GLP-1 increases heart rate by a direct action on the sinus node.

AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear. METHODS AND RESULTS: We employed a large animal model, the female landrace pig, and used multiple in-vivo and ex-vivo approaches including pharmacological challenges, electrophysiology and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate. In anaesthetized pigs, neither cervical vagotomy, adrenergic blockers (alpha, beta or combined alpha-beta blockade), ganglionic blockade (hexamethonium) nor inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ivabradine) abolished the marked chronotropic effect of GLP-1. GLP-1 administration to isolated perfused pig hearts also increased heart rate, which was abolished by GLP-1 receptor blockade. Electrophysiological characterization of GLP-1 effects in vivo and in isolated perfused hearts localized electrical modulation to the atria and conduction system. In isolated sinus nodes, GLP-1 administration shortened action potential cycle length of pacemaker cells and shifted the site of earliest activation. The effect was independent of HCN blockade. Collectively, these data support a direct effect of GLP-1 on GLP-1 receptors within the heart. Consistently, single nucleus RNA sequencing (snRNAseq) showed GLP-1 receptor expression in porcine pacemaker cells. Quantitative phosphoproteomics analyses of sinus node samples revealed that GLP-1 administration leads to phosphorylation changes of calcium cycling proteins of the sarcoplasmic reticulum, known to regulate heart rate. CONCLUSION: GLP-1 has direct chronotropic effects on the heart mediated by GLP-1 receptors in pacemaker cells of the sinus node, inducing changes in action potential morphology and the leading pacemaker site through a calcium signaling response characterized by PKA-dependent phosphorylation of Ca2+ cycling proteins involved in pace making. Targeting the pacemaker calcium clock may be a strategy to lower heart rate in GLP-1 RA recipients.

Embryonic heart rate is higher in species that experience greater nest predation risk during incubation.

Avian eggs develop outside of the female body, and therefore embryonic development is subject to multiple internal (physiological) and external (ecological) factors. Embryonic developmental rate has important consequences for survival. Within species, embryos that develop too quickly often experience deformities, disorders, or mortality, while embryos that develop slowly risk inviability and increase the time they are exposed to various sources of mortality in the nest. These contrasting forces may lead to interspecific variation in developmental rates. We investigated potential factors affecting embryonic heart rate (EHR), a proxy of development, across 14 passerine species in the field. More specifically, we investigated if nest predation risk, clutch size, seasonality, and egg volume influenced EHR. From previous research, we expected, and found, that EHR was positively associated with embryonic age and egg temperature. Species with greater nest predation risk had higher EHR, shorter incubation periods, and lower nest temperature variance. EHR increased as the season progressed and with egg volume, while EHR declined with clutch size. Bird species exhibit varying strategies to increase nestling and fledgling survival in response to predation risk, and these results suggest that variation in embryonic development may be related to species-specific differences in nest predation risk.

Cardiovascular Autonomic Deficits in Different Types of Achalasia.

Background and objective Achalasia cardia is a primary esophageal motility disorder, and the etiopathology of this disease's progression is not known. Moreover, autonomic dysfunction has not been studied in different types of achalasia. In light of this, we aimed to address this lack of data in this study. Methods The diagnosis of achalasia was done using high-resolution esophageal manometry (HRM)-based Chicago classification v4.0. Autonomic function tests (AFT) such as the head-up tilt test, deep breathing test (DBT), Valsalva maneuver (VM), handgrip test (HGT), and cold pressor test (CPT), as well as the heart rate variability (HRV) test, were performed among the cohort and the results were compared with those of 39 age- and sex-matched healthy controls. Results AFT and HRV tests were done on 62 patients (30 achalasia type I, 28 type II, and 4 type III) and compared with 39 age- and sex-matched healthy controls. The mean duration of symptoms, high Eckardt score, and dysphagia were most common in type I achalasia, followed by type II and III. The results of AFT showed a generalized loss of parasympathetic and baroreflex-independent sympathetic reactivity in all types of achalasia. However, baroreflex-dependent cardiovascular adrenergic reactivity was normal. Regarding cardiac autonomic tone, there was a loss of parasympathetic and sympathetic influence, but sympathovagal balance was maintained. The severity of the loss of autonomic functions was higher in type I, followed by type II. Conclusions In all types of achalasia, parasympathetic reactivity, baroreflex-independent sympathetic reactivity, and cardiac autonomic tone were lower compared to healthy controls, and the severity of dysfunction increased during the progression of the disease from type II to type I.

Flow in human-robot collaboration-multimodal analysis and perceived challenge detection in industrial scenarios.

Introduction: Flow state, the optimal experience resulting from the equilibrium between perceived challenge and skill level, has been extensively studied in various domains. However, its occurrence in industrial settings has remained relatively unexplored. Notably, the literature predominantly focuses on Flow within mentally demanding tasks, which differ significantly from industrial tasks. Consequently, our understanding of emotional and physiological responses to varying challenge levels, specifically in the context of industry-like tasks, remains limited. Methods: To bridge this gap, we investigate how facial emotion estimation (valence, arousal) and Heart Rate Variability (HRV) features vary with the perceived challenge levels during industrial assembly tasks. Our study involves an assembly scenario that simulates an industrial human-robot collaboration task with three distinct challenge levels. As part of our study, we collected video, electrocardiogram (ECG), and NASA-TLX questionnaire data from 37 participants. Results: Our results demonstrate a significant difference in mean arousal and heart rate between the low-challenge (Boredom) condition and the other conditions. We also found a noticeable trend-level difference in mean heart rate between the adaptive (Flow) and high-challenge (Anxiety) conditions. Similar differences were also observed in a few other temporal HRV features like Mean NN and Triangular index. Considering the characteristics of typical industrial assembly tasks, we aim to facilitate Flow by detecting and balancing the perceived challenge levels. Leveraging our analysis results, we developed an HRV-based machine learning model for discerning perceived challenge levels, distinguishing between low and higher-challenge conditions. Discussion: This work deepens our understanding of emotional and physiological responses to perceived challenge levels in industrial contexts and provides valuable insights for the design of adaptive work environments.

A comprehensive evaluation of linear and non-linear HRV parameters between paced breathing and stressful mental state.

Background: Heart rate variability (HRV) is a crucial metric that provides valuable insight into the balance between relaxation and stress. Previous research has shown that most HRV parameters improve during periods of mental relaxation, while decreasing during tasks involving cognitive workload. Although a comprehensive analysis of both linear and non-linear HRV parameters has been carried out in existing literature, there still exists a need for further research in this area. Additionally, limited knowledge exists regarding how specific interventions may influence the interpretation of these parameters and how the different parameters correlate under different interventions. This study aims to address these gaps by conducting a thorough comparison of different linear and non-linear HRV parameters under mentally relaxed versus stressful states. Methodology: Participants were randomly and equally divided among two between-subjects groups: relaxed-stress (RS) (N = 22) and stress-relaxed (SR) (N = 22). In the RS group, a paced breathing task was given for 5 min to create relaxation, and was followed by a 5-min time-based mental calculation task to create stress. In the SR group, the order of the stress and relaxed tasks was reversed. There was a washout period of 15 min after the first task in both groups. Results: Of the 37 HRV parameters, 33 differed significantly between the two interventions. The majority of the parameters exhibited an improving and degrading tendency of HRV parameters in the relaxed and stressed states, respectively. The correlation of the majority of HRV parameters decreases during stress, while prominent time domain and geometric domain parameters stand out in the correlation. Conclusion: Overall, HRV parameters can be reliably used to assess a person's relaxed and stressed mental states during paced breathing and mental arithmetic task respectively. Furthermore, non-linear HRV parameters provide accurate estimators of the mental state, in addition to the commonly used linear parameters.

Association of Smartwatch-Based Heart Rate and Physical Activity With Cardiorespiratory Fitness Measures in the Community: Cohort Study.

BACKGROUND: Resting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. OBJECTIVE: This study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. METHODS: Electronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. RESULTS: We included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)-adjusted P values <.001 for all. Reductions of 2.4 beats per minute in nonactive HR, or increases of nearly 1000 daily steps, corresponded to a 1.3 mL/kg/min higher peak VO2. In addition, ventilatory efficiency (VE/VCO2; FDR-adjusted P=.009), % predicted maximum HR (FDR-adjusted P<.001), and systolic blood pressure-to-workload slope (FDR-adjusted P=.01) were associated with nonactive HR but not associated with daily steps. CONCLUSIONS: Our findings suggest that smartwatch-based assessments are associated with a broad array of cardiorespiratory fitness responses in the community, including measures of global fitness (peak VO2), ventilatory efficiency, and blood pressure response to exercise. Metrics captured by wearable devices offer a valuable opportunity to use extensive data on health factors and behaviors to provide a window into individual cardiovascular fitness levels.

Agreement of Air Bike and Treadmill Protocols to Assess Maximal Oxygen Uptake: An Exploratory Study.

Maximal oxygen consumption (V̇O2max) is an important measure of aerobic fitness, with applications in evaluating fitness, designing training programs, and assessing overall health. While treadmill assessments are considered the gold standard, airbikes (ABs) are increasingly popular exercise machines. However, limited research exists on AB-based V̇O2max assessments, particularly regarding agreement with treadmill graded exercise tests. To address this gap, a randomized crossover study was conducted, involving 15 healthy adults (9M, 6F, 7 familiar with AB) aged 30.1 ± 8.6 years. Paired t-tests, intraclass correlation coefficients (ICC), Bland-Altman and Principal component (PC) analyses were used to assess agreement between protocols. The results demonstrated good to excellent agreement in V̇O2max, maximum heart rate (HR), and rating of perceived exertion (ICC range: 0.89-0.92). However, significant differences were observed in several measures, including V̇O2max and maximum HR (p < 0.01). Overall a systematic bias 3.31 mL/kg/min (treadmill > AB, 95%CI[1.67,4.94]) was observed, no proportional bias was present; however, regular AB users (systematic bias: 1.27 (95%CI[0.20,2.34]) mL/kg/min) exhibited higher agreement in V̇O2max measures compared to non-regular users (systematic bias: 5.09 (95%CI[3.69,6.49]) mL/kg/min). There were no significant differences in cardiorespiratory coordination, between the AB and the treadmill. These findings suggest that for individuals familiar with the AB, it can be a suitable alternative for assessing V̇O2max compared to the treadmill. Future research with larger samples should focus on developing prediction equations for field AB tests to predict V̇O2max. Practitioners should consider using the AB to assess V̇O2max in individuals who prefer it over running.

Prefrontal activity and heart rate variability during cognitive tasks may show different changes in young and older adults with and without mild cognitive impairment.

Background: Age-related decline in cognitive function is often linked to changed prefrontal cortex (PFC) activity and heart rate variability (HRV). Mild cognitive impairment (MCI), a transitional stage between normal aging and dementia, might have further degeneration beyond aging. This study aimed to investigate the differences between young and older adults with or without MCI in cognitive functions, task-induced PFC activation and HRV changes. Methods: Thirty-one healthy young adults (YA), 44 older adults (OA), and 28 older adults with MCI (OA-MCI) were enrolled and compared in this cross-sectional study. Each participant received a one-time assessment including cognitive and executive functions, as well as the simultaneous recording of PFC activity and HRV during a cognitive task paradigm. Results: We observed age-related decrease in global cognitive functions, executive functions, HRV, and increase in PFC activity. The MCI further deteriorated the global cognitive and executive performances, but not the HRV or the prefrontal activation. Conclusion: Older people showed lower performances in general cognitive function and executive function, compensatory increase of PFC activity, and reduced HRV. Older people with MCI had further deterioration in cognitive performance, but not in PFC activation and HRV.

Altered cardiac autonomic functioning associates with self-disorders in schizophrenia.

Elevated resting heart rate (RHR) and reduced heart rate variability (HRV) are signs of autonomic nervous system dysfunction identified in schizophrenia (SCZ). This dysfunction has been found to manifest prior to the onset of the clinical diagnosis. Yet whether such autonomic dysfunction is associated with vulnerability to schizophrenia remains unknown. This case-control study included recent onset SCZ patients (n = 35) and healthy controls (HC) (n = 33). Patients were scored for self-disorders (SD's) using the EASE manual and all participants underwent a 5-minute resting state electrocardiogram (ECG) recording. Patients were included from outpatient clinics in Denmark. The main measures comprised EASE total scores (SDs), RHR (beats per minute) and three standard HRV measures usually included in testing autonomic nervous system dysfunction: root mean squared of successive differences (RMSSD), standard deviation of normal-to-normal interval (SDNN) and high-frequency/ low frequency ratio (HF/LF). Pearson correlations and linear regression models adjusted for age, sex and medication were used in the SCZ group. The main finding was a positive moderate association between SDs and RHR (r = 0.463; p = 0.005) and a negative association between SDs and HRV (RMSSD) (r = -0.440; p = 0.008) in the SCZ group. Linear regression models found SDs to explain 22 % of the variance of RHR and 19 % in RMSSD. SDs correlated with LF/HF (r = 0.434; p = 0.009), but non-significantly with SDNN. The study provides evidence of an intriguing link between SDs as a susceptibility trait for schizophrenia spectrum disorders and altered cardiac autonomic functioning.

The dynamic role of the left dlPFC in neurovisceral integration: Differential effects of theta burst stimulation on vagally mediated heart rate variability and cognitive-affective processing.

Adapting to the ever-changing demands of the environment requires a complex interplay between cognitive-affective, neuronal, and autonomic processes. Vagally mediated heart rate variability (vmHRV) is positively associated with both cognitive-affective functioning and prefrontal cortex (PFC) activity. Accordingly, the Neurovisceral Integration Model has posited a shared role of the PFC in the regulation of cognitive-affective processes and autonomic nervous system (ANS) activity. While there are numerous correlational findings in this regard, no study so far has investigated whether the manipulation of PFC activity induces changes in vmHRV and cognitive-affective processing in an inter-dependent manner. In a sample of 64 participants, we examined the effects of continuous (cTBS; n = 21) and intermittent theta-burst stimulation (iTBS; n = 20) compared to sham stimulation (n = 23) over the left dorsolateral PFC (dlPFC) on vmHRV and cognitive-affective processing within an emotional stop-signal task (ESST). Our results revealed that both resting vmHRV and vmHRV reactivity predicted cognitive-affective processing. Furthermore, we found a dampening effect of cTBS on resting and on-task vmHRV, as well as an enhancing effect of iTBS on ESST performance. Our results show no direct association between vmHRV changes and ESST performance alterations following stimulation. We interpret our results in the light of a hierarchical model of neurovisceral integration, suggesting a dynamical situation-dependent recruitment of higher-order cortical areas like the dlPFC in the regulation of the ANS. In conclusion, our results highlight the complex interplay between PFC activity, autonomic regulation, and cognitive-affective processing, emphasizing the need for further research to understand the causal dynamics of the underlying neural mechanisms.

Assessment of toxicity of pyriproxyfen, Bacillus thuringiensis, and malathion and their mixtures used for mosquito control on embryo-larval development and behavior of zebrafish.

Pyriproxyfen (PPF), Bacillus thuringiensis israelensis (BTI), and malathion (MLT) are widely used worldwide to control the population of mosquitos that transmit arboviruses. The current work aimed to evaluate the toxicity of these single pesticides and their binary mixtures of PPF + BTI, PPF + MLT, and MLT + BTI on the embryo-larval stage of zebrafish (Danio rerio) as an animal model. Epiboly, mortality, apical endpoints, affected animals, heart rate, morphometric, thigmotaxis, touch sensitivity, and optomotor response tests were evaluated. PPF and MLT and all mixtures reduced the epiboly percentage. Mortality increased significantly in all exposed groups, except BTI, with MLT being the most toxic. The observed apical endpoints were pericardial and yolk sac edemas, and tail and spine deformation. Exposure to MLT showed a higher percentage of affected animals. A reduction in heart rate was also observed in MLT- and PPF + MLT-exposed groups. The PPF + MLT mixture decreased head measurements. Behavioral alterations were observed, with a decrease in thigmotaxis and touch sensitivity responses in PPF + MLT and MLT + BTI groups. Finally, optomotor responses were affected in all groups. The above data obtained suggest that the MLT + PFF mixture has the greatest toxicity effects. This mixture affected embryo-larval development and behavior and is close to the reality in several cities that use both pesticides for mosquito control rather than single pesticides, leading to a reevaluation of the strategy for mosquito control.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

High frequency heart rate variability is associated with sensitivity to affective touch.

C-tactile afferents (CTs) are a class of unmyelinated, mechanosensitive nerve fibre that respond optimally to skin temperature, slow moving touch typical of a caress. They are hypothesised to signal the rewarding value of affiliative tactile interactions. While CT firing frequency is positively correlated with subjective ratings of touch pleasantness, trait differences in sensitivity to the specific hedonic value of CT targeted touch have been reported. Inter-individual differences in vagally mediated, high frequency heart rate variability (HF-HRV) have been linked to variation in visual social cognition. Thus, the aim of the present study was to examine the relationship between resting state HF-HRV and sensitivity to socially relevant CT targeted touch. 58 healthy participants first had a 5-minute electrocardiogram. They then rated the pleasantness of 5 randomly presented velocities of robotically delivered touch. Three velocities fell within (1, 3, 10 cm/s) and two outside (0.3, 30 cm/s) the CT optimal range. Each velocity was delivered twice. On a group level, affective touch ratings were described by a negative quadratic function, with CT optimal velocities rated as more pleasant than slower and faster speeds. Simple regression analysis confirmed participants' HF-HRV was significantly predicted by the quadratic curve fit of their touch ratings, with higher HF-HRV associated with a better quadratic fit. These findings indicate that, in line with previous observations that higher HF-HRV is associated with enhanced sensitivity to visual social cues, trait differences in autonomic control could account for previously reported individual differences in CT sensitivity.

Genetic and polygenic investigation of heart rate variability to identify biomarkers associated with Anxiety disorders.

Given that anxiety disorders (AD) are associated with reduced vagally-mediated heart rate variability (HRV), genetic variants related to HRV may provide insight into anxiety etiology. This study used polygenic risk scores (PRS) to explore the genetic overlap between AD and HRV, and investigated whether HRV-related polymorphisms influence anxiety risk. Resting vagally-mediated HRV was measured using a wearable device in 188 European individuals (AD=101, healthy controls=87). AD PRS was tested for association with resting HRV, and HRV PRS for association with AD. We also investigated 15 significant hits from an HRV genome-wide association study (GWAS) for association with resting HRV and AD and if this association is mediated through resting HRV. The AD PRS and HRV PRS showed nominally significant associations with resting HRV and anxiety disorders, respectively. HRV GWAS variants associated with resting HRV were rs12980262 (NDUFA11), rs2680344 (HCN4), rs4262 and rs180238 (GNG11), and rs10842383 (LINC00477). Mediation analyses revealed that NDUFA11 rs12980262 A-carriers and GNG11 rs180238 and rs4262 C-carriers had higher anxiety risk through lower HRV. This study supports an anxiety-HRV genetic relationship, with HRV-related genetic variants translating to AD. This study encourages exploration of HRV genetics to understand mechanisms and identify novel treatment targets for anxiety.

Levilactobacillus brevis SG031 modulates mood-related behaviors and attenuates stress-related sleep disturbance and autonomic dysfunction via gut microbiota modulation in Wistar-Kyoto rats.

AIMS: The probiotic bacterium Levilactobacillus brevis (L. brevis) has been proposed as a potential solution to manage mood disorders and alleviate stress-related sleep disturbances. However, the underlying mechanisms of its effects have not been fully elucidated. The aim of this study was to explore the impact and potential mechanisms of L. brevis SG031 supplementation on anxiety/depression-like behaviors and stress-induced changes in sleep patterns and sleep-related autonomic function. MAIN METHODS: Male Wistar-Kyoto rats were administered low, medium, or high doses of L. brevis SG031 or a vehicle for 4 weeks, followed by behavioral tests to evaluate anxiety and depression. After an additional 2 weeks of SG031 or vehicle administration, a cage-exchange paradigm was performed with 24-hour physiological signal measurements under different stress conditions. Fecal samples were collected to construct a 16S rRNA library and assess fecal short-chain fatty acids (SCFAs). KEY FINDINGS: High-dose SG031 administration yielded reduced depression-like responses and enhanced social interaction in behavioral tests. It also exhibited a protective effect against stress-induced sleep disturbance characterized by decreased sleep time, increased awake time, and autonomic dysfunction during sleep. Fecal examination indicated that high-dose SG031 administration exerted beneficial effects on gut health by maintaining the gut microbial abundance, preserving stability of the microbial composition, and enriching the gut with SCFAs, which were associated with improvements in sleep and autonomic function. SIGNIFICANCE: These findings collectively underscore the multifaceted potential of SG031 in addressing mental health and stress-related sleep challenges through the modulation of the gut microbiota.

Despite plasticity, heatwaves are costly for a coral reef fish.

Climate change is intensifying extreme weather events, including marine heatwaves, which are prolonged periods of anomalously high sea surface temperature that pose a novel threat to aquatic animals. Tropical animals may be especially vulnerable to marine heatwaves because they are adapted to a narrow temperature range. If these animals cannot acclimate to marine heatwaves, the extreme heat could impair their behavior and fitness. Here, we investigated how marine heatwave conditions affected the performance and thermal tolerance of a tropical predatory fish, arceye hawkfish (Paracirrhites arcatus), across two seasons in Moorea, French Polynesia. We found that the fish's daily activities, including recovery from burst swimming and digestion, were more energetically costly in fish exposed to marine heatwave conditions across both seasons, while their aerobic capacity remained the same. Given their constrained energy budget, these rising costs associated with warming may impact how hawkfish prioritize activities. Additionally, hawkfish that were exposed to hotter temperatures exhibited cardiac plasticity by increasing their maximum heart rate but were still operating within a few degrees of their thermal limits. With more frequent and intense heatwaves, hawkfish, and other tropical fishes must rapidly acclimate, or they may suffer physiological consequences that alter their role in the ecosystem.

Aversive contexts enhance defensive responses to conditioned threat.

The ability to flexibly transition between defensive states is crucial for adaptive responding in life-threatening situations. Potentially threatening situations typically induce a sustained feeling of apprehension in association with hypervigilance, while acute threat is usually characterized by an intense and transient response to cope with the imminent danger. While potential and acute threat states have traditionally been viewed as mutually exclusive, this distinction is being challenged by a growing body of evidence suggesting a more complex interplay during simultaneous activation of these states. However, the interaction between potential and acute threat on a psychophysiological level remains elusive. To fill this gap, 94 healthy individuals participated in one of two contextual fear-conditioning paradigms. In both paradigms, a differential fear-learning phase was conducted, followed by a test phase in which the conditioned stimuli were presented in front of either conditioned or inherently aversive contextual images compared to neutral contexts. To capture defensive responses, we recorded subjective (threat and expectancy ratings) and physiological (electrodermal and cardiovascular) activity to the conditioned stimuli as a function of contextual threat. Besides indices of successful fear conditioning, our results revealed stronger threat and unconditioned stimulus expectancy ratings, cardiac deceleration, and skin conductance responses for threat and safety cues presented in inherently aversive compared to neutral contexts. Conditioned contexts had less impact on physiological responses to threat and safety cues than inherently aversive contexts. These findings provide new insights into the additive nature of defensive responses to fear cues and situations of contextual threat.

Simulation of plaque formation in a realistic geometry of a human aorta: effects of endothelial layer properties, heart rate, and hypertension.

Nowadays, cardiovascular diseases are the most common cause of death worldwide. Besides, atherosclerosis is a cardiovascular disease that occurs with persistent narrowing of arteries, especially medium and large-sized arteries. Atherosclerosis begins with a local elevation in the permeability of the arterial wall as a result of endothelial inflammation. Subsequently, excess LDL permeates into the arterial wall. Then, through several chemical responses and reactions, foam cells are produced. These foam cells serve as a crucial indicator for assessing the development of atherosclerosis within the arteries. In this study, the effect of endothelial layer modeling, heart rate (HR) and hypertension on the foam cell accumulation is numerically investigated in a patient-specific geometry of the human thoracic aorta. Navier-Stokes, Darcy, and mass transfer equations are used to obtain the velocity and concentration field within the domain. Regarding the dependence of endothelial cell properties on time-averaged wall shear stress, it is observed that foam cells are mainly concentrated in the outer curvature of the aortic arch, downstream of the left subclavian artery. However, considering oscillatory-shear-rate as the determinant of endothelial cell properties leads to the accumulation of foam cells in the inner curvature of the descending aorta. Regarding the HR, with the increase of HR, the volume average concentration of the foam cell decreases. However, there is no substantial difference between the cases of different HRs. Moreover, foam cell concentration significantly increases in the hypertension case. This result implies that a slight increase in the blood pressure may induce irreparable problems in the circulatory system.