CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.

Chitinase-3-like protein 1 (CHI3L1) is primarily secreted by activated astrocytes in the brain and is known as a reliable biomarker for inflammatory central nervous system (CNS) conditions such as neurodegeneration and autoimmune disorders like neuromyelitis optica (NMO). NMO is an astrocyte disease caused by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4) and leads to vision loss, motor deficits, and cognitive decline. In this study examining CHI3L1's biological function in neuroinflammation, we found that CHI3L1 expression correlates with cognitive impairment in our NMO patient cohort. Activated astrocytes secrete CHI3L1 in response to AQP4 autoantibodies, and this inhibits the proliferation and neuronal differentiation of neural stem cells. Mouse models showed decreased hippocampal neurogenesis and impaired learning behaviors, which could be rescued by depleting CHI3L1 in astrocytes. The molecular mechanism involves CHI3L1 engaging the CRTH2 receptor and dampening ß-catenin signaling for neurogenesis. Blocking this CHI3L1/CRTH2/ß-catenin cascade restores neurogenesis and improves cognitive deficits, suggesting the potential for therapeutic development in neuroinflammatory disorders.

The Generation and Functional Characterization of Human Microglia-Like Cells Derived from iPS and Embryonic Stem Cells.

The following protocol describes the generation of microglia cells from human-induced pluripotent stem cells (hiPSCs) using commercially available kits by StemCell Technologies. This protocol consists of three major steps: (1) Differentiation of hematopoietic precursor cells, (2) Microglia differentiation, and (3) Microglia maturation. Assays are described to characterize hematopoietic precursor cells and mature microglia.

Modeling Cellular Crosstalk of Neuroinflammation Axis by Tri-cultures of iPSC-Derived Human Microglia, Astrocytes, and Neurons.

Neuroinflammation is a common early pathological feature in many neurodegenerative disorders, including Alzheimer's disease (AD), which has been heavily implicated as a causative factor in disease pathology. However, the role neuroinflammation and inflammatory cells, including microglia and astrocytes, play in AD development and progression has not been fully defined. To try to better understand and study this neuroinflammatory role in AD pathogenesis, researchers use a variety of model systems, particularly in vivo animal models. Despite their usefulness, these models do come with a variety of limitations due to the inherent complexity of the brain and the human-specific nature of AD. Here, we describe a reductionist approach at modeling neuroinflammation by utilizing an in vitro tri-culture system of neurons, astrocytes, and microglia induced from human pluripotent stem cells. This tri-culture model is a powerful tool to dissect intercellular interactions that can facilitate future studies on neuroinflammation, particularly in the context of neurodegeneration and AD.

Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neurodegeneration and Alzheimer's disease.

Chitinase-3-like protein 1 (CHI3L1/YKL-40) has long been known as a biomarker for early detection of neuroinflammation and disease diagnosis of Alzheimer's disease (AD). In the brain, CHI3L1 is primarily provided by astrocytes and heralds the reactive, neurotoxic state triggered by inflammation and other stress signals. However, how CHI3L1 acts in neuroinflammation or how it contributes to AD and relevant neurodegenerative conditions remains unknown. In peripheral tissues, our group and others have uncovered that CHI3L1 is a master regulator for a wide range of injury and repair events, including the innate immunity pathway that resembles the neuroinflammation process governed by microglia and astrocytes. Based on assessment of current knowledge regarding CHI3L1 biology, we hypothesize that CHI3L1 functions as a signaling molecule mediating distinct neuroinflammatory responses in brain cells and misfunctions to precipitate neurodegeneration. We also recommend future research directions to validate such assertions for better understanding of disease mechanisms.

Percutaneous approach options for embolization of endoleak after iliac artery aneurysm repair: stick the sac or stick the gluteal artery.

Internal iliac artery aneurysms (IIAAs), isolated or associated with abdominal aortic aneurysms, are at rupture risk with growth. Treatment is recommended when symptomatic or greater than 3 cm. Surgical or endovascular therapy should exclude the arterial origin and outflow branches. If all outflow branches are not completely embolized, an endoleak can develop, pressurizing the sac leading to growth and rupture. Accessing the arteries involved can be technically challenging and understanding potential targets is critical. We describe two percutaneous approaches for treatment: percutaneously accessing the sac from an anterior trans-iliopsoas approach and percutaneously accessing the gluteal artery from a posterior approach.

Examining the Link Between Intolerance of Uncertainty and Positive and Negative Urgency in Veterans With Comorbid Posttraumatic Stress Disorder and Substance Use Disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are highly comorbid among the veteran population. Impulsivity, particularly negative and positive urgency, are prevalent within this dual-diagnosis population and associated with negative outcomes. One possible correlate of negative/positive urgency is intolerance of uncertainty (IU). IU is associated with exacerbated PTSD symptom severity and increased risk for substance use. However, few studies have examined the link between IU and negative/positive urgency in dual-diagnosis populations. This study aimed to examine whether there was a significant association between trait IU and baseline negative and positive urgency in veterans seeking treatment for both PTSD and SUD. In a sample of 114 veterans from a 6-week residential treatment program, IU was significantly associated with higher negative and positive urgency. Further research is warranted to extend these findings and examine whether IU plays an important role in negative/positive urgency for dual-diagnosis populations.

Postoperative Recurrent Cholesteatoma in Rural Versus Urban Populations.

OBJECTIVE: Chronic ear disease presents a unique challenge to otolaryngologists in both rural and urban settings. Cholesteatoma remains a difficult disease to treat in rural populations due to limited healthcare access and high risk of recurrence. The purpose of this study was to determine if there are differences in surgical outcomes among patients with acquired cholesteatoma residing in rural versus urban settings. STUDY DESIGN: Single-surgeon retrospective case series with chart review. SETTING: Tertiary care private otolaryngology practice. PATIENTS: One hundred twenty-two patients presenting to the Kentuckiana ENT otology and neurotology practice from January 2011 to May 2017. MAIN OUTCOME MEASURES: Surgical outcomes including recurrence, air-bone gap improvement, ossicular integrity, and complications were reviewed and compared between the rural and urban cohorts. RESULTS: Presence of postoperative residual cholesteatoma (OR = 8.667, 95% CI = 2.022-37.141, p = 0.008) and number of surgeries per patient (OR = 5.185, 95% CI = 1.086-24.763, p = 0.024) were significantly increased among patients in rural nonmetropolitan areas. No significant differences were found when comparing risk of recurrence, size of cholesteatoma, presence of complications, air-bone gap improvement, and ossicular chain integrity. There were significantly more second-look surgeries performed in privately insured patients (OR = 8.582, 95% CI = 1.937-38.017, p = 0.001). CONCLUSIONS: Patients in rural communities have an increased number of surgeries and postoperative risk for residual cholesteatoma compared to patients residing in urban settings. This study provides the basis for larger, multicenter, prospective examinations of outcomes among urban versus rural patients, which would enable a better understanding of difference in surgical outcomes between rural and urban cohorts.Level of Evidence: IV.

Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions.

In Alzheimer's disease (AD) and other neurodegenerative disorders, oligodendroglial failure is a common early pathological feature, but how it contributes to disease development and progression, particularly in the gray matter of the brain, remains largely unknown. The dysfunction of oligodendrocyte lineage cells is hallmarked by deficiencies in myelination and impaired self-renewal of oligodendrocyte precursor cells (OPCs). These two defects are caused at least in part by the disruption of interactions between neuron and oligodendrocytes along the buildup of pathology. OPCs give rise to myelinating oligodendrocytes during CNS development. In the mature brain cortex, OPCs are the major proliferative cells (comprising ~5% of total brain cells) and control new myelin formation in a neural activity-dependent manner. Such neuron-to-oligodendrocyte communications are significantly understudied, especially in the context of neurodegenerative conditions such as AD, due to the lack of appropriate tools. In recent years, our group and others have made significant progress to improve currently available protocols to generate functional neurons and oligodendrocytes individually from human pluripotent stem cells. In this manuscript, we describe our optimized procedures, including the establishment of a co-culture system to model the neuron-oligodendrocyte connections. Our illustrative results suggest an unexpected contribution from OPCs/oligodendrocytes to the brain amyloidosis and synapse integrity and highlight the utility of this methodology for AD research. This reductionist approach is a powerful tool to dissect the specific hetero-cellular interactions out of the inherent complexity inside the brain. The protocols we describe here are expected to facilitate future studies on oligodendroglial defects in the pathogenesis of neurodegeneration.

Effect of Fatigue on Equine Metacarpophalangeal Joint Kinematics-A Single Horse Pilot Study.

The objective was to validate a scientific method for characterizing equine metacarpophalangeal joint (MCPJ) motion in the nonfatigued and fatigued states using a single horse at trot, slow canter, and fast canter. One healthy Thoroughbred gelding exercised on a treadmill to exhaustion (fatigued state) (heart rate >190 BPM and blood lactate >10 mmol/L) while bilateral MCPJ angular data were acquired using electrogoniometry. Blood lactate and heart rate reflected transition from nonfatigued to fatigued states with increasing exercise duration and treadmill speed. Electrogoniometry consistently demonstrated: increase in mean MCPJ maximum extension angle with onset of fatigue; altered extension and flexion angular velocities with onset of fatigue; and increasing stride duration and decreasing stride frequency with onset of fatigue. The method allowed a preliminary but comprehensive characterization of the dynamic relationship between MCPJ kinematics and fatigue, prompting the need for multisubject studies that may enhance our ability to moderate exercise-related distal limb injury in equine athletes.

Pre- to Posttreatment Changes in Trauma-Cued Negative Emotion Mediate Improvement in Posttraumatic Stress Disorder, Depression, and Impulsivity.

Posttraumatic stress disorder (PTSD) is characterized by strong negative emotions, often in response to trauma cues or reminders. Subsequent emotion regulation strategies impact the maintenance of PTSD symptoms and other trauma-related outcomes (depression, substance use). This study aimed to examine a range of trauma-cued emotions to enhance our understanding of changes following treatment and their potential role in improving relevant outcomes. Participants included 67 veterans diagnosed with PTSD and a substance use disorder who completed a dual diagnosis residential program that used cognitive processing therapy. At pre- and posttreatment, we measured 8 negative emotions following a trauma recall and PTSD symptoms, depressive symptoms, and negative urgency (impulsivity following negative emotions) as treatment outcomes. We used t-tests to assess changes at posttreatment and a within-subjects mediational analysis to test whether changes in trauma-cued emotions mediated treatment outcomes. Participants reported moderate, significant decreases for 5 emotions at posttreatment: anger at self, disgust at self, fear, guilt, and sadness (d ≥ 0.50), whereas nonsignificant changes were found for anger at others, disgust at others, and shame. Mediation analyses indicated greater reductions in trauma-cued sadness had a significant indirect effect on improvement in PTSD symptoms, depressive symptoms, and negative urgency. Reductions in disgust at self and fear also demonstrated a significant indirect effect on depressive symptom improvement. In this dual diagnosis program, veterans reported a significant reduction in some, but not all, trauma-cued emotions, and improvements in only select emotions accounted for a significant portion of improvement in relevant treatment outcomes.

Can a policy-induced reduction in alcohol consumption improve health outcomes and stimulate the UK economy?: A potential 'double dividend'.

INTRODUCTION AND AIMS: The health benefits of reducing excessive alcohol consumption are well-documented and widely accepted, but policies directed to this end are often regarded as damaging to the economy. Previous UK alcohol impact studies typically focus on what are in effect the 'gross' impacts of a fall in alcohol consumption considered in isolation, so that estimated economic impacts are always negative. Here we investigate the 'net' impacts of a reduction in consumption accounting for the reallocation of household spending and the expenditure of any increase in government revenues. DESIGN AND METHODS: We employ a health-augmented, Input-Output modelling framework. We simulate the impact of a reduction in alcohol consumption due to: a change in consumer tastes that generate a reallocation of household spending; an increase in alcohol duties accompanied by the use of increased revenues to stimulate government expenditure. RESULTS: We find evidence of a trade-off between employment and health benefits for the case of a tastes-induced switch from alcohol consumption, but this is less severe than past analyses would suggest (and does not apply to economic activity more generally). For the case of increased taxation on alcohol (and increased government spending) we find that there is in fact no trade-off between employment on the one hand and health on the other; employment and economic activity are stimulated while health outcomes improve. DISCUSSION AND CONCLUSIONS: There is a potential 'double-dividend' of improved health outcomes and increased economic activity as a consequence of a rise in alcohol duties.

A cognitive processing therapy-based treatment program for veterans diagnosed with co-occurring posttraumatic stress disorder and substance use disorder: The relationship between trauma-related cognitions and outcomes of a 6-week treatment program.

Dysfunctional trauma-related cognitions are important in the emergence and maintenance of posttraumatic stress disorder (PTSD) and the modification of such cognitions is a proposed mechanism of trauma treatment. However, the authors are not aware of any research examining trauma-related cognitions as a treatment mechanism in a sample of individuals with comorbid PTSD and substance use disorder (SUD). Accordingly, the present study sought to address this gap in the literature and examined the relationship between trauma-related cognitions and treatment outcomes within a sample of seventy-two veterans diagnosed with PTSD and SUD. Veterans completed a 6-week day CPT-based treatment program that included cognitive processing therapy as a central component. Measures of trauma-related cognitions, PTSD symptoms, depressive symptoms, and trauma-cued substance craving were completed at pre- and post-treatment. As expected, trauma-related cognitions were associated with several PTSD-related variables prior to treatment. Furthermore, results of a within-subjects mediational analysis indicated that maladaptive trauma-related cognitions decreased during the treatment program and accounted for a significant portion of the variance in the reduction of PTSD and depressive symptoms at post-treatment. This study provides support for the position that attempts to modify dysfunctional trauma-related cognitions among veterans with co-occurring PTSD and SUD can lead to desirable treatment outcomes.

Increased Resilience is Associated with Positive Treatment Outcomes for Veterans with Comorbid PTSD and Substance Use Disorders.

OBJECTIVE: Resilience has been associated with less severe psychiatric symptomatology and better treatment outcomes among individuals with posttraumatic stress disorder (PTSD) and substance use disorders. However, it remains unknown whether resilience increases during psychotherapy within the comorbid PTSD and substance use disorder population with unique features of dual diagnosis, including trauma cue-related cravings. We tested whether veterans seeking psychotherapy for comorbid PTSD and substance use disorder reported increased resilience from pre- to posttreatment. We also tested whether increased resilience was associated with greater decreases in posttreatment PTSD and substance use disorder symptoms. METHODS: Participants were 29 male veterans (Mage = 49.07 years, SD = 11.24 years) receiving six-week residential day treatment including cognitive processing therapy for PTSD and cognitive behavioral therapy for substance use disorder. Resilience, PTSD symptoms, and trauma cue-related cravings were assessed at pre- and posttreatment. RESULTS: Veterans reported a large, significant increase in resilience posttreatment (Mdiff = 14.24, t = -4.22, p < .001, d = 0.74). Greater increases in resilience were significantly associated with fewer PTSD symptoms (ß = -0.37, p = .049, sr = -.36) and trauma-cued cravings (ß = -0.39, p = .006, sr = -.38) posttreatment when controlling for pretreatment scores and baseline depressive symptoms. CONCLUSIONS: Results suggest that evidence-based psychotherapy for comorbid PTSD and substance use disorder may facilitate strength-based psychological growth, which may further promote sustained recovery.

Economic Evaluation of Selective Neonatal Bacillus Calmette-Guérin Vaccination of High-risk Infants in Ireland.

BACKGROUND: In Western Europe, currently only Ireland and Portugal continue to provide universal neonatal bacillus Calmette-Guérin (BCG) vaccination programs, despite not being considered as high tuberculosis (TB) incidence countries. Other European countries only vaccinate infants considered at high risk of contracting TB. We evaluated the cost-effectiveness of selective BCG vaccination compared with strategies of universal and no vaccination. METHODS: An economic model was used to simulate a cohort from birth to life expectancy, taking the perspective of the publicly funded healthcare system. BCG protection was modeled to last 15 years. International vaccine efficacy data were combined with Irish epidemiologic and cost data. The model took into account long-term sequelae associated with TB meningitis and severe adverse reactions relating to the BCG vaccine. A fully probabilistic model was used to incorporate uncertainty across all parameters. RESULTS: At &OV0556;139,557 per quality-adjusted life year, selective vaccination was not cost-effective relative to a program of no vaccination. The incremental cost-effectiveness of universal vaccination was &OV0556;2.55 million per quality-adjusted life year relative to selective vaccination. There was substantial uncertainty regarding the effectiveness of BCG vaccination. The cost-effectiveness of selective vaccination could be substantially improved by reducing the cost of administering the vaccine. CONCLUSIONS: In the absence of changes to other aspects of TB control, a switch to selective vaccination will result in increased cases of childhood TB. Although not considered cost-effective, selective vaccination may be preferable to no vaccination until other changes to TB control may be implemented to reduce the risk of TB in children.

The Role of Impulsivity Dimensions in the Relation Between Probable Posttraumatic Stress Disorder and Aggressive Behavior Among Substance Users.

OBJECTIVE: Individuals with co-occurring posttraumatic stress disorder (PTSD) and substance use disorder report heightened levels of numerous risky and health-compromising behaviors, including aggressive behaviors. Given evidence that aggressive behavior is associated with negative substance use disorder treatment outcomes, research is needed to identify the factors that may account for the association between PTSD and aggressive behavior among patients with substance use disorder. Thus, the goal of this study was to examine the role of impulsivity dimensions (i.e., negative urgency, lack of premeditation, lack of perseverance, and sensation seeking) in the relations between probable PTSD status and both verbal and physical aggression. METHODS: Participants were 92 patients in residential substance use disorder treatment (75% male; 59% African American; M age = 40.25) who completed self-report questionnaires. RESULTS: Patients with co-occurring PTSD-substance use disorder (vs. substance use disorder alone) reported significantly greater verbal and physical aggression as well as higher levels of negative urgency and lack of premeditation. Lack of premeditation and lack of perseverance were significantly positively associated with verbal aggression, whereas negative urgency, lack of premeditation, and lack of perseverance were significantly positively associated with physical aggression. The indirect relation of probable PTSD status to physical aggression through negative urgency was significant. CONCLUSIONS: Results highlight the potential utility of incorporating skills focused on controlling impulsive behaviors in the context of negative emotional arousal in interventions for physical aggression among patients with co-occurring PTSD-substance use disorder.

The impact of changes in distress tolerance on PTSD symptom severity post-treatment among veterans in residential trauma treatment.

Given that rates of PTSD, particularly among military populations, are increasing, it is critical to gain a better understanding of factors associated with treatment response. Low distress tolerance (DT), conceptualized as the perceived or actual inability to tolerate negative emotional states, may impacts veterans' responses to PTSD treatment. Low DT has been associated with more severe PTSD symptoms in clinical and non-clinical samples; however, its impact on PTSD symptomatology across treatment has yet to be assessed. We examined the impact of changes in DT, from intake to discharge, on post-treatment PTSD symptom severity within two samples of veterans recruited from Veterans Affairs residential PTSD treatment facilities in the northwestern and southern United States (Total N=86; 87% male; 46% White, 39% Black, 9% Latino, 6% Other). Veterans completed the Distress Tolerance Scale and PTSD Checklist (PCL) at intake and discharge from residential PTSD treatment. Regression analyses revealed that, within each veteran sample, those with the greatest improvements in DT had the lowest PCL total and subscale scores at discharge after controlling for respective intake PCL scores. This suggests increases in DT across treatment help explain the degree of benefits experienced by veterans following PTSD treatment.

Evaluating the neonatal BCG vaccination programme in Ireland.

BACKGROUND: The aim of this study was to compare the cost effectiveness of the current Irish programme of universal BCG vaccination of infants versus a programme which considered selectively vaccinating high risk infants using decision analytical modelling. METHODS: The efficacy of the BCG vaccine was re-evaluated to inform a decision analytical model constructed to follow a birth cohort of vaccinated and unvaccinated infants over a 15 year time horizon. The number of life years gained (LYG) was the primary outcome measure and this was compared to the net cost of the vaccination strategies. RESULTS: In the base case analysis, the incremental cost effectiveness ratios (ICERs) for the universal strategy and selective strategy vs no vaccination were €204,373/LYG and €143,233/LYG respectively. When comparing the incremental difference in moving from the universal to the selective strategy, the selective strategy costs €1,055,692 less per 4.8 life years lost per birth cohort. One way sensitivity analyses highlighted that a move from the universal to the selective strategy was particularly sensitive to the estimate of vaccine efficacy against deaths, the cost of administering the vaccine and the multiplier used to apportion risk of contracting tuberculosis. Probabilistic analysis suggested that a move from a universal based strategy to a selective based strategy could be deemed cost effective (probability of cost effectiveness is 76.8 %). CONCLUSION: The results of the study support the protective effect of the BCG vaccine in infants and quantified the cost effectiveness of the current BCG vaccination strategy and the decremental difference in moving to a selective strategy. This analysis highlights that the additional protection offered by the universal vaccination strategy is small compared to that of the selective strategy. Consideration should therefore be given to the implementation of a selective vaccination strategy, and diverting resources to improve TB case management and control.

The impact of intolerance of emotional distress and uncertainty on veterans with co-occurring PTSD and substance use disorders.

The risk of developing a substance use disorder (SUD) is significantly higher among veterans with posttraumatic stress disorder (PTSD). Veterans with this co-occurrence have poorer outcomes than singly diagnosed veterans, which may be related to two risk factors: intolerance uncertainty (IU) and low tolerance of emotional distress (TED). We hypothesized low TED and high IU would independently and interactively relate to heightened PTSD symptomatology and trauma-cue elicited SUD cravings. A sample of 70 veterans (M age=50; 95% men; 65% Black) with co-occurring PTSD-SUD was recruited. The Posttraumatic Stress Disorder Checklist (PCL), Craving Questionnaire, Distress Tolerance Scale, and Intolerance of Uncertainty Scale were administered. In general, low TED and high IU were significantly correlated with the PCL total and subscale scores. When examined within regression models, low TED was associated with elevated PCL scores and trauma-cue elicited SUD cravings; IU was not. However, there was a significant interaction between IU and TED; veterans with elevated IU and low TED had higher PCL Total, Hyperarousal, and Intrusions scores. This highlights the importance of assessing TED and IU among veterans with co-occurring PTSD-SUD, as these risk factors may not only be prognostic indicators of outcomes, but also treatment targets.

Diagnostic Concordance between DSM-5 and ICD-10 Cannabis Use Disorders.

OBJECTIVES: With the recent federal mandate that all U.S. health care settings transition to ICD-10 billing codes, empirical evidence is necessary to determine if the DSM-5 designations map to their respective ICD-10 diagnostic categories/billing codes. The present study examined the concordance between DSM-5 and ICD-10 cannabis use disorder diagnoses. METHOD: Data were derived from routine clinical assessments of 6871 male and 801 female inmates recently admitted to a state prison system from 2000 to 2003. DSM-5 and ICD-10 diagnostic determinations were made from algorithms corresponding to the respective diagnostic formulations. RESULTS: Past 12-month prevalence rates of cannabis use disorders were comparable across classification systems. The vast majority of inmates with no DSM-5 diagnosis continued to have no diagnosis per the ICD-10, and a similar proportion with a DSM-5 severe diagnosis received an ICD-10 dependence diagnosis. Most of the variation in diagnostic classifications was accounted for by those with a DSM-5 moderate diagnosis in that approximately half of these cases received an ICD-10 dependence diagnosis while the remaining cases received a harmful use diagnosis. CONCLUSIONS: Although there appears to be a generally high level of agreement between diagnostic classification systems for those with no diagnosis or those evincing symptoms of a more severe condition, concordance between DSM-5 moderate and ICD-10 dependence diagnoses was poor. Additional research is warranted to determine the appropriateness and implications of the current DSM-5 coding guidelines regarding the assignment of an ICD-10 dependence code for those with a DSM-5 moderate diagnosis.

Examination of the Relationship Between PTSD and Distress Tolerance in a Sample of Male Veterans With Comorbid Substance Use Disorders.

Distress tolerance (DT), the perceived or actual ability to tolerate negative emotional or physical states, is inversely related to posttraumatic stress disorder (PTSD) symptoms in civilian, community samples. No studies to date have examined the relationship between DT and PTSD in clinical samples of veterans with a comorbid diagnosis of PTSD and a substance use disorder (SUD). Thus, the present study examined the relationship between DT and PTSD in a sample of predominately African American, male veterans (n = 75) diagnosed with comorbid PTSD and SUD (according to a structured clinical interview). Results of hierarchical linear regression models indicated that DT was inversely related to total PTSD symptom severity score, above and beyond depressive symptoms and SUD severity. Of the 4 symptom clusters, DT was inversely associated with intrusions and hyperarousal. These findings are discussed in light of previous work with civilian samples. Determining whether treatment incorporating DT skills would be useful for veterans undergoing PTSD treatment should be evaluated.