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Background: While there is a higher risk of surgical site infection (SSI) on the lower extremities following Mohs micrographic surgery (MMS), antibiotic prophylaxis (AP) is debated. Objective: To determine the role of shared decision making (SDM) in guiding AP usage during MMS on the lower extremities. Materials and methods: A prospective observational study was conducted whereby patients received a standardized SDM discussion or routine counseling. Patient satisfaction quantified by the shared decision-making questionnaire (SDMQ9) survey, rate of SSI, and rate of AP prescription were recorded. Results: In total, 51 patients were included. While there were less antibiotics prescribed in the treatment group (20% versus 50%, P = .025), this did not affect incidence of SSI (8% in treatment group versus 7.7% in control group, P = .668). Patient satisfaction was statistically greater in SDM group (4.73 versus 2.18 in control (P

Depression and anxiety symptoms have risen in the last decade, especially among college students. Virtues are potentially strong predictive factors of mental health symptoms, but a minimal amount of research has explored "which" virtues are the strongest predictors. We examined the relative predictive strength of gratitude, forgiveness, patience, intellectual humility, and self-control using dominance analyses. Results suggested that gratitude had the strongest predictive value for lower anxiety and depressive symptom scores compared to forgiveness, intellectual humility, patience, and self-control. An implication of these findings is that when considering intervention work with young emerging adults, researchers may do well to start with gratitude, then promote other virtues such as forgiveness and self-control.

Abstract Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these ‘real-world’ patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

Ostracod taxa from shallow freshwater lakes are sensitive to a range of limnological factors including temperature, hydrological habitat, lake level, and the distribution of aquatic plants. Ostracod assemblages preserved in Quaternary lake sediments can be used to reconstruct limnological change and are therefore potentially valuable palaeoenvironmental proxies. However, lack of autecological information about some taxa may limit the validity of such reconstructions. We use fossil ostracod assemblages recovered from radiocarbon-dated late Holocene sediments from Wallywash Great Pond, a small, shallow freshwater lake in southwestern Jamaica, to reconstruct limnological change over the past ∼ 1800 years. We circumvent ongoing taxonomic and ecological uncertainties associated with the identification of fossil ostracod taxa by drawing on observations of the ecology of ostracods found living in Jamaican water bodies. By combining this information with limnological data from the extant lake, and with sedimentological and isotopic data from the lake sediments, we show that a published interpretation of ostracod assemblages for the late Quaternary of Wallywash Great Pond is simplistic, at least for the late Holocene section of the sediment record. We conclude that changes in ostracod assemblages are linked to variations in the input of undersaturated groundwater to the northern part of the lake from which the core was recovered. These variations, which were driven by changes in the precipitation / evaporation ratio (effective moisture), also controlled sedimentation, with reduced effective moisture and a decline in undersaturated groundwater input favouring marl precipitation, whereas organic sediments are linked to increased effective moisture and enhanced groundwater input. Our findings suggest that the dramatic shifts in ostracod assemblages at this site are a complex response to changes in hydrology, sedimentology, and carbonate saturation rather than being a simple indicator of lake-level change. Combining ostracod assemblage data with the results of other palaeolimnological analyses also allows more detailed reconstructions to be made for this lake, and such a multiproxy approach is recommended for similar lakes elsewhere.

Background: Patients without urinary tract infection (UTI) symptoms but with a positive urine culture are considered to have asymptomatic bacteriuria (ASB). This often represents colonization and treatment is not recommended or clinically beneficial. Treatment of ASB can promote antimicrobial resistance and increased rates of Clostriodies difficile infections. Many cases of ASB are incorrectly assigned as CAUTIs due to over-culturing practices. We hypothesized that a urine culture algorithm, embedded within a best practice alert (BPA) in the electronic medical record (EMR), would reduce urine culturing practices for ASB. Methods: From Feb 2022 through May 2023, a multidisciplinary team implemented an Inpatient Urine Culturing Stewardship Guideline. A BPA fired when a provider placed a urinalysis with reflex to culture (UACC) or urine culture (UC) order for patients who met criteria (Image 1). The BPA directed providers to remove the order, select the appropriate pathway from the guideline, or provide a rationale for placing the order. The intervention was piloted on three intensive care units and two progressive care units, containing both medical and surgical patients. Monthly ordering practices, CAUTI rates, and gram-negative rod (GNR) bacteremia rates from a 13-month pre-intervention baseline period were compared to a 16-month intervention period. Over the same time periods, we also assessed changes in ordering practices for comparison units which did not implement the intervention. Pre-and-post intervention cohorts were analyzed using median two sample tests and Exact Poison Method, as appropriate. Results: On intervention units there was a 41.0% reduction in the median number of UACC and UC orders per 1000 patient days from 16.31 during the baseline period to 9.62 in the intervention period (p=0.0036). Pan cultures per 1000 patient days in which one of the orders was a UACC or UC fell by 42.2% from a median of 10.20 per 1000 patient days to 5.90 (p=0.0008). The comparison units saw no significant reductions in UACC and UC orders (p=0.21) or pan cultures (p=1.0). On the intervention units, the CAUTI rate for the baseline period was 1.31 per 1000 catheter days versus 0.79 in the intervention period (IRR = 1.65; p=0.44). GNR bacteremias remained stable on the intervention units between the baseline and intervention periods (p=0.82). Conclusion: This multidisciplinary intervention, leveraging EMR clinical decision support, reduced urine and pan culturing practices while demonstrating a trend towards a reduced CAUTI rate. The prevalence of GNR bacteremias remained consistent with baseline levels, suggesting the intervention did not cause harm.

RASopathies cause nonsarcomeric hypertrophic cardiomyopathy via dysregulated signaling through RAS and upregulated mitogen-activated protein kinase activity. We provide the first report of the successful treatment of an adult with RAF1-associated hypertrophic cardiomyopathy using trametinib, a MEK inhibitor.

Chronic kidney disease (CKD) can lead to cardiac dysfunction in a condition known as cardiorenal syndrome (CRS). It is postulated that the accumulation of uremic toxins in the bloodstream, as a consequence of declining kidney function, may contribute to these adverse cardiac effects. While CRS in adults has been extensively studied, there is a significant knowledge gap with pediatric patients. Uremic toxin levels in children remain inadequately characterized and quantified compared to adults. This review aims to systematically evaluate the association between uremic toxin concentrations and cardiac changes in pediatric CRS and to examine the impact of different dialysis modalities, specifically hemodialysis and peritoneal dialysis, on uremic toxin clearance and cardiovascular parameters. To address this, we conducted a systematic literature search of PubMed, following PRISMA guidelines. We used the terms “uremic toxins” and “cardiorenal syndrome” with variations in syntax to search for studies discussing the relationship between uremic toxin levels in CKD, the subsequent impact on cardiac parameters, and the emergence of cardiac dysfunction. Full-text articles written in English, conducted on humans aged from birth to 18 years, and published until December 2021 were included. A comprehensive literature search yielded six studies, and their risk of bias was assessed using JBI Critical Appraisal Checklists. Our systematic review is registered on PROSPERO, number CRD42023460072. This synthesis intends to provide an understanding of the role of uremic toxins in pediatric CRS. The findings reveal that pediatric patients with end-stage CKD on dialysis exhibit elevated uremic toxin levels, which are significantly associated with cardiovascular disease parameters. Additionally, the severity of CKD correlated with higher uremic toxin levels. No conclusive evidence was found to support the superiority of either hemodialysis or peritoneal dialysis in terms of uremic toxin clearance or cardiovascular outcomes. More pediatric-specific standardized and longitudinal studies are needed to develop targeted treatments and improve clinical outcomes and the quality of life for affected children.

The present study examined the attitudes and behavioral intentions of 336 children aged 7-11 toward a hypothetical peer with symptoms of attention-deficit hyperactivity disorder (ADHD) to determine whether they were influenced by labeling, social devaluation, or familiarity. Children read one of five vignettes describing the behavior of a gender-neutral peer before completing self-report measures of attitudes and behavioral intentions. Results showed children held predominantly negative attitudes toward the hypothetical peer, which were more pronounced for inattentive than hyperactive/impulsive symptoms. These findings suggest that children were more likely to devalue internalizing rather than externalizing behaviors. Children also reported being more likely to engage in active/recreational and social activities rather than academic activities. In addition, the diagnostic label "ADHD" led to more negative attitudes and behavioral intentions, while knowing someone with ADHD mediated the negative effect of hyperactive/impulsive symptoms on attitudes and behavioral intentions. Finally, significant positive relationships were found between attitudes and children's willingness to engage in social, academic, and physical activities. Policy and practice implications of these findings are discussed.

Background:. In recent years, self-tanners have become a well-liked alternative to sun tanning and tanning bed usage, as strikingly similar results can be achieved without the harmful side effects of ultraviolet exposure. Objective:. The aim of this study is to investigate the presence and prevalence of potential allergens in the most popular self-tanning products. Methods:. Five major retailers in the United States were evaluated, from which 17 different brands and 44 unique self-tanning products were analyzed. The ingredients in each self-tanning product were compared with 80 and 36 notable contact allergens taken from the North American Contact Dermatitis Group and Food and Drug Administration–approved T.R.U.E (Thin-Layer Rapid Use Epicutaneous Patch Test), respectively. Results:. We found that contact allergens are frequently present in self-tanning products; allergens especially common are propylene glycol, linalool, polysorbate, d-limonene, benzyl alcohol, tocopherol (vitamin E), fragrances, and other scented botanicals. On average, each self-tanner we analyzed contained 11.86 allergens. Limitations:. The limitation is that commercial names could not be eliminated from the analysis, introducing potential bias. Conclusion:. While self-tanning products are a safer alternative to tanning bed use or sunbathing, consumers and clinicians alike must be aware that they may cause an allergic reaction of the skin for some users.

Abstract Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (−5.3 kg [SD:1.0]) and genotype-discordant diets (−4.8 kg [SD:1.1]; adjusted difference: −0.6 kg [95% CI: −2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466.

This study utilizes in situ measurements and numerical weather prediction forecasts curated during the Coupled Air–Sea Processes Electromagnetic Ducting Research (CASPER) east field campaign to assess how thermodynamic properties in the marine atmospheric surface layer influence evaporation duct shape independent of duct height. More specifically, we investigate evaporation duct shape through a duct shape parameter, a parameter known to affect the propagation of X-band radar signals and is directly related to the curvature of the duct. Relationships between this duct shape parameter and air sea temperature difference (ASTD) reveal that during unstable periods (ASTD < 0), the duct shape parameter is generally larger than in near-neutral or stable atmospheric conditions, indicating tighter curvature of the M-profile. Furthermore, for any specific duct height, a strong linear relationship between the near-surface-specific humidity gradient and the duct shape parameter is found, suggesting that it is primarily driven by near-surface humidity gradients. The results demonstrate that an a priori estimate of duct shape, for a given duct height, is possible if the near-surface humidity gradient is known.

Abstract Background The objective was to test the efficacy of a scalable, virtually delivered, diabetes-tailored weight management program on glycemic control in adults with type 2 diabetes (T2D). Methods This was a single arm, three-site clinical trial. Participants had baseline HbA1c between 7–11% and BMI between 27–50 kg/m2. Primary outcome was change in HbA1c at 24 weeks. Secondary outcomes were changes in body weight, waist circumference, the Diabetes Distress Scale (DDS), quality of life (IWQOL-L), and hunger (VAS). Generalized linear effects models were used for statistical analysis. Results Participants (n = 136) were 56.8 ± 0.8 y (Mean ± SEM), 36.9 ± 0.5 kg/m2, 80.2% female, 62.2% non-Hispanic white. Baseline HbA1c, weight, and total DDS score were 8.0 ± 0.09%, 101.10 ± 1.47 kg, and 2.35 ± 0.08, respectively. At week 24, HbA1c, body weight, and total DDS decreased by 0.75 ± 0.11%, 5.74 ± 0.50%, 0.33 ± 0.10 units, respectively (all p

In this extract from, and commentary on, my master's thesis, "The Brooch of Bergen Belsen: A Journey of Historiographic Poiesis" (winning York University Department of Education Best Major Research Paper 2010), I explore a single aesthetic experience, an encounter with a small hand-made floral cloth brooch donated to the Holocaust Memorial Museum. At the start of my inquiry, I had only the object--the brooch itself--my emotional reaction to it, and the few lines of text on a curated museum card. I wondered, how do we create "spaces for remembrance" (Simon 2005) and what are the implications for teaching, learning and living in a just society? How are we accountable to Simon's (2004) demand for "non-indifference?" Arts-based research methodologies such as historiographic poiesis have allowed me to merge the scholar and artist, to engage in research as an iterative process where deeper questions engender more complex and embodied responses, and to create an aesthetic intervention: an open, dialogic text and artworks that provoke new understandings of narratives previously overlooked.

Key Clinical Message When screening tests of haemostasis are abnormal, it is important to identify at which point in the coagulation cascade dysfunction may be occurring. This may assist to identify a specific deficiency/dysfunction, the type of bleeding to be anticipated, and replacement therapy if required. Unmasking of an inherited coagulopathy or the development of an acquired coagulopathy may occur in the setting of a second (febrile) illness. Differentiating between inherited and acquired coagulopathies will rely on clinicians taking a thorough personal and family bleeding history, and correlating these findings with the haemostasis screening results.

BackgroundSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties.MethodsThis article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives’ strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model’s various components, which are presented in detail.ResultsThe Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support.DiscussionOur integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model’s effectiveness and hypothesized psychological mechanisms.

IntroductionCurrent published long-term provincial or territorial congenital anomaly data are lacking for Canada. We report on prevalence (per 1000 total births) and trends in 1997–2019, in Alberta, Canada, for selected congenital anomalies. Associated risk factors are also discussed. MethodsWe used data from the Alberta Congenital Anomalies Surveillance System (ACASS) to calculate the prevalence and perform chi-square linear trend analyses. ResultsFrom 1997 to 2019, the overall prevalence of neural tube defects was stable, at 0.74 per 1000 total births. The same was true for spina bifida (0.38), orofacial clefts (1.99), more severe CHDs (transposition of the great arteries, 0.38; tetralogy of Fallot, 0.33; and hypoplastic left heart syndrome, 0.32); and gastroschisis (0.38). Anencephaly, cleft palate and anorectal malformation significantly decreased with a prevalence of 0.23, 0.75 and 0.54 per 1000 total births, respectively. Significantly increasing trends were reported for anotia/microtia (0.24), limb reduction anomalies (0.73), omphalocele (0.36) and Down syndrome (2.21) and for hypospadias and undescended testes (4.68 and 5.29, respectively, per 1000 male births). ConclusionCongenital anomalies are an important public health concern with significant social and societal costs. Surveillance data gathered by ACASS for over 40 years can be used for planning and policy decisions and the evaluation of prevention strategies. Contributing genetic and environmental factors are discussed as is the need for continued surveillance and research.

IntroductionOn manque de données provinciales ou territoriales à long terme publiées et actuelles sur les anomalies congénitales Au Canada. Cette étude fait état de la prévalence (pour 1000 naissances totales) et des tendances pour diverses anomalies congénitales de 1997 à 2019 en Alberta (Canada). Les facteurs de risque associés sont également abordés. MethodsNous avons utilisé les données du Système de surveillance des anomalies congénitales de l’Alberta (ACASS) pour calculer la prévalence et effectuer des analyses de tendance linéaire par test du chi carré. ResultsEntre 1997 et 2019, la prévalence globale des anomalies du tube neural est demeurée stable, à 0,74 pour 1000 naissances totales. C’était également le cas pour le spina bifida (0,38), les fentes orofaciales (1,99), les cardiopathies congénitales graves (transposition des grandes artères, 0,38; tétralogie de Fallot, 0,33; hypoplasie du coeur gauche, 0,32) et le gastroschisis (0,38). L’anencéphalie, la fente palatine et les anomalies anorectales ont diminué significativement, avec une prévalence de respectivement 0,23, 0,75 et 0,54 pour 1000 naissances totales. Une tendance significativement à la hausse a été relevée pour l’anotie/microtie (0,24), les anomalies de raccourcissement des membres (0,73), l’omphalocèle (0,36) et le syndrome de Down (2,21), ainsi que pour l’hypospadias et la cryptorchidie (respectivement 4,68 et 5,29 pour 1 000 naissances masculines). ConclusionLes anomalies congénitales constituent un important problème de santé publique, qui est associé à des coûts sociaux et sociétaux substantiels. Les données de surveillance recueillies par l’ACASS sur plus de 40 ans peuvent servir à la planification et aux décisions en matière de politiques ainsi qu’à l’évaluation des stratégies de prévention. Les facteurs génétiques et environnementaux contributifs sont abordés, de même que la nécessité de poursuivre la surveillance et la recherche.

Attention-deficit/hyperactivity disorder (ADHD) rates have increased in recent years, resulting in the need for more classroom support. In Wales, support for many pupils with ADHD is provided by the 16,157 teaching assistants (TAs) employed by local authorities. This qualitative study interviewed 15 primary school TAs to answer three questions concerning their feelings about their job, and the facilitators and barriers to their work with children with ADHD. Using thematic analysis, the researchers identified 10 themes: positive feelings, negative effects, a need for change, support, improvement over time, one-to-one relationship, lack of support, negativity towards ADHD, classroom environment, and poor knowledge and experience with ADHD. This study illustrates the TAs' love for their job and the importance of positive relationships. It also highlights a lack of support for TAs and negativity towards ADHD. Implications of the study and recommendations for the future are discussed.

Background: The impact of adjunctive anti-inflammatory treatment on outcomes for patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs) is unknown. Methods: Using data from the International KD Registry in patients with ≥ medium CAA we evaluate associations of treatment with outcomes and major adverse cardiac events (MACE). Results: Medium or large CAA was present in 527 (32%) patients. All were treated with intravenous immunoglobulin (IVIG), 70% were male, and the median age was 1.3 years (interquartile range: 0.4-4.0 years). The most common acute therapies included single IVIG alone in 243 (46%), multiple IVIG in 100 (19%), multiple IVIG + corticosteroids in 75 (14%), and multiple IVIG + infliximab + corticosteroids in 44 (8%) patients. Patients who received therapy beyond single IVIG had a larger CA z-score at baseline (P < 0.001) and a higher rate of bilateral CAA (P < 0.001). Compared with IVIG alone, early adjunctive treatments (within 3 days of initial IVIG) were not associated with time to CAA regression or MACE, whereas later adjunctive therapy was associated with MACE and longer time to CAA regression. Patients receiving IVIG plus steroids vs IVIG alone had a trend towards shorter time to CAA regression and lower risk of MACE (P = 0.07). A larger CAA z-score at baseline was the strongest predictor of an increase in the CAA z-score over follow-up, lower likelihood of CAA regression, and higher risk of MACE. Conclusions: Persistence of CAA and MACE are more strongly associated with baseline severity CAA than with acute adjuvant anti-inflammatory therapy. Patients who received late adjunctive therapy are at higher risk for worse outcomes. Résumé: Contexte: L’incidence d’un traitement anti-inflammatoire d’appoint chez les patients atteints de la maladie de Kawasaki (MK) compliquée d’anévrismes coronariens est inconnue. Méthodologie: À partir de données provenant du registre international de la maladie de Kawasaki portant sur les patients ayant subi des anévrismes coronariens modérés ou importants, nous avons évalué l’incidence des différents traitements sur les résultats cliniques et les événements cardiovasculaires indésirables majeurs (ECIM). Résultats: Des anévrismes coronariens modérés ou importants ont été relevés chez 527 patients (32 %). Tous les patients recevaient des immunoglobulines administrées par voie intraveineuse (IgIV); 70 % d’entre eux étaient de sexe masculin, et leur âge médian était de 1,3 an (écart interquartile : de 0,4 an à 4,0 ans). Les traitements d’urgence les plus fréquents comprenaient un seul traitement par IgIV chez 243 patients (46 %), plusieurs traitements par IgIV chez 100 patients (19 %), une association de plusieurs traitements IgIV et de corticostéroïdes chez 75 patients (14 %) et une association de plusieurs traitements IgIV, de corticostéroïdes et d’infliximab chez 44 patients (8 %). Les patients ayant reçu un traitement autre qu’un seul traitement IgIV présentaient des scores z initiaux plus élevés pour le diamètre des artères coronaires (P < 0,001) et un taux plus élevé d’anévrismes coronariens bilatéraux (P < 0,001). En comparaison d’un traitement par IgIV seulement, les traitements d’appoint précoces (administrés dans les trois jours suivant le début du traitement par IgIV) n’ont pas eu d’incidence sur la durée avant la régression des anévrismes coronariens ni sur la survenue d’ECIM, alors que les traitements d’appoint plus tardifs ont été associés à un risque plus élevé d’ECIM et à une régression plus tardive des anévrismes coronariens. Les patients ayant reçu une association d’IgIV et de corticostéroïdes avaient tendance à présenter une régression plus rapide des anévrismes coronariens et un plus faible risque d’ECIM que ceux recevant uniquement un traitement par IgIV (P = 0,07). Un score z initial plus élevé pour un anévrisme coronarien était le facteur prédictif le plus puissant d’une augmentation du score z pendant la période de suivi, d’une probabilité plus faible de régression de l’anévrisme et d’un risque plus élevé d’ECIM. Conclusions: La gravité initiale de l’anévrisme coronarien est plus fortement associée à la persistance de l’anévrisme et à la survenue d’ECIM que le recours à un traitement anti-inflammatoire d’urgence en appoint. Les patients recevant un traitement d’appoint tardif étaient par ailleurs plus susceptibles de présenter des résultats défavorables.

BackgroundPsychedelic drug experiences are shaped by current-moment contextual factors, commonly categorized as internal (set) and external (setting). Potential influences of past environments, however, have received little attention.AimsTo investigate how previous environmental stimuli shaped the experiences of patients receiving ketamine for treatment-resistant depression (TRD), and develop the concept of “imprinting” to account for such time-lagged effects across diverse hallucinogenic drugs.MethodsRecordings of treatment sessions and phenomenological interviews from 26 participants of a clinical trial investigating serial intravenous ketamine infusions for TRD, conducted from January 2021 to August 2022, were retrospectively reviewed. A broad literature search was undertaken to identify potentially underrecognized examples of imprinting with both serotonergic and atypical psychedelics, as well as analogous cognitive processes and neural mechanisms.ResultsIn naturalistic single-subject experiments of a 28-year-old female and a 34-year-old male, subjective ketamine experiences were significantly altered by varying exposures to particular forms of digital media in the days preceding treatments. Higher levels of media exposure reduced the mystical/emotional qualities of subsequent psychedelic ketamine experiences, overpowering standard intention-setting practices and altering therapeutic outcomes. Qualitative data from 24 additional patients yielded eight further spontaneous reports of past environmental exposures manifesting as visual hallucinations during ketamine experiences. We identified similar examples of imprinting with diverse psychoactive drugs in past publications, including in the first-ever report of ketamine in human subjects, as well as analogous processes known to underly dreaming.Conclusions/interpretationPast environmental exposures can significantly influence the phenomenology and therapeutic outcomes of psychedelic experiences, yet are underrecognized and understudied. To facilitate future research, we propose expanding the contextual model of psychedelic drug actions to incorporate imprinting, a novel concept that may aid clinicians, patients, and researchers to better understand psychedelic drug effects.Clinical trial registrationClinicalTrials.gov, identifier NCT04701866.

IntroductionHuman motor learning processes are a fundamental part of our daily lives and can be adversely affected by neurologic conditions. Motor learning largely depends on successfully integrating cognitive and motor-related sensory information, and a simple, easily accessible treatment that could enhance such processes would be exciting and clinically impactful. Normobaric 100% oxygen treatment (NbOxTr) is often used as a first-line intervention to improve survival rates of brain cells in neurological trauma, and recent work indicates that improvements in elements crucial for cognitive-motor-related functions can occur during NbOxTr. However, whether NbOxTr can enhance the motor learning processes of healthy human brains is unknown. Here, we investigated whether a brief NbOxTr administered via nasal cannula improves motor learning processes during a visuomotor adaptation task where participants adapt to a visual distortion between visual feedback and hand movements.Methods40 healthy young adults (M = 21 years) were randomly assigned to a NbOxTr (N = 20; 100% oxygen) or air (N = 20; regular air) group and went through four typical visuomotor adaptation phases (Baseline, Adaptation, After-Effect, Refresher). Gas treatment (flow rate 5 L/min) was only administered during the Adaptation phase of the visuomotor experiment, in both groups.ResultsThe NbOxTr provided during the Adaptation phase led to significantly faster and about 30% improved learning (p < 0.05). Notably, these motor learning improvements consolidated into the subsequent experiment phases, i.e., after the gas treatment was terminated (p < 0.05).DiscussionWe conclude that this simple and brief NbOxTr dramatically improved fundamental human motor learning processes and may provide promising potential for neurorehabilitation and skill-learning approaches. Further studies should investigate whether similar improvements exist in elderly and neurologically impaired individuals, other motor learning tasks, and also long-lasting effects.

The intercalibration of age readings represents a crucial step in the ageing procedure; the use of different sampling methods, structures, preparation techniques, and ageing criteria can significantly affect age and growth data. This study evaluated the precision and accuracy of ageing for the most important North Atlantic (NA) and Mediterranean (M) ray species, Raja clavata, Raja brachyura, Torpedo marmorata, and Dipturus oxyrinchus, through exchange exercises carried out by readers from different laboratories. In addition, growth parameters were estimated from the obtained data. A total of 663 individual batoids were analysed. R. clavata and R. brachyura samples were obtained from both the NA and the M, while vertebral centra of T. marmorata and D. oxyrinchus were only available for the M. High reading variability was observed for all four evaluated species in terms of CV, APE, and PA. D. oxyrinchus and T. marmorata showed relatively slow growth and the von Bertalanffy model with fixed t0 and Gompertz’s model were, respectively, the most precise models for each of these species. In R. brachyura, females had a faster growth rate compared to combined sexes. The vbt0p proved the most precise model for describing growth in this species, and no statistical differences were found between the NO and the M. For R. clavata, the best-fitting model was the vbt0p for females and males in the NO and for females from the M, while the best-fitting model for males from the M and sexes combined for both areas was log.p. Distinct growth patterns were observed between the two study areas.

Onion thrips, Thrips tabaci (Lindeman), is a major pest of dry bulb onion throughout the US and across the world. Yield and quality damage from thrips feeding and the expense of insecticides used for thrips management have jeopardized profitable and sustainable onion production. To improve approaches to thrips management, researchers in multiple US onion-producing regions developed novel, integrated pest management (IPM)-based strategies employing threshold-based insecticide treatments and reduced fertilization practices. The purpose of this study was to estimate the benefits from public investment in research to develop IPM-based onion thrips management techniques using a cost–benefit analysis. Benefits were extended over a 20-year timespan and were measured by reduced insecticide and fertilizer costs. The estimated net present value of benefits from improved pest management tactics will depend on the adoption and use of novel approaches to management. Using a scenario that assumes a maximum adoption rate of 58%, the estimated net present value of the research is $15.91 million, the benefit–cost ratio is 4.00, and the internal rate of return is 32%. Assuming a scenario with a maximum adoption rate of 29%, the estimated net present value of the research is $8.3 million, the benefit–cost ratio is 3.34, and the internal rate of return is 24%. Even when estimated assuming conservative adoption scenarios, results indicate a healthy return on investment in research to develop and refine new approaches to manage onion thrips and optimize dry bulb onion production.

Introduction Type 2 diabetes mellitus (T2DM) is a powerful risk factor for cardiovascular disease (CVD), conferring a greater relative risk in women than men. We sought to examine sex differences in cardiometabolic risk factors and management in the contemporary cohort represented by the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methods GRADE enrolled 5047 participants (1837 women, 3210 men) with T2DM on metformin monotherapy at baseline. The current report is a cross-sectional analysis of baseline data collected July 2013 to August 2017.Results Compared with men, women had a higher mean body mass index (BMI), greater prevalence of severe obesity (BMI≥40 kg/m2), higher mean LDL cholesterol, greater prevalence of low HDL cholesterol, and were less likely to receive statin treatment and achieve target LDL, with a generally greater prevalence of these risk factors in younger women. Women with hypertension were equally likely to achieve blood pressure targets as men; however, women were less likely to receive ACE inhibitors or angiotensin receptor blockers. Women were more likely to be divorced, separated or widowed, and had fewer years of education and lower incomes.Conclusions This contemporary cohort demonstrates that women with T2DM continue to have a greater burden of cardiometabolic and socioeconomic risk factors than men, particularly younger women. Attention to these persisting disparities is needed to reduce the burden of CVD in women.Trial registration number ClinicalTrials.gov (NCT01794143)

IntroductionNaringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes. Retinoic acid is an RXR ligand metabolized from dietary carotenoids. The carotenoid β-carotene reduces adiposity and insulin resistance in clinical trials. Our goal was to examine if carotenoids strengthen the beneficial effects of naringenin on human adipocyte metabolism.MethodsHuman preadipocytes from donors with obesity were differentiated in culture and treated with 8µM naringenin + 2µM β-carotene (NRBC) for seven days. Candidate genes involved in thermogenesis and glucose metabolism were measured as well as hormone-stimulated lipolysis.ResultsWe found that β-carotene acts synergistically with naringenin to boost UCP1 and glucose metabolism genes including GLUT4 and adiponectin, compared to naringenin alone. Protein levels of PPARα, PPARγ and PPARγ-coactivator-1α, key modulators of thermogenesis and insulin sensitivity, were also upregulated after treatment with NRBC. Transcriptome sequencing was conducted and the bioinformatics analyses of the data revealed that NRBC induced enzymes for several non-UCP1 pathways for energy expenditure including triglyceride cycling, creatine kinases, and Peptidase M20 Domain Containing 1 (PM20D1). A comprehensive analysis of changes in receptor expression showed that NRBC upregulated eight receptors that have been linked to lipolysis or thermogenesis including the β1-adrenergic receptor and the parathyroid hormone receptor. NRBC increased levels of triglyceride lipases and agonist-stimulated lipolysis in adipocytes. We observed that expression of RXRγ, an isoform of unknown function, was induced ten-fold after treatment with NRBC. We show that RXRγ is a coactivator bound to the immunoprecipitated PPARγ protein complex from white and beige human adipocytes.DiscussionThere is a need for obesity treatments that can be administered long-term without side effects. NRBC increases the abundance and lipolytic response of multiple receptors for hormones released after exercise and cold exposure. Lipolysis provides the fuel for thermogenesis, and these observations suggest that NRBC has therapeutic potential.

Abstract Physical performance decrements observed during multi‐stressor military operations may be attributed, in part, to cellular membrane dysfunction, which is quantifiable using phase angle (PhA) derived from bioelectrical impedance analysis (BIA). Positive relationships between PhA and performance have been previously reported in cross‐sectional studies and following longitudinal exercise training programs, but whether changes in PhA are indicative of acute decrements in performance during military operations is unknown. Data from the Optimizing Performance for Soldiers II study, a clinical trial examining the effects of exogenous testosterone administration on body composition and performance during military stress, was used to evaluate changes in PhA and their associations with physical performance. Recreationally active, healthy males (n = 34; 26.6 ± 4.3 years; 77.9 ± 12.4 kg) were randomized to receive testosterone undecanoate or placebo before a 20‐day simulated military operation, which was followed by a 23‐day recovery period. PhA of the whole‐body (Whole) and legs (Legs) and physical performance were measured before (PRE) and after (POST) the simulated military operation as well as in recovery (REC). Independent of treatment, PhAWhole and PhALegs decreased from PRE to POST (p 0.05). Additionally, PhA was not associated with aerobic performance at any timepoint. In conclusion, reduced PhA from PRE to POST provides indirect evidence of cellular membrane disruption. Associations between PhA and strength and power were only evident at PRE and REC, suggesting PhA may be a useful indicator of strength and power, but not aerobic capacity, in non‐stressed conditions, and not a reliable indicator of physical performance during severe physiological stress.

ABSTRACT Many CAAX proteins, such as Ras GTPase, undergo a series of posttranslational modifications at their carboxyl terminus (i.e., cysteine prenylation, endoproteolysis of AAX, and carboxylmethylation). Some CAAX proteins, however, undergo prenylation-only modification, such as Saccharomyces cerevisiae Hsp40 Ydj1. We previously observed that altering the CAAX motif of Ydj1 from prenylation-only to canonical resulted in altered Ydj1 function and localization. Here, we investigated the effects of a reciprocal change that altered the well-characterized canonical CAAX motif of S. cerevisiae Ras2 to prenylation-only. We observed that the type of CAAX motif impacted Ras2 protein levels, localization, and function. Moreover, we observed that using a prenylation-only sequence to stage hyperactive Ras2-G19V as a farnesylated and nonproteolyzed intermediate resulted in a different phenotype relative to staging by a genetic RCE1 deletion strategy that simultaneously affected many CAAX proteins. These findings suggested that a prenylation-only CAAX motif is useful for probing the specific impact of CAAX proteolysis on Ras2 under conditions where other CAAX proteins are normally modified. We propose that our strategy could be easily applied to a wide range of CAAX proteins for examining the specific impact of CAAX proteolysis on their functions. IMPORTANCE CAAX proteins are subject to multiple posttranslational modifications: cysteine prenylation, CAAX proteolysis, and carboxylmethylation. For investigations of CAAX proteolysis, this study took the novel approach of using a proteolysis-resistant CAAX sequence to stage Saccharomyces cerevisiae Ras2 GTPase in a farnesylated and nonproteolyzed state. Our approach specifically limited the effects of disrupting CAAX proteolysis to Ras2. This represented an improvement over previous methods where CAAX proteolysis was inhibited by gene knockout, small interfering RNA knockdown, or biochemical inhibition of the Rce1 CAAX protease, which can lead to pleiotropic and unclear attribution of effects due to the action of Rce1 on multiple CAAX proteins. Our approach yielded results that demonstrated specific impacts of CAAX proteolysis on the function, localization, and other properties of Ras2, highlighting the utility of this approach for investigating the impact of CAAX proteolysis in other protein contexts.

We present an analysis of pre-service teachers' (PSTs) conceptions of their own learning, focusing on relationships between where PSTs learn and conceptions of their own learning. Our data come from in-depth interviews carried out over a six-month period with PSTs on different routes into teaching. We identify four components of learning to teach: beliefs about knowledge for teaching and the focus, timing and self-determination of reflection. We found weak relationships between PSTs' conceptions and their route into teaching (led by a school or university) and stronger relationships between conceptions of their own learning and their experience of mentoring in school.

A challenge for higher education, in the context of the 'Fourth Industrial Age', is to prepare students for uncertain futures. Proposed is a model of integrated scholarship drawing on, and developing, Boyer's scholarship (discovery, teaching, integration and application). We argue that such a model provides a connecting thread between the idea of a university as conceptualised in the 19th century, making links between the university of the past, present and future. Through reference of a case study example of the links between teaching and research presented in the 2017 UK Teaching Excellence Framework, we draw upon Boyer's scholarship as a conceptual lens to examine institutional texts which articulate teaching excellence. Our findings indicate that current judgements about effective linkages between teaching and research vary greatly with few examples or evidence. Our integrated scholarship model joins together institutional learning communities to discover, communicate and apply new knowledge across disciplines.

Parents of children with special educational needs and disabilities (SEND) took part in an online survey that explored their experiences of home-schooling during the coronavirus pandemic. Two hundred and thirty-eight parents from the UK responded to 49 questions about the resources and support they had received, their management and feelings surrounding home-schooling. Chi-square analyses were used to establish whether parents' experiences differed as a result of socio-economic status (SES) or the nature of their child's SEND. Results indicated that parents were dissatisfied with the resources and support they had received for their child's educational and psychological needs. Parents felt inadequate and unprepared and believed that non-attendance at school had and would have a detrimental effect on their child's education and mental health. Parents also described the negative impact of home-schooling on their and their family's well-being. Finally, SES and SEND-type were not associated with parents' experiences of home-schooling.