Heart Rate Responses Research Articles

A murine model of hypertensive heart disease in older women.

We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. P<0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, p=0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log2 fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Nppb, Col3a1, Col1a1, Ctgf Col8a1, and Cilp. Several circadian clock LV genes were modulated differently by AngII between control and Ovx females (Clock, Arntl, Per2, Cry2, and Ciart). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.

Evaluation of Local Anesthetic Blockade in Cats Undergoing Castration in a High-Quality, High-Volume Spay/Neuter Setting: A Randomized, Blinded, Placebo-Controlled Trial

Sustainable high-quality, high-volume spay/neuter (HQHVSN) clinic operations require optimal efficiency and resource-management, and humane patient care. Locoregional anesthesia is not standard across HQHVSN protocols because evidence that these techniques are safe, efficient, and cost-effective in the HQHVSN environment is lacking. The objective of this study was to compare the analgesic efficacy of local anesthesia to placebo in cats castrated in a HQHVSN setting. Eighty-eight shelter-owned male cats presenting to a HQHVSN clinic in the northeastern US between August 2019 and October 2020 were enrolled in this blinded, randomized, placebo-controlled trial. Inclusion criteria included estimated age ≥6 weeks and ≤8 years, body weight ≥3 pounds, and ASA 1 status. Cats were assigned via simple randomization to receive an intratesticular injection of saline placebo (Group SP; n=32), lidocaine 1mg/kg (Group L; n=34), or a mixture of lidocaine 1mg/kg and bupivacaine 1mg/kg (Group LB; n=22) prior to routine castration. Standard HQHVSN protocols for anesthesia and surgery were followed. Indicators of analgesic efficacy included perioperative heart rates, requirements for additional anesthesia, surgeon satisfaction with anesthetic depth and tissue quality, and postoperative pain scores and incisional complications. Treatment groups did not differ in demographic characteristics or baseline heart rate. Group SP showed a significant elevation in heart rate in response to surgical stimulus compared to Groups L (p=0.006) and LB (p=0.002) and to their baseline heart rate (p&lt;0.001). Perioperative heart rates measured in Groups L and LB did not differ. Surgeon-reported unsatisfactory anesthetic depth during castration occurred more frequently in Group SP (z=2.68; p=0.044). Additional anesthetic requirements, surgeon satisfaction with tissue quality, and postoperative pain and incision scores were statistically similar between groups. Despite the short duration between intratesticular injection to near completion of castration (median [IQR]=5.0 [3.0-7.0] minutes), local anesthesia was effective at decreasing nociception compared to placebo without increasing the frequency of incisional complications. These perioperative benefits support the inclusion of local blocks in multimodal anesthesia/analgesia protocols for HQHVSN clinics. Additional materials and labor costs for administering intratesticular blocks were estimated at $1.07-$1.19 per 4kg cat at the study location.

Heart Rate, Oxygen Uptake and Anaerobic Thresholds During a Maximal Treadmill Test with World Class Mixed Martial Arts Fighters

Measuring heart rate responses during a competitive mixed martial arts (MMA) fight is not feasible; therefore, a method is needed to assess physiological responses in MMA fighters outside of competition. Quantifying and evaluating heart rate, oxygen uptake, and anaerobic threshold during a maximal treadmill test can provide interpretation for in-competition physiological responses of MMA fighters The retrospective analysis was conducted on 20 world-class MMA fighters predating the beginning of their fight camps (ages 29.0 ± 4.8 years old). A maximal treadmill test utilizing a ramp protocol was conducted eight weeks prior to a professional competition. Fighters’ data were divided in two groups based on weight status: lighter, &lt; 185 pounds (n = 12) and heavier, ≥ 185 pounds (n = 8) weight groups. Heart rate (HR), anaerobic thresholds from respiratory exchange rate (RER-AT), and oxygen uptake (VO2max) were recorded and compared between weight groups. VO2max was the only physiological variable measured that differed between lighter (53.4 ± 4.5 ml . kg−1 . min−1) and heavier (48.1 ± 5.7 ml . kg−1 . min−1) fighters (p = 0.033). Previous literature has commonly used 1.0 RER to determine the breaking point in anaerobic thresholds. All other variables were not different (p ≥ 0.204) between groups. Differences in VO2max between lighter and heavier fighters is likely due to differences in body mass. While there were no differences in heart rates at RER-AT or time to exhaustion between weight status groups, using RER-AT at 0.95 or 1.0 RER may be a valuable way to ensure an MMA athlete achieve anaerobic training in fight preparation. Performance coaches may utilize physiological variables such as RER-AT acquired from maximal treadmill testing to guide the training demands of MMA competition.

External characteristics of cardio-strength load based on local exercises and heart rate response during its performance

In modern health-enhancing physical culture the use of complex training sessions with successive tasks solving is mainly provided and almost no attention to complex training sessions with parallel task solving. In this regard, it is important to find out the possibility of building training sessions that would allow influencing the cardio respiratory system through the use of strength exercises. The purpose of the study is to explore the characteristics of the load and heart rate changing in complex cardio-strength training sessions with parallel task solving. Experimental total training sessions included a warm-up (10-12 min) and 6 local strength exercises divided into three pairs (biceps - triceps, deltoid - latissimus dorsi, rhomboid - pectoral muscles) performed as circuit training. The duration of cardio- strength sessions – 30 min., intensity – 12 RM, repetition – 4, rest – changing exercises. A 62 years old man with high physical fitness for this age took place in a research. The heart rate study was carried out by the POLAR cardio-tracker. The sound recording of the exercise commentary was simultaneously activated with the heart rate sensor. This made it possible to study the duration of exercises, rests and heart rate during each exercise. Research has shown it is possible to ensure a cardiovascular reaction appropriate for cardio training by using strength exercises. But it requires certain resistance, repetition and rest between exercises at the training session. It is advisable to call such loads as cardio-strength loads. A person is able to provide the necessary duration of exercises and rests in such training sessions without a clock or sound leader. The current heart rate during certain cardio-strength exercise is determined by the complex, ambiguous interaction of several factors. For loads of 1/3 of 12 RM (4 repetitions per set) the most impotent is the initial position. In the initial position the most influential is the body position while performing exercises (lying, sitting, bending over and standing); the activity of the synergist muscles is also important here. In addition, the heart rate reaction depends on a resistance, the preliminary exercise and the activity during the changing exercises.

The role of self-reported and physiological stress in nocebo hyperalgesia

Negative expectations can increase pain sensitivity, leading to nocebo hyperalgesia. However, the physiological and psychological factors that predispose individuals to this phenomenon are still not well understood. The present study examined whether stress induced by a social stressor affects nocebo hyperalgesia, and whether this effect is mediated by self-reported and physiological stress responses. We recruited 52 healthy participants (15 men) who were randomly assigned to either the Trier Social Stress Test (TSST) or a control condition (a friendly version of the TSST). Nocebo hyperalgesia was induced using negative suggestions combined with a validated pain conditioning paradigm. We assessed self-reported (anxiety and stress) and physiological (cortisol, alpha-amylase, heart rate, and skin conductance) responses to stress. Both groups exhibited significant nocebo hyperalgesia. The stress group showed higher levels of anxiety, self-reported stress, and cortisol levels compared to the control group while no significant differences were found in other physiological markers. The stress and control groups did not differ in the magnitude of nocebo hyperalgesia, but anxiety levels partially mediated the effects of the stress test on nocebo hyperalgesia. Our findings suggest that an external social stressor does not directly affect nocebo hyperalgesia, but that increased anxiety due to the stressor enhances its magnitude. Thus, it may be worthwhile to investigate whether reducing stress-related anxiety in clinical settings would help alleviate nocebo effects.

The surge in heart rate and blood pressure at respiratory event termination is dampened in children with down syndrome

BackgroundChildren with Down syndrome (DS) have a high prevalence of sleep disordered breathing (SDB) and altered cardiovascular autonomic control. We aimed to analyze the effect of DS on the surge in heart rate (HR) and pulse transit time (PTT, an inverse surrogate measure of blood pressure change) at respiratory event termination. Methods44 children (3–19 y) with DS and 44 typically developing (TD) children matched for SDB severity, age and sex underwent overnight polysomnography. Multilevel modelling determined the effect of DS on HR and PTT changes between a 10s pre-event to the latter half of each respiratory event (late-event) and 15s post-event during NREM and REM, accounting for SDB severity and event length. ResultsThe children with DS had a significantly smaller % change in HR late-event to post-event (NREM: DS 26.4 % ± 17.5 % (mean ± SD), TD 30.7 % ± 21.0 %; REM DS 16.9 % ± 15.3 %, TD 21.0 % ± 14.0 %; p < 0.05 for both) compared with TD children for obstructive events, and central events (13.2 % ± 17.0 %, TD 18.8 % ± 17.0 %; p < 0.01) during REM. %change in PTT was significantly smaller in the DS group during NREM and REM from pre-event and late-event to post-event compared with TD children for obstructive and central events. ConclusionThese results suggest children with DS have dampened HR and BP responses to respiratory events compared with TD children. Whether this is symptomatic of autonomic dysfunction or a protective factor for the cardiovascular system in children with DS remains to be elucidated.

Higher final speed in 30–15 intermittent fitness tests correlates with soccer's locomotor demands, not heart rate responses in small-sided soccer games

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30–15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: − 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: − 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: − 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

Effects of hearing acuity on psychophysiological responses to effortful speech perception

In recent studies, psychophysiological measures have been used as markers of listening effort, but there is limited research on the effect of hearing loss on such measures. The aim of the current study was to investigate the effect of hearing acuity on physiological responses and subjective measures acquired during different levels of listening demand, and to investigate the relationship between these measures. A total of 125 participants (37 males and 88 females, age range 37–72 years, pure-tone average hearing thresholds at the best ear between -5.0 to 68.8 dB HL and asymmetry between ears between 0.0 and 87.5 dB) completed a listening task. A speech reception threshold (SRT) test was used with target sentences spoken by a female voice masked by male speech. Listening demand was manipulated using three levels of intelligibility: 20 % correct speech recognition, 50 %, and 80 % (IL20 %/IL50 %/IL80 %, respectively). During the task, peak pupil dilation (PPD), heart rate (HR), pre-ejection period (PEP), respiratory sinus arrhythmia (RSA), and skin conductance level (SCL) were measured. For each condition, subjective ratings of effort, performance, difficulty, and tendency to give up were also collected. Linear mixed effects models tested the effect of intelligibility level, hearing acuity, hearing asymmetry, and tinnitus complaints on the physiological reactivity (compared to baseline) and subjective measures. PPD and PEP reactivity showed a non-monotonic relationship with intelligibility level, but no such effects were found for HR, RSA, or SCL reactivity. Participants with worse hearing acuity had lower PPD at all intelligibility levels and showed lower PEP baseline levels. Additionally, PPD and SCL reactivity were lower for participants who reported suffering from tinnitus complaints. For IL80 %, but not IL50 % or IL20 %, participants with worse hearing acuity rated their listening effort to be relatively high compared to participants with better hearing. The reactivity of the different physiological measures were not or only weakly correlated with each other. Together, the results suggest that hearing acuity may be associated with altered sympathetic nervous system (re)activity. Research using psychophysiological measures as markers of listening effort to study the effect of hearing acuity on such measures are best served by the use of the PPD and PEP.

Cognitive workload classification of law enforcement officers using physiological responses

Motor vehicle crashes (MVCs) are a leading cause of death for law enforcement officers (LEOs) in the U.S. LEOs and more specifically novice LEOs (nLEOs) are susceptible to high cognitive workload while driving which can lead to fatal MVCs. The objective of this study was to develop a machine learning algorithm (MLA) that can estimate cognitive workload of LEOs while performing secondary tasks in a patrol vehicle. A ride-along study was conducted with 24 nLEOs. Participants performed their normal patrol operations while their physiological responses such as heartrate, eye movement, and galvanic skin response were recorded using unobtrusive devices. Findings suggested that the random forest algorithm could predict cognitive workload with relatively high accuracy (>70%) given that it was entirely reliant on physiological signals. The developed MLA can be used to develop adaptive in-vehicle technology based on real-time estimation of cognitive workload, which can reduce the risk of MVCs in police operations.

Tibetans exhibit lower hemoglobin concentration and decreased heart response to hypoxia during poikilocapnia at intermediate altitude relative to Han Chinese.

High-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia. We studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300m (∼4327ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ /ΔPetCO2 and ΔHR/ΔPetCO2, respectively). Male Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01). These results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

Physiological and Perceptual Demands During a Simulated “The Hundred” Batting Work-Bout in Female Cricketers

Abstract Purpose No research has investigated the physiological and perceptual demands of female cricket players at any level or for any format, making this study unique. This is despite the growth in popularity and professionalism of the women’s game. Therefore, the purpose of this study was to determine the physiological (heart rate, oxygen consumption) and perceptual (ratings of perceived exertion, body discomfort) demands of female cricketers during a simulated “The Hundred” protocol. Methods Twenty female cricketers (age: 19 ± 4.53 years, stature: 167.90 ± 7.28 cm; mass: 67.30 ± 13.51 kg) currently playing for a first-class county cricket club were recruited. The protocol consisted of six sets and was designed to mimic the nonpowerplay phase of a women’s “Hundred” match. Throughout the protocol selected physiological and perceptual responses were recorded. Results Heart rate responses increased significantly (P &lt; 0.05) from the first set (149 ± 14 beats/min) until the end of the third set (167 ± 10 beats/min). A further significant decrease (P &lt; 0.05) was observed between set three (167 ± 10 beats/min) and set six (165 ± 12 beats/min). Oxygen uptake responses increased significantly (P &lt; 0.05) from set one (22.06 ± 7.82 mL/kg/min) until set three (26.30 ± 7.58 mL/kg/min). A significant difference (P &lt; 0.05) was also observed between set three and all the other sets. Central ratings of perceived exertion increased significantly (P &lt; 0.05) throughout the protocol (9 ± 1.83–13 ± 3.17). Body discomfort, results indicated that the quadriceps and calves were the areas that felt the most discomfort during the protocol. Conclusion In conclusion, the design of training programs should mimic the demandsof the women?s format of the game and focus on individualised exercise preparation.

Biomarkers of Immersion in Virtual Reality Based on Features Extracted from the EEG Signals: A Machine Learning Approach.

Virtual reality (VR) enables the development of virtual training frameworks suitable for various domains, especially when real-world conditions may be hazardous or impossible to replicate because of unique additional resources (e.g., equipment, infrastructure, people, locations). Although VR technology has significantly advanced in recent years, methods for evaluating immersion (i.e., the extent to which the user is engaged with the sensory information from the virtual environment or is invested in the intended task) continue to rely on self-reported questionnaires, which are often administered after using the virtual scenario. Having an objective method to measure immersion is particularly important when using VR for training, education, and applications that promote the development, fine-tuning, or maintenance of skills. The level of immersion may impact performance and the translation of knowledge and skills to the real-world. This is particularly important in tasks where motor skills are combined with complex decision making, such as surgical procedures. Efforts to better measure immersion have included the use of physiological measurements including heart rate and skin response, but so far they do not offer robust metrics that provide the sensitivity to discriminate different states (idle, easy, and hard), which is critical when using VR for training to determine how successful the training is in engaging the user's senses and challenging their cognitive capabilities. In this study, electroencephalography (EEG) data were collected from 14 participants who completed VR jigsaw puzzles with two different levels of task difficulty. Machine learning was able to accurately classify the EEG data collected during three different states, obtaining accuracy rates of 86% and 97% for differentiating easy versus hard difficulty states and baseline vs. VR states. Building on these results may enable the identification of robust biomarkers of immersion in VR, enabling real-time recognition of the level of immersion that can be used to design more effective and translative VR-based training. This method has the potential to adjust aspects of VR related to task difficulty to ensure that participants are immersed in VR.

Predictive Modeling of Heart Rate Dynamics based on Physical Characteristics and Exercise Parameters: A Machine Learning Approach

To accurately forecast heart rate changes during exercise, which is essential for customized health monitoring and improving training regimens, it is necessary to comprehend both the physiological foundations and the technical capacities for data processing. This research utilizes Machine Learning (ML) methodologies to predict heart rate reactions based on physical characteristics and activity variables. Our research focuses on the health and sports aspects of our results, using a comprehensive dataset that includes a wide range of activity types and ambient circumstances across 12,000 sets. We establish a connection between the ability of models such as Linear Regression (LR) and Extreme Gradient Boosting (XGB) to predict outcomes and their practical use in exercise management and optimizing athlete performance. These models accurately forecast variations in heart rate and also provide insights into the cardiovascular demands of various physical activities. Standard metrics measure the effectiveness of these models. The Linear Regression (LR) model achieved a Mean Absolute Error (MAE) of 0.419, a Mean Squared Error (MSE) of 0.294, a Root Mean Squared Error (RMSE) of 0.543, and an R-Squared value of 0.997. On the other hand, the Extreme Gradient Boosting (XGB) Regressor model achieved a Mean Absolute Error (MAE) of 0.421, a Mean Squared Error (MSE) of 0.335, a Root Mean Squared Error (RMSE) of 0.578, and an R-Squared value of 0.996. These metrics demonstrate the usefulness of these models in real-world scenarios. Our study's findings demonstrate that the combination of physiological data and powerful machine learning models may improve an individual's comprehension of fitness levels and the requirements for adaptive training. This study not only adds to the field of computational physiology, but it also aids in the creation of adaptive, real-time therapies for improving health and performance.

Sympathetic Overactivity and Parasympathetic Impairment in Type 2 Diabetes: An Analysis of Cardiovascular Autonomic Functions.

Background Cardiovascular autonomic dysregulation is a known complication of Type 2 diabetes mellitus (T2DM), characterized by dysregulation in heart rate (HR) and blood pressure (BP). These disruptions in cardiovascular autonomic control can significantly influence the morbidity and mortality associated with the disease. Objectives This study aims to investigate how T2DM affects cardiovascular autonomic functions by comparing responses in HR, BP, and specific autonomic function tests between a control group without diabetes and a study group with diabetes. The research questions focus on assessing HR variability, baroreflex sensitivity, and other autonomic parameters to determine the extent of cardiovascular autonomic dysregulation in diabetic patients. Methods This cross-sectional study involved 200 adults, divided equally between a control group (n = 100) and a T2DM study group (n = 100). The exclusion criteria included cardiovascular diseases and renal impairment. Data collection involved assessing baseline characteristics such as age and BMI. Cardiovascular measures, including HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were recorded after a five-minute rest. Autonomic function tests assessed sympathetic and parasympathetic responses, including the cold pressor test and the isometric hand grip exercise test. The statistical analysis was conducted using IBMSPSSStatistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), focusing on independent t-tests to compare between groups, considering p-values <0.05 as significant. Potential confounding variables like age and BMI were accounted for in the analysis to ensure robust findings Results The study group showed a higher average BMI (28.95 ± 5.60) compared to the control group (26.50 ± 5.70) and an increased resting HR (74.20 ± 8.60 bpm vs. 69.30 ± 9.10 bpm). The SBP was slightly higher in the study group (115.00 ± 19.00 mmHg vs. 114.50 ± 8.90 mmHg), while the DBP was lower (71.50 ± 10.70 mmHg vs. 72.80 ± 6.70 mmHg). The autonomic function tests showed a smaller increase in SBP (106.80 ± 11.00 mmHg) and a larger increase in DBP (75.90 ± 8.30 mmHg) upon standing in the study group compared to controls. The cold pressor test indicated increased sympathetic activity in the study group, with significant rises in SBP (133.70 ± 10.30 mmHg) and DBP (83.40 ± 9.00 mmHg) compared to the control group (SBP: 114.31 ± 11.87 mmHg, DBP: 71.85 ± 8.67 mmHg). These findings demonstrate marked differences in cardiovascular autonomic responses between the groups. Conclusions This study demonstrates that T2DM significantly impacts cardiovascular autonomic functions, with diabetic patients showing altered HR and BP indicative of increased sympathetic and decreased parasympathetic activity. These autonomic dysfunctions may heighten cardiovascular risk in diabetic individuals. Our findings highlight the importance of monitoring and managing cardiovascular autonomic functions in diabetic patients to reduce their risk of cardiovascular complications. Further research should investigate the underlying mechanisms and the effectiveness of interventions to improve autonomic function in this population.

Event-related prefrontal activations during online video game playing are modulated by game mechanics, physiological arousal and the amount of daily playing

There is a trend to study human brain functions in ecological contexts and in relation to human factors. In this study, functional near-infrared spectroscopy (fNIRS) was used to record real-time prefrontal activities in 42 male university student habitual video game players when they played a round of multiplayer online battle arena game, League of Legends. A content-based event coding approach was used to analyze regional activations in relation to event type, physiological arousal indexed by heart rate (HR) change, and individual characteristics of the player. Game events Slay and Slain were found to be associated with similar HR and prefrontal responses before the event onset, but differential responses after the event onset. Ventrolateral prefrontal cortex (VLPFC) activation preceding the Slay onset correlated positively with HR change, whereas activations in dorsolateral prefrontal cortex (DLPFC) and rostral frontal pole area (FPAr) preceding the Slain onset were predicted by self-reported hours of weekly playing (HoWP). Together, these results provide empirical evidence to support the notion that event-related regional prefrontal activations during online video game playing are shaped by game mechanics, in-game dynamics of physiological arousal and individual characteristics the players.

Preliminary evidence for altered brain-heart coherence during anxiogenic movies

Abstract During states of anxiety, fundamental threat circuitry in the brain can increase heart rate via alterations in autonomic balance (increased sympathetic activity and parasympathetic withdrawal) and may serve to promote interoceptive integration and awareness of cardiac signals. Moreover, evidence indicates pathological anxiety could be associated with increased communication between the brain and the heart. Yet, this phenomenon remains not well understood. For instance, studies in this area have been conducted within the confines of tightly controlled experimental paradigms. Whether anxiety impacts brain-heart communication outside of such experimental settings, and in relatively more naturalistic contexts, is less clear. Here, we used a suspenseful movie fMRI paradigm to study induced anxiety (n = 29 healthy volunteers; Caltech Conte dataset; Kliemann et al., 2022). We predicted that brain responses across an anxiety-relevant “defensive response network” (amygdala, hypothalamus, periaqueductal gray, bed nucleus of the stria terminalis, dorsomedial prefrontal cortex, ventromedial prefrontal cortex, subgenual anterior cingulate, and anterior insula; Abend et al., 2022) would show increased coherence with heart rate as participants watched a suspenseful movie clip compared to a non-suspenseful movie clip. Counter to our predictions, we found decreased coherence between heart rate and brain responses during increased anxiety, namely in amygdala-prefrontal circuitry. We suggest these alterations may be underpinned by parasympathetic withdrawal and/or decreased interoceptive awareness during suspenseful movie-watching.

Abstract PO3-08-10: Somatic mutations of a multigene panel in Chinese HER2-positive patients undergoing neoadjuvant therapy and impact on prognosis based on TP53 status:a single-institution retrospective cohort

Abstract Background: Gene mutations and copy number variations (CNVs) are associated with the occurrence and development of tumors. Neoadjuvant therapy (NAT) has shown greater clinical benefit in the treatment of HER2-positive breast cancer (BC). The impact of genetic mutations on NAT efficacy in BC has been frequently reported, but the relationship between genetic mutations and NAT efficacy and the long-term prognosis in HER2-positive BC patients still requires more high-quality studies. Methods: This retrospective cohort study was conducted patients receiving NAT between September 2017 and March 2021 in the Department of Breast Surgery of Fudan University Shanghai Cancer Center (FUSCC). The genomic characteristics of 513 cancer-related genes from the archived tumour blocks were assessed by next-generation sequencing (NGS). The relationship between tumour mutated gene and the postoperative pathological complete response (pCR) as well as prognosis of the disease-free survival (DFS) were further explored.Statistical methods included Chi-square test, fisher's exact test, Kaplan-Meier survival analysis, all of which were completed by SPSS 20.0. Results: 208(47.8%) patients achieved pCR after HER2-targeted NAT and 40(9.2%) patients encountered DFS events. The frequency of somatic alterations in TP53(60%), PIK3CA (15%) and ERBB2(11%) was highest in women with HER2-positive breast cancer. KMT2C (P= 0.036) and TP53(P=0.037) mutations were significantly increased in patients with DFS events. In the HER2+/HR- cohort, patients who achieved pCR had significantly benefit in prognosis (HR=3.605, P=0.002), and CCND1 amplifications(p=0.014), ATM(p=0.016) and GATA3(p=0.016) mutations were more frequent. ERBB2 mutations were significantly associated with younger ages of diagnosis(p=0.018). TP53 mutations were associated with worse DFS (HR=3.242, P=0.0110) as well as more DFS events(p=0.048). Furthermore, TP53 mutations had significant prognostic importance in HER2-positive BC patients with HR-negative (HR=3.712, P=0.0266), pCR (HR=6.253, P=0.0268) and who received trastuzumab-only targeted therapy (HR=4.145, P=0.0105). Conclusions: Regard to diverse hormone receptor status or neoadjuvant efficacy, the genetic mutation maps of Chinese HER2+ patients receiving NAT are disparate. Our study found that TP53 mutations have significant prognostic value in patients with NAT for HER2-positive BC and patients benefit differently depending on HR status, neoadjuvant regimens and response. Citation Format: Min Xiong, Liren Wangxu, Jingyan Xue, Benlong Yang, Jiong Wu. Somatic mutations of a multigene panel in Chinese HER2-positive patients undergoing neoadjuvant therapy and impact on prognosis based on TP53 status:a single-institution retrospective cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-10.

Abstract PO1-15-09: Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer

Abstract Background: Immune checkpoint blockade (ICB) has substantially improved patient overall and progression-free survival in triple-negative breast cancer (TNBC), but its efficacy remains to be elucidated in the hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, which is characterized by generally impotent lymphocytic infiltration. In the I-SPY2 trial (NCT01042379), pembrolizumab- or durvalumab-containing neoadjuvant therapy increased the pathologic complete response of HR+/HER2- patients. However, pembrolizumab-containing therapy failed to improve the survival of metastatic HR+/HER2- breast cancer patients (NCT03051659). These inconsistent results underscored the necessity of the investigation of predictive biomarkers to pinpoint potential ICB responders in HR+/HER2- breast cancer. Method: In this study, we collected pretreatment tumor samples from 16 patients in two respective clinical trials (NCT: 04215003 and 04355858) and profiled droplet-based single-cell sequencing, bulk RNA-Seq. Patients were treated with camrelizumab (PD-1 inhibitor)-containing therapy, and five of them achieved partial relief after an 8-week course. We also leveraged the bulk RNA-Seq data from the I-SPY2 trial and Fudan University Shanghai Cancer Center (FUSCC) TNBC ICB trials (NCT04418154 and NCT04613674) for external validation. Another FUSCC transcriptome dataset consisting of 933 treatment-naïve HR+/HER2- or TNBC breast cancer patients was used to detect the abundance of cell types. In vitro and in vivo experiments were used to explore mechanisms of anti-tumor immune response. Results: Based on the single-cell sequencing results, we comprehensively delineated the microenvironmental landscape of HR+/HER2- breast cancer. We discovered responders of immunotherapy showed a higher presence of CXCL9/10+ M1-like macrophages and exhibited enrichment of tumor cells with ferroptosis. We further identified the upregulation of vitamin A metabolism and the vitamin A metabolic gene CRABP1 in tumor cells with ferroptosis. We verified the vitamin A metabolism could induce ferroptosis in HR+/HER2- breast cancers rather than TNBC by CRABP1-ERK axis, which could further recruit CXCL9/10+ M1-like macrophages and promote anti-tumor immune response in HR+/HER2- breast cancer. Combining anti-PD1 with enhancing vitamin A metabolism via retinoid acid possessed greater therapeutic efficacy than monotherapy in HR+/HER2- breast cancers. Finally, we developed an immune therapy response score and validated its reliability in predicting the immunotherapy efficacy for HR+/HER2-breast cancers through both internal and external cohorts. Conclusion: Our study represents the earliest efforts to decipher the microenvironmental landscape and the mechanisms underlying the response to ICB in HR+/HER2- breast cancer at single-cell resolution. We unraveled a HR+/HER2- breast cancer-specific Vitamin A-ferroptosis axis that mediated immunotherapy response and constructed a robust immunotherapy efficacy prediction score based on this Vitamin A-ferroptosis axis. Citation Format: Yi-Fan Zhou, Hu-Yun-Long Zhang, Xi Jin, Yi-Zhou Jiang, Zhi-Ming Shao. Vitamin A Metabolism Induces Ferroptosis to Enhance Immune Therapy Efficacy in HR+/HER2- Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-09.

Using virtual reality to enhance attention for autistic spectrum disorder with eye tracking

Attention deficit disorder is a frequently observed symptom in individuals with autism spectrum disorder (ASD). This condition can present significant obstacles for those affected, manifesting in challenges such as sustained focus, task completion, and the management of distractions. These issues can impede learning, social interactions, and daily functioning. This complexity of symptoms underscores the need for tailored approaches in both educational and therapeutic settings to support individuals with ASD effectively. In this study, we have expanded upon our initial virtual reality (VR) prototype, originally created for attention therapy, to conduct a detailed statistical analysis. Our objective was to precisely identify and measure any significant differences in attention-related outcomes between sessions and groups. Our study found that heart rate (HR) and electrodermal activity (EDA) were more responsive to attention shifts than temperature. The ‘Noise’ and ‘Score’ strategies significantly affected eye openness, with the ASD group showing more responsiveness. The control group had smaller pupil sizes, and the ASD group’s pupil size increased notably when switching strategies in Session 1. Distraction log data showed that both ‘Noise’ and ‘Object Opacity’ strategies influenced attention patterns, with the ‘Red Vignette’ strategy showing a significant effect only in the ASD group. The responsiveness of HR and EDA to attention shifts and the changes in pupil size could serve as valuable physiological markers to monitor and guide these interventions. These findings further support evidence that VR has positive implications for helping those with ASD, allowing for more tailored personalized interventions with meaningful impact.

Overexpression of Regulator of G-Protein Signaling 2 in the Paraventricular Nucleus Reduces Blood Pressure in Spontaneously Hypertensive Rats

The hypothalamic paraventricular nucleus (PVN) is important in mediating sympathetic activity to regulate blood pressure. The regulator of G protein signaling 2 (RGS2) is a negative G protein regulator. RGS2 selectively regulates Gαq signaling, an important cause of hypertension and cardiac hypertrophy. However, little-to-no studies are being done related to G-protein-RGS2 signaling on the central mechanisms of blood pressure control and sympathetic activation. In this study, we use spontaneously hypertensive rats (SHR) to aim for the pressor effects of central viral transfection over-expressing RGS2 in the PVN compared to a Wistar-Kyoto (WKY) control. These rats were outfitted with telemetry and measurements of blood pressure and heart rate over the next 14 days, with or without RGS2 adenovirus (AV) injection into the PVN. Metabolic experiments were conducted at the 7-day mark to examine kidney function, sodium excretion, urine output, and water and food intake. We saw significant ( p&lt;0.05) decreases in blood pressure for the SHR with AV-RGS2 throughout our telemetry experiment. In our metabolic experiments, sodium excretion significantly ( p&lt;0.05) increased in the SHR group with AV-RGS2 compared to the SHR with AV-GFP. Water intake, food intake, and urine output remained unchanged. Following this experiment, we gave capsaicin injections into the renal pelvis at 5, 10, and 20 μM to measure blood pressure and heart rate responses. Also, blood pressure responses to renal pelvis capsaicin injection appear to be attenuated in SHR and WKY rats with AV-RGS2 injection but was not significant ( p&gt;0.05). In addition, we conducted real-time qPCR on collected PVN tissue to evaluate gene expression changes over time. We saw expression peak at 3-days in G⍺q, G⍺s, G⍺i, and RGS2, and progressively decrease as time progressed. This study provides a value insight of central mechanisms related to G-protein-RGS2 signaling on blood pressure regulation. This study was funded by NIH R01-DK-129311 and USD G-RISE, NIH T32GM-136503. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.