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The general view in syntactic literature is that binding constraints can make antecedents syntactically inaccessible. However, several studies showed that antecedents which are ruled out by syntactic binding constraints still influence online processing of anaphora in some stages, suggesting that a cue-based retrieval mechanism plays a role during anaphora resolution. As in the syntactic literature, in semantic accounts like Discourse Representation Theory (DRT), formal constraints are formulated in terms of accessibility of the antecedent. We explore the discourse inaccessibility postulated in DRT by looking at its role in pronoun resolution of inter-sentential anaphoric relations in four off-line and two eye-tracking experiments. The results of the eye-tracking experiments suggest that accessibility has an effect on pronoun resolution from early on. The study quantifies evidence of inaccessible antecedents affecting pronoun resolution and shows that almost all evidence points to the conclusion that discourse-inaccessible antecedents are ruled out for pronoun resolution in processing. The only potential counter-example to this claim is also detected, but remains only as anecdotal evidence even after combining data from both eye-tracking studies. The findings in the study show that accessibility plays a significant role in the processing of pronoun resolution in a way which is potentially challenging for the cue-based retrieval mechanism. The paper argues that discourse accessibility can help expand the theories of retrieval beyond the syntactic and sentence-level domain and provides a window into the study of interference in discourse.

Abstract Lyme borreliosis (LB) is the most commonly diagnosed tick-borne disease in the northern hemisphere. Since an efficient vaccine is not yet available, prevention of transmission is essential. This, in turn, requires a thorough comprehension of the spatiotemporal dynamics of LB transmission as well as underlying drivers. This study aims to identify spatiotemporal trends and unravel environmental and socio-economic covariates of LB incidence in Poland, using consistent monitoring data from 2010 through 2019 obtained for 320 (aggregated) districts. Using yearly LB incidence values, we identified an overall increase in LB incidence from 2010 to 2019. Additionally, we observed a large variation of LB incidences between the Polish districts, with the highest risks of LB in the eastern districts. We applied spatiotemporal Bayesian models in an all-subsets modeling framework to evaluate potential associations between LB incidence and various potentially relevant environmental and socio-economic variables, including climatic conditions as well as characteristics of the vegetation and the density of tick host species. The best-supported spatiotemporal model identified positive relationships between LB incidence and forest cover, the share of parks and green areas, minimum monthly temperature, mean monthly precipitation, and gross primary productivity. A negative relationship was found with human population density. The findings of our study indicate that LB incidence in Poland might increase as a result of ongoing climate change, notably increases in minimum monthly temperature. Our results may aid in the development of targeted prevention strategies.

Objective: Simultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs – and thus inducing cardiovascular complications – are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models. Methods: In the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective β-AR agonist isoprenaline across various rodent β-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis. Results: Exposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis. Conclusions: Our results demonstrate that ATR-127 is a highly effective, novel β2- and β3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (body mass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Abstract Trees are pivotal to global biodiversity and nature’s contributions to people, yet accelerating global changes threaten global tree diversity, making accurate species extinction risk assessments necessary. To identify species that require expert-based re-evaluation, we assess exposure to change in six anthropogenic threats over the last two decades for 32,090 tree species. We estimated that over half (54.2%) of the assessed species have been exposed to increasing threats. Only 8.7% of these species are considered threatened by the IUCN Red List, whereas they include more than half of the Data Deficient species (57.8%). These findings suggest a substantial underestimation of threats and associated extinction risk for tree species in current assessments. We also map hotspots of tree species exposed to rapidly changing threats around the world. Our data-driven approach can strengthen the efforts going into expert-based IUCN Red List assessments by facilitating prioritization among species for re-evaluation, allowing for more efficient conservation efforts.

Abstract Autoreactive T lymphocytes crossing the blood-brain barrier (BBB) into the central nervous system (CNS) play a crucial role in the initiation of demyelination and neurodegeneration in multiple sclerosis (MS). Recently, extracellular vesicles (EV) secreted by BBB endothelial cells (BBB-EC) have emerged as a unique form of cell-to-cell communication that contributes to cerebrovascular dysfunction. However, the precise impact of different size-based subpopulations of BBB-EC-derived EV (BBB-EV) on the early stages of MS remains unclear. Therefore, our objective was to investigate the content and function of distinct BBB-EV subpopulations in regulating BBB integrity and their role in T cell transendothelial migration, both in vitro and in vivo. Our study reveals that BBB-ECs release two distinct size based EV populations, namely small EV (sEV; 30-150 nm) and large EV (lEV; 150-300 nm), with a significantly higher secretion of sEV during inflammation. Notably, the expression patterns of cytokines and adhesion markers differ significantly between these BBB-EV subsets, indicating specific functional differences in the regulation of T cell migration. Through in vitro experiments, we demonstrate that lEV, which predominantly reflect their cellular source, play a major role in BBB integrity loss and the enhanced migration of pro-inflammatory Th1 and Th17.1 cells. Conversely, sEV appear to protect BBB function by inducing an anti-inflammatory phenotype in BBB-EC. These findings align with our in vivo data, where the administration of sEV to mice with experimental autoimmune encephalomyelitis (EAE) results in lower disease severity compared to the administration of lEV, which exacerbates disease symptoms. In conclusion, our study highlights the distinct and opposing effects of BBB-EV subpopulations on the BBB, both in vitro and in vivo. These findings underscore the need for further investigation into the diagnostic and therapeutic potential of BBB-EV in the context of MS.

Abstract Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly.

Background: Blood transfusion is often necessary during and after lung transplantation surgery. Point-of-care guided bleeding strategies, such as rotational thromboelastometry (ROTEM), can reduce blood transfusion in cardiovascular surgery. This study aimed to assess the effect of ROTEM-guided bleeding management on the need for allogenic blood transfusion, prohemostatic medication, and clinical outcomes in lung transplantation patients. Methods: This single-center retrospective cohort study compared patients receiving bilateral lung transplantation between 2010-2014 and 2017-2020. The first cohort was treated with a clinically guided bleeding strategy and the second cohort with a ROTEM-guided bleeding strategy. Multivariable regression analyses were performed to determine the effects on primary outcomes. Results: A total of 167 (66 clinically guided vs 101 ROTEM-guided) patients were included for analysis. Baseline, intraoperative, and postoperative characteristics were mostly similar, but differed regarding the number of patients with cystic fibrosis, use of cardiopulmonary bypass, and surgical technique. The ROTEM-guided group received significantly less median red blood cells (7 [3; 13] vs 4 [1; 9] units, p

Khalil Rafiqi,1,2 Camilla Bang Hoeks,3 Bo Løfgren,3,4 Martin Bødtker Mortensen,5,6 Jens M Bruun1,4 1Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark; 2Emergency Department, Aarhus University Hospital, Aarhus, Denmark; 3Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark; 4Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 5Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark; 6Ciccarone Center for Prevention of Heart Disease, Johns Hopkins, Baltimore, MD, USACorrespondence: Khalil Rafiqi, Steno Diabetes Center Aarhus, Aarhus University Hospital, Palle Juul-Jensens Blvd. 11, Indgang A, Aarhus, 8200, Denmark, Email kharaf@rm.dkObjective: To investigate whether hs-CRP and IL-6 provide additional diagnostic value beyond that achieved by the HEART score in patients with chest pain suggestive of acute coronary syndrome (ACS) admitted to the emergency department (ED).Methods: This was a post hoc analysis using data from the RACING-MI study. Baseline data, including hs-CRP and IL-6 levels, were analyzed using the plasma from the biobank. A total of 818 patients with chest pain suggestive of ACS were included in this analysis. Of these, 98 were diagnosed with ACS (12%). Logistic regression was used to identify the independent predictors of ACS development in patients with chest pain.Results: hs-CRP levels > 2 mg/L were observed in 50% of all ACS cases. IL-6 levels > 1.3 pg/mL were observed in 71% of all ACS cases. hs-CRP had a sensitivity of 50% and specificity of 51% for the diagnosis of ACS, whereas IL-6 had a sensitivity of 71% and specificity of 29%. The diagnostic likelihood ratios for ACS was 1.0 for hs-CRP> 2 mg/L and IL-6 > 1.3 pg/mL, respectively. Logistic regression analysis revealed that age, male gender, and ongoing smoking were associated with ACS in patients with acute chest pain. No association was found between IL-6 or hs-CRP level and ACS. This was observed for both IL-6 and hs-CRP, whether assessed on a continuous scale or using prespecified cut-off values.Conclusion: Among the 818 patients admitted to the ED with chest pain suggestive of ACS, neither hs-CRP nor IL-6 provided an independent added diagnostic value. Our results suggest that inflammatory markers have limited diagnostic value in detecting patients with ACS in the ED.Keywords: admission hs-CRP and IL-6 values, HEART-score, acute coronary syndrome, diagnosis

Abstract Background Non-AT-III mediated heparin-resistance during CPB occurs by complex-forming with heparin-binding proteins. Currently, there are no specific recommendations for non-AT-III mediated heparin-resistance. Case presentation We present a fatal case of a 70-yr-old male-patient undergoing cardiac-surgery in which refractory heparin-resistance was observed. The massive AL amyloidosis found at autopsy is thought to be responsible and illustrates that awareness and knowledge of the etiology and perioperative strategies of non-AT-III mediated heparin-resistance is important. Conclusion For anticoagulation during cardiopulmonary bypass surgery in case of a non-AT-III medicated heparin resistance, we refer to the decision tree added to this manuscript and if necessary to consider direct thrombin inhibitors, such as bivalirudin or argatroban, as it bypasses the complexing pathway.

Abstract Cardiac energy status, measured as phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio with 31P-Magnetic Resonance Spectroscopy (31P-MRS) in vivo, is a prognostic factor in heart failure and is lowered in cardiometabolic disease. It has been suggested that, as oxidative phosphorylation is the major contributor to ATP synthesis, PCr/ATP ratio might be a reflection of cardiac mitochondrial function. The objective of the study was to investigate whether PCr/ATP ratios can be used as in vivo marker for cardiac mitochondrial function. We enrolled thirty-eight patients scheduled for open-heart surgery in this study. Cardiac 31P-MRS was performed before surgery. Tissue from the right atrial appendage was obtained during surgery for high-resolution respirometry for the assessment of mitochondrial function. There was no correlation between the PCr/ATP ratio and ADP-stimulated respiration rates (octanoylcarnitine R2

Abstract Background Several prediction models of survival after in-hospital cardiac arrest (IHCA) have been published, but no overview of model performance and external validation exists. We performed a systematic review of the available prognostic models for outcome prediction of attempted resuscitation for IHCA using pre-arrest factors to enhance clinical decision-making through improved outcome prediction. Methods This systematic review followed the CHARMS and PRISMA guidelines. Medline, Embase, Web of Science were searched up to October 2021. Studies developing, updating or validating a prediction model with pre-arrest factors for any potential clinical outcome of attempted resuscitation for IHCA were included. Studies were appraised critically according to the PROBAST checklist. A random-effects meta-analysis was performed to pool AUROC values of externally validated models. Results Out of 2678 initial articles screened, 33 studies were included in this systematic review: 16 model development studies, 5 model updating studies and 12 model validation studies. The most frequently included pre-arrest factors included age, functional status, (metastatic) malignancy, heart disease, cerebrovascular events, respiratory, renal or hepatic insufficiency, hypotension and sepsis. Only six of the developed models have been independently validated in external populations. The GO-FAR score showed the best performance with a pooled AUROC of 0.78 (95% CI 0.69–0.85), versus 0.59 (95%CI 0.50–0.68) for the PAM and 0.62 (95% CI 0.49–0.74) for the PAR. Conclusions Several prognostic models for clinical outcome after attempted resuscitation for IHCA have been published. Most have a moderate risk of bias and have not been validated externally. The GO-FAR score showed the most acceptable performance. Future research should focus on updating existing models for use in clinical settings, specifically pre-arrest counselling. Systematic review registration PROSPERO CRD42021269235. Registered 21 July 2021.

β2-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents. Here the authors report that two-weeks of treatment with the β2-agonist clenbuterol improves insulin-stimulated glucose disposal in healthy young men in a double-blinded, randomized cross-over trial.

Abstract Mitochondria are organelles that fuel cellular energy requirements by ATP formation via aerobic metabolism. Given the wide variety of methods to assess skeletal muscle mitochondrial capacity, we tested how well different invasive and noninvasive markers of skeletal muscle mitochondrial capacity reflect mitochondrial respiration in permeabilized muscle fibers. Nineteen young men (mean age: 24 ± 4 years) were recruited, and a muscle biopsy was collected to determine mitochondrial respiration from permeabilized muscle fibers and to quantify markers of mitochondrial capacity, content such as citrate synthase (CS) activity, mitochondrial DNA copy number, TOMM20, VDAC, and protein content for complex I–V of the oxidative phosphorylation (OXPHOS) system. Additionally, all participants underwent noninvasive assessments of mitochondrial capacity: PCr recovery postexercise (by 31P‐MRS), maximal aerobic capacity, and gross exercise efficiency by cycling exercise. From the invasive markers, Complex V protein content and CS activity showed the strongest concordance (Rc = 0.50 to 0.72) with ADP‐stimulated coupled mitochondrial respiration, fueled by various substrates. Complex V protein content showed the strongest concordance (Rc = 0.72) with maximally uncoupled mitochondrial respiration. From the noninvasive markers, gross exercise efficiency, VO2max, and PCr recovery exhibited concordance values between 0.50 and 0.77 with ADP‐stimulated coupled mitochondrial respiration. Gross exercise efficiency showed the strongest concordance with maximally uncoupled mitochondrial respiration (Rc = 0.67). From the invasive markers, Complex V protein content and CS activity are surrogates that best reflect skeletal muscle mitochondrial respiratory capacity. From the noninvasive markers, exercise efficiency and PCr recovery postexercise most closely reflect skeletal muscle mitochondrial respiratory capacity.

Background Medication administration errors (MAEs) are a major cause of morbidity and mortality. An updated barcode medication administration (BCMA) technology on infusion pumps is implemented in the operating rooms to automate double check at a syringe exchange.Objective The aim of this mixed-methods before-and-after study is to understand the medication administrating process and assess the compliance with double check before and after implementation.Methods Reported MAEs from 2019 to October 2021 were analysed and categorised to the three moments of medication administration: (1) bolus induction, (2) infusion pump start-up and (3) changing an empty syringe. Interviews were conducted to understand the medication administration process with functional resonance analysis method (FRAM). Double check was observed in the operating rooms before and after implementation. MAEs up to December 2022 were used for a run chart.Results Analysis of MAEs showed that 70.9% occurred when changing an empty syringe. 90.0% of MAEs were deemed to be preventable with the use of the new BCMA technology. The FRAM model showed the extent of variation to double check by coworker or BCMA.Observations showed that the double check for pump start-up changed from 70.2% to 78.7% postimplementation (p=0.41). The BCMA double check contribution for pump start-up increased from 15.3% to 45.8% (p=0.0013). The double check for changing an empty syringe increased from 14.3% to 85.0% (p

Objective: Mitochondrial network dynamics may play role in metabolic homeostasis. Whether mitochondrial network dynamics are involved in adaptations to day–night fluctuations in energy supply and demand is unclear. Here we visualized and quantified the mitochondrial network morphology in human skeletal muscle of young healthy lean and older individuals with obesity over the course of 24 h Methods: Muscle biopsies taken at 5 timepoints over a 24-hour period obtained from young healthy lean and older metabolically impaired obese males were analyzed for mitochondrial network integrity with confocal laser scanning microscopy. Variation of level of fragmentation over the course of the day were aligned with variation of mitochondrial respiration over the day Results: Young healthy lean individuals displayed a day–night rhythmicity in mitochondrial network morphology, which aligned with the day–night rhythmicity of mitochondrial respiratory capacity, with a more fused network coinciding with higher mitochondrial respiratory capacity. In the older individuals with obesity, the mitochondrial network was more fragmented overall compared to young healthy lean individuals and completely lacked 24 h rhythmicity, which was also true for the mitochondrial respiratory capacity Conclusions: Our data shows a paralleled rhythmicity between mitochondrial network morphology and mitochondrial oxidative capacity, which oscillates over the course of a mimicked real-life day in human skeletal muscle of young, healthy lean individuals. In older individuals with obesity, the lack of a 24-hour rhythmicity in mitochondrial network connectivity was also aligned with a lack in respiratory capacity. This suggests that 24-hour rhythmicity in mitochondrial network connectivity is a determinant of rhythmicity in mitochondrial respiratory capacity. Thus, restoring mitochondrial network integrity may promote mitochondrial respiratory capacity and hence contribute to blunting the metabolic aberrations in individuals with a disturbed 24-hour rhythmicity in metabolism, like older individuals with obesity.

Recurrent neural network (RNN) models of sentence process-ing have recently displayed a remarkable ability to learn as-pects of structure comprehension, as evidenced by their abilityto account for reading times on sentences with local syntac-tic ambiguities (i.e., garden-path effects). Here, we investi-gate if these models can also simulate the effect of semanticappropriateness of the ambiguity’s readings. RNN-based esti-mates of surprisal of the disambiguating verb of sentences withan NP/S-coordination ambiguity (as in ‘The wizard guards theking and the princess protects ...’) show identical patters to hu-man reading times on the same sentences: Surprisal is higheron ambiguous structures than on their disambiguated counter-parts and this effect is weaker, but not absent, in cases of poorthematic fit between the verb and its potential object (‘Theteacher baked the cake and the baker made ...’). These resultsshow that an RNN is able to simultaneously learn about struc-tural and semantic relations between words and suggest thatgarden-path phenomena may be more closely related to wordpredictability than traditionally assumed.

Evidence from preclinical models suggest that lowering levels of branched chain amino acids (BCAA) improves glucose metabolism. Here the authors report that NaPB, an accelerator of BCAA catabolism, improves peripheral insulin sensitivity in patients with type 2 diabetes in a randomized placebo-controlled crossover clinical trial.

The present research applied the framework of the Reasoned Action Approach (RAA) to investigate intention formation of adopting vegetarian and vegan diets among U.S. and Dutch samples. First, a belief elicitation study was carried out to determine salient beliefs regarding both dietary behaviors. The U.S. sample (N = 59) together provided a total of 551 beliefs (298 vegetarian, 253 vegan) and the Dutch sample (N = 30) 294 beliefs (171 vegetarian, 123 vegan). Second, a regression study determined which reasoned action variables—Attitude, Perceived Norm and Perceived Control—explained Intention to adopt a vegetarian or a vegan diet for two separate samples. For both samples RAA-variables explained Intention relatively well (i.e., between 30 and 43% of the variance). For U.S. participants (N = 204), Instrumental and Experiential Attitude were significant predictors of their Intention to have a vegetarian or a vegan diet. For Dutch participants (N = 345), Instrumental and Experiential Attitude and Descriptive Norm predicted Intention to adopt a vegetarian diet. For adopting a vegan diet, Experiential Attitude was the only predicting variable for the Dutch sample. Almost all salient beliefs collected in the belief elicitation study significantly correlated with Intention to adopt diet, regardless of which RAA-variable they belonged to. Based on our findings, we critically evaluate the use of RAA in explaining behavioral Intentions, especially for behavior with a strong social component. Moreover, we show the importance of—the often not employed—belief elicitation phase and as such, discourage using only a regression approach. From a societal perspective, we argue that there is a strong need for interventions if one wants to encourage behavior change in the field of vegetarianism and veganism as—amongst others—average Intention scores were very low. In addition, we show that while the U.S. and Dutch samples, sharing Western norms and values, often overlapped, they also differed in subtle—yet potentially important—ways when it comes to motivations and cognitions with regard to vegetarian and vegan dietary behavior. Hence, interventions may have to include different content in order to be effective for these seemingly similar target groups and target behaviors.

Objectives: This study compared the effects of two types of health warnings on cigarette packages: 'narrative visual warnings', showing an image portraying people plus a corresponding slogan that could evoke a story-like interpretation, and 'non-narrative visual warnings' with non-narrative content (i.e. body parts). Moreover, the mechanisms underlying the effects of these health warnings were explored. Design: A within-participants experiment was conducted comparing narrative and non-narrative visual warnings. Path analyses were performed to investigate the relationship between the narrative concepts transportation and identification, the emotions evoked by the health warning and the perceived effectiveness of the message. Method: Participants (N = 200) were presented with one narrative warning and one non-narrative warning. After each warning, they answered questions on narrative perception, transportation, identification, emotions and perceived effectiveness. Results: The narrative warnings were seen as more story-like than the non-narrative warnings. There was a statistical trend for narrative warnings to be perceived as more effective than the non-narratives. The narrative warnings caused more transportation, fear, sadness, compassion and anger; the non-narrative warnings evoked more disgust and surprise. For the narrative warnings, both narrative concepts of transportation and identification were directly related to perceived effectiveness, and also indirectly via sadness. For the non-narrative warnings, transportation was related to perceived effectiveness, both directly and indirectly via disgust. Conclusion: Seeing a story in a still picture with a slogan helps to increase the effectiveness of the antismoking message. Both narrative and non-narrative visual warnings may persuade receivers directly, but also by the evoking of emotions, although the specific emotions responsible for the persuasive effects may differ.

BACKGROUND At the onset of exercise, the speed at which phosphocreatine (PCr) decreases toward a new steady state (PCr on-kinetics) reflects the readiness to activate mitochondrial ATP synthesis, which is secondary to Acetyl-CoA availability in skeletal muscle. We hypothesized that PCr on-kinetics are slower in metabolically compromised and older individuals and are associated with low carnitine acetyltransferase (CrAT) protein activity and compromised physical function.METHODS We applied 31P-magnetic resonance spectroscopy (31P-MRS) to assess PCr on-kinetics in 2 cohorts of volunteers. Cohort 1 included patients who had type 2 diabetes, were obese, were lean trained (VO2max > 55 mL/kg/min), and were lean untrained (VO2max < 45 mL/kg/min). Cohort 2 included young (20–30 years) and older (65–80 years) individuals with normal physical activity and older, trained individuals. Previous results of CrAT protein activity and acetylcarnitine content in muscle tissue were used to explore the underlying mechanisms of PCr on-kinetics, along with various markers of physical function.RESULTS PCr on-kinetics were significantly slower in metabolically compromised and older individuals (indicating mitochondrial inertia) as compared with young and older trained volunteers, regardless of in vivo skeletal muscle oxidative capacity (P < 0.001). Mitochondrial inertia correlated with reduced CrAT protein activity, low acetylcarnitine content, and functional outcomes (P < 0.001).CONCLUSION PCr on-kinetics are significantly slower in metabolically compromised and older individuals with normal physical activity compared with young and older trained individuals, regardless of in vivo skeletal muscle oxidative capacity, indicating greater mitochondrial inertia. Thus, PCr on-kinetics are a currently unexplored signature of skeletal muscle mitochondrial metabolism, tightly linked to functional outcomes. Skeletal muscle mitochondrial inertia might emerge as a target of intervention to improve physical function.TRIAL REGISTRATION NCT01298375 and NCT03666013 (clinicaltrials.gov).FUNDING RM and MH received an EFSD/Lilly grant from the European Foundation for the Study of Diabetes (EFSD). VS was supported by an ERC starting grant (grant 759161) “MRS in Diabetes.”

Objective: SGLT2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may be metabolic adaptations due to urinary glucose loss. Here, we investigated the cellular and molecular effects of 5 weeks of dapagliflozin treatment on skeletal muscle metabolism in type 2 diabetes patients. Methods: Twenty-six type 2 diabetes mellitus patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. Skeletal muscle acetylcarnitine levels, intramyocellular lipid (IMCL) content and phosphocreatine (PCr) recovery rate were measured by magnetic resonance spectroscopy (MRS). Ex vivo mitochondrial respiration was measured in skeletal muscle fibers using high resolution respirometry. Intramyocellular lipid droplet and mitochondrial network dynamics were investigated using confocal microscopy. Skeletal muscle levels of acylcarnitines, amino acids and TCA cycle intermediates were measured. Expression of genes involved in fatty acid metabolism were investigated. Results: Mitochondrial function, mitochondrial network integrity and citrate synthase and carnitine acetyltransferase activities in skeletal muscle were unaltered after dapagliflozin treatment. Dapagliflozin treatment increased intramyocellular lipid content (0.060 (0.011, 0.110) %, p = 0.019). Myocellular lipid droplets increased in size (0.03 μm2 (0.01–0.06), p

Abstract Background Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. Methods A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. Results After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p