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Erythropoietin (EPO) exerts non-canonical roles beyond erythropoiesis that are developmentally, structurally, and physiologically relevant for the heart as a paracrine factor. The role for paracrine EPO signalling and cellular crosstalk in the adult is uncertain. Here, we provided novel evidence showing cardiomyocyte restricted loss of function in Epo in adult mice induced hyper-compensatory increases in Epo expression by adjacent cardiac endothelial cells via HIF-2α independent mechanisms. These hearts showed concentric cellular hypertrophy, elevated contractility and relaxation, and greater resistance to ischemia-reperfusion injury. Voluntary exercise capacity compared to control hearts was improved independent of any changes to whole-body metabolism or blood O 2 content or delivery (i.e., hematocrit). Our findings suggest cardiac EPO had a localized effect within the normoxic heart, which was regulated by cell-specific EPO-reciprocity between cardiomyocytes and endothelium. Within the heart, hyper-compensated endothelial Epo expression was accompanied by elevated Vegfr1 and Vegfb RNA, that upon pharmacological pan-inhibition of VEGF-VEGFR signaling, resulted in a paradoxical upregulation in whole-heart Epo . Thus, we provide the first evidence that a novel EPO-EPOR/VEGF-VEGFR axis exists to carefully mediate cardiac homeostasis via cardiomyocyte-endothelial EPO crosstalk., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Marrow, Alshamali, Edgett, Allwood, Cochrane, Al-Sabbag, Ayoub, Ask, Hare, Brunt and Simpson.)

Alternative models of traumatic stress and broader psychopathology have been proposed to address issues of heterogeneity, comorbidity, clinical utility, and equitable representation. However, systematic and practical methods and guidelines to organize and apply these models remain scarce. The Middle-Out Approach is a novel, integrative, contextually informed framework for organizing and applying existing empirical methods to evaluate current and alternative traumatic stress reactions. Rather than beginning to identify traumatic stress reactions from the top-down (i.e., disorder-first approach) or bottom-up (i.e., symptom-first approach), constructs are evaluated from the middle out (i.e., presentation-first approach), unconstrained by higher-order disorders or lower-order diagnostic symptoms. This approach provides innovation over previous methods at multiple levels, including the conceptualization of traumatic stress reactions as well as the type of assessments and data sources used and how they are used in statistical analyses. Conceptualizations prioritize the identification of middle-order phenotypes, representing person-centered clinical presentations, which are informed by the integration of multidimensional, transdiagnostic, and multimodal (e.g., psychosocial, physiological) assessments and/or data sources. Integrated data are then analyzed concurrently using person-centered statistical models to identify precise, discrete, and representative health outcomes within broader heterogeneous samples. Subsequent variable-centered analyses are then used to identify culturally sensitive and contextually informed correlates of phenotypes, their clinical utility, and the differential composition within and between broader traumatic stress reactions. Examples from the moral injury literature are used to illustrate practical applications that may increase clinical utility and the accurate representation of health outcomes for diverse individuals and communities., (© 2023 International Society for Traumatic Stress Studies.)

Objective: To determine if and how cardiometabolic conditions (MetC) may be associated with posttraumatic stress disorder (PTSD) symptoms over time when controlling for the influence of potentially confounding variables., Method: Parallel process latent growth modeling was applied to self-reported longitudinal data collected from 35,788 World Trade Center 9/11 survivors to determine how the development and course of PTSD symptoms and MetC influence each other when controlling for age, sex, race/ethnicity, preexisting traumas, physical health problems, general psychological distress, smoking, and alcohol use., Results: A unidirectional relationship was found in which the intercept of PTSD symptoms predicted the slope of MetC. Hyperarousal (β = .172) and emotional numbing (β = .171) PTSD symptoms demonstrated the strongest association with MetC changes over and above the effects of control variables and potential confounders. Post hoc analyses indicated that utilization of PTSD-related psychotherapy was associated with decreased early presentations of MetC following trauma, which may have vital implications for the integrated treatment of trauma-exposed individuals., Conclusions: Findings have strong theoretical and clinical implications for conceptualizing traumatic stress reactions as systemic processes and utilizing integrated treatment practices following psychological trauma. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The role of erythropoietin (EPO) has extended beyond hematopoiesis to include cytoprotection, inotropy, and neurogenesis. Extra-renal EPO has been reported for multiple tissue/cell types, but the physiological relevance remains unknown. Although the EPO receptor is expressed by multiple cardiac cell types and human recombinant EPO increases contractility and confers cytoprotection against injury, whether the heart produces physiologically meaningful amounts of EPO in vivo is unclear. We show a distinct circadian rhythm of cardiac EPO mRNA expression in adult mice and increased mRNA expression during embryogenesis, suggesting physiological relevance to cardiac EPO production throughout life. We then generated constitutive, cardiomyocyte-specific EPO knockout mice driven by the Mlc2v promoter (EPOfl/fl:Mlc2v-cre+/-; EPO Δ/Δ-CM ). During cardiogenesis, cardiac EPO mRNA expression and cellular proliferation were reduced in EPO Δ/Δ-CM hearts. However, in adult EPO Δ/Δ- CM mice, total heart weight was preserved through increased cardiomyocyte cross-sectional area, indicating the reduced cellular proliferation was compensated for by cellular hypertrophy. Echocardiography revealed no changes in cardiac dimensions, with modest reductions in ejection fraction, stroke volume, and tachycardia, whereas invasive hemodynamics showed increased cardiac contractility and lusitropy. Paradoxically, EPO mRNA expression in the heart was elevated in adult EPO Δ/Δ-CM , along with increased serum EPO protein content and hematocrit. Using RNA fluorescent in situ hybridization, we found that Epo RNA colocalized with endothelial cells in the hearts of adult EPO Δ/Δ-CM mice, identifying the endothelial cells as a cell responsible for the EPO hyper-expression. Collectively, these data identify the first physiological roles for cardiomyocyte-derived EPO. We have established cardiac EPO mRNA expression is a complex interplay of multiple cell types, where loss of embryonic cardiomyocyte EPO production results in hyper-expression from other cells within the adult heart., Competing Interests: Declaration of competing interest The authors report no commercial or proprietary interest in any product or concept discussed in this article., (Copyright © 2023. Published by Elsevier Ltd.)

In response to Marx et al.'s (2023) article, "The PTSD Criterion A debate: A brief history, current status, and recommendations for moving forward," this commentary offers agreement with the recommendation to conduct population-based studies to inform future Criterion A changes. However, to fully address the debate as to whether Criterion A should be expanded, limited, eliminated, or remain unchanged, it is critical that future population-based research focus on cultural inclusivity and the addition of potentially traumatic experiences that are collective and/or cumulative versus individual and discrete. To further understand the etiology of mental health distress and disorder and the role of adverse life experiences, it is also recommended that adverse event specifiers be added to disorders not currently considered to be event-related. The ability to identify the potential long-term effects of adverse life experiences in relation to disorders other than posttraumatic stress disorder (e.g., major depressive disorder) could help validate experiences, reduce stigma, and further advance research on etiology and interventions., (© 2024 International Society for Traumatic Stress Studies.)

Background: Diaphragm atrophy can contribute to dyspnea in patients with heart failure (HF) with its link to central neurohormonal overactivation. HF medications that cross the blood-brain barrier could act centrally and improve respiratory function, potentially alleviating diaphragmatic atrophy. Therefore, we compared the benefit of central- vs peripheral-acting HF drugs on respiratory function, as assessed by a single cardiopulmonary exercise test (CPET) and outcomes in HF patients., Methods: A retrospective study was conducted of 624 ambulatory adult HF patients (80% male) with reduced left ventricular ejection fraction ≤ 40% and a complete CPET, followed at a single institution between 2001 and 2017. CPET parameters, and the outcomes all-cause death, a composite endpoint (all-cause death, need for left ventricular assist device, heart transplantation), and all-cause and/or HF hospitalizations, were compared in patients receiving central-acting (n = 550) vs peripheral-acting (n = 74) drugs., Results: Compared to patients who receive peripheral-acting drugs, patients who receive central-acting drugs had better respiratory function (peak breath-by breath oxygen uptake [VO 2 ], P  = 0.020; forced expiratory volume in 1 second [FEV1], P  = 0.007), and ventilatory efficiency (minute ventilation / carbon dioxide production [VE/VCO 2 ], P < 0.001; end-tidal carbon dioxide tension [PETCO 2 ], P  = 0.015; and trend for forced vital capacity [FVC], P  = 0.056). Many of the associations between the CPET parameters and drug type remained significant after multivariate adjustment. Moreover, patients receiving central-acting drugs had fewer composite events ( P  = 0.023), and HF hospitalizations ( P  = 0.044), although significance after multivariant correction was not achieved, despite the hazard ratio being 0.664 and 0.757, respectively., Conclusions: Central-acting drugs were associated with better respiratory function as measured by CPET parameters in HF patients. This could extend to clinically meaningful composite outcomes and hospitalizations but required more power to be definitive in linking to drug effect. Central-acting HF drugs show a role in mitigating diaphragm weakness., (© 2024 The Authors.)

This study examined posttraumatic stress disorder (PTSD) symptoms in relation to physical assaults and weapons-related victimization, as well as the moderating roles of demographic characteristics and the context of victimization. The sample consisted of 910 racially and ethnically diverse adolescents and young adults from an urban commuter college in the Northeast U.S. Findings include significant sex differences and racial differences in reported victimization and symptoms. Men reported significantly more physical assaults, gun victimizations, and knife victimizations than women. Black participants reported significantly more gun victimization than all other groups, and Black, White, and Asian participants reported significantly more physical assault experiences than Latinx participants. Individuals victimized by physical assault or by gun victimization were more than twice as likely to report clinically significant PTSD symptoms than individuals without such experiences, even after adjusting for demographic differences. In addition, for gun victimization in the community, a two-way interaction (gun victimization by race) and a three-way interaction (gun victimization by race by sex) were significantly associated with clinically significant PTSD symptoms. Gun victimization in the community, which disproportionately impacts Black men, was the only context in which PTSD symptoms were highest for men compared to women. The overall finding of lower PTSD symptoms among men suggests that clinical practice must include an intentional focus on violence victimization, including the use of weapons, as well as the various ways that distress might manifest among men. In addition to symptoms of PTSD, other symptoms of distress, including substance use, anger, and retaliatory aggression, should be considered. Public policy and public health must also direct attention to the use of weapons in violence victimization and the proliferation of weapons violence.

Globally, individuals and communities that are marginalized based on their identities are at heightened risk for exposure to traumatic stress and socioeconomic hardship. Marginalization and disproportionate risk for many types of adversities correspond with disparities in physical health, mental health, and overall well-being. Together, the 12 empirical studies, one systematic review, and commentary in this special issue of the Journal of Traumatic Stress highlight the impact of discrimination and disproportionate adversity among groups marginalized based on race, ethnicity, nativity, caste, gender identity, sexual orientation, economic status, and medical status. Although most studies in this issue focus on the United States, the articles that focus on disparities and risk factors in India, El Salvador, Uganda, and Burundi provides a multicontinent global perspective. The global perspective, including the impact of the global pandemic, invites further examination of how disproportionate exposure to traumatic stress and adversity are associated with inequitable burden and health disparities worldwide. This special issue further highlights the developmental and multigenerational burden of systemic marginalization by including studies of children, young adults, adults, and parent-child dyads. Pathways for change and intervention are illustrated through a liberatory consciousness perspective, with one study utilizing liberatory media skills (e.g., positive media images and messages) to mitigate the adverse effects of trauma exposure on at-risk young adults of color. Worldwide, research on the effects of trauma, stress, and adversities must examine contextual factors (e.g., economic hardship), marginalization (e.g., discrimination, identity factors), and the differential impact on health among individuals and communities., (© 2021 International Society for Traumatic Stress Studies.)

Objective: Home violence exposure (HVE) varies by type and frequency of exposure, which can lead to uncertainty when determining what is traumatic and what is not, particularly when assessing posttraumatic stress symptoms (PTSS) and disorder (PTSD). The current study examined whether specific types of HVE were associated with specific types of PTSS to help determine what experiences may rise to the level of trauma., Method: Participants included 988 racially and ethnically diverse college students (74.1% women). Two latent class analyses were performed, examining types of HVE and types of PTSS to determine how classifications of HVE were associated with classifications of PTSS., Results: Four classifications of HVE were identified: high exposure (21.7%), vicarious exposure (28.9%), victimization (10.5%), and low exposure (38.9%). Four classifications of PTSS were also identified: high PTSS (20.9%), dysphoric arousal (17.4%), anxious arousal (21.3%), and low PTSS (40.4%). Even when considering other potentially traumatic events, participants with experiences of victimization were 2.55 times more likely than those with low exposure to meet criteria for PTSD. Victimization was uniquely associated with dysphoric arousal as well as all other PTSS. High exposure was associated with high PTSS and anxious arousal, with vicarious exposure associated only with anxious arousal., Conclusions: Findings provide unique evidence for the potentially traumatic effects of victimization in the home. Frequent and cumulative effects of HVE that do not meet DSM criteria for a potentially traumatic event may be associated with elevated PTSS, particularly symptoms of anxious and dysphoric arousal. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Physiological rhythms in mammals are essential for maintaining health, whereas disruptions may cause or exacerbate disease pathogenesis. As such, our objective was to characterize how cigarette smoke exposure affects physiological rhythms of otherwise healthy mice using telemetry and cosinor analysis., Methods: Female BALB/c mice were implanted with telemetry devices to measure body temperature, heart rate, systolic blood pressure (SBP), and activity. Following baseline measurements, mice were exposed to cigarette smoke for approximately 50 min twice daily during weekdays over 24 weeks. Physiological parameters were recorded after 1, 4, 8, and 24 weeks of exposure or after 4 weeks cessation following 4 weeks of cigarette smoke exposure., Results: Acute cigarette smoke exposure resulted in anapyrexia, and bradycardia, with divergent effects on SBP. Long term, cigarette smoke exposure disrupted physiological rhythms after just 1 week, which persisted across 24 weeks of exposure (as shown by mixed effects on mesor, amplitude, acrophase, and goodness-of-fit using cosinor analysis). Four weeks of cessation was insufficient to allow full recovery of rhythms., Conclusion: Our characterization of the pathophysiology of cigarette smoke exposure on physiological rhythms of mice suggests that rhythm disruption may precede and contribute to disease pathogenesis. These findings provide a clear rationale and guide for the future use of chronotherapeutics., (Copyright © 2020 Vanderstocken, Marrow, Allwood, Stampfli and Simpson.)

Techniques to comprehensively evaluate pulmonary function carry a variety of limitations, including the ability to continuously record intrathoracic pressures (ITP), acutely and chronically, in a natural state of freely behaving animals. Measurement of ITP can be used to derive other respiratory parameters, which provide insight to lung health. Our aim was to develop a surgical approach for the placement of a telemetry pressure sensor to measure ITP, providing the ability to chronically measure peak pressure, breath frequency, and timing of the respiratory cycle to facilitate circadian analyses related to breathing patterns. Applications of this technique are shown using a moderate hypoxic challenge. Male C57Bl/6 mice were implanted with radiotelemetry devices to record heart rate, temperature, activity, and ITP during 24-h normoxia, 24-h hypoxia ([Formula: see text] = 0.15), and return to 48-h normoxia. Radiotelemetry of ITP permitted the detection of hypoxia-induced increases in "the ITP equivalent" of ventilation, which were driven by increases in breathing frequency and ITP on a short-term time scale. Respiratory frequency, derived from pressure waveforms, was increased by a decrease in expiratory time without changes in inspiratory time. Chronically, telemetric recording allowed for circadian analyses of respiratory drive, as assessed by inspiratory pressure divided by inspiratory time, which was increased by hypoxia and remained elevated for 48 h of recovery. Furthermore, respiratory frequency demonstrated a circadian rhythm, which was disrupted through the recovery period. In conclusion, radiotelemetry of ITP is a viable, long-term, chronic methodology that extends traditional methods to evaluate respiratory function in mice. NEW & NOTEWORTHY We have demonstrated for the first time in mice that radiotelemetry is an effective tool for the continuous and chronic recording of intrathoracic pressure (ITP) to facilitate circadian rhythm analyses. We show that continuous 24-h hypoxic stress alters the circadian rhythms of heart rate, body temperature, activity, and respiratory parameters, acutely and perpetually, through normoxic recovery. Radiotelemetry of ITP can complement traditional methods for evaluating respiratory function and better our understanding of respiratory pathophysiology.

Objective: We examined whether perceptions of being bullied during middle and high school were associated with depressive, anxiety, and posttraumatic stress disorder (PTSD) symptoms during college. We also examined whether perceived social support (PSS) mediated the association between bullying and symptoms, and explored whether parental, peer, or other sources of support was most beneficial. Participants: Undergraduates ( N  = 270) from an urban commuter college in the Northeast participated during Spring 2013 or Fall 2015. Methods: Psychometrically sound self-report measures were used to assess symptoms and perceptions of bullying and social support. Results: As hypothesized, bullying was associated with more symptoms, and PSS significantly mediated the associations between bullying and symptoms of PTSD and depression. Conclusion: The college years provide another opportunity to address the effects of middle and high school bullying. Receiving current support for past bullying is beneficial but is not enough, college counseling services are needed to reduce symptoms.

Studies measuring Posttraumatic Stress Disorder (PTSD) symptoms from childhood into adulthood have been hampered by use of different measures across different developmental stages. Use of one measure across age groups would reduce measurement error and strengthen our understanding of the developmental progression of trauma. Thus, this study examined whether the UCLA PTSD Reaction-Index (PTSD-Index), which was developed for use with children and adolescents (aged 7 to 18), could be used with young adults. The utility of the measure was examined among three age groups of college students (17-18, 19-20, and 21-25). Sex differences and race/ethnicity differences were also examined. Findings indicate that the PTSD-Index is internally consistent and reliable when used with college students. Furthermore, the factor structure for the measure is similar for adolescents and for emerging adults. In sum, the PTSD-Index appears to be an appropriate screener for PTSD symptoms among young adults. The findings are relevant for both the DSM-IV and DSM-5 screening measures, and the findings have both research and clinical implications. The findings are particularly important for longitudinal studies that are challenged with addressing developmental progression of PTSD symptoms among participants, while also addressing changes in the PTSD nosology., (© Springer Nature Switzerland AG 2019.)

There is a paucity of knowledge concerning the underlying symptomatology of heterogeneous posttraumatic stress symptom (PTSS) trajectories following mass trauma, such as a terrorist attack. This study examined longitudinal PTSS trajectories using latent growth mixture modeling in 2,355 World Trade Center (WTC) tower survivors surveyed by the WTC Health Registry an average of 2.5, 5.5, and 10.5 years after the September 11, 2001 terrorist attacks. Covariates included sociodemographic characteristics, WTC-related exposure, and other traumas/stressors. Four curvilinear PTSS trajectories were identified: low symptom (74.9%), recovering (8.0%), worsening (6.7%), and chronic (10.4%). The majority of WTC survivors (85.3%) maintained stable symptom trajectories over time, with PTSS changes occurring less often. Although WTC-related exposure was associated with initial PTSS severity, exposure was not associated with chronicity or change of PTSS over time. Male gender and a higher number of post-WTC disaster life-stressors were associated with worsening symptom severity over time. Individuals with more severe hyperarousal symptoms at Wave 1, particularly of anxious arousal, were more likely to have PTSS that worsened over time, adjusted odds ratio (aOR) = 1.55. Less severe emotional numbing symptoms, particularly of dysphoria, at Wave 1, were marginally significantly associated with subsequent PTSS recovery, aOR = 0.75. Interventions that target hyperarousal and emotional numbing symptoms may mitigate a worsening of symptoms and facilitate posttraumatic recovery following future mass traumas, such as terrorist attacks. Further clinical implications are discussed., (© 2019 International Society for Traumatic Stress Studies.)

Key Points: In the present study, we provide evidence for divergent physiological responses to moderate compared to severe hypoxia, addressing an important knowledge gap related to severity, duration and after-effects of hypoxia encountered in cardiopulmonary situations. The physiological responses to moderate and severe hypoxia were not proportional, linear or concurrent with the time-of-day. Hypoxia elicited severity-dependent physiological responses that either persisted or fluctuated throughout normoxic recovery. The physiological basis for these distinct cardiovascular responses implicates a shift in the sympathovagal set point and probably not molecular changes at the artery resulting from hypoxic stress., Abstract: Hypoxia is both a consequence and cause of many acute and chronic diseases. Severe hypoxia causes hypertension with cardiovascular sequelae; however, the rare studies using moderate severities of hypoxia indicate that it can be beneficial, suggesting that hypoxia may not always be detrimental. Comparisons between studies are difficult because of the varied classifications of hypoxic severities, methods of delivery and use of anaesthetics. Thus, to investigate the long-term effects of moderate hypoxia on cardiovascular health, radiotelemetry was used to obtain in vivo physiological measurements in unanaesthetized mice during 24 h of either moderate ( F I O 2 = 0.15 ) or severe ( F I O 2 = 0.09 ) hypoxia, followed by 72 h of normoxic recovery. Systolic blood pressure was decreased during recovery following moderate hypoxia but increased following severe hypoxia. Moderate and severe hypoxia increased haeme oxygenase-1 expression during recovery, suggesting parity in hypoxic stress at the level of the artery. Severe but not moderate hypoxia increased the low/high frequency ratio of heart rate variability 72 h post-hypoxia, indicating a shift in sympathovagal balance. Moderate hypoxia dampened the amplitude of circadian rhythm, whereas severe disrupted rhythm during the entire insult, with perturbations persisting throughout normoxic recovery. Thus, hypoxic severity differentially regulates circadian blood pressure., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

The present study examined associations among parent and child reports of youth's stressful life events (SLEs), perceived stress, and biological measures of stress activity (i.e. cortisol and cardiovascular activity). Examining these aspects of youth stress presents several challenges. Unlike adult studies of individual differences in which information regarding SLEs, perceptions of events, and biological activity are gathered from one individual, assessment of individual differences among children usually involves other informants (e.g. parent). However, parent and child reports of SLEs and the child's psychological response to such events are often discordant. Moreover, examinations of youth perception of stress are hampered by limitations of child cognitive processes, as well as parents' limited knowledge of their child's perception of stress. In a preliminary effort to unscramble the complex effects of youth SLEs and perceived stress in relation to biological response to acute stressors, this study examined 51 boys and girls aged 7-16, with no history of psychopathology or medical concerns. Contrary to hypotheses, findings revealed that compared to actual experiences of stress, perceived stress has greater associations with both cortisol and cardiovascular activity. That is, perceived stress is more biologically salient relative to actual stress. Results also suggest that informant differences may explain some previous inconsistent findings in studies of youth's stress reactivity. The current findings mirror the adult studies that show appraisal and perception of traumatic and stressful events may be more predictive of negative health and mental health outcomes than the severity of the events. Further studies are needed to understand the impact of youth's perceptions of stress on their biological stress reactions and later health outcomes such as clinical disorders.

The obesity epidemic is considered one of the most serious public health problems of the modern world. Physical therapy is the most accessible form of treatment; however, compliance is a major obstacle due to exercise intolerance and dyspnea. Respiratory muscle atrophy is a cause of dyspnea, yet little is known of obesity-induced respiratory muscle dysfunction. Our objective was to investigate whether obesity-induced skeletal muscle wasting occurs in the diaphragm, the main skeletal muscle involved in inspiration, using the Zucker diabetic fatty (ZDF) rat. After 14 wk, ZDF rats developed obesity, hyperglycemia, and insulin resistance, compared with lean controls. Hemodynamic analysis revealed ZDF rats have impaired cardiac relaxation (P = 0.001) with elevated end-diastolic pressure (P = 0.006), indicative of diastolic dysfunction. Assessment of diaphragm function revealed weakness (P = 0.0296) in the absence of intrinsic muscle impairment in ZDF rats. Diaphragm morphology revealed increased fibrosis (P < 0.0001), atrophy (P < 0.0001), and reduced myosin heavy-chain content (P < 0.001), compared with lean controls. These changes are accompanied by activation of the myostatin signaling pathway with increased serum myostatin (P = 0.017), increased gene expression (P = 0.030) in the diaphragm and retroperitoneal adipose (P = 0.033), and increased SMAD2 phosphorylation in the diaphragm (P = 0.048). Here, we have confirmed the presence of respiratory muscle atrophy and weakness in an obese, diabetic model. We have also identified a pathological role for myostatin signaling in obesity, with systemic contributions from the adipose tissue, a nonskeletal muscle source. These findings have significant implications for future treatment strategies of exercise intolerance in an obese, diabetic population., (Copyright © 2015 the American Physiological Society.)

Introduction: Heme oxygenase-1 (HO-1) is a cytoprotective enzyme induced by stress. Heart failure is a condition of chronic stress-induced remodeling and is often accompanied by comorbidities such as age and hypertension. HO-1 is known to be protective in the setting of acute myocardial infarction. The role of HO-1 in heart failure is not known, particularly in the setting of pressure overload., Methods: Mice with alpha-myosin heavy chain restricted expression of HO-1 were aged for 1 year. In addition, mice underwent transverse aortic constriction (TAC) or were infused with isoproterenol (ISO) to induce heart failure., Results: HO-1 transgenic mice developed spontaneous heart failure after 1 year compared to their wild-type littermates and showed accelerated cardiac dysfunction 2 weeks following TAC. Wild-type mice undergoing pressure overload demonstrated extensive interstitial fibrosis that was prevented by HO-1 overexpression, yet HO-1 transgenic mice had reduced capillary density, contractile reserve, and elevated end-diastolic pressure. However, HO-1 transgenic mice had significantly attenuated ISO-induced cardiac dysfunction, interstitial fibrosis, and hypertrophy compared to control. Isolated cardiomyocytes from HO-1 transgenic mice treated with ISO did not show evidence of hypercontracture/necrosis and had reduced NADH oxidase activity., Conclusions: HO-1 is an effective mechanism for reducing acute myocardial stress such as excess beta-adrenergic activity. However, in our age and pressure overload models, HO-1 showed detrimental rather than therapeutic effects in the development of heart failure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Adolescents exposed to trauma are more likely to engage in alcohol and marijuana use compared to their nontrauma-exposed counterparts; however, little is known about factors that may moderate these associations. This study examined the potential moderating effect of cognitions relevant to exposure to trauma (i.e., negative view of self, world, and future) in the association between posttraumatic stress disorder (PTSD) diagnosis and substance use among a psychiatric inpatient sample of 188 adolescents. Findings were that PTSD diagnosis was not significantly associated with substance-use diagnoses, but was associated with substance-use symptoms, accounting for 2.9% and 9.6% of the variance in alcohol and marijuana symptoms, respectively. The association between PTSD diagnosis and substance use symptoms, however, was moderated by negative cognitions, with PTSD and high negative cognitions (but not low negative cognitions) being significantly positively associated with substance use symptoms. The relevant cognitions differed for alcohol symptoms and marijuana symptoms. Children and adolescents who experience trauma and PTSD may benefit from early interventions that focus on cognitive processes as one potential moderator in the development of posttrauma substance use., (Copyright © 2014 International Society for Traumatic Stress Studies.)

Recent studies have revealed evidence for interactions between autonomic nervous system (ANS) activity, indexed by saliva alpha amylase (sAA), and hypothalamic-pituitary-adrenocortical activity, in predicting psychological functioning. The present study extends this work by examining individual differences in sAA and cortisol stress reactivity in relation to behavioral and emotional adjustment in youth. Participants were 56 healthy children (age 7-16). sAA, cortisol, and other physiological and affective responses were measured before, during, and after stressor tasks (either performance or peer rejection). Basal and stress responsive sAA and cortisol as well as their interactions were assessed in relation to externalizing and internalizing behaviors and trait anxiety. sAA was positively related to anxiety, while sAA reactivity moderated associations between cortisol reactivity and problem behavior. Results highlight the importance of measuring multiple physiological systems to elucidate mechanisms underlying behavioral and emotional dysregulation., (Copyright © 2011 Elsevier B.V. All rights reserved.)

This study elaborated on associations between youth's trauma-related emotional numbing across multiple affective domains (e.g., fear, sadness, happiness, anger) and delinquent behaviors. The study also examined whether the effects of posttrauma emotional numbing varied by the occurrence of posttrauma arousal symptoms. Participants were 123 middle school boys and girls from working-class, urban communities. Emotional numbing, particularly diminished fear, was related to both home and community violence exposure. Numbing of fearful emotions was associated with all types of delinquent behaviors examined. In addition, numbing of sadness was associated with aggression. Interactions between numbing of fear and hyperarousal suggested a complex pattern of emotional processing following exposure to traumatic events in which numbing related to delinquent behavior only in the context of high posttrauma arousal. These patterns may coalesce to place youth at risk for early involvement in delinquent behaviors.

Two studies examined shared and unique relations of social information processing (SIP) to youth's anxious and depressive symptoms. Whether SIP added unique variance over and above trait affect in predicting internalizing symptoms was also examined. In Study 1, 215 youth (ages 8-13) completed symptom measures of anxiety and depression and a vignette-based interview measure of SIP. Anxiety and depression were each related to a more negative information-processing style. Only depression was uniquely related to a less positive information processing style. In Study 2, 127 youth (ages 10-13) completed measures of anxiety, depression, SIP, and trait affect. SIP's relations to internalizing symptoms were replicated. Over and above negative affect, negative SIP predicted both anxiety and depression. Low positive SIP added variance over and above positive affect in predicting only depression. Finally, SIP functioning partially mediated the relations of affect to internalizing symptoms.

Two studies describe the development of a comprehensive, vignette-based measure of social information processing (SIP) particularly relevant for children with internalizing problems. Study 1 (N = 219 3rd-6th graders) describes the creation of the Children's Evaluation of Everyday Social Encounters Questionnaire (ChEESE-Q) and evidence for its reliability and validity, including internal structure and relation of SIP variables to depressive and anxious symptoms. Study 2 (N = 127 5th-6th graders) replicated the factor structure and validity evidence found in Study 1 and provided support for the reliability of alternate forms of the ChEESE-Q. Overall, results supported ChEESE-Q scores' moderate temporal stability and internal consistency in assessing SIP. Results also supported the presence of positive- and negative-valenced SIP patterns. Child internalizing symptoms were strongly related to a negative SIP style across both depression and anxiety, whereas only depressive symptoms were negatively associated with positive aspects of SIP.

Objective: According to most studies, more than half of children exposed to war meet criteria for posttraumatic stress disorder (PTSD). Although we know that children are adversely affected by atrocities of war, we do not know which specific war events are associated with children's stress reactions. For example, it is unclear whether differences exist in response to violent versus nonviolent war-trauma experiences. This study examined the relationship of violent and nonviolent war experiences to children's trauma reactions and adjustment in a group of children from Bosnia., Method: During the 1994 siege in Sarajevo, 791 children aged 6 to 16 years participated in a study of trauma experience and response, in which assessment questionnaires (Impact of Event Scale, PTSD Reaction Index, Children's Depression Inventory, Child Behavior Checklist, and War Experience Questionnaire) were completed by children and their teachers., Results: In this sample 41% had clinically significant PTSD symptoms. Children were adversely affected by exposure to both violent and nonviolent war-traumas. An additive effect of trauma exposure on trauma reactions was also found. However, many war experiences were not associated with children's adjustment and trauma reactions., Conclusions: Additive effects of violence and deprivations during war may overwhelm the coping skills of children and leave them vulnerable to externalizing and internalizing adjustment difficulties and symptoms of PTSD.