both amnion and choriodecidua compartments., Results: In a tissue-specific fashion profile, pretreatment with the physiologic concentration of Gal-1 significantly diminished the LPS-dependent secretion of TNF-α, IL-1β, Il-6, MCP1, MIP1α, RANTES, and MMP-9., Conclusion: Gal-1 elicits an anti-inflammatory effect on the human fetal membranes stimulated with LPS, which supports the hypothesis that Gal-1 is part of the immunomodulatory mechanisms intended to stop the harmful effect of inflammation of the maternal-fetal interface., (© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)

Introduction: Methylthioninium chloride is used for multiple treatment purposes and is sometimes administered through peripheral intravenous lines. We highlight the potential adverse effects of methylthioninium chloride extravasation during continuous peripheral intravenous administration., Case Summary: A 38-year-old woman presented to the emergency department with multifactorial hypovolemic and septic shock. She was treated with a continuous peripheral infusion of intravenous methylthioninium chloride for shock refractory to multiple vasopressors., Images: One day after administration commenced, the patient developed blue staining of the left upper arm due to extravasation of methylthioninium chloride proximal to the site of infusion. Further images show its later spread., Conclusion: While reported cases of methylthioninium chloride extravasation are rare, it is our preference that methylthioninium chloride should be administered through a central line in cases of continuous infusion due to the risk of potential toxicity from extravasation.

Objective: To examine the specificities and limitations of bilateral and unilateral tasks for the assessment of hip abductor and adductor strength with a commercially-available fixed-frame dynamometer., Design: Correlational/validity study., Methods: Maximal voluntary isometric strength of hip abductors and adductors was evaluated in 130 healthy participants using unilateral and bilateral tasks. Surface EMG activity of agonist and stabilizer muscles was concomitantly recorded in a subgroup of 15 participants., Results: For both muscle groups, bilateral tasks resulted in higher strength values than unilateral tasks (∼25%; p < 0.001). The correlation between left- and right-side data was higher for bilateral than unilateral tasks (p < 0.05), thereby resulting in lower interlimb asymmetries (p < 0.001). Agonist EMG activity was lower for unilateral than bilateral tasks (p < 0.01). Stabilizer EMG activity (external abdominal oblique) was higher for unilateral than bilateral tasks (p < 0.05) on the ipsilateral and contralateral side for hip abductors and adductors, respectively., Conclusions: A large (25%) and quasi-systematic bilateral facilitation of strength was observed for both hip abductors and adductors. Bilateral testing led to an underestimation of interlimb asymmetries, due to higher side equivalence than unilateral tasks. Unilateral testing resulted in lower agonist EMG activity and higher stabilizer activity than bilateral tasks, especially in weaker subjects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Caregivers' ambivalent feelings toward the care recipient have been found to be associated with depression and anxiety. There is no research linking caregivers' ambivalent feelings and cardiovascular risk. This study was aimed to analyze longitudinally the effect of ambivalence on caregivers' cardiovascular risk, defined by circulating levels of high-sensitivity C-reactive protein, interleukin-6 (IL-6), and D-dimer., Method: Participants were 121 dementia family caregivers who were assessed three times during a 2-year period. Sociodemographic and health variables, behavioral and psychological symptoms of dementia (BPSD), ambivalent feelings, and C-reactive protein (CRP), IL-6, and D-dimer values were assessed. Mixed linear models were used to analyze the association between variables, including testing whether ambivalent feelings moderated the links between BPSD and biomarkers., Results: Increases over time in D-dimer were associated with increases in ambivalence, older age, female gender, and body mass index (BMI). Increases over time in CRP were associated with increases in BMI, older age, female gender, and the interaction of BPSD with caregivers' ambivalent feelings. The moderation analysis showed that increased BPSD was significantly associated with increased CRP when caregivers experienced high levels of ambivalence ( p = .006). In contrast, BPSD were not significantly associated with CRP when caregivers experienced low levels of ambivalence ( p = .73). Increases in IL-6 were associated with female gender and BMI. The tested model explained 42.85%, 33.15%, and 5.36% of longitudinal variance in CRP, D-dimer, and IL-6 levels, respectively., Conclusion: The findings suggest that high ambivalent feelings are relevant for understanding cardiovascular vulnerability in dementia caregivers. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Introduction: designing functional foods to control appetite could be a useful strategy for managing overweight and obesity. Fiber and proteins could be interesting ingredients to consider. Objectives: to evaluate the appetite profile of two experimental yogurts (fiber-enriched [FEY] and protein-enriched [PEY]) versus a control yogurt (CY) in a group of overweight/obesity people. Material and methods: an acute, randomized, double-blind, crossover clinical trial was carried out in a group of twelve healthy overweight/obesity type I people; randomized to consume 3 yogurts in a different order for 3 acute study days. The appetite profile (1. hunger, 2. satiety, 3. fullness, 4. prospective food consumption, 5. desire to eat something fatty, salty, sweet or savoury) was assessed using a Visual Analog Scale (ranging from 0 ''not at all'' to 10 ''extremely") at 12 moments in each acute study. Additionally, total food consumption in an ad libitum lunch was assessed. Results: FEY produce a significantly lower desire to consume any food at 30 (1.50 ± 0.42) and 60 minutes (2.78 ± 0.42) after consumption compared to PEY (3.46 ± 0.53; 4.33 ± 0.54) and CY (3.27 ± 0.69; 4.0 ± 0.78) respectively (p < 0.016). Also, FEY consumption produced a higher satiety and fullness and a lower desire to ingest something fatty, salty or savory after 90 minutes consumption compared to the other products, but the difference was not significance. Conclusion: FEY might be a good functional food prototype to control appetite in overweight and obese people.

Incontinence-associated dermatitis poses a significant risk for sacral pressure injuries, infection and morbidity in healthcare settings. Despite the availability of best practice guidelines, implementation remains a challenge., Aim: To outline the implementation of a hospital-wide programme using the Integrated Promoting Action on Research Implementation in Health Services framework to prevent and manage incontinence-associated dermatitis and improve hospital-acquired pressure injuries., Design: This is an empirical research study using mixed methods., Method: The study, conducted across surgical, medical and critical care wards between June and October 2023, aimed to address knowledge gaps, enhance clinical practice and evaluate the effectiveness of interventions. The implementation strategy included education modules, engagement of staff through focus groups and targeted interventions such as individualised toileting plans and structured skin care regimens. Data collection involved audits, incident reporting and clinician knowledge surveys., Results: Findings indicate a reduction in hospital-acquired incontinence-associated dermatitis and pressure injuries postimplementation, with observed improvements in clinician knowledge. However, challenges including workload, skill mix and resource limitations were identified as barriers to implementation. The sustainability and scalability of the programme were emphasised, with ongoing monitoring and evaluation essential for long-term success., Conclusion: This study underscores the importance of evidence-based interventions, interdisciplinary collaboration and leadership support in improving patient outcomes and reducing healthcare costs associated with preventable skin injuries. Further research is needed to assess implementation in community settings and scale up interventions across healthcare networks., Implications for the Profession And/or Patient Care: Analysing a hospital-wide programme using the Integrated Promoting Action on Research Implementation in Health Service framework to prevent and manage incontinence-associated dermatitis and improve hospital-acquired pressure injuries, could help identify the challenges for delivering patient-centred care., Patient or Public Contribution: No patient or public involvement., Reporting Method: To describe the implementation study, we referred to the StaRI Guideline., Trial Registration: This intervention study was applied to the whole population and was therefore not a trial and did not require trial registration. The study was considered low risk and the Human Research Ethics Application (HREA) was approved., (© 2024 John Wiley & Sons Ltd.)

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by γ-secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V 321 L) in the Nrg1 transmembrane domain that disrupts nuclear back signaling with minimal effects on forward signaling or local back signaling and was previously found to be associated with psychosis (Walss-Bass et al., 2006). We combined RNA sequencing, retroviral fate mapping of neural stem cells, behavioral analyses, and various network analyses of transcriptomic data to investigate the effect of disrupting Nrg1 nuclear back signaling in the dentate gyrus (DG) of male and female mice. The V 321 L mutation impairs nuclear translocation of the Nrg1 ICD and alters gene expression in the DG. V 321 L mice show reduced stem cell proliferation, altered cell cycle dynamics, fate specification defects, and dendritic dysmorphogenesis. Orthologs of known schizophrenia (SCZ)-susceptibility genes were dysregulated in the V 321 L DG. These genes coordinated a larger network with other dysregulated genes. Weighted gene correlation network analysis and protein interaction network analyses revealed striking similarity between DG transcriptomes of V 321 L mouse and humans with SCZ., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Rajebhosale et al.)

Objectives: Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal expansion of cytotoxic T-cells frequent somatic activating STAT3 mutations. Based on the disease overlap between LGL leukemia rheumatoid arthritis (RA)a putative role for CD8+ T-cells in RA we hypothesized that STAT3 mutations may be detected in RA patient CD8+ T-cells correlate with clinical characteristics., Methods: Blood samples, clinical parameters, and demographics were collected from 98 RA patients and 9 healthy controls (HCs). CD8+ cell DNA was isolated and analyzed via droplet digital (dd)PCR to detect STAT3 mutations common in LGL leukemia: Y640F, D661Y, and the S614 to G618 region. STAT3 data from 99 HCs from a public dataset supplemented our 9 HCs., Results: RA patients had significantly increased presence of STAT3 mutations compared to controls (Y640F p=0.0005, D661Y p=0.0005). The majority of these were low variant allele frequency (VAF) (0.008-0.05%) mutations detected in a higher proportion of the RA population (31/98 Y640F, 17/98 D661Y) vs. HCs (0/108 Y640F, 0/108 D661Y). In addition, 3/98 RA patients had a STAT3 mutation at a VAF >5% compared to 0/108 controls. Serological markers, RF and anti-CCP positivity, were more frequently positive in RA patients with STAT3 mutation relative to those without (88% vs 59% RF, p=0.047; 92% vs 58% anti-CCP, p=0.031, respectively)., Conclusions: STAT3 activating mutations were detected in RA patient CD8+ cells and associated with seropositivity. Thus, STAT3 activating mutations may play a role in disease pathogenesis in a subset of RA patients., Competing Interests: TL has received Scientific Advisory Board membership, consultancy fees, honoraria, and/or stock options from Keystone Nano, Flagship Labs 86, Dren Bio, Recludix Pharma, Kymera Therapeutics, and Prime Genomics. DF has received research funding, honoraria, and/or stock options from AstraZeneca, Dren Bio, Recludix Pharma, and Kymera Therapeutics. AR has received research funding, consultancy fees, and Honoria from AstraZeneca and MedGenome Labs. DK has served on the Aurinia Lupus Center Advisory Board, and Clinical Advisory Board for Landos Biopharma; and is a member of the Amgen Speaker’s Bureau. ED has also received grants from Pfizer and Bristol-Myers Squibb related to RA, personal fees from Celgene and Gilead outside of the submitted work and is a current employee of AstraZeneca. FA has received consulting fees and/or royalties from Celgene, Inova, Advise Connect Inspire, and Hillstar Bio, Inc. ED and FA are authors on licensed patent no. 8,975,033, entitled “Human autoantibodies specific for pad3 which are cross-reactive with pad4 and their use in the diagnosis and treatment of rheumatoid arthritis and related diseases”. There are no conflicts of interest with the work presented in this manuscript. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Moosic, Olson, Freijat, Khalique, Hamele, Shemo, Boodoo, Baker, Khurana, Schmachtenberg, Duffy, Ratan, Darrah, Andrade, Jones, Olson, Feith, Kimpel and Loughran.)

Background: HPV test-based primary cervical screening is replacing cytology in Canada. In other countries, women's unpreparedness and concerns hindered the transition and post-implementation screening uptake. We investigated psychosocial correlates of intentions of screening in eligible individuals to participate in HPV-based primary cervical screening., Methods: We conducted a nationwide web-based survey of individuals aged 21-70 years in 2022 and oversampled under-screened individuals. We used five Canadian-validated scales to measure HPV test-based screening knowledge, attitudes, and beliefs. Using the multistage Precaution Adoption Process Model, we assessed women's stage of intentions to participate in HPV testing and self-sampling. We estimated associations of psychosocial factors with intentions' stage using multinomial logistic regression., Findings: In both groups (adequately screened n = 1778; under-screened n = 1570), higher HPV knowledge was associated with intention for HPV testing and more personal barriers to the HPV test were associated with lower intentions to participate in HPV testing or use of self-sampling. In both groups, higher self-sampling concerns were associated with lower intentions for self-sampling and higher women's need for autonomy was associated with increased intentions for self-sampling. In the under-screened group, increased age was associated with lower intentions for HPV testing and self-sampling, while living in Canada for <10 years was associated with higher intentions., Interpretation: Our results could be used by policymakers and healthcare professionals to design communication strategies and ensure a smooth transition to HPV-based primary cervical screening, especially for under-screened individuals., Funding: Canadian Institutes of Health Research project grant 165905., Competing Interests: OT received support from the Canadian Institutes of Health Research (CIHR) through the Frederick Banting and Charles Best Doctoral award (Award No. FBD-170837) outside the scope of the submitted work. OT also serves as a part-time Research Associate Research Associate at the Lady Davis Institute for Medical Research (Montreal, Canada). GKS is supported by the Edith Kirchmann Postdoctoral Fellowship at Princess Margaret Cancer Centre and holds a CIHR 2019 fellowship award (CIHR MFE 171271) unrelated to the submitted study. GZ has received grants, contracts and consulting fees from Merck, has participated on the Data Safety Monitoring Board or Advisory Board for Merck and Moderna, and is a member of the Board of Directors of Unity Consortium, a non-profit organization. JW reports consultancy payments from Hologic to her institution for attending a cervical cancer patient advocacy workshop and participating in a discussion panel. She also received support from Hologic for travel expenses to attend patient advocacy meetings. MS has received grants and lecture honoraria from Abbott, Roche Diagnostics, Laboratories Biron and Attila Diagnostic. MS is the President of the International Society for STD Research, Co-President of the STI&HIV 2025 World Congress, and a board member of the International Papillomavirus Society. MS also reports receiving equipment from the National Cancer Institute. ZR reports unpaid leadership involvement as Vice-President of HPV Global Action, in a non-governmental organization, outside of the submitted work. LS reports consulting fees from the Canadian Partnership Against Cancer (Non-profit organization) EM, JB, KD, PZ, AL, BH, GO, SP, and MHM declare no conflicts of interest., (© 2024 The Author(s).)

The social imaginary that legitimizes sexual violence is continuously reinforced by discourses that are deployed in the aftermath of physical attacks. These, in turn, nourish a specific type of collective memory from which clear social identities emerge. This article identifies the textual trajectories of social meanings associated with sexual violence and their discursive expressions in media, legal, and political discourses. The examples provided here are related to the Spanish "wolf pack case" and its social and political consequences. It concludes that the case not only generated a conceptual battle about violence but also a mnemonic dispute related to newly interpellated subjectivities., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neuropsychological data suggest that being overweight or obese is associated with a tendency to perseverate behavior despite negative feedback. This deficit might be observed due to other cognitive factors, such as working memory (WM) deficits or decreased ability to deduce model-based strategies when learning by trial-and-error. In the present study, a group of subjects with overweight or obesity (Ow/Ob, n = 30) was compared to normal-weight individuals (n = 42) in a modified Reinforcement Learning (RL) task. The task was designed to control WM effects on learning by manipulating cognitive load and to foster model-based learning via deductive reasoning. Computational modelling and analysis were conducted to isolate parameters related to RL mechanisms, WM use, and model-based learning (deduction parameter). Results showed that subjects with Ow/Ob had a higher number of perseverative errors and used a weaker deduction mechanism in their performance than control individuals, indicating impairments in negative reinforcement and model-based learning, whereas WM impairments were not responsible for deficits in RL. The present data suggests that obesity is associated with impairments in negative reinforcement and model-based learning., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background/objectives: Dysgeusia contributes to the derangement of nutritional status in patients with cancer as well as worsening the quality of life. There has been a lack of effective treatments for taste disorders provided by the pharmaceutical industry., Methods: This was a pilot randomized, parallel, triple-blind, and placebo-controlled intervention clinical trial in which 31 malnourished patients with cancer and dysgeusia receiving antineoplastic treatment were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB or placebo tablet before each main meal. Using the nanopore methodology, we analyzed the oral microbiome of patients with cancer using saliva samples., Results: All patients with cancer and dysgeusia had dysbiosis in terms of lower bacterial diversity and richness. DMB consumption was associated with changes in oral microbiome composition. Neither selected bacteria nor taste perception, type of diet, and cytokine levels were associated with mucositis. Likewise, alcohol and tobacco consumption as well as general and digestive toxicity due to systemic therapy were not associated with specific changes of the oral microbiome, according to logistic binary regression. The standard dose of DMB resulted in a lower abundance of Veillonella compared with the high DMB dose and placebo at 3 months after intervention with DMB. In particular, some species such as Streptococcus parasanguinis , Veillonella parvula , and Streptococcus mutans were less abundant in the DMB standard-dose group. Additionally, the consumption of a standard dose of DMB revealed a negative association between the concentrations of TNF-α and the abundance of species such as Streptococcus thermophilus , Streptococcus pneumoniae , Streptococcus dysgalactiae and Streptococcus agalactiae ., Conclusions: Accordingly, regular DMB consumption could modify the oral microbiome in patients with cancer and dysgeusia, which may contribute to maintaining an appropriate immune response. However, as the present pilot study involved a small number of participants, further studies are necessary to draw robust conclusions from the data.

Younger adults, aged 18-39 years, exhibit low COVID-19 additional vaccine (i.e., vaccination beyond the original 2-dose series) uptake recommended in Canada. No study has examined how altruistic and individualistic messaging can influence COVID-19 additional dose intentions. The present study aimed to estimate the efficacy of altruism and individualism-based videos on vaccine intentions and to explore the multivariable associations between vaccine related individual psychosocial factors and intention to receive the COVID-19 vaccine. Using a web-based survey in a three-arm, pre-post randomized control trial design, we recruited Canadians aged 18-39 years in both English and French. Participants were randomly allocated in a 1:1:1 ratio to receive the active control (COVID-19 general information), control + altruism or control + altruism + individualism. The video interventions were developed with a media company, based on results of a focus group study conducted previously. The measurement of COVID-19 additional dosage intentions before and after completing the interventions was informed by the multistage Precaution Adoption Process Model. The McNemar Chi-square was used to evaluate within-group changes, and the Pearson Chi-square test was used to evaluate between-group changes post-intervention. The measurement of various psychosocial factors was informed by use of validated scale and self-report questions. We employed a generalized Structural Equation Model to evaluate the associations between COVID-19 vaccine intentions and the psychosocial factors. Analyses were performed on 3,431 participants (control: n  = 1,149, control + altruism: n  = 1,142, control + altruism + individualism: n  = 1,140). Within-group results showed that participants transitioned significantly in all three groups in the direction of higher intentions for receiving additional COVID-19 vaccine doses. The between-group differences in post intervention vaccine intentions were not significant. We found that psychosocial factors that include, collectivism, intellectual humility, intolerance to uncertainty, religiosity, identifying as gender diverse, and being indigenous were associated with higher vaccine intentions, whereas pandemic fatigue was associated with lower vaccine intentions. Our study highlighted that a short video that includes altruism and individualism messaging or general COVID-19 information can increase intentions to vaccine among young adults. Furthermore, we gained a comprehensive understanding of various psychosocial factors that influence ongoing COVID-19 vaccination. Our findings can be used to influence public health messaging around COVID-19 vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Batra, Tatar, Zhu, Perez, Haward, Zimet and Rosberger.)

Introduction: Pathogenic variants in the gene encoding for BMPR2 are a major genetic risk factor for heritable pulmonary arterial hypertension. Owing to incomplete penetrance, deep phenotyping of unaffected carriers of a pathogenic BMPR2 variant through multimodality screening may aid in early diagnosis and identify susceptibility traits for future development of pulmonary arterial hypertension., Methods: 28 unaffected carriers (44±16 years, 57% female) and 21 healthy controls (44±18 years, 48% female) underwent annual screening, including cardiac magnetic resonance imaging, transthoracic echocardiography, cardiopulmonary exercise testing and right heart catheterisation. Right ventricular pressure-volume loops were constructed to assess load-independent contractility and compared with a healthy control group. A transgenic Bmpr2 Δ71Ex1/+ rat model was employed to validate findings from humans., Results: Unaffected carriers had lower indexed right ventricular end-diastolic (79.5±17.6 mL·m -2 versus 62.7±15.3 mL·m -2 ; p=0.001), end-systolic (34.2±10.5 mL·m -2 versus 27.1±8.3 mL·m -2 ; p=0.014) and left ventricular end-diastolic (68.9±14.1 mL·m -2 versus 58.5±10.7 mL·m -2 ; p=0.007) volumes than control subjects. Bmpr2 Δ71Ex1/+ rats were also observed to have smaller cardiac volumes than wild-type rats. Pressure-volume loop analysis showed that unaffected carriers had significantly higher afterload (arterial elastance 0.15±0.06  versus 0.27±0.08 mmHg·mL -1 ; p<0.001) and end-systolic elastance (0.28±0.07  versus 0.35±0.10 mmHg·mL -1 ; p=0.047) in addition to lower right ventricular pulmonary artery coupling (end-systolic elastance/arterial elastance 2.24±1.03 versus 1.36±0.37; p=0.006). During the 4-year follow-up period, two unaffected carriers developed pulmonary arterial hypertension, with normal N-terminal pro-brain natriuretic peptide and transthoracic echocardiography indices at diagnosis., Conclusion: Unaffected BMPR2 mutation carriers have an altered cardiac phenotype mimicked in Bmpr2 Δ71Ex1/+ transgenic rats. Future efforts to establish an effective screening protocol for individuals at risk for developing pulmonary arterial hypertension warrant longer follow-up periods., Competing Interests: Conflicts of interest: F. Perros reports grants from French National Research Agency (ANR-20-CE14-0006) and INSERM (International Research Project (IRP) (Paris – Porto Pulmonary Hypertension Collaborative Laboratory (3PH)). D. Montani reports grants from Janssen, MSD and Acceleron; consultation fees from Janssen, MSD, Ferrer and Acceleron; and payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Janssen, Boehringer, Chiesi, GSK, Ferrer and Merck MSD. A. Vonk Nordegraaf reports research grants from Janssen, MSD and Ferrer. L. Zhao reports grants from British Heart Foundation (PG/18/2/33446 and BHF RE/18/4/34215). F.S. de Man reports support for the present study from Royal Netherlands Academy of Sciences (CVON-2017-10 Dolphin-Genesis); grants from Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organisation for Health Research and Development, The Netherlands Organisation for Scientific Research (NWO-VICI: 918.16.610, NWO-VIDI: 917.18.338), Royal Netherlands Academy of Sciences (CVON-2012-08 PHAEDRA and CVON-2018-29 PHAEDRA-IMPACT) and Dutch Heart Foundation (Post doc Dekker 2018T05). H-J. Bogaard reports support for the present study from Royal Netherlands Academy of Sciences (CVON-2017-10 Dolphin-Genesis); grants from MSD, Ferrer, Janssen, Dutch Federation of University Medical Centres, Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Netherlands Organisation for Health Research and Development, and the Royal Netherlands Academy of Sciences (CVON-2012-08 PHAEDRA and CVON-2018-29 PHAEDRA-IMPACT). The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

One in three patients admitted to intensive care will sustain a pressure injury (PI) from a medical device. These injuries are painful and when on the face, head or neck they can result in permanent disfigurement. Preliminary evidence of the efficacy of hyper-oxygenated fatty acids (HOFAs) to prevent facial pressure injuries from medical devices is promising; however, the feasibility of incorporating HOFAs into current standard care to prevent PI from a medical device of the face, head and neck has not been extensively explored. It is intended that the findings from this phase II feasibility study will inform the design of a larger phase III trial, by addressing two primary aims: (1) to assess the feasibility of incorporating HOFAs into standard care to prevent device-related pressure ulcers of the skin associated with the face, head and neck assess the feasibility and (2) efficacy preliminary effectiveness of HOFA. This feasibility study is an investigator-initiated mixed method study incorporating a multi-centre randomised controlled trial of using HOFAs as an adjunct to standard pressure injury prevention and care, compared with standard care alone to prevent facial, head or neck from medical devices among adults admitted to intensive care. The primary outcome of interest is the incidence of facial, head or neck pressure injuries during the first 14 days in intensive care. Secondary outcomes include PI staging, medical device exposure and intensive care and hospital outcomes. The primary analysis will be undertaken using Cox's Proportional Hazards model, and due to the exploratory nature of this phase II trial, efficacy will be based on a one-sided p-value for superiority set at 0.10. Type I and Type II error rates are set at 20%; therefore, a total sample size of 196 study participants is planned. To explore the feasibility of incorporating HOFA into usual care and to design a larger phase III trial, we will aim to interview between 10 and 20 nurses across participating intensive care unit sites. Pressure injuries of the face, head or neck from medical devices, among adults admitted to intensive care, are considered preventable. This phase II study will investigate the feasibility and efficacy of HOFAs as an adjunct to standard care. Importantly, we aim to inform the development of a larger phase III trial., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Pancreatic lipase (PNLIP) is the major lipolytic enzyme secreted by the pancreas. A recent study identified human PNLIP variants P245A, I265R, F300L, S304F, and F314L in European cohorts with chronic pancreatitis. Functional analyses indicated that the variants were normally secreted but exhibited reduced stability when exposed to pancreatic proteases. Proteolysis of the PNLIP variants yielded an intact C-terminal domain, while the N-terminal domain was degraded. The protease-sensitive PNLIP phenotype was strongly correlated with chronic pancreatitis, suggesting a novel pathological pathway underlying the disease. To facilitate preclinical mouse modeling, here we investigated how the human mutations affected the secretion and proteolytic stability of mouse PNLIP. We found that variants I265R, F300L, S304F, and F314L were secreted at high levels, while P245A had a secretion defect and accumulated inside the cells. Proteolysis experiments indicated that wild-type mouse PNLIP was resistant to cleavage, while variant I265R was readily degraded by mouse trypsin and chymotrypsin C. Variants F300L, S304F, and F314L were unaffected by trypsin but were slowly proteolyzed by chymotrypsin C. The proteases degraded the N-terminal domain of variant I265R, leaving the C-terminal domain intact. Structural analyses suggested that changes in stabilizing interactions around the I265R mutation site contribute to the increased proteolytic susceptibility of this variant. The results demonstrate that variant I265R is the best candidate for modeling the protease-sensitive PNLIP phenotype in mice., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, we identified the presence of sickle cell maculopathy and determined correlations between hemolysis indicators and systemic and ocular manifestations in children with sickle cell disease (SCD). Thirty-three patients with SCD 5 to 18 years of age underwent optical coherence tomography angiography (OCTA) as part of a thorough eye examination. The hematological indices and clinical data (hemoglobin, fetal hemoglobin, mean corpuscular volume, and frequency of sickle cell-associated complications and therapy) were collected. The SCD group contained 33 patients (66 eyes), and the control group contained 36 healthy participants (72 eyes). The SCD group had significantly thinner parafoveal thickness ( P =0.041) and significantly smaller parafoveal volume ( P =0.041) than the controls. The SCD group had lower deep capillary plexus density than the controls ( P =0.029). The SCD group had significantly smaller flow areas than the controls ( P <0.001). The foveal avascular zone (FAZ) perimeter, foveal density, and FAZ area in the entire retina did not differ significantly between the groups ( P >0.05). The platelet level was negatively correlated with parafoveal and perifoveal thickness and density. OCTA detected early macular microvascular changes in children and adolescents with asymptomatic SCD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cervical cancer is almost entirely preventable and treatable when detected early, making its elimination within reach for Canada and the world. However, cervical cancer is now the fastest-increasing cancer (+3.7% per year since 2015) in Canada as of 2023, marking the first significant increase in cervical cancer incidence since 1984. The human papillomavirus (HPV) vaccine and cervical screening are key preventive measures, with targets set by the WHO and the Canadian Partnership Against Cancer (CPAC) to eliminate cervical cancer in Canada by 2030 and 2040, respectively. These targets include increasing HPV vaccination rates, implementing primary HPV screening, and improving follow-up for abnormal HPV+ results. However, Canada's progress has been impeded by significant challenges. As of the most recent data, HPV vaccine coverage rates in Canada range from 47% to 81%, with an estimated national HPV vaccination completion rate of 64% in Canada, far below the target of 90% by 2025 set by the CPAC. With the exception of British Columbia and Prince Edward Island, the adoption of HPV DNA testing as the primary screening method has been slow across the Canadian provinces and territories despite its superior sensitivity compared with traditional cytology. This article reviews the current state of HPV vaccination and screening in Canada, emphasizing the need for coordinated efforts, transparency, and resource sharing to overcome barriers. Key recommendations include the dissemination of accessible educational materials, partnerships, and collaboration, including nationwide task forces and roundtables, and the implementation of standardized guidelines for HPV screening. Achieving cervical cancer elimination requires a united approach involving federal, provincial, and territorial health authorities, researchers, clinicians, NGOs, community groups, and patients' voices working together to ensure consistent, effective, timely, and meaningful cervical cancer prevention strategies are used across the country.

Background: Gestational diabetes mellitus (GDM) is the main cause of hyperglycemia in pregnancy and is related to complications throughout the gestational and post-partum period., Objectives: To analyze the pregnancy outcomes related to the occurrence of GDM in women and their offspring., Methods: Third-trimester pregnant women were interviewed and monitored until childbirth. The diagnosis of GDM, blood glucose ≥ 92 mg/dL, was defined by the criteria of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)., Results: A total of 138 women participated, and there were 136 births (due to 2 fetal losses); 23 (16.7%) were diagnosed with GDM. The risk of complications during childbirth was higher among pregnant women with GDM (RR 3.40; 95%CI 1.65-7.00), as was the occurrence of cesarean birth (RR 1.9; 95%CI 1.46-2.59). The occurrence of preterm birth did not show a significant difference between GDM/non-GDM groups. There was a non-significant association in adjusted analyses of macrosomia (birth weight ≥ 4000 g) among newborns born to mothers with GDM (RR 1.27; 95%CI 0.67-2.38). For newborns born to pregnant women with GDM, there was a higher risk for the following outcomes: large for gestational age (LGA) (3.29 95%CI 1.62-6.64), low Apgar (4.98 95%CI 2.32-10.69), and birth asphyxia (9.51 95%CI 3.42-26.48)., Conclusions: The findings reinforce that GDM is an important risk factor for adverse pregnancy outcomes for women and their offspring.

Background: The identification and referral (ID&R) of potential organ donors to provincial organ donation organizations (ODOs) is a critical first step in the organ donation process. However, even in provinces with mandatory referral legislation, there remains variability in ID&R rates across critical care units, with some units demonstrating high performance despite experiencing similar constraints associated with existing structures, policies, and practices., Objective: We sought to identify the enablers and specific strategies that high-performing critical care units leveraged to achieve their exceptional performance., Design: We conducted a descriptive qualitative study to inform ID&R improvement efforts as part of a positive deviance initiative., Setting: We identified three high-performing critical care units as study sites., Participants: Clinicians working in identified critical care units., Methods: At each site, we interviewed clinical team members about their perceptions and experiences of ID&R. Data analysis followed a thematic analysis approach., Results: We outline three themes describing how the high-performing hospitals achieve strong ID&R practices. First, all units demonstrated a high degree of integration between the concepts of high-quality end-of-life care and organ donation. Team members were consistently notified of successful transplants stemming from their unit, and all missed ID&Rs were tracked and discussed. Second, participants described a team approach with strong medical leadership, where all team members embrace their role in ensuring that no potential donor is missed. Finally, the units adopted strategies to support and simplify ID&R such as collectively simplifying triggers for referral, developing strong working relationships with provincial donor coordinators, and creating informal avenues of communication between clinicians and donor coordinators., Limitations: The lack of comparable data for potential organ donor referral rates across Canada impacted our ability to identify high-performing hospitals based on data. Instead, we contacted the ODOs directly to identify high-performing units that met our criteria. Second, our study sample was limited to three hospital sites from three different provinces and the three hospitals perform organ recovery and transplant on-site., Conclusion: Critical care units can adopt strategies and implement interventions to support ID&R improvement efforts. We provide examples informed by this study. We also highlight considerations that require attention when engaging in this work such as ensuring that all team members are aware of changes in care plans and physicians consistently engage in discussions about organ donation. Local medical leadership is critical to supporting these changes., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SZ disclosed funding from the Organ Donation and Transplant Collaborative. SDS disclosed that he is a medical advisor for deceased organ donation at Canadian Blood Services, and he disclosed government work. JL is employed by Canadian Blood Services., (© The Author(s) 2024.)

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson's disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases., (© 2024. The Author(s).)

Singlet fission (SF) is a promising approach in quantum information science because it can generate spin-entangled quintet triplet pairs by photoexcitation independent of temperature. However, it is still challenging to rationally achieve quantum coherence at room temperature, which requires precise control of the orientation and dynamics of triplet pairs. Here we show that the quantum coherence of quintet multiexcitons can be achieved at room temperature by arranging two pentacene chromophores in parallel and in close proximity within a macrocycle. By making dynamic covalent Schiff-base bonds between aldehyde-modified pentacene derivatives, macrocyclic parallel dimer-1 ( MPD-1 ) can be selectively synthesized in a high yield. MPD-1 exhibits fast subpicosecond SF in polystyrene film and generates spin-polarized quintet multiexcitons. Furthermore, the coherence time T 2 of the MPD-1 quintet is as long as 648 ns, even at room temperature. This macrocyclic parallel dimer strategy opens up new possibilities for future quantum applications using molecular multilevel qubits.

Background: Digital health interventions have the potential to improve linkage to care after HIV self-testing (HIVST). This study aimed to understand clients' and providers' perceptions of benefits, and barriers of a digital health intervention designed to improve linkage to care after HIV self-testing in Tanzania., Methods: This exploratory qualitative research study was conducted in Hai and Moshi, districts in Kilimanjaro region, Tanzania. Four health facilities were selected based on their involvement in an HIVST pilot program implemented by Elizabeth Glassier Pediatric AIDS Foundation (EGPAF) Tanzania through the USAID funded program. The study included female index clients and their partners, and healthcare providers at the healthcare facilities. We used a semi-structured interview guide with open-ended questions for data collection. Data collection was conducted from 16th January 2023 to 3rd February 2023. Thematic analysis of the qualitative data was conducted, guided by the Health Belief Model (HBM), and results were developed in collaboration with the community partners., Results: A total of 42 participants were included in the study, comprising 9 male clients, 17 female index clients, and 16 health care workers (HCWs) (4 male and 12 female) who were involved in delivering HIVST services. The study's findings revealed mixed feelings about the use of a digital health intervention. Majority of participants perceived digital health as a valuable intervention for enhancing linkage to care, improved health outcomes, improved communication with healthcare workers, and increased privacy. Therefore, they supported scale-up of a digital health intervention. Participants also expressed that the potential benefits of a digital health intervention include the convenience of accessing healthcare services from the comfort of their homes or any location. However, a few participants expressed concerns about potential risks associated with sending health-related text messages. They feared that recipients might not be in a safe space, leading to stigma and avoidance of engagement. A few female participants expressed concerns about confidentiality breaches, particularly regarding shared phones with family or friends. Fear of being judged or misunderstood by others could deter them from reading or acting upon these messages. Most participants recommended tailored strategies that prioritize confidentiality and trust. Recognizing these psychological aspects is vital for customizing digital health interventions to effectively address participants' concerns., Conclusions: Digital health interventions may improve the linkage of HIV self-testers to care. Recommendations include personalized and culturally relevant communication and technical accessibility to make interventions effective and inclusive. This study provides valuable insights for designing patient-centered interventions for HIV care and treatment., (© 2024. The Author(s).)

Introduction: Eye emergencies make up nearly 3% of US emergency department (ED) visits. While emergency physicians (EP) should diagnose and treat these ophthalmologic emergencies, many trainees report limited ocular exposure and insufficient training throughout their residency to confidently conduct a thorough slit-lamp exam., Methods: We created an interdisciplinary, simulation-based mastery learning (SBML) curriculum to teach emergency attending physicians how to operate the slit lamp with multimodal learning methodology at a tertiary academic center. The EPs first demonstrate their initial slit-lamp competency with a 20-item checklist, and they then review the necessary curricular content to pass their independent readiness test before completing their in-person teaching and demonstration session with an ophthalmology attending to demonstrate procedural mastery (minimal passing score >90%)., Results: Fifteen EPs were enrolled; all completed the final exam of the curriculum. The pre- and post-curriculum checklist scores increased by an average of seven points ( P  = .002); 86.7% of EPs felt confident in completing a slit-lamp exam after the curriculum, compared to 20% at the beginning. Five of 15 reported teaching learners within the two-month post-curricular period, ranging from 5-30 students. The hands-on teaching was the most positively reviewed element of the curriculum., Conclusion: The SBML program successfully trained EPs on performing a comprehensive slit-lamp exam with promising results of downstream education to junior learners. We encourage other institutions to leverage SBML as a teaching modality for procedural-based training and advocate cross-discipline education initiatives., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. This study received grant funding from the Center for Faculty Development and Nexus Learning (CFDNL) Pedagogy, Thomas Jefferson University. There are no other conflicts of interest or sources of funding to declare.

Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly. There is a need for shorter, safer and more tolerable regimens, including those active against bedaquiline-resistant tuberculosis. Transitioning from multiple regimen A versus regimen B trials to a single large phase III platform trial would accelerate the acquisition of robust estimates of relative efficacy and safety. Further efficiencies could be achieved by adopting modern adaptive platform designs. Collaboration among trialists, affected community representatives, funders and regulators is essential for developing such a phase III platform trial for drug-resistant tuberculosis treatment regimens., ((c) 2024 The authors; licensee World Health Organization.)

The dietary ecology of a species can provide information on habitat requirements, food resources, and trophic interactions, important to guide conservation efforts of wildlife populations in endangered habitats. In this study, we investigated the dietary ecology of bearded capuchin monkeys (Sapajus libidinosus) in Brasilia National Park, in the endangered Cerrado biome of central Brazil. To obtain diet composition and evaluate the role of these primates as seed dispersers of local tree species, fecal sample collections and feeding observations were performed for a 7-month period. To determine whether seeds germinated better after passing through a primate gut, we conducted germination trials with (i) pulped seeds from trees, (ii) depulped seeds from trees, (iii) seeds from feces planted with feces, and (iv) seeds from feces planted without feces. During experimental procedures, 7308 seeds from 8 families and 10 species were planted. We found that S. libidinosus spent more time feeding on fruits than on any other food item and the diet consisted of 33 plant species from 21 families. However, 20% of their diet consisted of anthropic food. Most seeds planted with feces germinated faster compared to seeds in other experimental treatments, suggesting that passing through the gut and being deposited with fecal material is advantageous. The bearded capuchins also defecated many medium- (5 species) and large-sized (2 species) seeds that may be inaccessible to smaller arboreal frugivores. The results obtained emphasize the important role of bearded capuchins as seed dispersers for the maintenance and conservation of the endangered Cerrado biome., (© 2024 Wiley Periodicals LLC.)

Background: Physical activity (PA) and weight management are critical for cardiovascular disease (CVD) secondary prevention. However, PA adherence during or after cardiac rehabilitation is low. Here, we assess the feasibility and acceptability of the Australian football-themed Aussie Fans in Training (Aussie-FIT) program and associated trial procedures when adapted for men with CVD., Method: A pragmatic randomised control trial, with waitlist control arm, and follow-up measures at 3 and 6 months. Men with a CVD diagnosis and body mass index ≥25 kg/m 2 were recruited from community and clinical settings, and randomised, following baseline measures of health and health behaviours. The intervention arm attended 12 face-to-face football-themed education and PA sessions. Feasibility (recruitment, retention, attendance, and adherence to trial procedures) was assessed via mixed methods., Results: A total of 74% (64/86) of participants expressing interest met the eligibility criteria. Of those, 49 men (mean age=61.4, standard deviation=9.5, mean body mass index=31.3, standard deviation=4.2) were randomised. Program attendance rates (87% attended ≥80% of sessions) and retention (92%) were high. Trial retention at the primary end point (3 months) was high (86%) and at the 6-month follow-ups reduced to 67%. Program and trial procedures were acceptable, except for the request to visit a pathologist for the blood draw., Conclusions: Using a football theme and setting may be a feasible way to engage men with CVD in health behaviour change. Given the existing pilot evidence for men at risk of CVD, and that recruitment rates were under the target, trialling a program for men with or at risk of CVD is recommended., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Ecto-5'-nucleotidase (CD73) hydrolyses 5'AMP to adenosine and inorganic phosphate. Breast cancer cells (MDA-MB-231) express high CD73 levels, and this enzyme has been found to play a tumour-promoting role in breast cancer. However, no studies have sought to investigate whether CD73 has differential affinity or substrate preferences between noncancerous and cancerous breast cells. In the present study, we aimed to biochemically characterise ecto-5'-nucleotidase in breast cancer cell lines and assess whether its catalytic function and tumour progression are correlated in breast cancer cells. The results showed that compared to nontumoral breast MCF-10A cells, triple-negative breast cancer MDA-MB-231 cells had a higher ecto-5'-nucleotidase expression level and enzymatic activity. Although ecto-5'-nucleotidase activity in the MDA-MB-231 cell line showed no selectivity among monophosphorylated substrates, 5'AMP was preferred by the MCF-10A cell line. Compared to the MCF-10A cell line, the MDA-MB-231 cell line has better hydrolytic ability, lower substrate affinity, and high inhibitory potential after treatment with a specific CD73 inhibitor α,β‑methylene ADP (APCP). Therefore, we demonstrated that a specific inhibitor of the ecto-5-nucleotidase significantly reduced the migratory and invasive capacity of MDA-MB-231 cells, suggesting that ecto-5-nucleotidase activity might play an important role in metastatic progression., (© 2024 International Federation for Cell Biology.)

Introduction: The COVID pandemic and affiliated infodemic led to widespread health misinformation, generating confusion and distrust. Physicians must identify and address misinformation, with attention to cultural/health literacy, equity, and autonomy. Most medical students receive training in core communication techniques but are rarely taught how to combat misinformation with patients and lack opportunities for practice in diverse settings., Methods: We used mixed methods to evaluate the impact of a role-play-based training curriculum on 44 third- and fourth-year medical students' comfort and confidence applying ask-respond-tell-seek solutions (ARTS) and motivational interviewing (MI) to discuss vaccine hesitancy, using COVID-19 as an example. There were three training iterations: prior to volunteering at a community health fair, during a medicine clinical rotation, and during a pediatrics rotation. Pre- and postsession questionnaires were administered. Likert-scale questions assessed comfort and confidence using ARTS and MI. Narrative responses focused on previous experiences with vaccine hesitancy, challenges faced, and session takeaways., Results: Students' comfort, confidence with ARTS/MI, and self-reported ability to discuss COVID-19 vaccinations improved as measured by pre- and postsession surveys ( p < .05). Qualitatively, students reported increased confidence delivering recommendations in plain language and exploring patients' thought processes behind choices., Discussion: Reinforcement of core communications strategies in medical school can positively impact trainees' ability and ease addressing misinformation. We recommend this 45-minute training session to effectively increase medical students' comfort and confidence in discussing COVID-19 vaccines with patients. It can be adapted to any health professions school with an existing communications thread., (© 2024 Pelin et al.)

Using an intersectionality lens and the minority stress theory as our theoretical grounding, this qualitative study is the first to examine the mental health of Arab sexual minority women (SMW) migrants to the United States. The study aimed to (1) explore the perceptions and experiences of intersectional minority identity-related life stressors and (2) discern their impact on the mental health of first-generation Arab SMW migrants. From December 2022 to March 2023, we conducted 20 semi-structured interviews with Arab SMW migrants. Guided by principles of community engagement in research, four community advisors, including three Arab SMW migrants and a mental health service provider, assisted in mock interviews, recruitment, and data analysis. This enriched our thematic analysis providing a nuanced understanding of Arab SMW migrant experiences. Participants reflected diverse nationalities, socioeconomic statuses, and religions and identified as lesbian, bisexual, or queer. Our sample included asylum seekers, documented migrants, and non-binary individuals (assigned female at birth). Findings revealed three major themes: (1) Community- and Interpersonal-Level Stressors, (2) Strategies for Coping with Stressors, and (3) Impact of Intersectional Life Stressors on Mental Health. Community- and interpersonal-level stressors included challenges navigating migration-related stressors, rejection and discrimination from the Arab, queer, and dominant-group (i.e., non-Arab, non-White) communities, and experiences of invalidation of their intersectional identities. Coping mechanisms included avoidance, identity concealment, and seeking social support. Participants reported various mental health impacts, from anxiety, depression to suicidal thoughts, emphasizing the urgency for tailored interventions. Participants called for the development of support groups specifically for Arab SMW migrants., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Caffeine and anabolic-androgenic steroids (AAS) are commonly used to improve muscle mass and athletic performance. Nandrolone Decanoate (ND) is one of the most abused AAS worldwide, leading to behavioral changes in both humans and rodents. Caffeine, the most widely consumed psychostimulant globally, is present in various thermogenic and gym supplements. Low and moderate doses of caffeine antagonize adenosine receptors and have been linked to improved memory and pain relief. We have previously demonstrated that consuming caffeine prevents the risk-taking behavior triggered by nandrolone. In this study, we aimed to investigate the long-term effects of ND and caffeine, either alone or in combination, on passive avoidance memory and nociception. We used the step-down and hot-plate tasks in male and female Lister Hooded rats. Our results confirmed the antinociceptive effect of caffeine and indicated that chronic administration of the ND-caffeine association promotes the evocation of aversive memory in female rats., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the role of the C-reactive protein-to-prealbumin (CP) ratio and the C-reactive protein-to-albumin (CA) ratio as nutritional and prognostic markers. A retrospective study was conducted on hospitalized patients who underwent a nutritional assessment and the measurement of C-reactive protein, prealbumin, and albumin ( n = 274). Receiver operating characteristic (ROC) curve analysis was used. The area under the curve (AUC) of the CP ratio for predicting mortality was 0.644, 95%CI (0.571 to 0.717), and the CA ratio had an AUC of 0.593, 95%CI (0.518 to 0.669). The AUC of the CP ratio for the differential diagnosis between severe and moderate disease-related malnutrition (DRM) was 0.643, 95%CI (0.564 to 0.722), and the CA ratio had an AUC of 0.650, 95%CI (0.572 to 0.728). The CP and CA ratios showed greater accuracy in predicting mortality compared to C-reactive protein as an isolated marker ( p = 0.011 and p = 0.006, respectively). Both ratios also improved the ability of prealbumin and albumin to identify severe DRM ( p = 0.002 and p = 0.044, respectively). In conclusion, these results suggest that the CP and CA ratios may have a limited role in predicting mortality and identifying severe DRM by outperforming isolated protein markers.

Limited research on sexual minority women migrants demonstrate that they face elevated rates of mental health problems compared to their heterosexual and male counterparts, and less is known about their healthcare seeking behaviours. This study aimed to identify barriers and facilitators to mental and physical healthcare utilisation among first-generation (foreign-born) Arab sexual minority women migrants in the USA and to assess whether Penchansky and Thomas' theory of access can be used to understand their healthcare utilisation behaviours. We conducted 20 semi-structured interviews via Zoom. Employing community-engaged research methods, four advisors, Arab sexual minority women migrants and a mental health service provider, assisted in recruitment and thematic data analysis providing a rich and nuanced understanding of study findings. Five main themes demonstrated the pivotal role of cultural humility from providers and access to medical insurance in shaping healthcare-seeking decisions. Difficulties finding therapists and navigating the referral process and wait times encouraged participants to seek care outside of the USA in their Arab countries of origin. Stigma and social support further influenced participants' decisions to seek mental healthcare. The study findings inform policy and practice to foster the development of inclusive healthcare services grounded in cultural humility and to develop support groups specifically for Arab sexual minority women migrants to the USA.

Increased attraction to humans and their objects often arises after repeated and positive human-wildlife encounters (e.g. food provided in tourist settings). The causes of this 'over-attraction', which may result from a learned association between humans and food, are still poorly studied in wild animals. Understanding the influence of humans on animals' responses is yet crucial to prevent negative effects (e.g. aggression). We presented three novel objects to two groups of free-ranging brown skuas ( Catharacta antarctica ssp. lonnbergi ) in the remote sub-Antarctic, where their habitats show no or minimal human disturbance. Skuas in one group (Verte) had previously participated in repeated food-rewarded behavioural and cognitive tasks with a human experimenter; skuas in the other group (Ratmanoff) had never done so. Objects consisted of (i) one natural-food-resembling object (plastic fish), (ii) one anthropogenic food object (real cake slice), and (iii) one anthropogenic non-food object (yellow glove). Verte group skuas approached the human experimenter and pecked significantly more and sooner at novel objects. Human-food association may have thus resulted in increased attraction to humans and novelty exploration in previously naive brown skuas, making this species a useful model for investigating the consequences of experience with humans on wildlife behaviour.

Objective: To explore the experience of patients with incontinence and incontinence-associated dermatitis (IAD) in acute care hospitals and their family caregivers, including their perceptions and management, as well as the impact on their wellbeing., Method: A qualitative exploratory study design was employed in 18 wards across six acute/subacute hospitals in New South Wales, Australia. Patients with incontinence (with or without IAD) were invited to participate. Where interviews were not possible with the patient, their family caregiver was invited to participate. Semi-structured interviews were conducted., Results: There were 45 interviewees in the study; 41 were patients with incontinence (11 of whom had IAD) and four were family caregivers. The experience of incontinence was captured by three themes: 'incontinence interrupts every aspect of my life'; 'actively concealing and cloaking'; and 'perceived as irreversible'. Incontinence was expected by the patients at their age and did not come as a surprise. It was normalised and approached with stoicism. As such, patients self-managed their incontinence by developing strategies to ensure they avoided episodes of incontinence during their stay. Incontinence left patients feeling anxious, embarrassed and with a sense of shame, and they did not communicate these feelings, or engage with health professionals about their incontinence, nor did health professionals discuss their incontinence with them. There was a strong sense of resignation that incontinence was irreversible and nothing could be done to improve it. All participants displayed little knowledge of IAD. The experience of having IAD was characterised by the theme 'debilitating and desperate for relief' and was experienced as a particularly painful, itching and burning condition that left patients distressed and irritable., Conclusion: Patients with incontinence in acute settings required further education from health professionals to reduce the stigma of incontinence, and provide further support to manage their incontinence. Health professionals can also play a key role in educating patients about the risks of developing IAD and how it can be prevented.