Evaluating the Performance of the Primary Care Posttraumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) in a Trauma-Exposed, Socioeconomically Vulnerable Patient Population.

The properties and utility of the Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) remain unstudied in community-based populations. This study evaluates the performance of the PC-PTSD-5 to determine whether it can be used as a brief alternative to the PTSD Checklist for DSM-5 (PCL-5) in a large public hospital in the southeastern United States. Participants (N = 422; 92.7% Black; 85.8% female; Mage = 42.0 years, SDage = 13.4 years) completed the PCL-5 and PC-PTSD-5 after recruitment from medical clinic waiting rooms and admission lists. Using chance-corrected test quality indices and item response theory (IRT) analyses, we determined optimal cut-scores for screening and examined item performance. Approximately 45.0% of the sample screened positive for probable DSM-5 PTSD using the PCL-5. The PC-PTSD-5 demonstrated high internal consistency and strong associations with PCL-5 scores (total, r = .79; items, rs = .51-.61). A cut-score of one was optimally sensitive for screening (κ[1] = .96), and a cut-score of four had the highest quality of probable efficiency (κ[.5] = .66) for detecting self-reported DSM-5 PTSD on the PCL-5. IRT analyses indicated Item 1 (nightmares, intrusive memories) provided the most information, and other items may not be incrementally useful for this sample. Findings provide preliminary support for the use of the PC-PTSD-5 as a brief alternative to the PCL-5 among chronically trauma-exposed patients in the public healthcare setting.

Self-Rated Versus Clinician-Rated Assessment of Posttraumatic Stress Disorder: An Evaluation of Discrepancies Between the PTSD Checklist for DSM-5 and the Clinician-Administered PTSD Scale for DSM-5.

Posttraumatic stress disorder (PTSD) is commonly assessed with self-rated or clinician-rated measures. Although scores from these assessment modalities are strongly associated, they are often discrepant for individual symptoms, total symptom severity, and diagnostic status. To date, no known studies have empirically identified the sources of these discrepancies. In the present study, we had three aims: (a) replicate previously identified discrepancies; (b) examine contribution of possible objective predictors of discrepancies, including negative response bias, random responding, conscientiousness, neuroticism, and verbal IQ; and (c) identify subjective sources of discrepancies through analysis of participant feedback. Trauma-exposed undergraduates (N = 60) were administered the PTSD Checklist for DSM-5 (PCL-5), the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), and other questionnaires. Interviewers identified discrepancies between corresponding PCL-5/CAPS-5 scores and asked participants to describe their attributions for discrepancies. Discrepancies, both dimensional and dichotomous, occurred at the item, cluster, and total score level. Objective predictors were weakly associated with discrepancies. The most commonly reported reasons for discrepancies were time-frame reminders, comprehension of symptoms, trauma-related attribution errors, increased awareness, and general errors. These findings help explain discordance between the PCL-5 and CAPS-5, and inform use and interpretation of these two widely used PTSD measures in clinical and research applications.

Distinguishing PTSD, complex PTSD, and borderline personality disorder using exploratory structural equation modeling in a trauma-exposed urban sample.

There is debate about the validity of the complex posttraumatic stress disorder (CPTSD) diagnosis and whether disturbances in self-organization (DSO) in CPTSD can be differentiated from borderline personality disorder (BPD). How PTSD is defined may matter. The present study used exploratory structural equation modeling (ESEM) to replicate and extend prior work by including two models to examine how PTSD (ICD-11, DSM-5), DSO, and BPD symptoms relate. Participants (N = 470; 98.1% women; 97.7% Black) were recruited from medical clinics within an urban hospital. PTSD, CPTSD, and BPD were assessed using semi-structured interviews and trauma-related avoidance, aggressive behavior, and anxious attachment were assessed using self-report measures. ESEM models of PTSD, DSO, and BPD symptoms were run. We found a three-factor ESEM model of CPTSD (ICD-11 PTSD and DSO symptoms) and BPD symptoms best fit the data and found support for discriminant validity between factors across trauma-related avoidance, aggressive behavior, and anxious attachment. For DSM-5 PTSD, a two-factor ESEM model was best-fitting (PTSD and DSO/BPD). The findings demonstrate clear distinguishing and overlapping features of ICD-11 PTSD, CPTSD, and BPD and the necessity to consider the diagnostic structure of PTSD in determining the additive value of CPTSD as a distinct construct.

Comparing Veterans with Posttraumatic Stress Disorder Related to Military Sexual Trauma or Other Trauma Types: Baseline Characteristics and Residential Cognitive Processing Therapy Outcomes.

The Veterans Health Administration (VHA) has called for improved assessment and intervention for survivors of military sexual trauma (MST) to mitigate deleterious sequalae, including posttraumatic stress disorder (PTSD). Research on the impact of MST-related PTSD (MST-IT) on men is limited, and few studies have examined the differential effects of treatment across genders and MST-IT. Additionally, studies have utilized varying definitions of MST (e.g., sexual assault only vs. including sexual harassment), contributing to disparate outcomes across studies. Utilizing data from 343 veterans seeking residential cognitive processing therapy (CPT) for PTSD in VHA, this study examined the impact of MST-IT and gender on differences in demographic characteristics; pre-treatment severity of PTSD (overall and clusters), depression, and negative posttraumatic cognitions (NPCs); and post-treatment severity of these variables after accounting for pre-treatment severity. Results from 2x2 factorial ANOVAs found no differences in pre-treatment depression or overall PTSD by MST-IT, gender, or their interaction; however, MST-IT survivors presented with greater pre-treatment avoidance, global NPCs, and self-blame. Results from hierarchical linear regression models found only pre-treatment symptom severity significantly predicted post-treatment severity for overall PTSD and all NPCs. These findings suggest veteran survivors of MST-IT appear to benefit similarly from CPT delivered in a VHA residential PTSD program compared to veterans with other index traumas, regardless of gender. Although there were minimal post-treatment differences in PTSD and NPCs by MST-IT status and gender, residual symptoms related to negative cognitions and mood appear to differ across gender and MST-IT status. Specifically, in individuals without MST-IT, post-treatment PTSD symptoms of negative alterations in cognition and mood were higher in men than women. Moreover, women with MST-IT reported more symptoms of depression than both men with MST-IT and women without MST-IT. These findings suggest depressive symptoms decrease through residential PTSD treatment differentially by MST-IT status and gender and warrant further examination.

Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis.

The structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360° catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an α-subunit in a loop in the γ-subunit, as proposed before, but also a "fail-safe" mechanism involving the b'-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bδ-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the α-subunits. The auto-inhibitory plus the associated "fail-safe" mechanisms and the modes of attachment of the α-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel.

An item response theory analysis of the PTSD checklist for DSM-5: Implications for DSM-5 and ICD-11.

The PTSD Checklist (PCL) is a widely used, extensively validated questionnaire for posttraumatic stress disorder (PTSD). The PCL was revised for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5; Friedman, 2013), and the updated version, the PCL-5, has continued the strong psychometric performance of the original version. To further explore the PCL-5's psychometric properties, we used item response theory (IRT) to examine item difficulty and discrimination parameters in separate samples of trauma-exposed undergraduates (N = 1213) and community members (N = 367). Considering item difficulty, nightmares, flashbacks, and reckless or self-destructive behavior emerged among the most difficult items across samples and internal avoidance emerged as the least difficult items across samples. In terms of item discrimination, inability to experience positive emotions, detachment from others, diminished interest, and negative emotions emerged as highly discriminating items in both samples, and traumatic amnesia and reckless or self-destructive behavior emerged as the least discriminating items in both samples. These results have implications for the divergent conceptualizations of PTSD in DSM-5 versus International Classification of Diseases, 11th Edition (ICD-11; WHO, 2018). Future research should employ IRT in a clinical population.

The Detailed Assessment of Posttraumatic Stress-Second Edition (DAPS-2): Initial Psychometric Evaluation in an MTurk-Recruited, Trauma-Exposed Community Sample.

The Detailed Assessment of Posttraumatic Stress (DAPS; Briere, 2001) is a comprehensive questionnaire that assesses posttraumatic stress disorder (PTSD) diagnostic criteria as well as peritraumatic responses and associated problems such as dissociation, suicidality, and substance abuse. DAPS scores have demonstrated excellent reliability, validity, and clinical utility, performing as well or better than leading PTSD questionnaires. The present study was an initial psychometric evaluation of the unreleased DAPS (DAPS-2), revised for Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5), in an MTurk-recruited mixed trauma sample (N = 367). DAPS-2 PTSD scale and associated features scales demonstrated high internal consistency and strong convergent and discriminant validity. In confirmatory factor analyses, the DSM-5 four-factor model of PTSD provided adequate fit, but the leading seven-factor model provided superior fit. These results indicate the DAPS-2 is a psychometrically sound measure of DSM-5 PTSD symptoms.

Structure of F1-ATPase from the obligate anaerobe Fusobacterium nucleatum.

The crystal structure of the F1-catalytic domain of the adenosine triphosphate (ATP) synthase has been determined from the pathogenic anaerobic bacterium Fusobacterium nucleatum. The enzyme can hydrolyse ATP but is partially inhibited. The structure is similar to those of the F1-ATPases from Caldalkalibacillus thermarum, which is more strongly inhibited in ATP hydrolysis, and in Mycobacterium smegmatis, which has a very low ATP hydrolytic activity. The ßE-subunits in all three enzymes are in the conventional 'open' state, and in the case of C. thermarum and M. smegmatis, they are occupied by an ADP and phosphate (or sulfate), but in F. nucleatum, the occupancy by ADP appears to be partial. It is likely that the hydrolytic activity of the F. nucleatum enzyme is regulated by the concentration of ADP, as in mitochondria.

Structure of the NDH-2 - HQNO inhibited complex provides molecular insight into quinone-binding site inhibitors.

Type II NADH:quinone oxidoreductase (NDH-2) is a proposed drug-target of major pathogenic microorganisms such as Mycobacterium tuberculosis and Plasmodium falciparum. Many NDH-2 inhibitors have been identified, but rational drug development is impeded by the lack of information regarding their mode of action and associated inhibitor-bound NDH-2 structure. We have determined the crystal structure of NDH-2 complexed with a quinolone inhibitor 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). HQNO is nested into the slot-shaped tunnel of the Q-site, in which the quinone-head group is clamped by Q317 and I379 residues, and hydrogen-bonds to FAD. The interaction of HQNO with bacterial NDH-2 is very similar to the native substrate ubiquinone (UQ1) interactions in the yeast Ndi1-UQ1 complex structure, suggesting a conserved mechanism for quinone binding. Further, the structural analysis provided insight how modifications of quinolone scaffolds improve potency (e.g. quinolinyl pyrimidine derivatives) and suggests unexplored target space for the rational design of new NDH-2 inhibitors.

Crystal structure of type II NADH:quinone oxidoreductase from Caldalkalibacillus thermarum with an improved resolution of 2.15†Å.

Type II NADH:quinone oxidoreductase (NDH-2) is a respiratory enzyme found in the electron-transport chain of many species, with the exception of mammals. It is a 40-70 kDa single-subunit monotopic membrane protein that catalyses the oxidation of NADH and the reduction of quinone molecules via the cofactor FAD. NDH-2 is a promising new target for drug development given its essential role in many bacterial species and intracellular parasites. Only two bacterial NDH-2 structures have been reported and these structures are at moderate resolution (2.3-2.5 Å). In this communication, a new crystallization platform is reported that produced high-quality NDH-2 crystals that diffracted to high resolution (2.15 Å). The high-resolution NDH-2 structure was used for in silico quinone substrate-docking studies to investigate the binding poses of menadione and ubiquinone molecules. These studies revealed that a very limited number of molecular interactions occur at the quinone-binding site of NDH-2. Given that the conformation of the active site is well defined, this high-resolution structure is potentially suitable for in silico inhibitor-compound screening and ligand-docking applications.