A liquid chromatographic-mass spectrometric procedure for analysis of pentaerythrityl tetranitrate metabolites - Development, validation and application to ovine serum and human plasma samples.

Pentaerythrityl tetranitrate (PETN) is an established drug in the treatment of coronary heart disease and heart failure. It is assumed, that the vasodilative and vasoprotective effects of PETN also have a positive impact on pregnant patients with impaired placental perfusion and studies evaluating the effect of PETN in risk pregnancies have been carried out. In the context of these clinical trials, measuring of serum levels of PETN and its metabolites pentaerythrityl trinitrate (PETriN), pentaerythrityl dinitrate (PEDN), pentaerythrityl mononitrate (PEMN) and pentaerythritol (PE) were required. To evaluate the transfer of PETN and its metabolites (PEXN) from the mother to the fetus using samples from a human clinical trial and animal study, the present work aimed to develop a rapid and simple method to simultaneously analyze PEXN in human and ovine samples. A method employing a rapid and simple liquid-liquid extraction followed by reversed-phase (C18) liquid chromatography coupled to high-resolution mass spectrometry with negative electrospray ionization was developed and validated for the detection of PETN and PEXN in human and ovine samples. PE could only be qualitatively detected at higher concenrations. Method validation requirements, including accuracy, repeatability and intermediate precision were fulfilled in ovine and human samples for all other PEXN with exception PETriN in human samples. The recovery (RE) in ovine samples was 76.7 % ± 12 % for PEMN, 98 % ± 23 % for PEDN, 94 % ± 22 % for PETriN, in human samples RE was 59 % ± 16 % for PEMN, 67 % ± 19 % for PEDN, 71 % ± 17 %. The matrix effects (ME) in ovine samples were 90 % ± 11 % for PEMN, 70 % ± 30 % for PEDN, 107 % ± 17 % for PETriN, in human samples the ME were 93 % ± 13 % for PEMN, 84 % ± 17 % for PEDN, 98 % ± 16 % for PETriN. The limits of quantification (LOQ) in ovine samples were 1.0 ng/mL for PETriN and 0.1 ng/mL for PEMN and PEDN. The LOQs in human samples were 5.0 ng/mL for PETriN and 0.3 ng/mL for PEMN und PEDN. The newly developed method was used to analyze 184 ovine serum samples and 18 human plasma samples. In ovine maternal samples, the highest observed PEDN concentration was 3.5 ng/mL and the highest PEMN concentration was 10 ng/mL, the respective concentrations in fetal serum samples were 4.9 ng/mL for PEDN and 5.4 ng/mL for PEMN. PETriN was only detected in traces in maternal and fetal samples, whereas PETN could not be detected at all. In human maternal samples, the highest concentration for PEDN was 27 ng/mL and for PEMN 150 ng/mL. In umbilical cord plasma, concentrations of 2.3 ng/mL for PEDN and 73 ng/mL for PEMN were detected. Although the PEMN and PEDN concentrations in the human samples were several times higher than in ovine samples, neither PETN nor PETriN signals could be detected. These results demonstrated that the metabolites were transferred from mother to fetus with a slight time delay.

Evaluation of biochemical assays and optimization of LC-MS-MS analysis for the detection of synthetic urine.

Ensuring specimen validity is an essential aspect of toxicological laboratories. In recent years, substituting authentic urine specimens for synthetic urine (SU) has become increasingly popular. Such SU products consist of components expected in normal urine and show physiological values for specific gravity and pH. Thus, standard specimen validity testing may fail in revealing adulteration by SU. The present study investigated three methods to distinguish authentic and SU specimens: enzymatic detection of uric acid, the commercially available Axiom Test True SU and liquid chromatography coupled with (tandem) mass spectrometry (LC-MS-MS) analysis of 10 endogenous biomolecules. Additionally, novel direct markers of SU were investigated. Two specimen sets were analyzed by each method. Specimen set A consisted of eight SU products purchased from the Austrian/German market and 43 urine specimens from volunteers of known authenticity, which underwent double-blind analysis. Specimen set B consisted of 137 real urine specimens submitted for drug testing, which were selected due to initial suspicious test results in adulteration testing and reanalyzed by all three methods. Uric acid and LC-MS-MS-based endogenous biomolecule testing showed 100% sensitivity and specificity for set A. The commercial test had 87.5% sensitivity and 97.7% specificity for set A. For set B, uric acid and LC-MS-MS analysis showed almost similar results, even if uric acid was missing one presumptive authentic urine specimen according to LC-MS-MS findings. Nearly half of the SU assignments for the commercial test were presumptive false positives. New SU markers were observed for SU products from the Austrian/German market. One specimen in set B had both an endogenous biomolecule pattern and SU markers suggesting urine dilution with SU. In conclusion, several analytes or methods should be used rather than one, and the most reliable results are achieved if both indirect and direct markers of urine substitution are analyzed.

Sensory functions and their relation to balance metrics: a secondary analysis of the LIMBIC-CENC multicenter cohort.

Introduction: Among patients with traumatic brain injury (TBI), balance problems often persist alongside hearing and vision impairments that lead to poorer outcomes of functional independence. As such, the ability to regain premorbid independent gait may be dictated by the level of sensory acuity or processing decrements that are shown following TBI assessment. This study explores the relationships between standardized sensory acuity and processing outcomes to postural balance and gait speed. Methods: Secondary analysis was performed on the Long-Term Impact of Military- Relevant Brain Injury Consortium Chronic Effects of Neurotrauma Consortium LIMBIC (CENC) data set. Separate regression analyses were carried out for each of the balance assessments (via Computerized Dynamic Posturography, CDP) and walking speed. Discussion: TBI frequency was significantly related to the majority of single CDP outcomes (i.e., Conditions 2-6), while various sensory processing outcomes had task-specific influences. Hearing impairments and auditory processing decrements presented with lower CDP scores (CDP Conditions 3,5,6, and 1-3 respectively), whereas greater visual processing scores were associated with better CDP scores for Conditions 2,5, and 6. In sum, patients with TBI had similar scores on static balance tests compared to non-TBI, but when the balance task got more difficult patients with TBI scored worse on the balance tests. Additionally, stronger associations with sensory processing than sensory acuity measures may indicate that patients with TBI have increased fall risk.

Long-term resting EEG correlates of repetitive mild traumatic brain injury and loss of consciousness: alterations in alpha-beta power.

Objective: Long-term changes to EEG spectra after mild traumatic brain injury (mTBI, i.e., concussion) have been reported; however, the role of injury characteristics in long-term EEG changes is unclear. It is also unclear how any chronic EEG changes may underlie either subjective or objective cognitive difficulties, which might help explain the variability in recovery after mTBI. Methods: This study included resting-state high-density electroencephalography (EEG) and mTBI injury data from 340 service members and veterans collected on average 11 years after injury as well as measures of objective and subjective cognitive functioning. The average absolute power within standard bands was computed across 11 spatial regions of the scalp. To determine how variation in brain function was accounted for by injury characteristics and aspects of cognition, we used regression analyses to investigate how EEG power was predicted by mTBI history characteristics [number, number with post-traumatic amnesia and witnessed loss of consciousness (PTA + LOC), context of injury (combat or non-combat), potentially concussive blast exposures], subjective complaints (TBIQOL General Cognitive and Executive Function Concerns), and cognitive performance (NIH Toolbox Fluid Intelligence and premorbid IQ). Results: Post-traumatic amnesia (PTA) and loss of consciousness (LOC), poorer cognitive performance, and combat experience were associated with reduced power in beta frequencies. Executive function complaints, lower premorbid IQ, poorer cognitive performance, and higher psychological distress symptoms were associated with greater power of delta frequencies. Multiple regression confirmed the relationship between PTA + LOC, poor cognitive performance, cognitive complaints, and reduced power in beta frequencies and revealed that repetitive mTBI was associated with a higher power in alpha and beta frequencies. By contrast, neither dichotomous classification of the presence and absence of mTBI history nor blast exposures showed a relationship with EEG power variables. Conclusion: Long-term alterations in resting EEG spectra measures of brain function do not appear to reflect any lasting effect of a history of mTBI or blast exposures. However, power in higher frequencies reflects both injury characteristics and subjective and objective cognitive difficulties, while power in lower frequencies is related to cognitive functions and psychological distress associated with poor long-term outcomes after mTBI.

Isolation of Glycosomes from Trypanosoma brucei.

Glycosomes, belonging to the sub-class of peroxisomes, are single-membrane-bound organelles of trypanosomatid parasites. Glycosomes compartmentalize mainly glycolytic and other essential metabolic pathways such as gluconeogenesis, pentose phosphate pathway, sugar nucleotide biosynthesis, etc. Since glycosomes are parasite-specific and their biogenesis is essential for the parasite survival, they have attracted a lot of interest over the years. Understanding the glycosomal enzyme composition and machinery involved in the biogenesis of this organelle requires the knowledge of the glycosomal proteome. Here we describe a method to isolate highly purified glycosomes and further enrichment of the glycosomal membrane proteins from the pro-cyclic form of Trypanosoma brucei. The isolation method is based on the controlled rupture of the cells by silicon carbide, followed by the differential centrifugation, and density gradient centrifugation. Further, the glycosomal membrane proteins are enriched from the purified glycosomes by the successive treatments with low-salt, high-salt, and alkaline carbonate buffer extractions.

Long time stability of 35 small endogenous biomolecules in dried urine spotted on various surfaces and environmental conditions.

Analysis of endogenous biomolecules is an important aspect of many forensic investigations especially with focus on DNA analysis for perpetrator/victim identification and protein analysis for body fluid identification. Recently, small endogenous biomolecules have been used for differentiation of synthetic "fake" urine from authentic urine and might be also useful for biofluid identification. Therefore, the aim of this study was to adapt and optimize a method for analysis of small EBs and to investigate long time stability of 35 small endogenous biomolecules (including acylcarnitines with their isomers and metabolites as well as amino acids with their metabolites) in spotted urine samples. Urine samples were spotted on seven different surfaces (Whatman 903 Protein Saver Cards, cotton swabs, cotton glove, denim, underwear, and smooth and rough flagstone) and stored under six environmental conditions (reference condition, sunlight, LED light, 4 °C, 37 °C, humidity of 95%). At certain time points (d0, d7, d28 and d56) samples were analyzed in triplicates by an optimized extraction and LC-HRMS approach. In addition, the urine marker Tamm-Horsfall-Protein was determined on cotton swabs at the same time points using a commercial lateral flow test. Twenty-one of 35 small endogenous biomolecules were stable on most materials/surfaces and under most storage conditions. Significant lower endogenous biomolecule peak areas were found for rough flagstone and underwear as well as for high humidity storage. Kynurenic acid proved to be photo labile. While high long time stabilities were found for 19 of 28 acylcarnitines, nine acylcarnitines showed aberrant stability patterns without evident structural reason. For Tamm-Horsfall-Protein degradation within 28 days was observed even under reference conditions. The presented study demonstrated the value of sensitive LC-HRMS analysis for small endogenous biomolecules / pattern. However, further studies will be indispensable for unambiguous body fluid identification by small endogenous biomolecules.

Randomized trial of rTMS in traumatic brain injury: improved subjective neurobehavioral symptoms and increases in EEG delta activity.

PRIMARY OBJECTIVE: While repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for cognitive difficulties accompanying depression, it is unknown if it can improve cognition in persons with traumatic brain injury. RESEARCH DESIGN: Using a sham-controlled crossover design, we tested the capacity of high frequency rTMS of the prefrontal cortex to improve neuropsychological performance in attention, learning and memory, and executive function. METHODS: Twenty-six participants with cognitive complaints and a history of mild-to-moderate traumatic brain injury were randomly assigned to receive first either active or sham 10 Hz stimulation for 20 minutes (1200 pulses) per session for five consecutive days. After a one-week washout, the other condition (active or sham) was applied. Pre- and post-treatment measures included neuropsychological tests, cognitive and emotional symptoms, and EEG. MAIN OUTCOMES AND RESULTS: Results indicated no effect of treatment on cognitive function. Subjective measures of depression, sleep dysfunction, post-concussive symptoms (PCS), and executive function showed significant improvement with stimulation, retaining improved levels at two-week follow-up. EEG delta power exhibited elevation one week after stimulation cessation. CONCLUSIONS: While there is no indication that rTMS is beneficial for neuropsychological performance, it may improve PCS and subjective cognitive dysfunction. Long-term alterations in cortical oscillations may underlie the therapeutic effects of rTMS.

Executive function and relation to static balance metrics in chronic mild TBI: A LIMBIC-CENC secondary analysis.

Introduction: Among patients with traumatic brain injury (TBI), postural instability often persists chronically with negative consequences such as higher fall risk. One explanation may be reduced executive function (EF) required to effectively process, interpret and combine, sensory information. In other populations, a decline in higher cognitive functions are associated with a decline in walking and balance skills. Considering the link between EF decline and reduction in functional capacity, we investigated whether specific tests of executive function could predict balance function in a cohort of individuals with a history of chronic mild TBI (mTBI) and compared to individuals with a negative history of mTBI. Methods: Secondary analysis was performed on the local LIMBIC-CENC cohort (N = 338, 259 mTBI, mean 45 ± STD 10 age). Static balance was assessed with the sensory organization test (SOT). Hierarchical regression was used for each EF test outcome using the following blocks: (1) the number of TBIs sustained, age, and sex; (2) the separate Trail making test (TMT); (3) anti-saccade eye tracking items (error, latency, and accuracy); (4) Oddball distractor stimulus P300 and N200 at PZ and FZ response; and (5) Oddball target stimulus P300 and N200 at PZ and FZ response. Results: The full model with all predictors accounted for between 15.2% and 21.5% of the variability in the balance measures. The number of TBI's) showed a negative association with the SOT2 score (p = 0.002). Additionally, longer times to complete TMT part B were shown to be related to a worse SOT1 score (p = 0.038). EEG distractors had the most influence on the SOT3 score (p = 0.019). Lastly, the SOT-composite and SOT5 scores were shown to be associated with longer inhibition latencies and errors (anti-saccade latency and error, p = 0.026 and p = 0.043 respectively). Conclusions: These findings show that integration and re-weighting of sensory input when vision is occluded or corrupted is most related to EF. This indicates that combat-exposed Veterans and Service Members have greater problems when they need to differentiate between cues when vision is not a reliable input. In sum, these findings suggest that EF could be important for interpreting sensory information to identify balance challenges in chronic mTBI.

Auditory evoked brain potentials as markers of chronic effects of mild traumatic brain injury in mid-life.

OBJECTIVE: Auditory event-related potential (ERP) correlates of pre-dementia in late-life may also be sensitive to chronic effects of mild traumatic brain injury (mTBI) in mid-life. In addition to mTBI history, other clinical factors may also influence ERP measures of brain function. This study's objective was to evaluate the relationship between mTBI history, auditory ERP metrics, and common comorbidities. METHODS: ERPs elicited during an auditory target detection task, psychological symptoms, and hearing sensitivity were collected in 152 combat-exposed veterans and service members, as part of a prospective observational cohort study. Participants, with an average age of 43.6 years, were grouped according to positive (n = 110) or negative (n = 42) mTBI history. Positive histories were subcategorized into repetitive mTBI (3 + ) (n = 40) or non-repetitive (1-2) (n = 70). RESULTS: Positive history of mTBI was associated with reduced N200 amplitude to targets and novel distractors. In participants with repetitive mTBI compared to non-repetitive and no mTBI, P50 was larger in response to nontargets and N100 was smaller in response to nontargets and targets. Changes in N200 were mediated by depression and anxiety symptoms and hearing loss, with no evidence of a supplementary direct mTBI pathway. CONCLUSIONS: Auditory brain function differed between the positive and negative mTBI groups, especially for repetitive injury, which implicated more basic, early auditory processing than did any mTBI exposure. Symptoms of internalizing psychopathology (depression and anxiety) and hearing loss are implicated in mTBI's diminished brain responses to behaviorally relevant and novel stimuli. SIGNIFICANCE: A mid-life neurologic vulnerability conferred by mTBI, particularly repetitive mTBI, may be detectable using auditory brain potentials, and so auditory ERPs are a target for study of dementia risk in this population.

Dyadic Coping of Kidney Transplant Recipients and Their Partners: Sex and Role Differences.

Background: Coping with stressful health issues - e.g., organ transplantation - can affect interpersonal relationships. Objective: The study examines individual and dyadic coping (DC) in kidney transplant recipients and their partners under consideration of sex and role differences. The Dyadic Coping Inventory allows analyzing partners' perception of their own DC and also of their partner's behavior and investigating different perspectives with three discrepancy indexes (similarity, perceived similarity, congruence). Methods: Fifty-six kidney transplant recipients and their partners completed self-report questionnaires (N = 112) on DC, depression, anxiety, and relationship satisfaction. The average age of the patients was 58.1 years and of the partners 57.2 years; 64.3% of the patients were male; time since transplantation was on average 9.7 years. Results: (1) Individual and dyadic functioning: In couples with male patients female caregivers showed higher own supportive DC than the males. In couples with female patients, women reported higher own stress communication, supportive DC, total positive DC and total DC as well as depression compared to men. (2) Regarding the discrepancy indexes, in couples with male patients lower levels of similarity in DC reactions of the couple was associated with higher depression of the males as well as higher anxiety of the females. Moreover, lower comparability of the own DC with partner-perception was correlated with higher depression in males. In couples with female patients, higher comparability was associated with higher DC. Higher DC of the males was associated with lower own anxiety and better similarity in DC reactions. Lower levels of similarity of the male spouse showed correlations with higher depression and anxiety of the females. (3) Sex and role differences occurred. No significant differences between male patients and male partners occurred whereas female patients showed higher own stress communication, supportive DC, common DC, total positive DC, total DC and relationship satisfaction compared to female caregivers (role differences). The same differences were found comparing female with male patients. No differences occurred between male and female caregivers (sex differences). (4) Regarding male's relationship quality, male's DC total score and similarity index seem to be important predictors in couples with male patients. Discussion: The results demonstrate the relevance of DC in couples with kidney transplantation and show differences between males and females as well as between patients and partners.

Is balance performance reduced after mild traumatic brain injury?: Interim analysis from chronic effects of neurotrauma consortium (CENC) multi-centre study.

OBJECTIVES: Determine if mild traumatic brain injury (mTBI) history is associated with balance disturbances. SETTING: Chronic Effects of Neurotrauma Consortium (CENC) centres. PARTICIPANTS: The CENC multi-centre study enrols post-9/11 era Service Members and Veterans with combat exposure. This sample (n = 322) consisted of enrolees completing initial evaluation by September 2016 at the three sites conducting computerized dynamic post-urography (CDP) testing. DESIGN: Observational study with cross-sectional analyses using structural equation modelling. MAIN MEASURES: Comprehensive structured interviews were used to diagnose all lifetime mild traumatic brain injuries (mTBIs). The outcome, Sensory Organization Test (SOT), was measured on CDP dual-plate force platform. Other studied variables were measured by structured interviews, record review and questionnaires. RESULTS: The overall positive/negative mTBI classification did not have a significant effect on the composite equilibrium score. However, the repetitive mTBI classification showed lower scores for participants with ≥ 3 mTBI versus 1-2 lifetime mTBIs. For repetitive mTBI, pain interference acted as a mediator for the indirect effect, and a direct effect was evident on some sensory condition equilibrium scores. CONCLUSION: These findings show that repeated mTBI, partially mediated by pain, may lead to later balance disturbances among military combatants. Further study of CDP outcomes within this accruing cohort is warranted.

[Impact of Emotion Regulation and Emotional Arousal on Quality of Life and Adherence of Couples after Kidney Transplantation]. / Einfluss von Emotionsregulation und emotionaler Erregung auf Lebensqualität und Adhärenz bei Paaren nach Nierentransplantation.

INTRODUCTION: Nonadherence to immunosuppressive medication increases the risk of graft failure. Maladaptive emotion regulation strategies (ERS) seem to be a risk factor for nonadherence, whereas for patients in relationships spousal support appears as a protective resource. Emotional arousal, objectively measured by the fundamental frequency (f0) during spousal supportive communication is associated with supportive behavior. MATERIALS & METHODS: This study examined the relationship between beliefs about immunosuppressive medication, quality of life, ERS, emotions and emotional arousal, assessed during social support interactions of both spouses of N=50 couples after kidney transplantation. RESULTS: Maladaptive ERS of the transplant recipient were associated with lower mental quality of life of the partner, marginally higher own negative affect and lower beliefs about medication. Maladaptive ERS of the partner showed negative correlations with own mental quality of life. Regarding f0, gender differences were found. Higher f0 of the male transplant recipient were associated with more maladaptive ERS of the female partner. Marginally significate correlations were found with lower own beliefs about medication. Higher f0 of the wife of the male transplant recipient showed correlations with lower own positive affect, more negative affect of the male patient and lower beliefs about medication. Higher f0 of female transplant recipients were associated with lower own maladaptive ERS and lower maladaptive ERS of the husband. DISCUSSION: The findings support the relevance of early interventions focusing on identifying and modifying maladaptive ERS for both the patient and partner.

Evaluating the Contribution of EEG Power Profiles to Characterize and Discriminate Posttraumatic Stress Symptom Factors in a Combat-Exposed Population.

This study investigated the use of resting-state electroencephalography (EEG) data to help differentiate posttraumatic stress disorder (PTSD) symptom factors. The sample, 147 combat-exposed OIF/OEF (Operation Iraqi Freedom/Operation Enduring Freedom) Veterans and service members, was a polytrauma population with variable PTSD and mild traumatic brain injury (mTBI) diagnoses. Participants completed the PTSD Checklist (PCL) and resting-state EEG was assessed for 10 minutes, with eyes closed. Regional averages of absolute power in alpha, beta, delta, and theta frequency bands were computed to estimate a single EEG common factor per band. An oblique 4 common-factor model was then fit to the 17 PCL items that included a residual EEG factor as an exogenous predictor with the group mean effect of mTBI on the EEG factor removed. Separate comparative model testing sequences for the alpha, beta, delta, and theta EEG factor frequency bands were conducted. An inverse relationship of delta and theta frequency bands on avoidance and numbing symptom factors (but not re-experiencing and hyperarousal) was found. Results provide evidence for possible neurobiological basis for the 4 PTSD symptom factors.

Rapid-Response Impulsivity Predicts Depression and Posttraumatic Stress Disorder Symptomatology at 1-Year Follow-Up in Blast-Exposed Service Members.

OBJECTIVE: To determine if elevated rapid-response impulsivity after blast exposure (as a putative marker of ventral prefrontal cortex [vPFC] damage) is predictive of future elevated affective symptomatology in blast-exposed service members. DESIGN: Longitudinal design with neurocognitive testing at initial assessment and 1-year follow-up assessment of psychiatric symptomatology by telephone interview. SETTING: Veterans Administration medical centers and postdeployment assessment centers at military bases. PARTICIPANTS: Blast-exposed U.S. military personnel (N=84) ages 19 to 39 years old. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Center for Epidemiological Studies-Depression Scale (CES-D) scores, Posttraumatic Stress Disorder Checklist Version 5 (PCL-5) scores, and Alcohol Use Disorders Identification Test-C (AUDIT-C) scores at the 12-month follow-up telephone interview. RESULTS: After controlling for age and affective symptom scores reported at the initial assessment, commission errors on the Continuous Performance Test-II of the initial assessment were predictive of higher symptom scores on the CES-D and PCL-5 at follow-up, but were not predictive of AUDIT-C scores. CONCLUSIONS: Elevated rapid-response impulsivity, as a behavioral marker of reduced top-down frontocortical control, is a risk factor for elevated mood and posttraumatic stress disorder symptoms over time in blast-exposed individuals. Future longitudinal studies with predeployment neurobehavioral testing could enable attribution of this relation to blast-related vPFC damage.

Symptom Trajectories After Military Blast Exposure and the Influence of Mild Traumatic Brain Injury.

BACKGROUND: Blast-related mild traumatic brain injury (blast mTBI) is a signature wound of recent US military conflicts in the Middle East, but the relatedness of postconcussive symptoms (PCS) to the blast mTBI is unclear, and longitudinal symptom data are sparse. OBJECTIVES: To characterize postdeployment symptom levels and trajectories and to determine relationship to blast mTBI. METHODS: A total of 216 participants within 2 years of blast exposure during deployment underwent structured interviews or algorithmic questionnaires for blast mTBI. Detailed symptom inventories for PCS, pain, posttraumatic stress disorder, and depression were taken serially at enrollment, 6 months, and 12 months later. Repeated-measure analysis of variance models were built. RESULTS: Up to 50% of participants had at least 1 high-grade blast mTBI (with posttraumatic amnesia), 31% had low-grade only, and 19% had neither. Within the entire cohort, all 4 composite symptom scores started high and stayed unchanged. Between blast mTBI groups, symptom scores differed at every time point with some evidence of convergence over time. The PCS groups, different by definition to start, diverged further over time with those initially more symptomatic becoming relatively more so. CONCLUSIONS: History of blast mTBI accompanied by posttraumatic amnesia is associated with greater nonspecific symptoms after deployment, and prognosis for improvement when symptoms are prominent is poor.

Laboratory impulsivity and depression in blast-exposed military personnel with post-concussion syndrome.

In military populations, traumatic brain injury (TBI) also holds potential to increase impulsivity and impair mood regulation due to blast injury effects on ventral frontal cortex - to put military personnel at risk for suicide or substance abuse. We assessed a linkage between depression and impaired behavioral inhibition in 117 blast-exposed service members (SM) and veterans with post-concussion syndrome (PCS), where PCS was defined using a Rivermead Postconcussive Symptom Questionnaire (RPQ) modified to clarify whether each symptom worsened compared to pre-blast. Center for Epidemiological Studies-Depression Scale (CES-D) scores, PTSD Checklist 5 (PCL-5) scores, and RPQ raw subscale scores correlated positively with commission and perseverative errors on the continuous performance test II (CPT-II). In contrast, the number of RPQ symptoms ostensibly worsened post-blast did not correlate with impulsive errors on the CPT-II. These data replicate earlier findings that link increased affective symptomatology to impaired behavior inhibition in military TBI populations, but where additional effects on impulsivity from the blast itself remain equivocal.

Distinction in EEG slow oscillations between chronic mild traumatic brain injury and PTSD.

Spectral information from resting state EEG is altered in acute mild traumatic brain injury (mTBI) and in disorders of consciousness, but there is disagreement about whether mTBI can elicit long term changes in the spectral profile. Even when identified, any long-term changes attributed to TBI can be confounded by psychiatric comorbidities such as PTSD, particularly for combat-related mTBI where postdeployment distress is commonplace. To address this question, we measured spectral power during the resting state in a large sample of service members and Veterans varying in mTBI history and active PTSD diagnosis but matched for having had combat blast exposure. We found that PTSD was associated with decreases in low frequency power, especially in the right temporoparietal region, while conversely, blast-related mTBI was associated with increases in low frequency power, especially in prefrontal and right temporal areas. Results support the idea that long-term neurophysiological effects of mTBI share some features with states of reduced arousal and cognitive dysfunction, suggesting a role for EEG in tracking the trajectory of recovery and persisting vulnerabilities to injury. Additionally, results suggest that EEG power reflects distinct pathophysiologies for current PTSD and chronic mTBI.

Characterizing effects of mild traumatic brain injury and posttraumatic stress disorder on balance impairments in blast-exposed servicemembers and Veterans using computerized posturography.

The high rate of blast exposures experienced by U.S. servicemembers (SMs) during the recent conflicts in Iraq and Afghanistan has resulted in frequent combat-related mild traumatic brain injuries (mTBIs). Dizziness and postural instability can persist after mTBI as a component of postconcussion syndrome, but also occur among the somatic complaints of posttraumatic stress disorder (PTSD). The goals of this study were to examine the use of computerized posturography (CPT) to objectively characterize chronic balance deficits after mTBI and to explore the utility of CPT in distinguishing between combat and blast-exposed participants with and without mTBI and PTSD. Data were analyzed from a subject pool of 166 combat-exposed SMs and Veterans who had a blast experience within the past 2 yr while deployed. Using nonparametric tests and measures of impairment, we found that balance was deficient in participants diagnosed with mTBI with posttraumatic amnesia (PTA) or PTSD versus those with neither and that deficits were amplified for participants with both diagnoses. In addition, unique deficiencies were found using CPT for individuals having isolated mTBI with PTA and isolated PTSD. Computerized balance assessment offers an objective technique to examine the physiologic effects and provide differentiation between participants with combat-associated mTBI and PTSD.

Insomnia symptoms and behavioural health symptoms in veterans 1 year after traumatic brain injury.

OBJECTIVE: Insomnia and behavioural health symptoms 1 year after traumatic brain injury (TBI) were examined in a clinical sample representative of veterans who received inpatient treatment for TBI-related issues within the Veterans Health Administration. METHODS: This was a cross-sectional sub-study (n = 112) of the Polytrauma Rehabilitation Centres' traumatic brain injury model system programme. Prevalence estimates of insomnia, depression, general anxiety, nightmares, headache and substance use, stratified by injury severity, were derived. Univariate logistic regression was used to examine unadjusted effects for each behavioural health problem and insomnia by injury severity. RESULTS: Participants were primarily male, < 30 years old and high school educated. Twenty-nine per cent met study criteria for insomnia; those with mild TBI were significantly more likely to meet criteria (43%) than those with moderate/severe TBI (22%), χ(2)(1, n = 112) = 5.088, p ≤ 0.05. Univariable logistic regression analyses revealed depressive symptoms and general anxiety were significantly associated with insomnia symptoms after TBI of any severity. Headache and binge drinking were significantly inversely related to insomnia symptoms after moderate/severe TBI, but not MTBI. CONCLUSIONS: Veterans with history of TBI, of any severity, and current insomnia symptoms may be at increased risk for depression and anxiety 1 year after TBI.

Factor analysis of persistent postconcussive symptoms within a military sample with blast exposure.

OBJECTIVE: To determine the factor structure of persistent postconcussive syndrome symptoms in a blast-exposed military sample and validate factors against objective and symptom measures. SETTING: Veterans Affairs medical center and military bases. PARTICIPANTS: One hundred eighty-one service members and veterans with at least 1 significant exposure to blast during deployment within the 2 years prior to study enrollment. DESIGN: Confirmatory and exploratory factor analyses of the Rivermead Postconcussion Questionnaire. MAIN MEASURES: Rivermead Postconcussion Questionnaire, PTSD (posttraumatic stress disorder) Symptom Checklist-Civilian, Center for Epidemiological Studies Depression scale, Sensory Organization Test, Paced Auditory Serial Addition Test, California Verbal Learning Test, and Delis-Kaplan Executive Function System subtests. RESULTS: The 3-factor structure of persistent postconcussive syndrome was not confirmed. A 4-factor structure was extracted, and factors were interpreted as reflecting emotional, cognitive, visual, and vestibular functions. All factors were associated with scores on psychological symptom inventories; visual and vestibular factors were also associated with balance performance. There was no significant association between the cognitive factor and neuropsychological performance or between a history of mild traumatic brain injury and factor scores. CONCLUSION: Persistent postconcussive symptoms observed months after blast exposure seem to be related to 4 distinct forms of distress, but not to mild traumatic brain injury per se, with vestibular and visual factors possibly related to injury of sensory organs by blast.