The impact of irritant challenge on the skin barrier and myeloid resident immune cells in post-menopausal women is modulated by hormone replacement therapy.

BACKGROUND: Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. Therefore, we examined how menopause and HRT affect skin barrier and immune cell composition in post-menopausal women following irritant challenge. METHODS: Two cohorts of post-menopausal women were recruited to the study, one untreated (HRT-; n = 10; mean age 56.5 yrs [range 48-63 yrs]) and the other receiving HRT (n = 8; mean age 54 yrs [range 48-63 yrs]). Skin irritation was induced by applying 1.25% topical Sodium Lauryl Sulfate (SLS) to occluded buttock skin for 48 hours. Clinical assessment was conducted after 24 hours, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. RESULTS: Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in trans-epidermal water loss (p<0.05), filaggrin deposition and keratin-10-positive cell layers (p<0.01) was observed in individuals receiving HRT compared to the HRT- group. Following SLS challenge in individuals taking HRT, a significant (p<0.01) reduction of CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans' cells (LCs). Significantly fewer migrating LCs were observed in those not receiving HRT (p<0.01). Furthermore, the number of dermal dendritic cells (DCs), macrophages, and CD11c+CD206- and CD68+CD206- subsets were found to be significantly (p<0.05) higher in those taking HRT following SLS challenge. CONCLUSION: Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased keratin-10-positive epidermal cell layers. Following challenge, HRT users exhibited elevated counts of LCs, inflammatory DCs, and macrophages in the dermis. These may render skin both, more prone to inflammation and more capable of resolving it, while also promoting skin repair.

Associations between media parenting practices and early adolescent screen use.

BACKGROUND: To assess the prevalence of various media parenting practices and identify their associations with early adolescent screen time and problematic social media, video game, and mobile phone use. METHODS: Cross-sectional data from Year 3 of the Adolescent Brain Cognitive Development (ABCD) Study (2019-2022) that included 10,048 adolescents (12-13 years, 48.3% female, 45.6% racial/ethnic minorities) in the US were analyzed using multiple linear regression analyses adjusting for potential confounders. RESULTS: Parent screen use, family mealtime screen use, and bedroom screen use were associated with greater adolescent screen time and problematic social media, video game, and mobile phone use. Parental use of screens to control behavior (e.g., as a reward or punishment) was associated with higher screen time and greater problematic video game use. Parental monitoring of screens was associated with lower screen time and less problematic social media and mobile phone use. Parental limit setting of screens was associated with lower screen time and less problematic social media, video game, and mobile phone use. DISCUSSION: Parent screen use, mealtime screen use, and bedroom screen use were associated with higher adolescent problematic screen use and could be limited in a family media use plan. Parental monitoring and limiting of screen time are associated with less problematic screen use. IMPACT STATEMENT: Although the American Academy of Pediatrics provides guidance for screen use for children 5-18 years, there is a paucity of evidence-based guidance for media parenting practices, specifically for early adolescents. In a diverse sample of 10,048 early adolescents across the US, we found cross-sectional associations between parent, mealtime, and bedroom screen use and higher adolescent problematic screen use. Parental monitoring and limiting of adolescent screen time were cross-sectionally associated with less problematic screen use in our analytic sample and may be incorporated into a family media use plan.

Prospective association of screen time with binge-eating disorder among adolescents in the United States: The mediating role of depression.

OBJECTIVE: Screen time has been reported to be associated with binge-eating disorder (BED) among adolescents in the US; however, potential mediators remain unclear. This study aimed to evaluate depression symptoms as a mediator of the prospective association between screen time and BED. METHOD: We utilized data from 9465 children (aged 9-11 years at baseline) from the Adolescent Brain Cognitive Development (ABCD) study (2016-2021). A generalized structural equation model was used to examine the prospective association between average daily screen time at baseline and BED at year 2, adjusting for baseline BED diagnosis, and other potential covariates (e.g., age, sex, and income). Mediation was examined using bias-corrected (BC) 95% confidence intervals for the indirect effect of baseline screen time on year 2 BED through depression symptoms (change from baseline to year 1). RESULTS: One hundred and one participants (42.7% male, 49.4% racial/ethnic minority) met the criteria for BED in year 2. Participants were 9.9 years of age on average at baseline, 51.3% identified as male, and 43.1% identified as a racial/ethnic minority. Adjusting for covariates, screen time was prospectively associated with BED (OR = 1.09, 95% CI [1.03, 1.14], p = .005). Depression symptoms (B = .19, BC 95% CI [0.10, 0.28]) partially mediated (9.2%) the prospective association between screen time and BED. DISCUSSION: Among US adolescents, higher baseline screen time was prospectively associated with BED diagnosis at year 2, and this relationship was partially mediated by increased depression symptoms. Preventive approaches targeting high screen use may have utility for reducing BED risk among adolescents. PUBLIC SIGNIFICANCE: Among U.S. adolescents, higher screen time was prospectively associated with the incidence of BED. This association was partially mediated by the change in depressive symptoms. Preventive approaches targeting high screen use may have utility for reducing BED risk among adolescents.

Association of physical activity and screen time with cardiovascular disease risk in the Adolescent Brain Cognitive Development Study.

BACKGROUND: According to the Physical Activity Guidelines Advisory Committee Scientific Report, limited evidence is available on sedentary behaviors (screen time) and their joint associations with physical activity (steps) for cardiovascular health in adolescence. The objective of this study was to identify joint associations of screen time and physical activity categories with cardiovascular disease (CVD) risk factors (blood pressure, hemoglobin A1c, cholesterol) in adolescence. METHODS: This study analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, comprising a diverse sample of 4,718 U.S. adolescents aged 10-15 years between 2018 and 2021. Steps were measured by a Fitbit wearable device and levels were categorized as low (1,000-6,000), medium (> 6,000-12,000), and high (> 12,000) averaged daily step counts. Self-reported recreational screen time hours per day were classified as low (0-4), medium (> 4-8), and high (> 8) hours per day. CVD risk factors including blood pressure, hemoglobin A1c, and cholesterol (total and HDL) were measured. RESULTS: The analytical sample averaged 6.6 h of screen time per day and 9,722 steps per day. In models including both screen time and steps, the high screen time category was associated with a 4.27 higher diastolic blood pressure percentile (95% CI 1.83-6.73) and lower HDL cholesterol (B= -2.85, 95% CI -4.77 to -0.94 mg/dL) compared to the low screen time category. Medium (B = 3.68, 95% CI 1.24-6.11) and low (B = 7.64, 95% CI 4.07-11.20) step categories were associated with higher diastolic blood pressure percentile compared to the high step category. The medium step category was associated with lower HDL cholesterol (B= -1.99, 95% CI -3.80 to -0.19 mg/dL) compared to the high step category. Findings were similar when screen time and step counts were analyzed as continuous variables; higher continuous step count was additionally associated with lower total cholesterol (mg/dL). CONCLUSIONS: Combinations of low screen time and high steps were generally associated with favorable cardiovascular health markers including lower diastolic blood pressure and higher HDL cholesterol, which can inform future adolescent health guidelines.

Right Ventricular Structure and Function in Adolescent Athletes: A 3D Echocardiographic Study.

The aim of this study was to characterize the right ventricular (RV) contraction pattern and its associations with exercise capacity in a large cohort of adolescent athletes using resting three-dimensional echocardiography (3DE). We enrolled 215 adolescent athletes (16±1 years, 169 males, 12±6 hours of training/week) and compared them to 38 age and sex-matched healthy, sedentary adolescents. We measured the 3DE-derived biventricular ejection fractions (EF). We also determined the relative contributions of longitudinal EF (LEF/RVEF) and radial EF (REF/RVEF) to the RVEF. Same-day cardiopulmonary exercise testing was performed to calculate VO2/kg. Both LV and RVEFs were significantly lower (athletes vs. controls; LVEF: 57±4 vs 61±3, RVEF: 55±5 vs 60±5%, p<0.001). Interestingly, while the relative contribution of radial shortening to the global RV EF was also reduced (REF/RVEF: 0.40±0.10 vs 0.49±0.06, p<0.001), the contribution of the longitudinal contraction was significantly higher in athletes (LEF/RVEF: 0.45±0.08 vs 0.40±0.07, p<0.01). The supernormal longitudinal shortening correlated weakly with a higher VO2/kg (r=0.138, P=0.044). Similarly to the adult athlete's heart, the cardiac adaptation of adolescent athletes comprises higher biventricular volumes and lower resting functional measures with supernormal RV longitudinal shortening. Characteristic exercise-induced structural and functional cardiac changes are already present in adolescence.

Social Media Use and Alcohol Sipping in Early Adolescents: A Prospective Cohort Study.

BACKGROUND: Social media can influence alcohol initiation behaviors such as sipping, which can lead to future adverse alcohol-related outcomes. Few studies have examined the role of problematic social media use, characterized by addiction, mood modification, tolerance, withdrawal, conflict, and relapse, especially in early adolescence. OBJECTIVE: To examine the prospective association between social media use and sipping alcohol in a nationwide sample of early adolescents, and the extent to which problematic social media use mediates the association. METHODS: We analyzed prospective data from the Adolescent Brain Cognitive Development Study (N = 7514; ages 9-10 years at baseline; 2016-2018) to estimate associations between social media time (Year 1) and alcohol sipping (Year 3) using modified Poisson regression, adjusting for confounders and testing problematic social media use (Year 2) as a mediator. RESULTS: Social media time (Year 1) was prospectively associated with 1.31 (95% confidence interval 1.20-1.43) times higher risk of new-onset sipping (Year 3). The association between social media time and new-onset alcohol sipping was partially mediated by problematic social media use at Year 2 (25.0% reduction in the association between the former two factors after adding problematic social media use, p = 0.002). CONCLUSIONS: Time spent on social media was associated with a higher risk of alcohol sipping in a diverse national sample of early adolescents, and the association was partially mediated by problematic social media use. Media literacy education and family media use plans could advise early adolescents about exposure to alcohol content on social media and warning signs for problematic use.

Risk for depression tripled during the COVID-19 pandemic in emerging adults followed for the last 8 years.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic. METHODS: Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms. RESULTS: The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms. CONCLUSIONS: The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.

Short and mid-term characteristics of COVID-19 disease course in athletes: A high-volume, single-center study.

INTRODUCTION: At the pandemic's beginning, significant concern has risen about the prevalence of myocardial involvement after SARS-CoV-2 infection. We assessed the cardiovascular burden of SARS-CoV-2 in a large cohort of athletes and identified factors that might affect the disease course. We included 633 athletes in our study on whom we performed extensive cardiology examinations after recovering from SARS-CoV-2 infection. More than half of the athletes (n = 322) returned for a follow-up examination median of 107 days after the commencement of their infection. RESULTS: Troponin T positivity was as low as 1.4% of the athletes, where the subsequently performed examinations did not show definitive, ongoing myocardial injury. Altogether, 31% of the athletes' rapid training rebuild was hindered by persistent or reoccurring symptoms. Female athletes reported a higher prevalence of return to play (RTP) symptoms than their male counterparts (34% vs. 19%, p = 0.005). The development of long COVID symptoms was independently predicted by increasing age and acute symptoms' severity in a multiple regression model (AUC 0.75, CI 0.685-0.801). Athletes presenting with either or both cough and ferritin levels higher than >150 µg/L had a 4.1x (CI 1.78-9.6, p = 0.001) higher odds ratio of developing persistent symptoms. CONCLUSION: While SARS-CoV-2 rarely affects the myocardium in athletes, about one in three of them experience symptoms beyond the acute phase. Identifying those athletes with a predisposition to developing long-standing symptoms may aid clinicians and trainers in finding the optimal return-to-play timing and training load rebuild pace.

Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease.

Fibrates and omega-3 polyunsaturated acids are used for the treatment of hypertriglyceridemia but have not demonstrated consistent effects on cardiovascular (CV) risk. In this study, we investigate how these two pharmacological agents influence plasma levels of bioactive lipid mediators, aiming to explore their efficacy beyond that of lipid-lowering agents. Plasma from overweight patients with non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12 weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200 mg or 4 g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides. OM-3CA reduced plasma concentrations of proinflammatory PGE2 , as well as PGE1 , PGD1 and thromboxane B2 but increased prostacyclin, and eicosapentaenoic acid- and docosahexaenoic acid-derived lipids of lipoxygenase and cytochrome P450 monooxygenase (CYP) (e.g., 17-HDHA, 18-HEPE, 19,20-DiHDPA). Fenofibrate reduced plasma concentrations of vasoactive CYP-derived eicosanoids (DHETs). Although OM-3CA increased plasma levels of the NAE docosahexaenoyl ethanolamine and docosapentaenoyl ethanolamine, and fenofibrate increased palmitoleoyl ethanolamine, the effect of both treatments may have been masked by the placebo (olive oil). Fenofibrate was more efficacious than OM-3CA in significantly reducing plasma ceramides, pro-inflammatory lipids associated with CV disease risk. Neither treatment affected putative lipid species associated with NAFLD. Our results show that OM-3CA and fenofibrate differentially modulate the plasma mediator lipidome, with OM-3CA promoting the formation of lipid mediators with potential effects on chronic inflammation, while fenofibrate mainly reducing ceramides. These findings suggest that both treatments could ameliorate chronic inflammation with possible impact on disease outcomes, independent of triglyceride reduction.

Is cardiac involvement prevalent in highly trained athletes after SARS-CoV-2 infection? A cardiac magnetic resonance study using sex-matched and age-matched controls.

OBJECTIVES: To investigate the cardiovascular consequences of SARS-CoV-2 infection in highly trained, otherwise healthy athletes using cardiac magnetic resonance (CMR) imaging and to compare our results with sex-matched and age-matched athletes and less active controls. METHODS: SARS-CoV-2 infection was diagnosed by PCR on swab tests or serum immunoglobulin G antibody tests prior to a comprehensive CMR examination. The CMR protocol contained sequences to assess structural, functional and tissue-specific data. RESULTS: One hundred forty-seven athletes (94 male, median 23, IQR 20-28 years) after SARS-CoV-2 infection were included. Overall, 4.7% (n=7) of the athletes had alterations in their CMR as follows: late gadolinium enhancement (LGE) showing a non-ischaemic pattern with or without T2 elevation (n=3), slightly elevated native T1 values with or without elevated T2 values without pathological LGE (n=3) and pericardial involvement (n=1). Only two (1.4%) athletes presented with definite signs of myocarditis. We found pronounced sport adaptation in both athletes after SARS-CoV-2 infection and athlete controls. There was no difference between CMR parameters, including native T1 and T2 mapping, between athletes after SARS-CoV-2 infection and the matched athletic groups. Comparing athletes with different symptom severities showed that athletes with moderate symptoms had slightly greater T1 values than athletes with asymptomatic and mildly symptomatic infections (p<0.05). However, T1 mapping values remained below the cut-off point for most patients. CONCLUSION: Among 147 highly trained athletes after SARS-CoV-2 infection, cardiac involvement on CMR showed a modest frequency (4.7%), with definite signs of myocarditis present in only 1.4%. Comparing athletes after SARS-CoV-2 infection and healthy sex-matched and age-matched athletes showed no difference between CMR parameters, including native T1 and T2 values.

Multifaceted amelioration of cutaneous photoageing by (0.3%) retinol.

BACKGROUND: Although retinol skin care products improve the appearance of photoaged skin, there is a need for an effective retinol concentration that provides skin benefits without irritation. OBJECTIVE: To compare the efficacy of topical 0.1%, 0.3% and 1% retinol in remodelling the cutaneous architecture in an in vivo experimental patch test study, and to determine tolerance of the most effective formulations when used in a daily in-use escalation study. METHODS: For the patch test study, retinol products were applied under occlusion, to the extensor forearm of photoaged volunteers (n = 5; age range 66-84 years), and 3 mm skin biopsies obtained after 12 days. Effects of different retinol concentrations, and a vehicle control, on key epidermal and dermal biomarkers of cellular proliferation and dermal remodelling were compared to untreated baseline. Separately, participants (n = 218) recorded their tolerance to 0.3% or 1% retinol over a six-week, approved regimen, which gradually increased the facial applications to once nightly. RESULTS: Retinol treatment induced a stepwise increase in epidermal thickness and induced the expression of stratum corneum proteins, filaggrin and KPRP. 0.3% retinol and 1% retinol were comparably effective at inducing keratinocyte proliferation in the epidermis, whilst reducing e-cadherin expression. Fibrillin-rich microfibril deposition was increased following treatment with 0.3% and 1% retinol (p < 0.01); other dermal components remained unaltered (e.g., fibronectin, collagen fibrils, elastin), and no evidence of local inflammation was detected. The in-use study found that 0.3% retinol was better tolerated than 1% retinol, with fewer and milder adverse events reported (χ2 (1) = 23.97; p < 0.001). CONCLUSIONS: This study suggests that 1% and 0.3% retinol concentrations were similarly effective at remodelling photodamaged skin in an in vivo model of long-term use. Use of 0.3% retinol in the escalation study was associated with fewer adverse reactions when applied daily. Hence, 0.3% retinol may be better tolerated than 1% retinol, thereby allowing longer-term topical application.

CONTEXTE: Même si les produits de soins pour la peau à base de rétinol améliorent l'apparence de la peau photovieillie, il est nécessaire d'obtenir une concentration efficace de rétinol procurant des bénéfices cutanés sans irritation. OBJECTIF: Comparer l'efficacité du rétinol à 0.1%, 0.3% et 1% en application locale dans le remodelage de l'architecture cutanée dans une étude d'irritation cutanée in vivo expérimental, et déterminer la tolérance des formulations les plus efficaces lorsqu'elles sont utilisées dans une étude à doses progressives quotidiennes en cours d'utilisation. MÉTHODES: Pour l'étude d'irritation cutanée, des produits à base de rétinol ont été appliqués sous occlusion, sur le muscle extenseur de l'avant-bras de volontaires présentant des signes de photovieillissement (n = 5; tranche d'âge: 66 à 84 ans), et des biopsies cutanées de 3 mm ont été obtenues après 12 jours. Les effets des différentes concentrations de rétinol, et d'un véhicule témoin sur les principaux biomarqueurs épidermiques et dermiques de la prolifération cellulaire et du remodelage dermique ont été comparés à ceux observés à une région non traitée. Séparément, les participants (n = 218) ont enregistré leur tolérance au rétinol à 0.3% ou 1% au cours d'un schéma posologique approuvé de six semaines, qui a progressivement augmenté les applications faciales à une fois par nuit. RÉSULTATS: Le traitement par rétinol a induit une augmentation progressive de l'épaisseur épidermique, et a induit l'expression des protéines de la couche cornée, la filaggrine et le KPRP. Le rétinol à 0.3% et le rétinol à 1% étaient aussi efficaces pour induire la prolifération des kératinocytes dans l'épiderme, tout en réduisant l'expression de la cadhérine E. Le dépôt de microfibrilles riches en fibrilline a augmenté après un traitement par rétinol à 0.3% et 1% (p < 0.001). CONCLUSIONS: Cette étude suggère que les concentrations de rétinol de 1% et 0.3% étaient aussi efficaces pour remodeler la peau photolésée dans un modèle in vivo lors d'une utilisation à long terme. L'utilisation de rétinol à 0.3% dans l'étude à doses progressives a été associée à moins d'effets indésirables lorsqu'il est appliqué quotidiennement. Par conséquent, le rétinol à 0.3% peut être mieux toléré que le rétinol à 1%, permettant ainsi une application topique à plus long terme.

Geometrical remodeling of the mitral and tricuspid annuli in response to exercise training: a 3-D echocardiographic study in elite athletes.

Intense exercise exposes the heart to significant hemodynamic demands, resulting in adaptive changes in cardiac morphology and function. Nevertheless, the athletic adaptation of the atrioventricular valves remains to be elucidated. Our study aimed to characterize the geometry of mitral (MA) and tricuspid (TA) annuli in elite athletes using 3-D echocardiography. Thirty-four athletes presented with functional mitral regurgitation (FMR) were retrospectively identified and compared with 34 athletes without mitral regurgitation (MR) and 34 healthy, sedentary volunteers. 3-D echocardiographic datasets were used to quantify MA and TA geometry and leaflet tenting by dedicated softwares. MA and TA areas, as well as tenting volumes, were higher in athletes compared with controls. MA area was significantly higher in athletes with MR compared with those without (8.2 ± 1.0 vs. 7.2 ± 1.0 cm2/m2, P < 0.05). Interestingly, athletes with MR also presented with a significantly higher TA area (7.2 ± 1.1 vs. 6.5 ± 1.1 cm2/m2, P < 0.05). Nonplanar angle describing the MA's saddle shape was less obtuse in athletes without MR, whereas the values of athletes with MR were comparable with controls. The exercise-induced relative increases in left ventricular (35 ± 25%) and left atrial (40 ± 29%) volumes were similar; however, the increment in the MA area was disproportionately higher (63 ± 23%, overall P < 0.001). The relative increase in TA area (40 ± 23%) was also higher compared with the increment in right ventricular volume (34 ± 25%, P < 0.05). Atrioventricular annuli undergo a disproportionate remodeling in response to regular exercise. Athletic adaptation is characterized by both annular enlargement and increased leaflet tenting of both valves. There are differences in MA geometry in athletes presented with versus without FMR.NEW & NOTEWORTHY We have characterized the annular geometry of mitral and tricuspid valves in elite athletes using 3-D echocardiography. We have found that exercise-induced remodeling of the atrioventricular annuli comprises a disproportionate dilation of annular dimensions and increased leaflet tenting of both valves. Moreover, we have demonstrated a more pronounced saddle shape of the mitral annulus in athletes without mitral regurgitation, which was not present in those who had mild regurgitation.

Geographical variation in pace-of-life in a long-distance migratory bird: implications for population management.

Life-history theory predicts that animals should develop adaptive trade-offs between survival and reproduction to maximize their fitness. This results in a continuum of life-history strategies among species, ranging from slow to fast paces-of-life. The optimal pace-of-life has been shown to vary within environmental gradients, with a commonly observed pattern of a slow-to-fast continuum from the tropics to the poles. Within species, pace-of-life variability has however received much less attention. In this study, we investigated whether or not the pace-of-life of populations within a species follows the expected slow-fast continuum associated with latitude. We analysed the variability of life-history strategies among populations of the European roller Coracias garrulus, a long-distance migratory species, comparing breeding parameters and adult survival between populations across a latitudinal gradient. The findings showed a negative correlation between survival and clutch size in roller populations, with a slower pace-of-life in the northern populations and a faster pace-of-life in the southern populations: a reverse gradient to what might be expected from inter-specific studies. These results suggest that northern populations would benefit from measures enhancing adult survival probability, such as reduction in harvesting rates, while southern populations would respond better to actions favouring reproductive success, such as nesting site provisioning. This study highlights that life-history traits can vary substantially between populations of a single species with a large latitudinal breeding range, and pinpoint how knowledge about this variability may be key in anticipating different populations' responses to threats as well as to conservation strategies.

Exercise-induced shift in right ventricular contraction pattern: novel marker of athlete's heart?

Data about the functional adaptation of the right ventricle (RV) to intense exercise are limited. Our aim was to characterize the RV mechanical pattern in top-level athletes using three-dimensional echocardiography. A total of 60 elite water polo athletes (19 ± 4 yr, 17 ± 6 h of training/wk, 50% women and 50% men) and 40 healthy sedentary control subjects were enrolled. We measured the RV end-diastolic volume index (RVEDVi) and ejection fraction (RVEF) using dedicated software. Furthermore, we determined RV global longitudinal (RV GLS) and circumferential strain (RV GCS) and the relative contribution of longitudinal ejection fraction (LEF) and radial ejection fraction (REF) to RVEF using the ReVISION method. Athletes also underwent cardiopulmonary exercise testing [O2 consumption (V̇o2)/kg]. Athletes had significantly higher RVEDVi compared with control subjects (athletes vs. control subjects, 88 ± 11 vs. 65 ± 10 ml/m2, P < 0.001); however, they also demonstrated lower RVEF (56 ± 4% vs. 61 ± 5%, P < 0.001). RV GLS was comparable between the two groups (-22 ± 5% vs. -23 ± 5%, P = 0.24), whereas RV GCS was significantly lower in athletes (-21 ± 4% vs. -26 ± 7%, P < 0.001). Athletes had higher LEF and lower REF contribution to RVEF (LEF/RVEF: 0.50 ± 0.07 vs. 0.42 ± 0.07, P < 0.001; REF/RVEF: 0.33 ± 0.08 vs. 0.45 ± 0.08, P < 0.001). Moreover, the pattern of RV functional shift correlated with V̇o2/kg (LEF/RVEF: r = 0.30, P < 0.05; REF/RVEF: r = -0.27, P < 0.05). RV mechanical adaptation to long-term intense exercise implies a functional shift; the relative contribution of longitudinal motion to global function was increased, whereas the radial shortening was significantly decreased, in athletes. Moreover, this functional pattern correlates with aerobic exercise performance, representing a potential new resting marker of an athlete's heart. NEW & NOTEWORTHY Intensive regular physical exercise results in significant changes of right ventricular morphology and function. By separate quantification of the right ventricular longitudinal and radial function, a relative dominance of longitudinal motion and a decrease in radial motion can be observed compared with sedentary controls. Moreover, this contraction pattern correlates with cardiopulmonary fitness. According to these results, this functional shift of the right ventricle may represent a novel marker of an athlete's heart.

Similarity between an unfamiliar human and the owner affects dogs' preference for human partner when responding to an unsolvable problem.

This study investigates whether dogs are able to differentiate between people according to whether or not they show similarities to their owners. We hypothesized that dogs would show a preference for the "similar" partner when interacting with unfamiliar humans. After having familiarized with two experimenters displaying different degrees of similarity to their owners, dogs (N = 36) participated in a situation where the desired toy object was made inaccessible in order to find out whether they initiate interaction with the two partners differently. Two different types of "similarity cues" were used (either alone or combined with each other): (1) persistent behavioral characteristics (i.e., familiar vs. strange motion pattern and language usage) and (2) an unfamiliar arbitrary group marker (i.e., one of the potential helpers was wearing clothing similar to that worn by the owner). Results show that although dogs payed equal attention to the human partners displaying various types of similarity to their owners during familiarization, they exhibited a visual attention preference for the human whose motion pattern and language usage were similar to their owner's in the inaccessible-toy task. However, there was weak evidence of discrimination based on the arbitrary group marker (clothing). Although dogs' different tendencies to interact with the potential helpers do not necessarily imply an underlying ability to create social categories based on the degree of similarity between the owner and unfamiliar people, these results suggest that functionally human infant-analogue forms of social categorization may have emerged in dogs.

Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits.

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (KATP) in vascular smooth muscle. Because airway smooth muscle also expresses KATP, we characterized the protective potential of levosimendan against increased airway and respiratory tissue resistances. Animals were administered levosimendan alone (group L), levosimendan after pretreatment with a KATP channel blocker (glibenclamide, group LG), glibenclamide only (group G), or solvent alone (dextrose, group C). Airway resistance (Raw), tissue damping, and elastance were determined by forced oscillations under baseline conditions and following provocation tests with intravenous methacholine (MCh). Cardiac output (CO) was assessed by transpulmonary thermodilution. The same sequence of measurements was then repeated during intravenous infusion of levosimendan in groups L and LG or glucose in groups G and C Sham treatments in groups C and G had no effect on lung responsiveness. However, levosimendan treatment in group L elevated CO and inhibited the MCh-induced airway responses [Raw changes of 87.8 ± 83% (SD) vs. 24.4 ± 16% at 4 µg·kg-1·min-1 MCh, P < 0.001], and in G (35.2 ± 12.7 vs. 25.2 ± 12.9%, P < 0.05). The preventive affect of levosimendan against lung constriction vanished in the LG group. Levosimendan exerts a KATP-mediated potential to prevent bronchoconstriction and may prohibit adverse lung peripheral changes both in the small bronchi and the pulmonary parenchyma. The identification of a further pleiotropic property of levosimendan that is related to the pulmonary system is of particular importance for patients with decreased cardiorespiratory reserves for which simultaneous circulatory support is complemented with prevention of adverse respiratory events.

Detailed heart rate variability analysis in athletes.

OBJECTIVE: Heart rate variability (HRV) analysis has been used to evaluate patients with various cardiovascular diseases. While the vast majority of HRV studies have focused on pathological states, our study focuses on the less explored area of HRV analysis across different training intensity and sports. We aimed to measure HRV in healthy elite and masters athletes and compare to healthy, but non-athletic controls. METHODS: Time-domain HRV analysis was applied in 138 athletes (male 110, age 28.4 ± 8.3) and 100 controls (male 56, age 28.3 ± 6.9) during Holter monitoring (21.3 ± 3.0 h). RESULTS: All studied parameters were higher in elite athletes compared to controls [SDNN (CI) 225.3 (216.2-234.5) vs 158.6 (150.2-167.1) ms; SDNN Index (CI) 99.6 (95.6-103.7) vs 72.4 (68.7-76.2) ms; pNN50 (CI) 24.2 (22.2-26.3) vs 14.4 (12.7-16.3) %; RMSSD (CI) 71.8 (67.6-76.2) vs 50.8 (46.9-54.8) ms; p < 0.001]. Masters had higher HRV values than controls, but no significant differences were found between elite athletes and masters athletes. Some parameters were higher in canoeists-kayakers and bicyclists than runners. Lower cut-off values in elite athletes were SDNN: 147.4 ms, SDNN Index: 66.6 ms, pNN50: 9.7 %, RMSSD: 37.9 ms. INTERPRETATION: Autonomic regulation in elite athletes described with HRV is significantly different than in healthy controls. Sports modality and level of performance, but not age- or sex-influenced HRV. Our study provides athletic normal HRV values. Further investigations are needed to determine its role in risk stratification, optimization of training, or identifying overtraining.

[Clinico-pathologically focused breast cancer research]. / Klinikopatológiai szemléletû emlõrákkutatások.

In the second half of the 20th century research focusing to breast carcinomas at the Semmelweis University had been mostly linked to the 2nd Department of Pathology. Nowadays, following the rapidly improving treatment modalities in breast cancer there is an increasing need for defining new predictive and prognostic markers. The modern molecular pathological approach helps tremendously in mapping the biological behavior of individual cases of breast cancers and meanwhile, it is one of the prerequisites of a more efficient treatment both in neoadjuvant and adjuvant settings, as well as in metastatic disease. We provide a brief review of the relevant results we have obtained in breast cancer research between 2000 and 2015.

Mapping glucose-mediated gut-to-brain signalling pathways in humans.

OBJECTIVES: Previous fMRI studies have demonstrated that glucose decreases the hypothalamic BOLD response in humans. However, the mechanisms underlying the CNS response to glucose have not been defined. We recently demonstrated that the slowing of gastric emptying by glucose is dependent on activation of the gut peptide cholecystokinin (CCK1) receptor. Using physiological functional magnetic resonance imaging this study aimed to determine the whole brain response to glucose, and whether CCK plays a central role. EXPERIMENTAL DESIGN: Changes in blood oxygenation level-dependent (BOLD) signal were monitored using fMRI in 12 healthy subjects following intragastric infusion (250ml) of: 1M glucose+predosing with dexloxiglumide (CCK1 receptor antagonist), 1M glucose+placebo, or 0.9% saline (control)+placebo, in a single-blind, randomised fashion. Gallbladder volume, blood glucose, insulin, and GLP-1 and CCK concentrations were determined. Hunger, fullness and nausea scores were also recorded. PRINCIPAL OBSERVATIONS: Intragastric glucose elevated plasma glucose, insulin, and GLP-1, and reduced gall bladder volume (an in vivo assay for CCK secretion). Glucose decreased BOLD signal, relative to saline, in the brainstem and hypothalamus as well as the cerebellum, right occipital cortex, putamen and thalamus. The timing of the BOLD signal decrease was negatively correlated with the rise in blood glucose and insulin levels. The glucose+dex arm highlighted a CCK1-receptor dependent increase in BOLD signal only in the motor cortex. CONCLUSIONS: Glucose induces site-specific differences in BOLD response in the human brain; the brainstem and hypothalamus show a CCK1 receptor-independent reduction which is likely to be mediated by a circulatory effect of glucose and insulin, whereas the motor cortex shows an early dexloxiglumide-reversible increase in signal, suggesting a CCK1 receptor-dependent neural pathway.

Sleep, brain systems, and persistent stress in early adolescents during COVID-19: Insights from the ABCD study.

PURPOSE: The first year of the COVID-19 pandemic constituted a major life stress event for many adolescents, associated with disrupted school, behaviors, social networks, and health concerns. However, pandemic-related stress was not equivalent for everyone and could have been influenced by pre-pandemic factors including brain structure and sleep, which both undergo substantial development during adolescence. Here, we analyzed clusters of perceived stress levels across the pandemic and determined developmentally relevant pre-pandemic risk factors in brain structure and sleep of persistently high stress during the first year of the COVID-19 pandemic. METHODS: We investigated longitudinal changes in perceived stress at six timepoints across the first year of the pandemic (May 2020-March 2021) in 5559 adolescents (50 % female; age range: 11-14 years) in the United States (U.S.) participating in the Adolescent Brain Cognitive Development (ABCD) study. In 3141 of these adolescents, we fitted machine learning models to identify the most important pre-pandemic predictors from structural MRI brain measures and self-reported sleep data that were associated with persistently high stress across the first year of the pandemic. RESULTS: Patterns of perceived stress levels varied across the pandemic, with 5 % reporting persistently high stress. Our classifiers accurately detected persistently high stress (AUC > 0.7). Pre-pandemic brain structure, specifically cortical volume in temporal regions, and cortical thickness in multiple parietal and occipital regions, predicted persistent stress. Pre-pandemic sleep difficulties and short sleep duration were also strong predictors of persistent stress, along with more advanced pubertal stage. CONCLUSIONS: Adolescents showed variable stress responses during the first year of the COVID-19 pandemic, and some reported persistently high stress across the whole first year. Vulnerability to persistent stress was evident in several brain structural and self-reported sleep measures, collected before the pandemic, suggesting the relevance of other pre-existing individual factors beyond pandemic-related factors, for persistently high stress responses.