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In the present paper we present the outlines of a model that may help to guide us in our understanding of the relationship between perseverative thinking and health. We will emphasize the relationship between perseverative thinking and vagal cardiac control and propose a group of underlying neural structures that serve to integrate these functions in the service of self-regulation and adaptability of the organism. We will attempt to place this network in the context of systems models which involve feedback and feedforward circuits with special attention to negative feedback mechanisms and inhibitory processes. From a systems perspective, inhibitory processes can be viewed as negative feedback circuits that allow for the interruption of ongoing behavior and the re-deployment of resources to other tasks. When these negative feedback mechanisms are compromised, positive feedback loops may develop as a result of dis-inhibition. From this perspective, the relative sympathetic activation seen in perseverative thinking may represent dis-inhibition due to faulty inhibitory mechanisms. [ABSTRACT FROM AUTHOR]

We analyzed language use to examine age differences in people's representations of their own emotions as compared with those of others. Participants (N = 365, aged 18-85 years, M = 42.8, SD = 19.2) read hypothetical emotion-eliciting scenarios and described how they themselves and the social partners involved in the scenarios would feel. Compared with those of younger adults, older adults' descriptions involved a higher frequency of positive and a lower frequency of negative emotions. Older adults were also more likely to describe a co-occurrence of positive and negative emotions, but less likely to describe the simultaneous experience of multiple negative emotions. Age effects showed similar patterns for participants' descriptions of their own emotions as compared with those of others. We discuss the implications for theoretical accounts of emotional aging. [ABSTRACT FROM AUTHOR]

Objective: In healthy volunteers, a positive association has previously been observed between emotional awareness (EA), the ability to identify and describe emotional experiences in oneself and others, and resting heart rate variability (HRV), which is dominated by vagus nerve activity. The current study aimed to investigate the EA-HRV association across multiple assessments in a "real-world" ambulatory context in patients with long QT syndrome (LQTS) who are at genetic risk for sudden cardiac death., Methods: Participants (157 LQTS patients; Mean Age = 35.1, SD Age = 10.4; 115 women) completed the levels of emotional awareness scale (LEAS) on one occasion, which served as our measure of EA. In an ecological momentary assessment study involving 10 assessments per day over 3 days, multiple 5-minute ECG assessments (mean = 24.6, SD = 5.1) were obtained in each patient using a Holter monitor, from which high-frequency HRV (HF-HRV) was computed on each occasion., Results: There was a significant positive association between LEAS scores and HF-HRV controlling for biobehavioral covariates. We also detected a similar inverse relation between EA and mean heart rate., Conclusion: These findings suggest that, in patients with a well-defined genetic risk for ventricular arrhythmia and sudden death, the ability to experience emotions in a complex and differentiated way covaries with greater parasympathetic influences on the heart. These findings are consistent with the overlapping neural substrates of EA and HRV and their common contribution to adaptive emotional responding, consistent with the Neurovisceral Integration Model., (Copyright © 2024 by the American Psychosomatic Society.)

Emotional awareness (EA) is thought to facilitate psychological health by aiding emotion regulation in oneself and garnering social support from others. This study tested these potential relationships within a one-year longitudinal study of 460 women (age 23-91 years, mean 56.4 years) recently diagnosed with breast cancer (i.e., within four months). The women completed measures of emotional awareness, social support, social stress, affective symptoms, and well-being. Linear models tested EA as a moderator of social support and stress on affective symptoms and well-being. In those with higher EA, low social support was associated with greater depression and lower optimism. There was some evidence that higher EA predicted greater depression at baseline but lower depression at nine-month follow-up. These results support the idea that EA increases sensitivity to available social support and facilitates emotional adjustment over time, suggesting that assessment of EA could help guide clinicians in identifying those at greatest risk of adverse mental health outcomes in this population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The increased sensitivity of novel DNA sequencing techniques has made it possible to identify somatic mutations in small circulating clones of haematopoietic stem cells. When the mutation affects a 'driver' gene, the mutant clone gains a competitive advantage and has the potential to expand over time, a phenomenon referred to as clonal haematopoiesis (CH), which is emerging as a new risk factor for various non-haematological conditions, most notably cardiovascular disease (e.g. heart failure). Dilated cardiomyopathy (DCM) is a form of non-ischaemic heart failure that is characterized by a heterogeneous aetiology. The first evidence is arising that CH plays an important role in the disease course in patients with DCM, and a strong association of CH with multiple aetiologies of DCM has been described (e.g. inflammation, chemotherapy, and atrial fibrillation). The myocardial inflammation induced by CH may be an important trigger for DCM development for an already susceptible heart, e.g. in the presence of genetic variants, environmental triggers, and comorbidities. Studies investigating the role of CH in the pathogenesis of DCM are expected to increase rapidly. To move the field forward, it will be important to report the methodology and results in a standardized manner, so results can be combined and compared. The accurate measurement of CH in patients with DCM can provide guidance of specific (anti-inflammatory) therapies, as mutations in the CH driver genes prime the inflammasome pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The inflammatory foreign body response (FBR) is the main driver of biomaterial implant failure. Current strategies to mitigate the onset of a FBR include modification of the implant surface, release of anti-inflammatory drugs, and cell-scale implant porosity. The microporous annealed particle (MAP) scaffold platform is an injectable, porous biomaterial composed of individual microgels, which are annealed in situ to provide a structurally stable scaffold with cell-scale microporosity. MAP scaffold does not induce a discernible foreign body response in vivo and, therefore, can be used a "blank canvas" for biomaterial-mediated immunomodulation. Damage associated molecular patterns (DAMPs), such as IL-33, are potent regulators of type 2 immunity that play an important role in tissue repair. In this manuscript, IL-33 is conjugated to the microgel building-blocks of MAP scaffold to generate a bioactive material (IL33-MAP) capable of stimulating macrophages in vitro via a ST-2 receptor dependent pathway and modulating immune cell recruitment to the implant site in vivo, which indicates an upregulation of a type 2-like immune response and downregulation of a type 1-like immune response., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

The need for safe and effective methods to manage deep vein thrombosis (DVT), given the risks associated with anticoagulants and thrombolytic agents, motivated research into innovative approaches to resolve blood clots. In response to this challenge, sonothrombolysis is being explored as a technique that combines microbubbles, ultrasound, and thrombolytic agents to facilitate the aggressive dissolution of thrombi. Prior studies have indicated that relatively large microbubbles accelerate the dissolution process, either in an in vitro or an arterial model. However, sonothrombolysis using large microbubbles must be evaluated in venous thromboembolism diseases, where blood flow velocity is not comparable. In this study, the efficacy of sonothrombolysis was validated in a murine model of pre-existing DVT. During therapy, microfluidically produced microbubbles of 18 μm diameter and recombinant tissue plasminogen activator (rt-PA) were administered through a tail vein catheter for 30 min, while ultrasound was applied to the abdominal region of the mice. Three-dimensional ultrasound scans were performed before and after therapy for quantification. The residual volume of the thrombi was 20% in animals post sonothrombolysis versus 52% without therapy ( p = 0.012 < 0.05 ), indicating a significant reduction in DVT volume. Histological analysis of tissue sections confirmed a reduction in DVT volume post-therapy. Therefore, large microbubbles generated from a microfluidic device show promise in ultrasound-assisted therapy to address concerns related to venous thromboembolism., (© 2024. The Author(s).)

Objective: The influence of unconscious emotional processes on pain remains poorly understood. The present study tested whether cues to forgotten unpleasant images might amplify pain (i.e., in the absence of conscious recall)., Methods: Seventy-two healthy female adults (19 to 34 years) performed an adapted Think/No-think paradigm (T/NT) using 72 combinations of neutral face images (cues) paired with 36 neutral and 36 unpleasant images. After completion of the T/NT task, cues associated with forgotten neutral or unpleasant images were identified. Cues to either neutral or unpleasant images from the NT condition were then presented in randomized order while participants received intermediate-level thermal pain stimulation on the left hand. Ratings of both pain intensity and unpleasantness were acquired after each trial., Results: Mean pain unpleasantness ratings were greater during presentation of cues to forgotten negative versus neutral images (5.52 [SD = 2.06] versus 5.23 [SD = 2.10]; p = .02). This pattern was also present when comparing cues to remembered negative versus neutral images (5.62 [SD = 1.94] versus 5.04 [SD = 1.90]; p < .001). Mean pain intensity ratings were higher for cues to negative versus neutral images when remembered (5.48 [SD = 1.79] versus 5.00 [SD = 1.69]; p < .001), but not when forgotten (5.27 [SD = 1.96] versus 5.16 [SD = 1.93]; p = .30)., Conclusions: Using an adapted T/NT-Pain paradigm, this study demonstrated that cues to nonrecallable (but potentially unconsciously activated) negative emotional memories amplify pain unpleasantness, similar to known effects of conscious negative emotions., (Copyright © 2024 by the American Psychosomatic Society.)

The term "lovebirds" is often used to describe the loving behaviors and interactions between two romantic partners, but what specific processes distinguish these flourishing lovebird relationships from other committed but "numbed" relationships? The present study aimed to address this knowledge gap through the development and preliminary validation of the Lovebird Scale. The Lovebird Scale describes the thoughts, feelings, behaviors, and habits that constitute and maintain relationship flourishing, which in turn could promote aspects of individual flourishing such as positive affect. We conducted three studies using data collected from 996 English-speaking U.S. adults (64.2% Female, M = 39.2 years old) who reported being in a romantic relationship for at least six months ( M = 11.2 years). In Study 1, we conducted an exploratory factor analysis to determine the underlying factor structure. In Study 2, confirmatory factor analyses revealed a three-factor model nested within a higher-order factor representing lovebird relationships. In Study 3, we cross-validated the higher-order structure, examined the construct validity of the scale, and explored associations between the Lovebird Scale and affective state. Finally, we discuss how the Lovebird Scale contributes to the growing field of positive relationship science as well as conceptual and clinical implications of the scale.

Background: This study explored the association between emotion word repertoire (EWR), attachment, reflective functioning and personality organization (PO) and suicidal behavior in borderline personality disorder (BPD) patients., Methods: The current study performed a secondary data analysis from a randomized control trial for BPD patients (all female; n = 87; age: m = 27; SD = 7.42). EWR was assessed via machine-scoring transcripts of Adult Attachment Interviews (AAI) for affective words using the VETA electronic scoring software for the Levels of Emotional Awareness Scale (LEAS). Generated scores were related to impairments in PO (Structured Interview for Personality Organization; STIPO), attachment organization (AAI) and mentalization (Reflective Functioning Scale), general symptom severity (Brief Symptom Inventory; BSI-53), self-harm and suicidal behavior. Independent effects of the investigated predictors were studied using Bayesian path analysis., Results: Corrected for education, findings in Bayesian path analysis suggest an independent negative association between EWR and suicide attempts (BE = -.32; 95 % CI [-.51, -.12]) and positive associations of deficits in PO with psychiatric symptoms (BE = .23; 95 % CI [.01, .44]) as well as suicide attempts (BE = .30; 95 % CI [.08, .49])., Discussion: The findings underscore the potential role of high EWR and PO as a protective factor for suicidal behavior in individuals with BPD., Competing Interests: Richard D. Lane has disclosed an outside interest in the Electronic Levels of Emotional Awareness Scale to the University of Arizona. Conflicts of interest resulting from this interest are being managed by The University of Arizona in accordance with its policies., (© 2024 The Authors.)

Background: The present longitudinal investigation had two major goals. First, we intended to clarify whether depressed patients are characterized by impairments of emotional awareness for the self and the other during acute illness and whether these impairments diminish in the course of an inpatient psychiatric treatment program. Previous research based on the performance measure Levels of Emotional Awareness Scale (LEAS) provided inconsistent findings concerning emotional self-awareness in clinical depression. Second, we investigated whether cognitive and affective empathic abilities change from acute illness to recovery in depressed patients., Methods: Fifty-eight depressed patients were tested on admission and after 6-8 weeks of inpatient psychiatric treatment. A sample of fifty-three healthy individuals were also examined twice at an interval of 6-8 weeks. The LEAS and the Interpersonal Reactivity Index (IRI) were administered to assess emotional awareness and empathic abilities. Written texts were digitalized and then analyzed using the electronic scoring program geLEAS, the German electronic Levels of Emotional Awareness Scale., Results: Depressed patients reported more depressive symptoms than healthy controls and less severe depressive symptomatology at time 2 compared to time 1. Independent of time, depressed individuals tended to show lower geLEAS self scores and had lower geLEAS other scores than healthy individuals. Depressed patients showed higher personal distress scores than healthy individuals at both measurement times. No group differences were observed for the cognitive empathy scales of the IRI (perspective taking and fantasy) and empathic concern, but empathic concern decreased significantly in depressed patients from time 1 to time 2. Empathic abilities as assessed by the IRI were not significantly correlated with emotional awareness for others, neither in the whole sample, nor in the patient and control subsample., Conclusions: Depressed patients seem to be characterized by impairments in emotional awareness of others during acute illness and recovery, but they also tend to show deficits in emotional self-awareness compared to healthy individuals. Self-reported cognitive empathic abilities seem to be at normal levels in depressed patients, but their heightened self-focused affective empathy may represent a vulnerability factor for depressive disorders., (© 2024. The Author(s).)

Importance: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes., Objective: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis., Design, Setting, and Participants: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024., Exposure: The number of minutes from emergency department arrival to antibiotic administration., Main Outcomes and Measures: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome., Results: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes., Conclusions and Relevance: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Background: Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI)., Methods: Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21., Results: Aortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p < 0.01) in post-MI mice versus sham-treated animals at day 3 and 21. Treatment with NAC and ADAMTS13 significantly attenuated the post-MI increase for all four molecular targets by > 50% (p < 0.05 vs. non-treated at day 3 and 21). On aortic root histology, mice undergoing MI versus controls had 2-4 fold greater plaque size and macrophage content (p < 0.05), approximately 20-fold greater platelet adhesion (p < 0.05), and increased staining for markers of platelet transforming growth factor-β1 signaling. Accelerated plaque growth and inflammatory activation was almost entirely prevented by ADAMTS13 and NAC. Inhibition of FXI had no significant effect on molecular imaging signal or plaque morphology., Conclusions: Plaque inflammatory activation in remote arteries after MI is strongly influenced by VWF-mediated platelet adhesion to the endothelium. These findings support investigation into new secondary preventive therapies for reducing non-culprit artery events after MI., (© 2024. The Author(s).)

Socioemotional skills, such as the ability to recognize, understand, and regulate the emotions of self and others, are associated with both physical and emotional health. The present study tested the effectiveness of a recently validated online training program for increasing these emotional skills in adults. In this study, 448 participants (323 female) were randomly assigned to complete this training program or a placebo control program. Among those who completed the training program or placebo ( N = 326), the training program led to improved scores post-training on measures of interoceptive and emotional awareness, mindfulness, emotion recognition, and emotion regulation strategies (e.g., reduced emotion suppression and greater impulse control) relative to placebo. In a smaller group of participants who also completed a 6-month follow-up visit ( N = 94), sustained improvements were observed on several measures in those who completed the training program, while the placebo group instead showed decreased performance. This suggested a potentially protective effect against emotional challenges associated with the COVID-19 pandemic occurring during this time. These results suggest that this online training program shows promise in improving emotional skills relevant to adaptive social and emotional functioning, and that it might be useful as an intervention within at-risk populations and those with emotional disorders associated with reduced application of these skills. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Objectives: Evidence suggests that emotional awareness-the ability to identify and label emotions-may be impaired in schizophrenia and related to positive symptom severity. Exposure to childhood maltreatment is a risk factor for both low emotional awareness and positive symptoms., Methods: The current investigation examines associations between a performance-based measure of emotional awareness, positive symptom severity, and childhood maltreatment exposure in 44 individuals with a schizophrenia-spectrum disorder and 48 healthy comparison participants using the electronic Levels of Emotional Awareness Scale (eLEAS), Positive and Negative Syndrome Scale (PANSS) and Childhood Trauma Questionnaire (CTQ)., Results: Patients demonstrated significant deficits in emotional awareness overall, which was true for both self and others. In patients, lower emotional awareness was significantly associated with more severe positive symptoms. Emotional awareness was significantly impaired in patients with schizophrenia with self-reported maltreatment exposure, relative to other groups. Severity of maltreatment was not significantly associated with emotional awareness or positive symptoms when looking continuously, and there was no significant indirect effect., Conclusion: These data suggest that emotional awareness impairments observed in schizophrenia may be exacerbated by exposure to childhood maltreatment, possibly putting individuals at greater risk for experiencing positive symptoms of psychosis., Competing Interests: RL has disclosed an outside interest in the Electronic Levels of Emotional Awareness Scale owned by Equanimity Health Technologies, LLC to the University of Arizona. Conflicts of interest resulting from this interest are being managed by The University of Arizona in accordance with its policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Beals, Torregrossa, Smith, Lane and Sheffield.)

Early adversity has been consistently linked to mental health outcomes, but the underlying pathways remain unclear. One previous study found an association between early adversity and trait emotional awareness (EA), which has itself been linked to health outcomes, but links to mental health were not explicitly examined. The aim of the current study was to test the hypothesis that the association between early adversity and health can be partially accounted for by differences in EA within a large student sample (n = 196). Participants completed measures of early adversity, EA, and current emotional functioning (i.e., depression, anxiety, somatization, positive/negative affect). Bayesian analyses found the most evidence for models with an interaction between sex and early adversity in predicting emotional functioning - revealing the expected negative relationship between early adversity and EA in females, but a positive relationship in males. Early adversity, but not EA, was associated with depression, anxiety, and implicit negative affect. Only explicit positive affect was associated with both early adversity and EA, and EA partially mediated the negative association between early adversity and positive affect. These results provide limited support for EA as a mediating pathway for the effects of early adversity on mental health., Competing Interests: Declaration of Interest: None of the authors have any conflicts of interest to disclose.

Purpose of Review: Improvements in ultrasound methods for detecting microbubble ultrasound enhancing agents have led to an increase in the use of perfusion imaging with myocardial contrast echocardiography (MCE). This technique is now beginning to play an important role in specific clinical scenarios, which is the focus of this review., Recent Findings: MCE was originally conceived as a technique for detecting resting perfusion abnormalities related to ischemia at rest or during stress from coronary artery disease. More recently, MCE has increasingly been used in circumstances where the technique's ability to provide rapid, quantitative, or bedside assessment of perfusion is advantageous. Quantitative MCE is also increasingly being used as a research technique for evaluating pathobiology and therapy that involve changes in the myocardial microcirculation. While MCE was developed and validated decades ago, it is only now beginning to be used by an increasing number of clinicians due to improvements in imaging technology and recognition of specific situations where the technique is impactful., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Immunothrombosis-immune-mediated activation of coagulation-is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1β and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy and is approved for the treatment of hypoxaemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps, and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19., Competing Interests: Conflict of interest: N.P. has received a training fellowship from the International Society on Thrombosis and Haemostasis and research funding from the International Network of VENous Thromboembolism Clinical Research Networks (INVENT), outside of the present work. Y.K. is an inventor on a patent application (US20180369278A1) by the University of Michigan on the use of biogases in vascular disease. M.D.N. reports personal fees as an invited speaker from Bayer, Daiichi Sankyo, and Viatris, personal fees for advisory board membership from LEO Pharma and Pfizer, and institutional funding from LEO Pharma. G.K. has received honorary fees from Swedish Orphan Biovitrum, Chugai-Roche, and Amgen. A.B. received a travel grant from Kiniksa Pharmaceuticals Ltd to attend the 2019 AHA Scientific Sessions and honoraria from Effetti s.r.l. (Milan, Italy) to collaborate on the medical website http://www.inflammology.org, outside the present work. J.M.C. has received personal fees for scientific advisory boards and consulting from Abbott, Anthos, Alnylam, Bristol Myers Squibb, Five Prime Therapeutics, Pfizer, Takeda, and research funding from CSL Behring, outside of the submitted work. R.D.C. has received personal fees from Boehringer-Ingelheim, Bayer, BMS-Pfizer, Daiichi Sankyo, Novartis, Roche, Sanofi, Amgen, Milestone, Menarini, AstraZeneca, and Guidotti, outside the submitted work. A.A. has received research grant funding and has served as a paid scientific advisor to Implicit Biosciences, Kiniksa, Lilly, Merck, Novartis, Novo Nordisk, Olatec, R-Pharm, Serpin Pharma, and Swedish Orphan Biovitrum, outside of the submitted work. E.G. has nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Emotional intelligence (EI) is associated with a range of positive health, wellbeing, and behavioral outcomes. The present article describes the development and validation of an online training program for increasing EI abilities in adults. The training program was based on theoretical models of emotional functioning and empirical literature on successful approaches for training socioemotional skills and resilience., Methods: After an initial design, programming, and refinement process, the completed online program was tested for efficacy in a sample of 326 participants (72% female) from the general population. Participants were randomly assigned to complete either the EI training program ( n = 168) or a matched placebo control training program ( n = 158). Each program involved 10-12 hours of engaging online content and was completed during either a 1-week ( n = 175) or 3-week ( n = 151) period., Results: Participants who completed the EI training program showed increased scores from pre- to post-training on standard self-report (i.e., trait) measures of EI (relative to placebo), indicating self-perceived improvements in recognizing emotions, understanding emotions, and managing the emotions of others. Moreover, those in the EI training also showed increased scores in standard performance-based (i.e., ability) EI measures, demonstrating an increased ability to strategically use and manage emotions relative to placebo. Improvements to performance measures also remained significantly higher than baseline when measured six months after completing the training. The training was also well-received and described as helpful and engaging., Discussion: Following a rigorous iterative development process, we created a comprehensive and empirically based online training program that is well-received and engaging. The program reliably improves both trait and ability EI outcomes and gains are sustained up to six months post-training. This program could provide an easy and scalable method for building emotional intelligence in a variety of settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Durham, Smith, Cloonan, Hildebrand, Woods-Lubert, Skalamera, Berryhill, Weihs, Lane, Allen, Dailey, Alkozei, Vanuk and Killgore.)

Introduction: Current literature on pharmacy students' and residents' experience attending camps for children with diabetes focuses on the experience at an individual campsite. The objective of this study was to examine the demographics and gains in understanding that pharmacy learners achieve when volunteering as medical staff at camps for children with type 1 diabetes (T1D)., Methods: National listservs were used to identify pharmacists who precept pharmacy students and residents at diabetes camps. These self-identified pharmacists shared pre- and post-camp electronic surveys with their respective pharmacy learners. Statistical analysis was completed using SPSS Version 25 (IBM, Corp.)., Results: Eighty-six pharmacy learners completed the pre-camp survey and 69 completed the post-camp survey. Most were Caucasian, in their fourth professional year, and participated in residential camps that lasted six and one-half days on average. Learners consistently engaged in patient care activities including: carbohydrate counting (87%), bolus insulin dose calculations (86%), treatment of hypo/hyperglycemic episodes (86%), blood glucose testing (83%), blood sugar trend evaluation (78%), basal insulin dosing calculations (74%), and insulin pump site changes (72%). Learners demonstrated statistically significant gains in every index measured with the exception of glucometer use. Eighty-seven percent indicated they learned how to appropriately manage T1D, 37% gained empathy for those living with T1D, and 13% learned how to work in a medical team., Conclusions: Pharmacy learners who volunteered at diabetes camps experienced large gains in their understanding of concepts and devices, comfort with performing patient care tasks, and compassion for children and their families living with T1D., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Emotional awareness is the ability to identify, interpret, and verbalize the emotional responses of oneself and those of others. The Levels of Emotional Awareness Scale (LEAS) is an objective performance inventory that accurately measures an individual's emotional awareness. LEAS assessments are typically scored manually and are therefore both time consuming and cognitively demanding. This study presents a German electronic scoring program for the LEAS (geLEAS), the first non-English computerized assessment approach of the LEAS., Methods: Data were collected from a healthy German community sample ( N = 208). We developed a modern software for computerizing LEAS scoring, an open-source text-based emotion assessment tool called VETA (Verbal Emotion in Text Assessment). We investigated if the software would arrive at similar results as hand scoring in German and if emotional awareness would show similar associations to sociodemographic information and psychometric test results as in previous studies., Results: The most frequently used scoring method of the geLEAS shows excellent internal consistency (α = 0.94) and high correlations with hand scoring ( r = 0.97, p < 0.001). Higher emotional awareness measured by the geLEAS is associated with female gender, older age, and higher academic achievement (all p < 0.001). Moreover, it is linked to the ability to identify emotions in facial expressions ( p < 0.001) and more accurate theory of mind functioning ( p < 0.001)., Discussion: An automated method for evaluating emotional awareness greatly expands the ability to study emotional awareness in clinical care and research. This study aims to advance the use of emotional awareness as a clinical and scientific parameter., Competing Interests: RL has disclosed an outside interest in the Electronic Levels of Emotional Awareness Scale owned by Equanimity Health Technologies, LLC to the University of Arizona. Conflicts of interest resulting from this interest are being managed by The University of Arizona in accordance with its policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Herpertz, Taylor, Allen, Herpertz, Opel, Richter, Subic-Wrana, Dieris-Hirche and Lane.)

We sought to develop new quantitative approaches to characterize the spatial distribution of mammographic density and contrast enhancement of suspicious contrast-enhanced mammography (CEM) findings to improve malignant vs. benign classifications of breast lesions. We retrospectively analyzed all breast lesions that underwent CEM imaging and tissue sampling at our institution from 2014-2020 in this IRB-approved study. A penalized linear discriminant analysis was used to classify lesions based on the averaged histograms of radial distributions of mammographic density and contrast enhancement. T-tests were used to compare the classification accuracies of density, contrast, and concatenated density and contrast histograms. Logistic regression and AUC-ROC analyses were used to assess if adding demographic and clinical data improved the model accuracy. A total of 159 suspicious findings were evaluated. Density histograms were more accurate in classifying lesions as malignant or benign than a random classifier (62.37% vs. 48%; p < 0.001), but the concatenated density and contrast histograms demonstrated a higher accuracy (71.25%; p < 0.001) than the density histograms alone. Including the demographic and clinical data in our models led to a higher AUC-ROC than concatenated density and contrast images (0.81 vs. 0.70; p < 0.001). In the classification of invasive vs. non-invasive malignancy, the concatenated density and contrast histograms demonstrated no significant improvement in accuracy over the density histograms alone (77.63% vs. 78.59%; p = 0.504). Our findings suggest that quantitative differences in the radial distribution of mammographic density could be used to discriminate malignant from benign breast findings; however, classification accuracy was significantly improved with the addition of contrast-enhanced imaging data from CEM. Adding patient demographic and clinical information further improved the classification accuracy.

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these high-dimensional profiles need to be reduced to have relevance in the context of CD. Machine learning approaches are optimally suited to bridge this gap in knowledge by contextualizing the metabolic alterations in CD using genome-scale metabolic network reconstructions. Our work presents a framework for studying altered metabolic reactions between patients with CD and controls using publicly available transcriptomic data and existing gene-driven metabolic network reconstructions. Additionally, we apply the same methods to patient-derived ileal enteroids to explore the utility of using this experimental in vitro platform for studying CD. Furthermore, we have piloted an untargeted metabolomics approach as a proof-of-concept validation strategy in human ileal mucosal tissue. These findings suggest that in silico metabolic modeling can potentially identify pathways of clinical relevance in CD, paving the way for the future discovery of novel diagnostic biomarkers and therapeutic targets., (© 2022. The Author(s).)

It is unclear at present whether psychopathic tendencies are associated with lower or higher levels of emotional awareness (EA). Given that psychopathy includes a proficiency for manipulating others, one might expect an elevated ability to identify and use information about others' emotions. On the other hand, empathic deficits in psychopathy could arise from reduced emotional awareness. Further, heterogeneity in psychopathy may also play a role, wherein 'secondary' psychopathy is associated with early adversity and high negative affect, while 'primary' psychopathy is not. In this paper, we tested the relationship between EA and psychopathic tendencies in 177 undergraduate students (40 males) who completed the levels of emotional awareness scale (LEAS), the triarchic psychopathy measure (TPM), the affective (empathy-related) subscales of the interpersonal reactivity index (IRI), and two measures of early adversity: the childhood experiences of care and abuse questionnaire (CECA) and the childhood trauma questionnaire (CTQ). We found that lower LEAS scores were associated with higher TPM and lower IRI empathy scores, but these relationships were primarily present in those with early adversity and high negative affect. This suggests that lower EA may be selectively associated with higher levels of secondary psychopathy, while those with higher levels of primary psychopathy remain capable of higher EA., Competing Interests: Richard Lane has disclosed an outside interest in the Electronic Levels of Emotional Awareness Scale owned by Equanimity Health Technologies, LLC to the University of Arizona. Conflicts of interest resulting from this interest are being managed by The University of Arizona in accordance with its policies. All other authors have declared that no competing interests exist. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2022 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Perfusion defects during stress can occur in hypertrophic cardiomyopathy (HCM) from either structural or functional abnormalities of the coronary microcirculation. In this study, vasodilator stress myocardial contrast echocardiography (MCE) was used to quantify and spatially characterize hyperemic myocardial blood flow (MBF) deficits in HCM., Methods: Regadenoson stress MCE was performed in patients with septal-variant HCM (n = 17) and healthy control subjects (n = 15). The presence and spatial distribution (transmural diffuse, patchy, subendocardial) of perfusion defects was determined by semiquantitative analysis. Kinetic analysis of time-intensity data was used to quantify MBF, microvascular flux rate (β), and microvascular blood volume. In patients undergoing septal myectomy (n = 3), MCE was repeated > 1 years after surgery.  RESULTS: In HCM subjects, perfusion defects during stress occurred in the septum in 80%, and in non-hypertrophied regions in 40%. The majority of septal defects (83%) were patchy or subendocardial, while 67% of non-hypertrophied defects were transmural and diffuse. On quantitative analysis, hyperemic MBF was approximately 50% lower (p < 0.001) in the hypertrophied and non-hypertrophied regions of those with HCM compared to controls, largely based on an inability to augment β, although hypertrophic regions also had blood volume deficits. There was no correlation between hyperemic MBF and either percent fibrosis on magnetic resonance imaging or outflow gradient, yet those with higher degrees of fibrosis (≥ 5%) or severe gradients all had low septal MBF during regadenoson. Substantial improvement in hyperemic MBF was observed in two of the three subjects undergoing myectomy, both of whom had severe pre-surgical outflow gradients at rest., Conclusion: Perfusion defects on vasodilator MCE are common in HCM, particularly in those with extensive fibrosis, but have a different spatial pattern for the hypertrophied and non-hypertrophied segments, likely reflecting different contributions of functional and structural abnormalities. Improvement in hyperemic perfusion is possible in those undergoing septal myectomy to relieve obstruction.  TRIAL REGISTRATION: ClinicalTrials.gov NCT02560467., (© 2022. The Author(s).)

Introduction: Anaphylaxis is a life-threatening condition necessitating emergent management. However, the benefits of prolonged observation and indications for hospitalization are not well established. Through the implementation of a disposition-focused clinical decision support tool (CDST), this quality improvement initiative aimed to reduce hospitalization for low-risk patients presenting to the pediatric emergency department (PED) with anaphylaxis from 49% to ≤12% within 12 months of implementation., Methods: The intervention included patients 18 years and younger of age presenting with anaphylaxis to the PED. A multidisciplinary team identified a 2006 evidence-based guideline as a significant contributor to hospitalization. The updated guideline incorporated a disposition-focused CDST that stratified patients as low-risk or high-risk and recommended discharge of low-risk patients after a 4-hour observation period. The primary outcome measure was the percentage of low-risk patients hospitalized. Balancing measures included low-risk patient 72-hour return rate and PED length of stay for all comers. Secondary outcomes included a focused cost analysis., Results: Fifty-three children preintervention and 43 children postintervention presenting with anaphylaxis met low-risk criteria. Postimplementation, hospitalization of low-risk patients decreased from 49% to 7% ( P < 0.0001). No low-risk patients returned in 72 hours for an anaphylaxis-related concern ( P = 0.83). The median PED length of stay increased from 189 to 193 minutes ( P < 0.0001). The median cost per low-risk encounter decreased by $377 ( P = 0.013)., Conclusions: After implementing an evidence-based disposition-focused CDST, hospitalization of low-risk patients presenting to the PED with anaphylaxis significantly decreased without an increase in 72-hour returns. In addition, patient encounters demonstrated cost savings., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Type 1 diabetes (T1D) is caused by the autoimmune loss of insulin-producing beta cells in the pancreas. The only clinical approach to patient management of blood glucose that doesn't require exogenous insulin is pancreas or islet transplantation. Unfortunately, donor islets are scarce and there is substantial islet loss immediately after transplantation due, in part, to the local inflammatory response. The delivery of stem cell-derived beta cells ( e.g., from induced pluripotent stem cells) and dissociated islet cells hold promise as a treatment for T1D; however, these cells typically require re-aggregation in vitro prior to implantation. Microporous scaffolds have shown high potential to serve as a vehicle for organization, survival, and function of insulin-producing cells. In this study, we investigated the use of microporous annealed particle (MAP) scaffold for delivery of enzymatically dissociated islet cells, a model beta cell source, within the scaffold's interconnected pores. We found that MAP-based cell delivery enables survival and function of dissociated islets cells both in vitro and in an in vivo mouse model of T1D., Competing Interests: Competing Interests: Donald Griffin has financial interests in Tempo Therapeutics which aims to commercialize MAP technology for dermal wound healing.

Biomaterials capable of generating growth factor gradients have shown success in guiding tissue regeneration, as growth factor gradients are a physiologic driver of cell migration. Of particular importance, a focus on promoting endothelial cell migration is vital to angiogenesis and new tissue formation. Microporous Annealed Particle (MAP) scaffolds represent a unique niche in the field of regenerative biomaterials research as an injectable biomaterial with an open porosity that allows cells to freely migrate independent of material degradation. Recently, we have used the MAP platform to heterogeneously include spatially isolated heparin-modified microgels (heparin microislands) which can sequester growth factors and guide cell migration. In in vitro sprouting angiogenesis assays, we observed a parabolic relationship between the percentage of heparin microislands and cell migration, where 10% heparin microislands had more endothelial cell migration compared to 1% and 100%. Due to the low number of heparin microisland ratios tested, we hypothesize the spacing between microgels can be further optimized. Rather than use purely empirical methods, which are both expensive and time intensive, we believe this challenge represents an opportunity to use computational modeling. Here we present the first agent-based model of a MAP scaffold to optimize the ratio of heparin microislands. Specifically, we develop a two-dimensional model in Hybrid Automata Library (HAL) of endothelial cell migration within the unique MAP scaffold geometry. Finally, we present how our model can accurately predict cell migration trends in vitro, and these studies provide insight on how computational modeling can be used to design particle-based biomaterials. STATEMENT OF SIGNIFICANCE: While the combination of experimental and computational approaches is increasingly being used to gain a better understanding of cellular processes, their combination in biomaterials development has been relatively limited. Heparin microislands are spatially isolated heparin microgels; when located within a microporous annealed particle (MAP) scaffold, they can sequester and release growth factors. Importantly, we present the first agent-based model of MAP scaffolds to optimize the ratio of heparin microislands within the scaffold to promote endothelial cell migration. We demonstrate this model can accurately predict trends in vitro, thus opening a new avenue of research to aid in the design of MAP scaffolds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)