"Studying injured minds" - the Vietnam head injury study and 40 years of brain injury research.
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ABSTRACT:
SUBMITTER: Raymont V
PROVIDER: S-EPMC3093742 | biostudies-other | 2011
REPOSITORIES: biostudies-other
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"Studying injured minds" - the Vietnam head injury study and 40 years of brain injury research.
Raymont Vanessa V Salazar Andres M AM Krueger Frank F Grafman Jordan J
Frontiers in neurology 20110328
The study of those who have sustained traumatic brain injuries (TBI) during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology, and neuroimaging. The Vietnam Head Injury Study (VHIS) is a prospective, long-term follow-up study of a cohort of 1,221 Vietnam veterans with mostly penetrating brain injuries, which has stretched over more than 40 years. The scope of this study, both in terms of the types of injury and fields of exa ...[more]
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Project description:BackgroundTraumatic brain injury (TBI) is a major public health concern with far-reaching consequences on individuals' lives. Despite the abundance of works published on TBI rehabilitation, few studies have bibliometrically analyzed the published TBI rehabilitation research. This study aims to characterize current international trends and global productivity by analyzing articles on TBI rehabilitation using bibliometric approaches and visualization methods.MethodsWe conducted a bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection database to examine the evolution and thematic trends in TBI rehabilitation research up until December 31, 2022. The specific characteristics of the research articles on TBI rehabilitation were evaluated, such as publication year, countries/regions, institutions, authors, journals, research fields, references, and keywords.ResultsOur analysis identified 5,541 research articles on TBI rehabilitation and observed a progressive increase in publications and citations over the years. The United States (US, 2,833, 51.13%), Australia (727, 13.12%), and Canada (525, 9.47%) were the most prolific countries/regions. The University of Washington (226, 4.08%) and Hammond FM (114, 2.06%) were the most productive institution and author, respectively. The top three productive journals were Brain Injury (862; 15.56%), Archives of Physical Medicine and Rehabilitation (630; 11.37%), and Journal of Head Trauma Rehabilitation (405, 7.31%). The most frequent research fields were Rehabilitation, Neurosciences, and Clinical Neurology. Co-citation references primarily addressed "outcome assessment," "community integration" and "TBI management," and "injury chronicity" and "sequelae" have gained more attention in recent years. "Mild TBI," "outcome," "stroke" and "children" were the commonly used keywords. Additionally, the analysis unveiled emerging research frontiers, including "return to work," "disorder of consciousness," "veterans," "mild TBI," "pediatric," "executive function" and "acquired brain injury."ConclusionThis study provides valuable insights into the current state of TBI rehabilitation research, which has experienced a rapid increase in attention and exponential growth in publications and citations in the last three decades. TBI rehabilitation research is characterized by its multi-disciplinary approach, involving fields such as Rehabilitation, Neurosciences, and Clinical Neurology. The analysis revealed emerging research subjects that could inform future research directions.
| S-EPMC10225562 | biostudies-literature
Project description:Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions' role in regulating anxiety. In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas.
| S-EPMC3644343 | biostudies-literature
Project description:IntroductionStudying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management. Experience in paediatric TBI (PTBI) is limited to single-centre studies despite disproportionately higher incidence of morbidity and mortality in PTBI than in adult TBI.ProjectWe describe the protocol to study cerebral autoregulation using PRx in PTBI. The project called Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics is a multicentre prospective ethics approved research database study from 10 centres across the UK. Recruitment started in July 2018 with financial support from local/national charities (Action Medical Research for Children, UK).Methods and analysisThe first phase of the project is powered to detect optimal thresholds of PRx associated with favourable outcome in PTBI by recruiting 135 patients (initial target of 3 years which has changed to 5 years due to delays related to COVID-19 pandemic) from 10 centres in the UK with outcome follow-up to 1-year postictus. The secondary objectives are to characterise patterns of optimal cerebral perfusion pressure in PTBI and compare the fluctuations in these measured parameters with outcome. The goal is to create a comprehensive research database of a basic set of high-resolution (full waveforms resolution) neuromonitoring data in PTBI for scientific use.Ethics and disseminationFavourable ethical approval has been provided by Health Research Authority, Southwest-Central Bristol Research Ethics Committee (Ref: 18/SW/0053). Results will be disseminated via publications in peer-reviewed medical journals and presentations at national and international conferences.Trial registration numberNCT05688462.
| S-EPMC10008199 | biostudies-literature
Project description:Patient Selection: Three hospitals were involved in the study: Dong Thap Provincial and An Giang Provincial hospitals, both located in the Mekong Delta Region of Vietnam where most of the Typhoid patients were admitted, and the Hospital for Tropical Diseases, Ho Chi Minh City, where the malarial patients were admitted. Infection status of each patient was determined by blood culture for the Typhoid patients and by microscopic examination of stained thick and thin peripheral-blood slides for the patients suspected of having Malaria. Patients with blood cultures positive for S. Typhi or S. enterica serovar Paratyphi A (S. Paratyphi A) (samples designated ST) or peripheral blood smears positive for Plasmodium falciparum or Plasmodium vivax (samples designated PF) were consented and enrolled in the study. A total of 28 S. Typhi positive patients and one S. Paratyphi A positive patient were enrolled in the first phase of the study and a further 9 S. Typhi and one S. Paratyphi A positive patient were enrolled in the second phase. Nine patients with Malaria caused by P. falciparum and one caused by P. vivax were enrolled. Sixteen uninfected healthy individuals (samples designated HC) were also enrolled in the study (one sample each). The Typhoid patients were randomly chosen to receive either Azithromycin or Gatifloxicin (20mg/kg/day for 7 days) antibiotics. Uncomplicated malaria patients were treated for 3 days with Artekin (dihydroartemisinin with piperaquine phosphate). Venous blood (2.5ml) was collected for total RNA extraction into PaxGene RNA collection tubes (Qiagen) at various times. The first sample (T1) was taken immediately on admission or entry into the study, then samples were collected, 3 (T3), 6-9 (T9 for Typhoid, T7 for Malaria), and 28-45 (T28) days following entry into the study and an average of 9 months (T9M) later. The PaxGene tubes were stored at 4degC until RNA was extracted as per the manufacturers instructions. Purified RNA was shipped on dry ice to Stanford University, CA for use in Microarray analyses. Microarrays: Experimental and reference samples (Human Universal RNA reference {Stratagene}) were amplified using the MessageAmp II aRNA Kit (Ambion) as per the manufacturer's instructions. Four micrograms amplified RNA was labeled through indirect incorporation of Cy5 (experimental) and Cy3 (reference) dyes (protocols can be found at http://cmgm.stanford.edu/pbrown/protocols/index.html). The labeled probes were then mixed and hybridized to Stanford Human cDNA arrays with 42 K features. Arrays were scanned using a Genepix 4000A laser scanner and data extracted with Genepix Pro Software version 5.1 (Axon Instruments). The data were then uploaded into the Stanford Microarray Database (SMD). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Compound Based Treatment: Drugs used for treatment Disease State: Malaria, Typhoid or Healthy Controls Keywords: disease_state_design
2010-01-04 | GSE7000 | GEO
Project description:ObjectiveTo determine whether a structured and quantitative assessment of differential olfactory performance-recognized between a blast-injured traumatic brain injury (TBI) group and a demographically comparable blast-injured control group-can serve as a reliable antecedent marker for preclinical detection of intracranial neurotrauma.MethodsWe prospectively and consecutively enrolled 231 polytrauma inpatients, acutely injured from explosions during combat operations in either Afghanistan or Iraq and requiring immediate stateside evacuation and sequential admission to our tertiary care medical center over a 2½-year period. This study correlates olfactometric scores with both contemporaneous neuroimaging findings as well as the clinical diagnosis of TBI, tabulates population-specific incidence data, and investigates return of olfactory function.ResultsOlfactometric score predicted abnormal neuroimaging significantly better than chance alone (area under the curve = 0.78, 95% confidence interval [CI] 0.70-0.87). Normosmia was present in all troops with mild TBI (i.e., concussion) and all control subjects. Troops with radiographic evidence of frontal lobe injuries were 3 times more likely to have olfactory impairment than troops with injuries to other brain regions (relative risk 3.0, 95% CI 0.98-9.14). Normalization of scores occurred in all anosmic troops available for follow-up testing.ConclusionQuantitative identification olfactometry has limited sensitivity but high specificity as a marker for detecting acute structural neuropathology from trauma. When considering whether to order advanced neuroimaging, a functional disturbance with central olfactory impairment should be regarded as an important tool to inform the decision process.Classification of evidenceThis study provides Class III evidence that central olfactory dysfunction identifies patients with TBI who have intracranial radiographic abnormalities with a sensitivity of 35% (95% CI 20.6%-51.7%) and specificity of 100% (95% CI 97.7%-100.0%).
| S-EPMC4408285 | biostudies-literature
Project description:BackgroundNo agents that are specifically neuroprotective are currently approved to emergently treat patients with traumatic brain injury (TBI). The histone deacetylase inhibitor, high-dose valproic acid (VPA) has been shown to have cytoprotective potential in models of combined TBI and hemorrhagic shock, but it has not been tested in an isolated TBI model. We hypothesized that VPA, administered after isolated TBI, will penetrate the injured brain, attenuate the lesion size, and activate prosurvival pathways.MethodsYorkshire swine were subjected to severe TBI by cortical impact. One hour later, animals were randomized to VPA treatment (150 mg/kg delivered intravenously for 1 hour; n = 4) or control (saline vehicle; n = 4) groups. Seven hours after injury, animals were sacrificed, and brain lesion size was measured. Mass spectrometry imaging was used to visualize and quantitate brain tissue distribution of VPA. Sequential serum samples were assayed for key biomarkers and subjected to proteomic and pathway analysis.ResultsBrain lesion size was 50% smaller (p = 0.01) in the VPA-treated animals (3,837 ± 948 mm) compared with the controls (1,900 ± 614 mm). Endothelial regions had eightfold higher VPA concentrations than perivascular regions by mass spectrometry imaging, and it readily penetrated the injured brain tissues. Serum glial fibrillary acid protein was significantly lower in the VPA-treated compared with the control animals (p < 0.05). More than 500 proteins were differentially expressed in the brain, and pathway analysis revealed that VPA affected critical modulators of TBI response including calcium signaling pathways, mitochondria metabolism, and biosynthetic machinery.ConclusionValproic acid penetrates injured brain tissues and exerts neuroprotective and prosurvival effects that resulted in a significant reduction in brain lesion size after isolated TBI. Levels of serum biomarkers reflect these changes, which could be useful for monitoring the response of TBI patients during clinical studies.
| S-EPMC7830776 | biostudies-literature
Project description:ObjectiveReconfiguration of trauma services, with direct transport of patients with traumatic brain injury (TBI) to specialist neuroscience centres (SNCs)-bypassing non-specialist acute hospitals (NSAHs), could improve outcomes. However, delays in stabilisation of airway, breathing and circulation (ABC) may worsen outcomes when compared with selective secondary transfer from nearest NSAH to SNC. We conducted a pilot cluster randomised controlled trial to determine the feasibility and plausibility of bypassing suspected patients with TBI -directly into SNCs-producing a measurable effect.SettingTwo English Ambulance Services.Participants74 clusters (ambulance stations) were randomised within pairs after matching for important characteristics. Clusters enrolled head-injured adults-injured nearest to an NSAH-with internationally accepted TBI risk factors and stable ABC. We excluded participants attended by Helicopter Emergency Medical Services or who were injured more than 1?hour by road from nearest SNC.InterventionsIntervention cluster participants were transported directly to an SNC bypassing nearest NSAH; control cluster participants were transported to nearest NSAH with selective secondary transfer to SNC.OutcomesTrial recruitment rate (target n=700 per annum) and percentage with TBI on CT scan (target 80%) were the primary feasibility outcomes. 30-day mortality, 6-month Extended Glasgow Outcome Scale and quality of life were secondary outcomes.Results56 ambulance station clusters recruited 293 patients in 12 months. The trial arms were similar in terms of age, conscious level and injury severity. Less than 25% of recruited patients had TBI on CT (n=70) with 7% (n=20) requiring neurosurgery. Complete case analysis showed similar 30-day mortality in the two trial arms (control=8.8 (2.7-14.0)% vs intervention=9.4(2.3-14.0)%).ConclusionBypassing patients with suspected TBI to SNCs gives an overtriage (false positive) ratio of 13:1 for neurosurgical intervention and 4:1 for TBI. A measurable effect from a full trial of early neuroscience care following bypass is therefore unlikely.Trial registration numberISRCTN68087745.
| S-EPMC5640033 | biostudies-literature
Project description:To address the continued rise of multi-drug-resistant microorganisms, the development of novel drugs with new modes of action is urgently required. While humans biosynthesize the essential isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) via the established mevalonate pathway, pathogenic protozoa and certain pathogenic eubacteria use the less well-known methylerythritol phosphate pathway for this purpose. Important pathogens using the MEP pathway are, for example, Plasmodium falciparum, Mycobacterium tuberculosis, Pseudomonas aeruginosa and Escherichia coli. The enzymes of that pathway are targets for antiinfective drugs that are exempt from target-related toxicity. 2C-Methyl-D-erythritol 4-phosphate (MEP), the second enzyme of the non-mevalonate pathway, has been established as the molecular target of fosmidomycin, an antibiotic that has so far failed to be approved as an anti-infective drug. This review describes the development and anti-infective properties of a wide range of fosmidomycin derivatives synthesized over the last four decades. Here we discuss the DXR inhibitor pharmacophore, which comprises a metal-binding group, a phosphate or phosphonate moiety and a connecting linker. Furthermore, non-fosmidomycin-based DXRi, bisubstrate inhibitors and several prodrug concepts are described. A comprehensive structure-activity relationship (SAR) of nearly all inhibitor types is presented and some novel opportunities for further drug development of DXR inhibitors are discussed.
| S-EPMC9782300 | biostudies-literature
Project description:Our objective was to examine associations of head injury with total and regional brain amyloid deposition. We performed cross-sectional analyses of 329 non-demented participants (81 with prior head injury) in the Atherosclerosis Risk in Communities-Positron Emission Tomography (ARIC-PET) Study who underwent 18-florbetapir PET imaging in 2012-2014. A history of head injury was defined by self-report or emergency department/hospitalization International Classification of Diseases, Ninth Revision codes. Generalized linear regression models adjusted for demographic, socioeconomic, and dementia/cardiovascular risk factors were used to estimate prevalence ratios (PRs; 95% confidence intervals [CIs]) for elevated (> 1.2) global and regional standard uptake value ratios (SUVRs). Mean age of participants was 76 years, 57% were women, and 43% were black. Head injury was associated with increased prevalence of elevated SUVR >1.2 globally (PR: 1.31; 95% CI: 1.19-1.57), as well as in the orbitofrontal cortex (PR: 1.23); (95% CI: 1.04-1.46), prefrontal cortex (PR: 1.18; 95% CI: 1.00-1.39), superior frontal cortex (PR: 1.24; 95% CI: 1.05-1.48), and posterior cingulate (PR: 1.26; 95% CI: 1.04-1.52). There also was evidence for a dose-response relationship, whereby a history of ≥1 head injury was associated with elevated SUVR >1.2 in the prefrontal cortex and superior frontal cortex compared with persons with a history of one head injury (all, p < 0.05). In conclusion, head injury was associated with increased amyloid deposition globally and in the frontal cortex and posterior cingulate, with suggestion of a dose-response association of head injuries with beta-amyloid deposition. Further work is needed to determine if increased amyloid deposition contributes to dementia in this population.
| S-EPMC6909743 | biostudies-literature
Project description:Forty years ago, few cohort studies of cardiovascular disease (CVD) included women and fewer still included diabetes or glycemia as a risk factor. I describe here the Rancho Bernardo Study (RBS), a single-site, >40-year cohort study of sex differences in heart disease and how diabetes modifies women's natural cardioprotection. More than 6000 participants were followed for morbidity and mortality, with nearly 3000 survivors (and death certificates for >85% of decedents). In RBS more than half of diabetes was undiagnosed without an oral glucose tolerance test (OGTT); more women than men had isolated post-challenge hyperglycemia (IPH) as their only glucose evidence of diabetes; men had more diabetes than women, with higher fasting but lower post-challenge glucose levels than women; women with diabetes had more classical CVD risk factors than men; excess risk-factor clustering partially explained how diabetes eradicates female cardioprotection. Post-challenge glucose was a stronger CVD risk factor than fasting glucose. Endogenous insulin was not an independent CVD risk factor in women or men. Men with higher testosterone levels developed less diabetes and had fewer metabolic syndrome components. In men higher total testosterone levels predicted a reduced risk of all-cause and CVD but not cancer mortality. In women both extremes of bioavailable testosterone predicted fatal coronary heart disease but not all-cause mortality. Summary point estimates from large systematic reviews of individual data have replicated most RBS findings. Ongoing research can further clarify how diabetes modifies women's cardioprotection from mid-life to old age.
| S-EPMC3810980 | biostudies-other