Beta-adrenergic signaling and T-lymphocyte-produced catecholamines are necessary for interleukin 17A synthesis.

Background: Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities. Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases. Previously, using a preclinical model of PTSD, we demonstrated that elimination of sympathetic signaling to T-lymphocytes specifically limited their ability to produce pro-inflammatory interleukin 17A (IL-17A); a cytokine implicated in the development of many autoimmune disorders. However, the mechanism linking sympathetic signaling to T-lymphocyte IL-17A production remained unclear. Methods: Using a modified version of repeated social defeat stress (RSDS) that allows for both males and females, we assessed the impact of adrenergic receptor blockade (genetically and pharmacologically) and catecholamine depletion on T-lymphocyte IL-17A generation. Additionally, we explored the impact of adrenergic signaling and T-lymphocyte-produced catecholamines on both CD4+ and CD8+ T-lymphocytes polarized to IL-17A-producing phenotypes ex vivo. Results: Only pharmacological inhibition of the beta 1 and 2 adrenergic receptors (ß1/2) significantly decreased circulating IL-17A levels after RSDS, but did not impact other pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IL-10). This finding was confirmed using RSDS with both global ß1/2 receptor knock-out mice, as well as by adoptively transferring ß1/2 knock-out T-lymphocytes into immunodeficient hosts. Furthermore, ex vivo polarized T-lymphocytes produced significantly less IL-17A with the blockade of ß1/2 signaling, even in the absence of exogenous sympathetic neurotransmitter supplementation, which suggested T-lymphocyte-produced catecholamines may be involved in IL-17A production. Indeed, pharmacological depletion of catecholamines both in vivo and ex vivo abrogated T-lymphocyte IL-17A production demonstrating the importance of immune-generated neurotransmission in pro-inflammatory cytokine generation. Conclusions: Our data depict a novel role for ß1/2 adrenergic receptors and autologous catecholamine signaling during T-lymphocyte IL-17A production. These findings provide a new target for pharmacological therapy in both psychiatric and autoimmune diseases associated with IL-17A-related pathology.

The role of long-term power-law memory in controlling large-scale dynamical networks.

Controlling large-scale dynamical networks is crucial to understand and, ultimately, craft the evolution of complex behavior. While broadly speaking we understand how to control Markov dynamical networks, where the current state is only a function of its previous state, we lack a general understanding of how to control dynamical networks whose current state depends on states in the distant past (i.e. long-term memory). Therefore, we require a different way to analyze and control the more prevalent long-term memory dynamical networks. Herein, we propose a new approach to control dynamical networks exhibiting long-term power-law memory dependencies. Our newly proposed method enables us to find the minimum number of driven nodes (i.e. the state vertices in the network that are connected to one and only one input) and their placement to control a long-term power-law memory dynamical network given a specific time-horizon, which we define as the 'time-to-control'. Remarkably, we provide evidence that long-term power-law memory dynamical networks require considerably fewer driven nodes to steer the network's state to a desired goal for any given time-to-control as compared with Markov dynamical networks. Finally, our method can be used as a tool to determine the existence of long-term memory dynamics in networks.

Development of a framework for action to advocate for a coherent prevention policy for tobacco, alcohol, and foods high in fats, salt, or sugar: a mixed-methods approach.

BACKGROUND: Tobacco, alcohol, and foods high in fats, salt, or sugar (HFSS) are health harming products. Limited progress in prevention is partly due to health-harming industry lobbying. Action on Smoking and Health (ASH), Alcohol Health Alliance, and Obesity Health Alliance collaborated with the aim of developing a framework for action to address the saturation of these products in our environment. METHODS: We used a mixed-methods approach. Focus groups with academic experts, local government, and national government, recruited through snowball sampling were held in Nov 3, 2022 (14 participants); April 25, 2023 (20 participants); and June 15, 2023 (20 participants). Iteratively, data analysis was presented, and key themes tested. Commissioned economic analysis of national survey datasets quantified consumer spend on tobacco, alcohol, and food products above government recommendations (all tobacco use, >14 units of alcohol, and national dietary guidelines) and industry percentage of revenues (net of tax). Public opinion data from the ASH YouGov Smokefree Survey 2022 on a nationally representative sample of 13 088 adults were descriptively analysed for specific policy options. FINDINGS: The framework for action to achieve a coherent prevention approach across products included three key enablers (secure funding for prevention, a comprehensive strategy, and protecting health policy from industry interference). Five key actions were: regulate advertising to limit harm, regulate product use and environments they can be used in, promote healthy messaging, raise the price of health-harming products, and fund treatment services. Economic analysis identified 100% of tobacco usage, 43·4% of alcohol purchased, and 28·8% of food purchased by households was above government recommendations. Post-tax industry revenue was £7·3 billion for tobacco, £11·2 billion for alcohol, and £34·2 billion for HFSS foods. Strong public support for levies (5%, n=8495) and protecting health policy from industry influence (69%, n=9006) was apparent. INTERPRETATION: A coherent approach to prevention across health-harming products is effective and has public support. Strengths include the iterative process to develop the framework for action among focus groups and use of nationally representative datasets. Limitations include the snowball sampling. The findings were built into a strategy intended to inform future collaborative work in the area. FUNDING: Cancer Research UK (grant PICADV-Feb22\100004).

S100a9 Protects Against the Effects of Repeated Social Defeat Stress.

Background: Posttraumatic stress disorder, a consequence of psychological trauma, is associated with increased inflammation and an elevated risk of developing comorbid inflammatory diseases. However, the mechanistic link between this mental health disorder and inflammation remains elusive. We previously found that S100a8 and S100a9 messenger RNA, genes that encode the protein calprotectin, were significantly upregulated in T lymphocytes and positively correlated with inflammatory gene expression and the mitochondrial redox environment in these cells. Therefore, we hypothesized that genetic deletion of calprotectin would attenuate the inflammatory and redox phenotype displayed after psychological trauma. Methods: We used a preclinical mouse model of posttraumatic stress disorder known as repeated social defeat stress (RSDS) combined with pharmacological and genetic manipulation of S100a9 (which functionally eliminates calprotectin). A total of 186 animals (93 control, 93 RSDS) were used in these studies. Results: Unexpectedly, we observed worsening of behavioral pathology, inflammation, and the mitochondrial redox environment in mice after RSDS compared with wild-type animals. Furthermore, loss of calprotectin significantly enhanced the metabolic demand on T lymphocytes, suggesting that this protein may play an undescribed role in mitochondrial regulation. This was further supported by single-cell RNA sequencing analysis demonstrating that RSDS and loss of S100a9 primarily altered genes associated with mitochondrial function and oxidative phosphorylation. Conclusions: These data demonstrate that the loss of calprotectin potentiates the RSDS-induced phenotype, which suggests that its observed upregulation after psychological trauma may provide previously unexplored protective functions.

Repeated social defeat stress leads to immunometabolic shifts in innate immune cells of the spleen.

Psychosocial stress has been shown to prime peripheral innate immune cells, which take on hyper-inflammatory phenotypes and are implicated in depressive-like behavior in mouse models. However, the impact of stress on cellular metabolic states that are thought to fuel inflammatory phenotypes in immune cells are unknown. Using single cell RNA-sequencing, we investigated mRNA enrichment of immunometabolic pathways in innate immune cells of the spleen in mice subjected to repeated social defeat stress (RSDS) or no stress (NS). RSDS mice displayed a significant increase in the number of splenic macrophages and granulocytes (p < 0.05) compared to NS littermates. RSDS-upregulated genes in macrophages, monocytes, and granulocytes significantly enriched immunometabolic pathways thought to play a role in myeloid-driven inflammation (glycolysis, HIF-1 signaling, MTORC1 signaling) as well as pathways related to oxidative phosphorylation (OXPHOS) and oxidative stress (p < 0.05 and FDR<0.1). These results suggest that the metabolic enhancement reflected by upregulation of glycolytic and OXPHOS pathways may be important for cellular proliferation of splenic macrophages and granulocytes following repeated stress exposure. A better understanding of these intracellular metabolic mechanisms may ultimately help develop novel strategies to reverse the impact of stress and associated peripheral immune changes on the brain and behavior.

Defining the nuanced nature of redox biology in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a mental health disorder that arises after experiencing or witnessing a traumatic event. Despite affecting around 7% of the population, there are currently no definitive biological signatures or biomarkers used in the diagnosis of PTSD. Thus, the search for clinically relevant and reproducible biomarkers has been a major focus of the field. With significant advances of large-scale multi-omic studies that include genomic, proteomic, and metabolomic data, promising findings have been made, but the field still has fallen short. Amongst the possible biomarkers examined, one area is often overlooked, understudied, or inappropriately investigated: the field of redox biology. Redox molecules are free radical and/or reactive species that are generated as a consequence of the necessity of electron movement for life. These reactive molecules, too, are essential for life, but in excess are denoted as "oxidative stress" and often associated with many diseases. The few studies that have examined redox biology parameters have often utilized outdated and nonspecific methods, as well as have reported confounding results, which has made it difficult to conclude the role for redox in PTSD. Herein, we provide a foundation of how redox biology may underlie diseases like PTSD, critically examine redox studies of PTSD, and provide future directions the field can implement to enhance standardization, reproducibility, and accuracy of redox assessments for the use of diagnosis, prognosis, and therapy of this debilitating mental health disorder.

Evaluation of an open forecasting challenge to assess skill of West Nile virus neuroinvasive disease prediction.

BACKGROUND: West Nile virus (WNV) is the leading cause of mosquito-borne illness in the continental USA. WNV occurrence has high spatiotemporal variation, and current approaches to targeted control of the virus are limited, making forecasting a public health priority. However, little research has been done to compare strengths and weaknesses of WNV disease forecasting approaches on the national scale. We used forecasts submitted to the 2020 WNV Forecasting Challenge, an open challenge organized by the Centers for Disease Control and Prevention, to assess the status of WNV neuroinvasive disease (WNND) prediction and identify avenues for improvement. METHODS: We performed a multi-model comparative assessment of probabilistic forecasts submitted by 15 teams for annual WNND cases in US counties for 2020 and assessed forecast accuracy, calibration, and discriminatory power. In the evaluation, we included forecasts produced by comparison models of varying complexity as benchmarks of forecast performance. We also used regression analysis to identify modeling approaches and contextual factors that were associated with forecast skill. RESULTS: Simple models based on historical WNND cases generally scored better than more complex models and combined higher discriminatory power with better calibration of uncertainty. Forecast skill improved across updated forecast submissions submitted during the 2020 season. Among models using additional data, inclusion of climate or human demographic data was associated with higher skill, while inclusion of mosquito or land use data was associated with lower skill. We also identified population size, extreme minimum winter temperature, and interannual variation in WNND cases as county-level characteristics associated with variation in forecast skill. CONCLUSIONS: Historical WNND cases were strong predictors of future cases with minimal increase in skill achieved by models that included other factors. Although opportunities might exist to specifically improve predictions for areas with large populations and low or high winter temperatures, areas with high case-count variability are intrinsically more difficult to predict. Also, the prediction of outbreaks, which are outliers relative to typical case numbers, remains difficult. Further improvements to prediction could be obtained with improved calibration of forecast uncertainty and access to real-time data streams (e.g. current weather and preliminary human cases).

Life-history stage and the population genetics of the tiger mosquito Aedes albopictus at a fine spatial scale.

As a widespread vector of disease with an expanding range, the mosquito Aedes albopictus Skuse (Diptera: Culicidae) is a high priority for research and management. A. albopictus has a complex life history with aquatic egg, larval and pupal stages, and a terrestrial adult stage. This requires targeted management strategies for each life stage, coordinated across time and space. Population genetics can aid in A. albopictus control by evaluating patterns of genetic diversity and dispersal. However, how life stage impacts population genetic characteristics is unknown. We examined whether patterns of A. albopictus genetic diversity and differentiation changed with life stage at a spatial scale relevant to management efforts. We first conducted a literature review of field-caught A. albopictus population genetic papers and identified 101 peer-reviewed publications, none of which compared results between life stages. Our study uniquely examines population genomic patterns of egg and adult A. albopictus at five sites in Wake County, North Carolina, USA, using 8425 single nucleotide polymorphisms. We found that the level of genetic diversity and connectivity between sites varied between adults and eggs. This warrants further study and is critical for research aimed at informing local management.

Beyond the Basics: A Novel Approach to Integrating a Social Determinants of Health Curriculum into an Emergency Medicine Course.

Background: Our aim was to implement and evaluate a novel social determinants of health (SDoH) curriculum into the required fourth-year emergency medicine (EM) course at the University of Vermont Larner College of Medicine with the goal to teach students how to assess and address SDoH in clinical practice. The objectives were as follows: 1. Assess the SDoH, risk factors, and barriers to healthcare facing patients from diverse socioeconomic and cultural backgrounds in the ED. 2. Examine how social work consult services operate in the ED setting and how to identify appropriate referrals, resources, and treatment plans for patients in the ED. 3. Examine and interpret the impact health disparities have on patients in the ED and develop potential solutions to reduce these disparities to improve health outcomes. 4. Analyze the experiences and lessons learned and use them to inform future patient interactions. Curricular Design: The curriculum was developed by a workgroup that considered the following: scope; target learners; overall structure; instructional and delivery methods; and session scheduling. The curriculum consisted of four components that took place over the four-week EM course. Students completed a required end-of-course survey. Survey results underwent a mixed-methods analysis to assess student attitudes and the impact of the curriculum. Impact/Effectiveness: We received a 78.7% (74/94) completion rate for the 2021-2022 academic year. Of all respondents, 92% (68/74) indicated that they would apply lessons learned from the SDoH components of the curriculum; 74% (54/74) rated the SDoH curriculum as good, very good, or excellent; and 81% (60/74) felt that the EM course increased their understanding of diversity, equity, and inclusion as it relates to the practice of medicine. The thematic analyses revealed four main themes: 1) general comments; 2) course design; 3) interprofessional collaboration; and 4) expanding the scope of the curriculum. Conclusion: Social medicine integration into core EM courses is a generalizable approach to experiential and collaborative exposure to the social determinants of health. Of student respondents, 92% indicated they will use lessons learned from this curriculum in their future practice. This can improve the way future generations of physicians identify SDoH and address the social needs that affect their patients, thereby advancing and promoting health equity.

Sampling-Based Nonlinear Stochastic Optimal Control for Neuromechanical Systems.

Determining how the nervous system controls tendon-driven bodies remains an open question. Stochastic optimal control (SOC) has been proposed as a plausible analogy in the neuroscience community. SOC relies on solving the Hamilton-Jacobi-Bellman equation, which seeks to minimize a desired cost function for a given task with noisy controls. We evaluate and compare three SOC methodologies to produce tapping by a simulated planar 3-joint human index finger: iterative Linear Quadratic Gaussian (iLQG), Model-Predictive Path Integral Control (MPPI), and Deep Forward-Backward Stochastic Differential Equations (FBSDE). We show that averaged over 128 repeats these methodologies can place the fingertip at the desired final joint angles but-because of kinematic redundancy and the presence of noise-they each have joint trajectories and final postures with different means and variances. iLQG in particular, had the largest kinematic variance and departure from the final desired joint angles. We demonstrate that MPPI and FBSDE have superior performance for such nonlinear, tendon-driven systems with noisy controls.Clinical relevance- The mathematical framework provided by MPPI and FBSDE may be best suited for tendon-driven anthropomorphic robots, exoskeletons, and prostheses for amputees.

Short-Term, Large-Area Survey of Container Aedes spp. (Diptera: Culicidae): Presence and Abundance is Associated with Fine-scale Landscape Factors in North Carolina, USA.

Container Aedes mosquitoes are responsible for the transmission of anthroponotic and zoonotic viruses to people. The surveillance and control of these mosquitoes is an important part of public health protection and prevention of mosquito-borne disease. In this study, we surveyed 327 sites over 2 weeks in late June and early July in 2017 in North Carolina, USA for the presence and abundance of Aedes spp. eggs in an effort to better target potential Ae. aegypti collections. We examined the ability of 2 types of landscape data, Light Detection And Ranging (LIDAR) and National Land Cover Database (NLCD) to explain the presence and abundance of eggs using principal component analysis to deal with collinearity, followed by generalized linear regression. We explained variation of both egg presence and abundance for Aedes albopictus (Skuse) and Aedes triseriatus (Say) using both NLCD and LIDAR data. However, the ability to make robust predictions was limited by variation in the data. Increased sampling time and better landscape data would likely improve the predictive ability of our models, as would a better understanding of oviposition behavior.

Identification of candidate loci for adaptive phenotypic plasticity in natural populations of spadefoot toads.

Phenotypic plasticity allows organisms to alter their phenotype in direct response to changes in the environment. Despite growing recognition of plasticity's role in ecology and evolution, few studies have probed plasticity's molecular bases-especially using natural populations. We investigated the genetic basis of phenotypic plasticity in natural populations of spadefoot toads (Spea multiplicata). Spea tadpoles normally develop into an "omnivore" morph that is favored in long-lasting, low-density ponds. However, if tadpoles consume freshwater shrimp or other tadpoles, they can alternatively develop (via plasticity) into a "carnivore" morph that is favored in ephemeral, high-density ponds. By combining natural variation in pond ecology and morph production with population genetic approaches, we identified candidate loci associated with each morph (carnivores vs. omnivores) and loci associated with adaptive phenotypic plasticity (adaptive vs. maladaptive morph choice). Our candidate morph loci mapped to two genes, whereas our candidate plasticity loci mapped to 14 genes. In both cases, the identified genes tended to have functions related to their putative role in spadefoot tadpole biology. Our results thereby form the basis for future studies into the molecular mechanisms that mediate plasticity in spadefoots. More generally, these results illustrate how diverse loci might mediate adaptive plasticity.

A Statewide Survey of Container Aedes Mosquitoes (Diptera: Culicidae) in North Carolina, 2016: A Multiagency Surveillance Response to Zika Using Ovitraps.

Native and invasive container-inhabiting Aedes mosquitoes (Diptera: Culicidae) play important roles in the transmission of endemic and traveler-introduced arboviruses in the United States. In response to the emergence of Zika virus into the Americas, we surveyed the distribution of container Aedes spp. of public health importance within North Carolina during 2016 using ovitraps. A seasonal survey was conducted in 18 counties from the mountains to the coast to identify species incriminated in the transmission of chikungunya, dengue, La Crosse, yellow fever, and Zika viruses. Multiple local, state, and federal agencies participated in the study and submitted more than 3,600 ovistrips. Aedes albopictus (Skuse) (81.4%, n = 54,458) was the most common and widespread species found in this survey, followed by Aedes triseriatus (Say) (10.7%, n = 7,169) and Aedes japonicus (Theobald) (7.9%, n = 5,262). We did not find Aedes aegypti and rarely found Aedes hendersoni (Cockerell). We assessed broad-scale climatic and other factors and determined that longitude, elevation, rainfall, and temperature had significant effects on explaining the variation in presence, abundance, and phenology of container Aedes in North Carolina. However, much of the variation in these outcomes was not explained at this coarse scale and may benefit from finer-scale analyses. These efforts represent the largest ovitrap survey ever conducted in the state.

Animal models of Wilson disease.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency.

Neighborhood Characteristics: Influences on Pain and Physical Function in Youth at Risk for Chronic Pain.

Neighborhood features such as community socioeconomic status, recreational facilities, and parks have been correlated to the health outcomes of the residents living within those neighborhoods, especially with regard to health-related quality of life, body mass index, and physical activity. The interplay between one's built environment and one's perceptions may affect physical health, well-being, and pain experiences. In the current study, neighborhood characteristics and attitudes about physical activity were examined in a high-risk (youths with a parent with chronic pain) and low-risk (youths without a parent with chronic pain) adolescent sample. There were significant differences in neighborhood characteristics between the high-risk (n = 62) and low-risk (n = 77) samples (ages 11-15), with low-risk participants living in residences with more walkability, closer proximity to parks, and higher proportion of neighborhood residents having college degrees. Results indicate that neighborhood features (e.g., walkability and proximity to parks), as well as positive attitudes about physical activity were correlated with lower levels of pain and pain-related disability, and higher performance in physical functioning tests. These findings suggest that the built environment may contribute to pain outcomes in youth, above and beyond the influence of family history of pain.

Finely tuned response of native prey to an invasive predator in a freshwater system.

Lack of shared evolutionary history reduces the expectation that native prey will detect and respond to invasive predators. Four mechanisms may explain the adaptive response that is nevertheless seen in various systems: prey may perceive the invasive predator through cue similarity with preexisting predators, cues of conspecifics eaten by the invasive predator, a learned response based on experience with the invasive predator (e.g., cue association), and cues from the invasive predator that are specific to it. We performed laboratory experiments in which zooplankton (Daphnia mendotae) responded adaptively to the zooplanktivore Bythotrephes longimanus (migrating downward), showed no response to taxonomically similar predatory cladocerans, and responded adaptively to more taxonomically distant native fish (migrating downward) and native shrimp (migrating upward). Conspecific cues associated with Bythotrephes predation actually reduced the response of D. mendotae to Bythotrephes. Combined with previous experiments that rule out learning, our experiments rule out the first three mechanisms above, demonstrating that D. mendotae respond to cues specific to and produced directly by Bythotrephes. This finely tuned response may be retained from an ancestral species that coevolved with Bythotrephes in its native range, or may have rapidly evolved due to strong selection by the invasive predator.

Sample selection, preparation methods, and the apparent tensile properties of silkworm (B. mori) cocoon silk.

Reported literature values of the tensile properties of natural silk cover a wide range. While much of this inconsistency is the result of variability that is intrinsic to silk, some is also a consequence of differences in the way that silk is prepared for tensile tests. Here we explore how measured mechanical properties of Bombyx mori cocoon silk are affected by two intrinsic factors (the location from which the silk is collected within the cocoon, and the color of the silk), and two extrinsic factors (the storage conditions prior to testing, and different styles of reeling the fiber). We find that extrinsic and therefore controllable factors can affect the properties more than the intrinsic ones studied. Our results suggest that enhanced inter-laboratory collaborations, that lead to standardized sample collection, handling, and storage protocols prior to mechanical testing, would help to decrease unnecessary (and complicating) variation in reported tensile properties.

Biomimicry as a route to new materials: what kinds of lessons are useful?

We consider the attributes of a successful engineered material, acknowledging the contributions of composition and processing to properties and performance. We recognize the potential for relevant lessons to be learned from nature, at the same time conceding both the limitations of such lessons and our need to be selective. We then give some detailed attention to the molecular biomimicry of filamentous phage, the process biomimicry of silk and the structure biomimicry of hippopotamus 'sweat', in each case noting that the type of lesson now being learned is not the same as the potential lesson that originally motivated the study.

Accuracy of automated auscultatory blood pressure measurement during supine exercise and treadmill stress electrocardiogram-testing.

OBJECTIVES: Monitoring of brachial blood pressure during exercise-electrocardiogram (ECG) testing is mandatory and changes in blood pressure (BP) can provide critical management evidence. Patient movement, mechanical vibration, artifactual sounds and observer variability make standard manual techniques problematic. This was an investigator-initiated study to assess an automated auscultatory technique of BP assessment [Tango exercise blood pressure monitor (SunTech Medical Instruments, NC, USA)] to adequately measure BP during stress-ECG testing. METHODS: Initially five fit young male volunteers underwent invasive right brachial artery BP recording using a low-compliance fluid-filled catheter with simultaneous manual and automated assessment. Secondarily, during exercise-ECG testing, the system was assessed against beat-to-beat brachial blood pressures obtained from a catheter-tip solid-state pressure manometer positioned in the ipsilateral brachial artery. RESULTS: In the supine study overall mean difference (+/-SEM) between invasive and manual blood pressures was 3.26 (1.53) and 3.89 (1.90) mmHg for diastolic BP (DBP) and systolic BP (SBP) respectively. Corresponding differences between invasive and automated results, and manual and automated were 3.68 (0.84) and -7.31 (1.83) mmHg, and -0.64 (+/-1.43) and -11.42 (+/-1.59) mmHg. During treadmill exercise-ECG testing the combined mean difference (+/-SEM) between invasive and automated SBP and DBP was 4.79 (+/-0.14) and 6.33 (+/-0.10) mmHg, respectively. CONCLUSION: Automated BP assessment during exercise-ECG testing is feasible with the use of appropriate automatic devices likely to be at least as accurate as manual BP registration. The Tango device is tolerant to exercise and provides reliable automatic BP assessment with absolute differences within an acceptable clinical range.