Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals.

White Matter Alterations in Military Service Members With Remote Mild Traumatic Brain Injury.

Importance: Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis.

Objective: To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).

Lifetime Blast Exposure Is Not Related to White Matter Integrity in Service Members and Veterans With and Without Uncomplicated Mild Traumatic Brain Injury.

This study examines the impact of lifetime blast exposure on white matter integrity in service members and veterans (SMVs). Participants were 227 SMVs, including those with a history of mild traumatic brain injury (mTBI;  = 124), orthopedic injury controls ( = 58), and non-injured controls ( = 45), prospectively enrolled in a Defense and Veterans Brain Injury Center (DVBIC)/Traumatic Brain Injury Center of Excellence (TBICoE) study. Participants were divided into three groups based on number of self-reported lifetime blast exposures: none ( = 53); low (i.

Military-related mild traumatic brain injury: clinical characteristics, advanced neuroimaging, and molecular mechanisms.

Mild traumatic brain injury (mTBI) is a significant health burden among military service members. Although mTBI was once considered relatively benign compared to more severe TBIs, a growing body of evidence has demonstrated the devastating neurological consequences of mTBI, including chronic post-concussion symptoms and deficits in cognition, memory, sleep, vision, and hearing. The discovery of reliable biomarkers for mTBI has been challenging due to under-reporting and heterogeneity of military-related mTBI, unpredictability of pathological changes, and delay of post-injury clinical evaluations.

Altered lateralization of the cingulum in deployment-related traumatic brain injury: An ENIGMA military-relevant brain injury study.

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI.

An examination of volumetric and cortical thickness correlates of posttraumatic nightmares in male active duty service members.

Posttraumatic nightmares commonly occur after a traumatic experience. Despite significant deleterious effects on well-being and their role in posttraumatic stress disorder, posttraumatic nightmares remain understudied. The neuroanatomical structures of the amygdala, medial prefrontal cortex, hippocampus, and anterior cingulate cortex constitute the AMPHAC model (Levin and Nielsen, 2007), which is implicated in the neurophysiology of disturbing dreams of which posttraumatic nightmares is a part.

¹⁸F-fluorodeoxyglucose-positron emission tomography findings are not related to cognitive functioning in service members with remote history of mild traumatic brain injury.

Objective: Determine whether glucose uptake as measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is associated with cognitive performance and cognitive deficits in active duty service members with a history of mild traumatic brain injury (mTBI).

Method: 287 patients with a history of mTBI underwent FDG-PET scans at rest and neuropsychological testing at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. Glucose uptake in the bilateral frontal, parietal, occipital, and temporal lobes, and 58 cortical/cerebellar regions were correlated with seven neuropsychological composite scores, with and without relevant covariates.

White Matter Integrity Relates to Cognition in Service Members and Veterans after Complicated Mild, Moderate, and Severe Traumatic Brain Injury, But Not Uncomplicated Mild Traumatic Brain Injury.

The extant literature investigating the relationship between diffusion tensor imaging (DTI) and cognition following traumatic brain injury (TBI) is limited by small sample sizes and inappropriate control groups. The present study examined DTI metric differences between service members and veterans (SMVs) with bodily injury (Trauma Control; TC), uncomplicated mild TBI (mTBI), complicated mild TBI (compTBI), and severe-moderate TBI combined (smTBI), and how DTI metrics related to cognition within each group. Participants were 226 SMVs (56 TC, 112 mTBI, 29 compTBI, 29 smTBI) with valid neuropsychological testing and DTI at least 11 months post-injury.

Novel chemical entities inhibiting Mycobacterium tuberculosis growth identified by phenotypic high-throughput screening.

We performed a high-throughput phenotypic whole cell screen of Mycobacterium tuberculosis against a diverse chemical library of approximately 100,000 compounds from the AbbVie corporate collection and identified 24 chemotypes with anti-tubercular activity. We selected two series for further exploration and conducted structure-activity relationship studies with new analogs for the 4-phenyl piperidines (4PP) and phenylcyclobutane carboxamides (PCB). Strains with mutations in MmpL3 demonstrated resistance to both compound series.

Development of the Blast Ordnance and Occupational Exposure Measure for Self-Reported Lifetime Blast Exposures.

Introduction: To address the military gap in the standardized collection of lifetime blast exposures across clinical and research endeavors, researchers at the National Intrepid Center of Excellence (NICoE) completed a quality improvement project that utilized systematic, iterative focus groups that leveraged the input from various stakeholders including subject matter experts, clinical providers, and service members (SMs) to develop a comprehensive, self-report blast exposure inventory that could be completed within 5-10 minutes. This manuscript outlines the process of the development of this inventory.

Materials And Methods: This project included three phases of focus groups that occurred at the NICoE between August 2020 and March 2021 to collect feedback and input from relevant military stakeholders.

Longitudinal changes of white matter microstructure following traumatic brain injury in U.S. military service members.

The purpose of this study was to analyze quantitative diffusion tensor imaging measures across the spectrum of traumatic brain injury severity and evaluate their trajectories in military service members. Participants were 96 U.S.

Altered Metabolic Interrelationships in the Cortico-Limbic Circuitry in Military Service Members with Persistent Post-Traumatic Stress Disorder Symptoms Following Mild Traumatic Brain Injury.

Comorbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) are common in military service members. The aim of this study is to investigate brain metabolic interrelationships in service members with and without persistent PTSD symptoms after mTBI by using F-fluorodeoxyglucose (FDG) positron emission tomography. Service members ( = 408) diagnosed with mTBI were studied retrospectively.

White Matter Hyperintensities Are Not Related to Symptomatology or Cognitive Functioning in Service Members with a Remote History of Traumatic Brain Injury.

This study aimed to determine whether magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) are associated with symptom reporting and/or cognitive performance in 1202 active-duty service members with prior single or multiple mild traumatic brain injury (mTBI). Patients with mTBI evaluated at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center (WRNMMC) were divided into those with ( 632) and without ( 570) WMHs. The groups were compared on several self-report scales including the Neurobehavioral Symptom Inventory (NSI), Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), Satisfaction with Life Scale (SWLS), and Short Form-36 Health Survey (SF-36).

Cerebrovascular Reactivity Measures Are Associated With Post-traumatic Headache Severity in Chronic TBI; A Retrospective Analysis.

Objective: To characterize the relationship between persistent post-traumatic headache (pPTH) and traumatic cerebrovascular injury (TCVI) in chronic traumatic brain injury (TBI). Cerebrovascular reactivity (CVR), a measure of the cerebral microvasculature and endothelial cell function, is altered both in individuals with chronic TBI and migraine headache disorder (Amyot et al., 2017; Lee et al.

Coordinating Global Multi-Site Studies of Military-Relevant Traumatic Brain Injury: Opportunities, Challenges, and Harmonization Guidelines.

Traumatic brain injury (TBI) is common among military personnel and the civilian population and is often followed by a heterogeneous array of clinical, cognitive, behavioral, mood, and neuroimaging changes. Unlike many neurological disorders that have a characteristic abnormal central neurologic area(s) of abnormality pathognomonic to the disorder, a sufficient head impact may cause focal, multifocal, diffuse or combination of injury to the brain. This inconsistent presentation makes it difficult to establish or validate biological and imaging markers that could help improve diagnostic and prognostic accuracy in this patient population.

Post-Traumatic Stress Disorder Is Associated with Neuropsychological Outcome but Not White Matter Integrity after Mild Traumatic Brain Injury.

The aim of this study was to examine neuropsychological functioning and white matter integrity, in service members and veterans (SMVs) after mild traumatic brain injury (MTBI), with versus without post-traumatic stress disorder (PTSD). Participants were 116 U.S.

Cortical thinning in military blast compared to non-blast persistent mild traumatic brain injuries.

In the military, explosive blasts are a significant cause of mild traumatic brain injuries (mTBIs). The symptoms associated with blast mTBIs causes significant economic burdens and a diminished quality of life for many service members. At present, the distinction of the injury mechanism (blast versus non-blast) may not influence TBI diagnosis.

8-Hydroxyquinolines are bactericidal against Mycobacterium tuberculosis.

There is an urgent need for new treatments effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. The 8-hydroxyquinoline series is a privileged scaffold with anticancer, antifungal, and antibacterial activities. We conducted a structure-activity relationship study of the series regarding its antitubercular activity using 26 analogs.

Assessment of Brain Venous Structure in Military Traumatic Brain Injury Patients using Susceptibility Weighted Imaging and Quantitative Susceptibility Mapping.

Brain venous volume above the lateral ventricle in military patients with traumatic brain injury (TBI) was assessed using two segmentation approaches on susceptibility weighted images (SWI) and quantitative susceptibility maps (QSM). This retrospective study included a total of 147 subjects: 14 patients with severe TBI; 38 patients with moderate TBI, 58 patients with mild TBI (28 with blast-related injuries and 30 with non-blast-related injuries), and 37 control subjects without history of TBI. Using the multiscale vessel enhancement filter on SWI images, patients with severe TBI demonstrated significantly higher segmented venous volumes compared with controls.

A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis.

Tuberculosis is a disease of global importance for which novel drugs are urgently required. We developed a whole-cell phenotypic screen which can be used to identify inhibitors of Mycobacterium tuberculosis growth. We used recombinant strains of virulent M.

Identification of Compounds with pH-Dependent Bactericidal Activity against Mycobacterium tuberculosis.

To find new inhibitors of Mycobacterium tuberculosis that have novel mechanisms of action, we miniaturized a high throughput screen to identify compounds that disrupt pH homeostasis. We adapted and validated a 384-well format assay to determine intrabacterial pH using a ratiometric green fluorescent protein. We screened 89000 small molecules under nonreplicating conditions and confirmed 556 hits that reduced intrabacterial pH (below pH 6.

Acquired Sleep-Related Hypermotor Epilepsy with Disrupted White Matter Tracts Assessed by Multishell Diffusion Magnetic Resonance Imaging.

Sleep-related hypermotor epilepsy (SHE) (previously frontal lobe epilepsy) is a rare seizure disorder commonly misdiagnosed or unrecognized, causing negative patient sequelae. While usually reported in familial studies, it is more commonly acquired. Diagnosis is a challenge due to its low incidence in comparison with the more common sleep disorders or psychogenic etiologies in the differential diagnosis.

A Target-Based Whole Cell Screen Approach To Identify Potential Inhibitors of Mycobacterium tuberculosis Signal Peptidase.

The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular space. We developed a target-based whole cell assay to screen for potential inhibitors of LepB, the sole signal peptidase in Mycobacterium tuberculosis, using a strain engineered to underexpress LepB (LepB-UE).

Compromised Neurocircuitry in Chronic Blast-Related Mild Traumatic Brain Injury.

The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison.