Comorbid treatment of traumatic brain injury and mental health disorders.

BACKGROUND: The Emory Healthcare Veterans Program (EHVP) is a multidisciplinary intensive outpatient treatment program for post-9/11 veterans and service members with invisible wounds, including posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), substance use disorders (SUD), and other anxiety- and depression-related disorders. OBJECTIVE: This article reviews the EHVP. METHODS: The different treatment tracks that provide integrated and comprehensive treatment are highlighted along with a review of the standard, adjunctive, and auxiliary services that complement individualized treatment plans. RESULTS: This review particularly emphasizes the adjunctive neurorehabilitation service offered to veterans and service members with a TBI history and the EVHP data that indicate large reductions in PTSD and depression symptoms across treatment tracks that are maintained across 12 months follow up. Finally, there is a discussion of possible suboptimal treatment response and the pilot programs related to different treatment augmentation strategies being deploying to ensure optimal treatment response for all. CONCLUSION: Published data indicate that the two-week intensive outpatient program is an effective treatment program for a variety of complex presentations of PTSD, TBI, SUD, and other anxiety- and depression-related disorders in veterans and active duty service members.

Substance Use after Completion of an Intensive Treatment Program with Concurrent Treatment for Posttraumatic Stress Disorder and Substance Use among Veterans: Examining the Role of PTSD Symptoms.

OBJECTIVE: Substance use disorders (SUDs) and posttraumatic stress disorder (PTSD) are costly and highly co-occurring diagnoses, particularly among veterans, suggesting a need to understand this comorbidity and effectively treat both disorders among this population. METHODS: The current study aimed to examine substance use outcomes among post-9/11 veterans and service members (N = 48) who completed a two-week intensive outpatient program with concurrent treatment for and PTSD using Prolonged Exposure and substance use. Substance use was assessed at two weeks and three months posttreatment. RESULTS: The intensive program had high completion rates and demonstrated decreases in substance use at two weeks and three months posttreatment. Additionally, lower PTSD symptoms at treatment completion were related to less substance use posttreatment. CONCLUSIONS: Concurrent intensive treatment of PTSD and SUDs can lead to symptom improvement in a short period of time. Findings support the self-medication model, such that PTSD symptoms at treatment completion were related to substance use at follow-up.

Transient water wires mediate selective proton transport in designed channel proteins.

Selective proton transport through proteins is essential for forming and using proton gradients in cells. Protons are conducted along hydrogen-bonded 'wires' of water molecules and polar side chains, which, somewhat surprisingly, are often interrupted by dry apolar stretches in the conduction pathways, inferred from static protein structures. Here we hypothesize that protons are conducted through such dry spots by forming transient water wires, often highly correlated with the presence of the excess protons in the water wire. To test this hypothesis, we performed molecular dynamics simulations to design transmembrane channels with stable water pockets interspersed by apolar segments capable of forming flickering water wires. The minimalist designed channels conduct protons at rates similar to viral proton channels, and they are at least 106-fold more selective for H+ over Na+. These studies inform the mechanisms of biological proton conduction and the principles for engineering proton-conductive materials.

Abdominal biofidelity assessment of 5th percentile female ATD responses relative to recently developed belt and bar loading corridors.

OBJECTIVE: The objective of this study was the quantitative evaluation and comparison of the responses of the Hybrid III 5th percentile female (HIII-05F) and the 5th percentile female Test Device for Human Occupant Restraint (THOR-05F) anthropomorphic test devices (ATDs) subjected to abdominal loading conditions. METHOD: The HIII-05F and THOR-05F were subjected to 3 different abdominal loading conditions: fixed-back belt pull (low compression), fixed-back belt pull (high compression), and free-back rigid bar impact at 6 m/s. The stroke of the impact was controlled to represent injurious and noninjurious loading conditions as observed in the experiments with postmortem human subjects (PMHS). Quantitative comparisons were made between the ATD abdominal force and compression responses and biofidelity corridors obtained from matched-pair PMHS tests under identical loading conditions, using the most recent version of the NHTSA Biofidelity Ranking System (BRS). RESULTS: The overall THOR-05F BRS scores across all tests (BRS score = 1.84) indicated good biofidelity. For the belt loading test conditions, the average BRS scores for both THOR-05F (BRS scores = 1.45 and 1.34) and HIII-05F (BRS scores = 1.42 and 1.01) showed good biofidelity. For the rigid bar loading condition, the THOR-05F (BRS score = 2.74) showed better biofidelity compared to HIII-05F (BRS score = 10.63), with the HIII-05F exhibiting poor performance in this condition. The average pressures recorded by the abdomen pressure twin sensors (APTS) in the current study ranged from 45 to 130 kPa, increasing proportionally with higher stroke and loading rate. CONCLUSIONS: Overall, the THOR-05F BRS scores were better than the HIII-05F BRS scores, which suggests improved biofidelity of the THOR-05F abdomen. The abdominal insert in the HIII-05F did not provide enough room for compression, leading to higher stiffness and occupant motion as observed in the rigid bar tests. Because of practical challenges in measuring abdomen deflection in a soft ATD abdomen component, use of APTS in THOR-05F provides the ability to measure the restraint loading to the abdomen and assess the risk of abdominal injury. With good BRS scores observed in this study for THOR-05F, pressure and other measurements included in the THOR-05F may be used to develop abdominal injury risk functions in the future.

Simulation-based Ultrasound Curriculum for Novice Clinicians to Assess Neonatal Endotracheal Tube Position.

Background: To evaluate the efficacy of a simulation-based mastery curriculum to train clinicians with limited-to-no sonography experience how to use ultrasound (US) to assess neonatal endotracheal tube (ETT) positioning. Methods: In a single-centered, prospective, educational study, 29 neonatology clinicians participated in a simulation-based mastery curriculum composed of a didactic lecture, followed by a one-on-one simulation session using a newly designed, three-dimensional (3D) printed US phantom model of the neonatal trachea and aorta. After mastery training, clinicians were evaluated with a performance checklist on their skills obtaining US images and assessing ETT positioning in the US phantom model. They also completed pre- and postcurriculum knowledge assessment tests and self-assessment surveys. The data were analyzed using Wilcoxon signed rank tests and repeated measures analysis of variance. Results: The mean checklist score improved significantly during three attempts (mean difference: 2.6552; 95% confidence interval [CI]: 2.2578-3.0525; P < 0.0001). The mean time to perform US decreased significantly from the first to third attempt (mean difference: -1.8276 min; 95% CI: -3.3391 to - 0.3161; P = 0.0196). In addition, there was a significant improvement in median knowledge assessment scores (50% vs. 80%; P < 0.0001) and survey ratings on knowledge and self-efficacy (P < 0.0001). Conclusion: Clinicians with limited-to-no sonography experience demonstrated improved knowledge and skill acquisition in using US to assess ETT positioning through simulation-based mastery training. The use of 3D modeling enhances simulation experiences and optimizes the quality of training during limited opportunities to achieve procedural competency in a controlled environment before further application into the clinical setting.

A Laboratory Test of Alcohol-Related Intimate Partner Aggression: Expectancies Are Not to Blame.

Background: The role of alcohol expectancies and evaluations (i.e., perceived outcomes of drinking and whether these outcomes are desirable) in alcohol-related intimate partner aggression (IPA) has been debated, with some researchers arguing that expectancies fully account for the alcohol-IPA relationship and others suggesting they play a minimal if any role in alcohol-related IPA. In the current study, we examine the impact of expectancies and evaluations on alcohol-related IPA observed in the lab, in order to clarify what impact, if any, alcohol expectancies have on alcohol-related IPA. Consistent with findings from laboratory studies examining general aggression, we expected that individuals who were intoxicated would display greater IPA than individuals who were sober, but that alcohol expectancies and evaluations would be unrelated to in vivo IPA. Method: Participants were 69 dating couples (total N = 138), randomly assigned to consume either an alcohol or placebo beverage. IPA was measured with an in vivo aggression task based on the Taylor Aggression Paradigm. Results: As expected, alcohol intoxication predicted in vivo IPA following provocation (p < .03), whereas alcohol expectancies and evaluations were not related to IPA. Conclusions: These findings provide further support that alcohol expectancies and evaluations play little if any role in alcohol-related IPA. Rather, intoxication likely increases risk for IPA through its physiological effects on perception and thought. Further, treatments targeting alcohol use, rather than beliefs about outcomes of drinking, may have a greater impact on alcohol-related IPA.

Frequency and correlates of suicidal ideation and behaviors in treatment-seeking Post-9/11 Veterans.

OBJECTIVE: Post-9/11 U.S. veterans and servicemembers are at increased risk for suicide, indicating an important need to identify and mitigate suicidal ideation and behaviors in this population. METHOD: Using data modeling techniques, we examined correlates of suicidal ideation and behavior at intake in 261 Post-9/11 veterans and servicemembers seeking mental health treatment. RESULTS: Our sample endorsed high rates of suicidal ideation and behavior. Approximately 40% of our sample scored in a range on the Suicide Behaviors Questionnaire-Revised (SBQ-R), indicating high clinical risk for suicide. Results from multivariate analyses indicate that greater state and/or trait depression severity, greater anger and anger expression, less impulse control, and lower rank were consistently associated with suicidal ideation and behavior across our models. Negative posttraumatic thoughts about the self, gender, and military branch of service were also significantly associated with suicidal ideation and behavior. CONCLUSIONS: Suicidal ideation and behaviors are common in veterans seeking mental health treatment. State and/or trait depression, anger and impulse control were predictors of increased risk for suicidal ideation and behavior across models. Consistencies and differences across models as well as limitations and practical implications for the findings are discussed.

Long-term effectiveness of a prolonged exposure-based intensive outpatient program for veterans with posttraumatic stress disorder.

Empirically-supported psychotherapies for posttraumatic stress disorder (PTSD) are highly effective and recommended as first-line treatments, yet dropout rates from standard outpatient therapy are high. Intensive outpatient programs (IOPs) that provide these therapies in condensed format with complementary interventions show promise, as they have demonstrated similar efficacy and higher retention rates. The current study examined initial and long-term outcomes up to 12-months following a 2-week PTSD IOP involving daily prolonged exposure therapy (PE) and adjunctive interventions for veterans and military service members. Participants (N = 376) demonstrated high retention (91%) and large effect size reductions in self-reported PTSD and depression symptoms after two weeks. Small increases in symptoms occurred after 3 months but these stabilized and large reductions compared to baseline were maintained up to 12 months. Piecewise multilevel modeling indicated that demographic variables did not predict PTSD or depression symptom trajectories. Higher PTSD and depression severity at intake predicted higher symptomatology across timepoints and larger relative gains during treatment. Greater alcohol use prior to treatment was associated with higher PTSD symptomatology but did not affect the magnitude of gains. A history of childhood sexual abuse was associated with greater reduction in depression symptoms over treatment, although this effect faded over follow-up. Together these findings underscore the long-term effectiveness of a PE-based IOP across a diverse range of veterans and service members.

Acquisition, extinction, and return of fear in veterans in intensive outpatient prolonged exposure therapy: A fear-potentiated startle study.

Prolonged exposure (PE) therapy is a first-line treatment for posttraumatic stress disorder (PTSD) and involves repeated presentation of trauma-related cues without aversive outcomes. A primary learning mechanism of PE is fear extinction (new learning that a dangerous cue is now safe) and its retention (maintaining this new learning over time). Extant research suggests extinction is impaired in PTSD patients. In this study, we employed an established fear-potentiated startle-based paradigm to examine fear acquisition, extinction learning and retention before and after completion of intensive outpatient treatment. First, PTSD patients undergoing PE (n = 55) were compared to trauma-exposed patients without PTSD (n = 57). We identified excessive fear in PTSD patients during acquisition and extinction before treatment compared to non-PTSD patients. At post-treatment, we examined the return of fear after extinction in PTSD patients showing high or low treatment response to PE (≥50% change in PTSD symptom severity vs. < 50%). High PE responders maintained fear extinction learning whereas low PE responders showed significant return of fear at post-treatment. These results replicate and extend previous findings of impaired extinction in PTSD and provide support for the proposed theoretical link between fear extinction and PE response.

Multiscale Simulation of an Influenza A M2 Channel Mutant Reveals Key Features of Its Markedly Different Proton Transport Behavior.

The influenza A M2 channel, a prototype for viroporins, is an acid-activated viroporin that conducts protons across the viral membrane, a critical step in the viral life cycle. Four central His37 residues control channel activation by binding subsequent protons from the viral exterior, which opens the Trp41 gate and allows proton flux to the interior. Asp44 is essential for maintaining the Trp41 gate in a closed state at high pH, resulting in asymmetric conduction. The prevalent D44N mutant disrupts this gate and opens the C-terminal end of the channel, resulting in increased conduction and a loss of this asymmetric conduction. Here, we use extensive Multiscale Reactive Molecular Dynamics (MS-RMD) and quantum mechanics/molecular mechanics (QM/MM) molecular dynamics simulations with an explicit, reactive excess proton to calculate the free energy of proton transport in this M2 mutant and to study the dynamic molecular-level behavior of D44N M2. We find that this mutation significantly lowers the barrier of His37 deprotonation in the activated state and shifts the barrier for entry to the Val27 tetrad. These free energy changes are reflected in structural shifts. Additionally, we show that the increased hydration around the His37 tetrad diminishes the effect of the His37 charge on the channel's water structure, facilitating proton transport and enabling activation from the viral interior. Altogether, this work provides key insight into the fundamental characteristics of PT in WT M2 and how the D44N mutation alters this PT mechanism, and it expands understanding of the role of emergent mutations in viroporins.

The relations between C-reactive protein and trauma exposure, PTSD and depression symptoms, and PTSD psychotherapy treatment response in treatment seeking veterans and service members.

While inflammatory markers have been implicated in the link between PTSD and poor health outcomes, there is a paucity of research investigating C-reactive protein (CRP) and psychotherapy treatment response for posttraumatic stress disorder (PTSD). The present study utilized a large, well-characterized sample of veterans and service members (N = 493) engaged in intensive psychotherapy to investigate the associations between CRP, trauma exposure, related variables, and PTSD and depression, as well as investigating if CRP was associated with PTSD psychotherapy treatment response. Bivariate correlation results indicate that CRP was significantly associated with BMI (r = 0.48) and severity of experiences of childhood physical and sexual abuse (r = 0.14 and 0.15, respectively) and was not significantly associated with baseline PTSD total symptom severity, PTSD symptom clusters, or depression symptom severity (rs ranging from -0.03 to 0.04). In multivariate regression models investigating if CRP and related variables were associated with PTSD baseline symptom severity, CRP was not a significant predictor (ß = -0.03). Hierarchical linear modeling did not identify CRP as a significant predictor of PTSD psychotherapy outcome. Given that findings indicate that CRP was broadly elevated in this treatment seeking sample but not associated with PTSD and depression symptom severity, results suggest CRP may not be a specific biomarker for PTSD or depression but may be elevated in psychiatric disease more generally.

Physical and Sexual Intimate Partner Aggression Among College Students: Examining the Roles of Cyber Intimate Partner Aggression and Alcohol Use.

Intimate partner aggression (IPA) is a serious and prevalent problem among college students. Two factors that may increase risk for in-person IPA are cyber IPA and alcohol use. This study examines the interaction between three types of cyber IPA (cyber psychological, stalking, and sexual IPA) and alcohol use in predicting in-person physical and sexual IPA perpetration. Participants were 268 undergraduate students, who participated in a mass screening at a large midwestern university. More than half of the sample reported perpetrating cyber IPA. A multivariate logistic regression model was used to examine study hypotheses. The R2 for physical IPA perpetration was .69 and the R2 for sexual IPA perpetration was .46. Cyber stalking IPA and alcohol interacted to predict physical IPA perpetration, such that the relationship between cyber stalking IPA and physical IPA perpetration was stronger among individuals who used more alcohol. Contrary to expectations, cyber IPA and alcohol did not interact to predict sexual IPA. However, consistent with hypotheses, cyber stalking IPA was positively associated with sexual IPA perpetration. The high prevalence of cyber IPA and its association with in-person IPA perpetration suggests that prevention programs targeting cyber IPA on college campuses may be warranted.

The Utility of Point-of-Care Ultrasound in the Pediatric Intensive Care Unit.

Objectives: Point of care ultrasound (POCUS) in adult critical care environments has become the standard of care in many hospitals. A robust literature shows its benefits for both diagnosis and delivery of care. The utility of POCUS in the pediatric intensive care unit (PICU), however, is understudied. This study describes in a series of PICU patients the clinical indications, protocols, findings and impact of pediatric POCUS on clinical management. Design: Retrospective analysis of 200 consecutive POCUS scans performed by a PICU physician. Patients: Pediatric critical care patients who required POCUS scans over a 15-month period. Setting: The pediatric and cardiac ICUs at a tertiary pediatric care center. Interventions: Performance of a POCUS scan by a pediatric critical care attending with advanced training in ultrasonography. Measurement and Main Results: A total of 200 POCUS scans comprised of one or more protocols (lung and pleura, cardiac, abdominal, or vascular diagnostic protocols) were performed on 155 patients over a 15-month period. The protocols used for each scan reflected the clinical question to be answered. These 200 scans included 133 thoracic protocols, 110 cardiac protocols, 77 abdominal protocols, and 4 vascular protocols. In this series, 42% of scans identified pathology that required a change in therapy, 26% confirmed pathology consistent with the ongoing plans for new therapy, and 32% identified pathology that did not result in initiation of a new therapy. Conclusions: POCUS performed by a trained pediatric intensivist provided useful clinical information to guide patient management.

A Dyadic Analysis of PTSD and Psychological Partner Aggression Among U.S. Iraq and Afghanistan Veterans: The Impact of Gender and Dual-Veteran Couple Status.

Posttraumatic stress disorder (PTSD) symptoms have been repeatedly linked to intimate partner aggression (IPA), and previous research has suggested that this association may be stronger among veterans and men. However, few studies have examined veteran status and gender as moderators of the association between PTSD and psychological IPA, taking both partners' perspectives into account (i.e., within a dyadic framework). The current study aimed to address this limitation by using dyadic multilevel modeling to examine the association between PTSD symptoms and psychological IPA perpetration among a sample of 159 Operation Iraqi Freedom and Operation Enduring Freedom veterans and their partners (N = 318 participants). Findings revealed that both one's own and one's partner's PTSD symptoms were positively associated with greater psychological IPA. In addition, the effects of partner PTSD symptoms on psychological IPA perpetration differed across gender and veteran status. Results suggested that the association of partner PTSD and IPA perpetration may be stronger for male veterans than for female veterans. Findings from the current study are consistent with previous research showing associations between PTSD and IPA, and have clinical implications for treatment of PTSD and IPA among Operation Iraqi Freedom and Operation Enduring Freedom veterans.

An intensive outpatient program with prolonged exposure for veterans with posttraumatic stress disorder: Retention, predictors, and patterns of change.

High rates of drop-out from treatment of PTSD have challenged implementation. Care models that integrate PTSD focused psychotherapy and complementary interventions may provide benefit in retention and outcome. The first 80 veterans with chronic PTSD enrolled in a 2-week intensive outpatient program combining Prolonged Exposure (PE) and complementary interventions completed symptom and biological measures at baseline and posttreatment. We examined trajectories of symptom change, mediating and moderating effects of a range of patient characteristics. Of the 80 veterans, 77 completed (96.3%) treatment and pre- and posttreatment measures. Self-reported PTSD (p < .001), depression (p < .001) and neurological symptoms (p < .001) showed large reductions with treatment. For PTSD, 77% (n = 59) showed clinically significant reductions. Satisfaction with social function (p < .001) significantly increased. Black veterans and those with a primary military sexual trauma (MST) reported higher baseline severity than white or primary combat trauma veterans respectively but did not differ in their trajectories of treatment change. Greater cortisol response to the trauma potentiated startle paradigm at baseline predicted smaller reductions in PTSD over treatment while greater reductions in this response from baseline to post were associated with better outcomes. Intensive outpatient prolonged exposure combined with complementary interventions shows excellent retention and large, clinically significant reduction in PTSD and related symptoms in two weeks. This model of care is robust to complex presentations of patients with varying demographics and symptom presentations at baseline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics.

Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl amine class of inhibitors bind to M2 and disrupt and interact with the channel's water network, providing insight into the critical properties that enable their effective inhibition in wild-type M2. In this work, we examine the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel's natural ability to stabilize an excess protonic charge and act as a hydronium mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts.

Heterogeneity of posttraumatic stress symptomatology and social connectedness in treatment-seeking military veterans: a longitudinal examination.

Elucidating whether PTSD symptoms predict poorer social connectedness over time (i.e. social erosion) and/or that poor social connectedness contributes to maintenance of PTSD (i.e. social causation) has implications for PTSD treatment and relapse prevention. Most extant research has been cross-sectional and examined overall PTSD symptoms. Evidence of longitudinal associations among heterogeneous PTSD symptom clusters and social connectedness could provide insight into more nuanced targets for intervention. Using data from 1,491 U.S. military veterans in residential treatment for PTSD at 35 Department of Veterans Affairs facilities, we evaluated a two-wave cross-lagged panel model including a five-factor model of PTSD and two aspects of social connectedness. PTSD, quality of connectedness (i.e. degree of distress related to interpersonal conflict), and structural social support (i.e. number of days of contact with supportive loved ones) in the past 30 days were assessed at baseline and 4 months after discharge. The largest effect was greater severity of PTSD dysphoric arousal symptoms (i.e. irritability/anger, poor concentration, and sleep problems) at baseline predicting more conflict-related distress at follow-up (ß = 0.43). Post-hoc symptom-level analyses indicated that irritability/anger drove this association. In addition, conflict-related distress predicted greater PTSD symptom severity across all five clusters (ß's = 0.10 to 0.14, p's < 0.01). More days of contact predicted lower severity of avoidance and numbing symptoms (ß's = -.05 and -.07, p's < 0.01), along with individual symptoms within these clusters, plus flashbacks. Results support both social erosion and social causation models. Engaging loved ones in veterans' treatment and targeting dysphoric arousal symptoms, particularly anger and irritability, may improve long-term PTSD and relationship outcomes, respectively.

通过阐明PTSD症状是否预测随着时间推移社会联结性较差（即，社会退化模型）和/或社会联结较弱促进PTSD的维持（即，社会因果关系模型），以期对创伤后应激障碍治疗和复发预防提供建议。大多数现存的研究都是对PTSD整体症状的横断研究。提供异质PTSD症状簇与社会联结的纵向关联的证据可以为更细致的干预目标提供见解。利用美国退伍军人事务部35个部门的1491名美国退伍军人住院治疗PTSD的数据，我们评估了一个双波交叉滞后面板模型，包括PTSD的五因子模型和社会联结的两个因子。在进行评估基线和出院后4个月评估了PTSD，过去30天内的联结质量（即与人际冲突有关的痛苦程度）和结构性社会支持（即与支持性亲人接触的天数）。基线时更严重的PTSD焦虑唤醒症状（即烦躁/愤怒，注意力不集中和睡眠问题）预测随访时更多与冲突相关的痛苦具有最大的效应（r = 0.43）。事后症状水平分析表明，烦躁/愤怒主要推动了这种关联。此外，与冲突相关的痛苦预测所有五个PTSD症状簇更高严重程度（r's = 0.10至0.14，p <0.01）。更多的接触天数可预测回避和麻木症状的较低严重程度（r's = −.05和-.07，p <0.01），以及这些症状簇中的单个症状和闪回。研究结果支持社会退化和社会因果关系模型。让亲近的人参与退伍军人的治疗，并针对焦虑唤醒的症状（特别是愤怒和烦躁）可分别改善长期PTSD和关系结果。.

Proton-Induced Conformational and Hydration Dynamics in the Influenza A M2 Channel.

The influenza A M2 protein is an acid-activated proton channel responsible for acidification of the inside of the virus, a critical step in the viral life cycle. This channel has four central histidine residues that form an acid-activated gate, binding protons from the outside until an activated state allows proton transport to the inside. While previous work has focused on proton transport through the channel, the structural and dynamic changes that accompany proton flux and enable activation have yet to be resolved. In this study, extensive Multiscale Reactive Molecular Dynamics simulations with explicit Grotthuss-shuttling hydrated excess protons are used to explore detailed molecular-level interactions that accompany proton transport in the +0, + 1, and +2 histidine charge states. The results demonstrate how the hydrated excess proton strongly influences both the protein and water hydrogen-bonding network throughout the channel, providing further insight into the channel's acid-activation mechanism and rectification behavior. We find that the excess proton dynamically, as a function of location, shifts the protein structure away from its equilibrium distributions uniquely for different pH conditions consistent with acid-activation. The proton distribution in the xy-plane is also shown to be asymmetric about the channel's main axis, which has potentially important implications for the mechanism of proton conduction and future drug design efforts.

Self-Assessment of Preparedness among Critical Care Trainees Transitioning from Fellowship to Practice.

This study evaluated the subjective assessment of preparedness needs of critical care trainees and recent graduates between 2013 and 2014. A questionnaire was developed and validated by the subcommittee of the In-Training Section of Society of Critical Care Medicine (SCCM). The survey was deployed twice between December 2013 and January 2014 via email to any trainee or individual graduated from a critical care fellowship within the previous three years. Six percent (180) of all individuals completed the survey, and 67% of respondents had recently interviewed for a job. Northeast was the preferred location for a job (47%), and academia was favored over private practice (80% vs. 15%). Of the respondents that secured an interview, 55% felt prepared for the interview, 67% felt prepared to build an adequate job portfolio, 33% received formal guidance from their mentor/training program. 89% of total respondents agreed it is important to participate in a formal training course in job search, portfolio development, and interviewing process. The preferred sources of training were equally distributed between their home institution, webinars, and SCCM. There is an ongoing need in education regarding the transition period from fellowship to practice.