Unveiling the performance of the prehospital Rapid Emergency Medicine Score (pREMS): How the predictive score impacts in-hospital outcomes in traumatic brain injury (TBI): A retrospective observational cohort study.

INTRODUCTION: This study aimed to evaluate the predictive accuracy of the prehospital rapid emergency medicine score (pREMS) for predicting the outcomes of hospitalized patients with traumatic brain injury (TBI) who died, were discharged, were admitted to the intensive care unit (ICU), or were admitted to the operating room (OR) within 72 h. METHODS: A retrospective cohort analysis was performed on a sample of 513 TBI patients admitted to the emergency department (ED) of Besat Hospital in 2023. Only patients of both sexes aged 18 years or older who were not pregnant and had adequate documentation of vital signs were included in the analysis. Patients who died during transport and patients who were transferred from other hospitals were excluded. The predictive power of the pREMS for each outcome was assessed by calculating the sensitivity and specificity curves and by analyzing the area under the receiver operating characteristic curve (AUROC). RESULTS: The mean pREMS scores for hospital discharge, death, ICU admission and OR admission were 11.97 ± 3.84, 6.32 ± 3.15, 8.24 ± 5.17 and 9.88 ± 2.02, respectively. pREMS accurately predicted hospital discharge and death (AOR = 1.62, P < 0.001) but was not a good predictor of ICU or OR admission (AOR = 1.085, P = 0.603). The AUROCs for the ability of the pREMS to predict outcomes in hospitalized TBI patients were 0.618 (optimal cutoff point = 7) for ICU admission and OR and 0.877 (optimal cutoff point = 9.5) for hospital discharge and death at 72 h. CONCLUSION: The results indicate that the pREMS, a new preclinical trauma score for traumatic brain injury, is a useful tool for prehospital risk stratification (RST) in TBI patients. The pREMS showed good discriminatory power for predicting in-hospital mortality within 72 h in patients with traumatic brain injury.

Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury.

Traumatic brain injuries are extremely common, and although most patients recover from their injuries many TBI patients suffer prolonged symptoms and remain at a higher risk for developing cardiovascular disease and neurodegeneration. Moreover, it remains challenging to identify predictors of poor long-term outcomes. Here, we tested the hypothesis that preexisting cerebrovascular impairment exacerbates metabolic and vascular dysfunction and leads to worse outcomes after TBI. Male mice underwent a mild surgical reduction in cerebral blood flow using a model of bilateral carotid artery stenosis (BCAS) wherein steel microcoils were implanted around the carotid arteries. Then, 30 days post coil implantation, mice underwent TBI or sham surgery. Gene expression profiles, cerebral blood flow, metabolic function, oxidative damage, vascular health and angiogenesis were assessed. Single nuclei RNA sequencing of endothelial cells isolated from mice after TBI showed differential gene expression profiles after TBI and BCAS, that were further altered when mice underwent both challenges. TBI but not BCAS increased mitochondrial oxidative metabolism. Both BCAS and TBI decreased cerebrovascular responses to repeated whisker stimulation. BCAS induced oxidative damage and inflammation in the vasculature as well as loss of vascular density, and reduced the numbers of angiogenic tip cells. Finally, intravascular protein accumulation was increased among mice that experienced both BCAS and TBI. Overall, our findings reveal that a prior vascular impairment significantly alters the profile of vascular health and function of the cerebrovasculature, and when combined with TBI may result in worsened outcomes.

Decompressive Craniectomy: From Ancient Practices to Modern Neurosurgery.

Decompressive craniectomy (DC) is a neurosurgical strategy that expels a parcel of the cranium to relieve pressure on a swollen or herniating brain. This review article explores the history of DC, from its ancient roots in trepanning to its contemporary applications. It then examines the mechanisms by which DC reduces intracranial pressure (ICP) and improves cerebral blood flow. The article highlights the efficacy of DC in treating patients with severe traumatic brain injury (TBI), stroke, and other conditions that cause increased ICP. However, it also acknowledges the potential complications of DC, such as infection and bleeding. The ethical considerations surrounding DC are explored in detail, particularly the challenging decision-making process for patients who are unable to give consent. A specific focus is given to the use of DC in pediatric patients, where the developing brain is especially vulnerable to pressure changes.

Symptomatic Recovery from Concussion in Military Service Members with and Without Associated Bodily Injuries.

Research has found that service members (SMs) with mild traumatic brain injury (mTBI) and co-occurring bodily injuries endorse lower chronic postconcussive symptom severity than SMs with mTBI and no bodily injuries. Investigations were conducted with primarily post-9/11 war-era SMs with blast injuries. The current study explores these findings in a cohort of more heterogeneous and recently evaluated military SM. Possible reasons suggested for the earlier findings include SMs with bodily injuries report fewer postconcussive symptoms due to (1) focusing attention on extra-cranial injuries and associated pain; (2) receiving more interpersonal and medical support, lowering distress; (3) using analgesics such as morphine or opioids; or (4) experiencing delayed postconcussive symptoms. The current investigation evaluates each of these hypothesized reasons for the earlier findings and the generalizability of the findings to a more recent sample. Data were extracted from 165 SMs in a TBI repository at a U.S. military medical center. All participants reported a history of an mTBI, confirmed by a clinical interview to meet Veterans Affairs and Department of Defense criteria. Other bodily injuries received at the time of the mTBI were documented with the Abbreviated Injury Scale (AIS). Multiple regression models evaluated the ability of the four hypothesized mechanisms to predict postconcussive symptom severity, measured by the Neurobehavioral Symptom Inventory. SMs with bodily injuries (n = 48) reported nonsignificantly lower postconcussive symptoms than SMs with no bodily injuries (n = 117). The level of subjective pain was a determinant of postconcussive symptom severity among SMs with a history of mTBI, with or without associated bodily injuries. Social support was a weaker negative predictor of postconcussive symptoms among SMs with no associated bodily injuries.

The death of a neurotrauma trial lessons learned from the prematurely halted randomized evaluation of surgery in elderly with traumatic acute subdural hematoma (RESET-ASDH) trial.

Introduction: Acute subdural hematoma (ASDH) due to traumatic brain injury (TBI) constitutes an increasing global health problem, especially in the elderly population. Treatment decisions on surgical versus conservative management pose a neurosurgical dilemma. Large practice variation exists between countries, hospitals, and individual neurosurgeons, illustrating the presence of 'clinical equipoise'. The RESET-ASDH trial aimed to address this dilemma but was terminated prematurely due to insufficient patient recruitment. Research question: What factors may have contributed to the premature discontinuation of the RESET-ASDH trial? Materials and methods: The RESET-ASDH was a multicenter randomized controlled trial (RCT) comparing functional outcome at 1 year after early surgery or an initial conservative treatment in elderly patients (≥65 years) with a traumatic ASDH. Logs of registry data, medical-ethical approval timelines and COVID-19 related research documents were analyzed. Furthermore, non-structured interviews with involved clinical research personnel were conducted. Results: The concept of clinical equipoise was broadly misinterpreted by neurosurgeons as individual uncertainty, hampering patient recruitment. Also, the elderly target population complicated the inclusion process as elderly and their informal caregivers were hesitant to participate in our acute surgical trial. Moreover, the COVID-19 pandemic added additional hurdles like delayed medical-ethical approval, a decline in eligible patients and repeated trial halts during the peaks of the pandemic. Discussion and conclusion: The premature termination of the RESET-ASDH study may have been related to the trial's methodology and target population with an additional impact of COVID-19. Future acute neurosurgical trials in elderly may consider these challenges to prevent premature trial termination.

Anterior Pituitary Dysfunction After Traumatic Brain Injury: A Prospective Study.

OBJECTIVE: Anterior pituitary dysfunction is one of the major causes of disability and morbidity in patients suffering from traumatic brain injury (TBI). The present study was undertaken to evaluate the incidence of anterior pituitary dysfunction in cases of moderate and severe TBI, its value in long-term prognostication, and the factors that predispose to a higher incidence of anterior pituitary dysfunction in acute and chronic phases. METHODS: This was a prospective cohort study wherein 216 patients with moderate and severe TBI were evaluated within 72 hours of TBI (acute phase) and at 6 months (chronic phase). RESULTS: At 6 months, out of the 216 patients, 95 patients had expired and 35 patients were lost to follow-up. The remaining 86 patients were evaluated at 6 months. In the acute phase, hypopituitarism was seen in 82.4% patients, thyroid axis deficiency was seen in 57.4% patients, gonadal axis deficiency in 54.2% patients, and adrenal axis deficiency in 13.8% patients. In the chronic phase, hypopituitarism was seen in 59.3% patients, thyroid axis deficiency was seen in 24.4% patients, gonadal axis deficiency in 32.6% patients, and adrenal axis deficiency in 23.3% patients. Patients with thyroid axis deficiency at admission had significant association with a bad modified Rankin Scale score at 6 months. CONCLUSIONS: Thyroid and gonadotropin axes were most commonly affected and deficiency of at least 1 axis was found in 82.4% patients in the acute phase and 59.3% in the chronic phase. Thyroid axis deficiency had a negative impact on prognosis in post-TBI patients.

Efficacy of N-Methyl-D-Aspartate (NMDA) Receptor Antagonists in Treating Traumatic Brain Injury-Induced Brain Edema: A Systematic Review and Meta-analysis of Animal Studies.

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

Incorporating intensity modulated total body irradiation into a Children's Oncology Group trial: Rationale, techniques, and safeguards.

Historically, total body irradiation (TBI) has been delivered using static, parallel opposed photon beams (2D-TBI). Recently, centers have increasingly used intensity-modulated radiation therapy (IMRT) techniques for TBI. Relative to 2D-TBI, IMRT can reduce doses to critical organs (i.e., lungs and kidneys) while delivering myeloablative doses to the rest of the body, so it may decrease the risk of toxicity while maintaining oncologic outcomes. Despite these potential benefits, delivering TBI using IMRT introduces new challenges in treatment planning and delivery. We describe the extensive experience with IMRT-based TBI at Stanford University and City of Hope Cancer Center. These groups, and others, have reported favorable clinical outcomes and have developed methods to optimize treatment planning and delivery. A critical next step is to evaluate the broader adoption of this approach. Therefore, IMRT-based TBI will be incorporated into a prospective, multi-institutional Children's Oncology Group study with careful procedures and safeguards in place.

Prehospital care for traumatic brain injuries: A review of U.S. state emergency medical services protocols.

Traumatic brain injury (TBIs) necessitates a rapid and comprehensive medical response to minimize secondary brain injury and reduce mortality. Emergency medical services (EMS) clinicians serve a critical role in the management of prehospital TBI, responding during an initial phase of care with significant impact on patient outcomes. We used versions two and three of the Brain Trauma Foundation (BTF) Prehospital Guidelines for the Management of Traumatic Brain Injury and the NASEMSO National Model Clinical Guidelines to determine key elements for a TBI prehospital protocol and included common factors across sources such as recommendations concerning patient monitoring, hypoxia, hypotension, hyperventilation, cerebral herniation, airway management, hyperosmolar therapy, and transport destination. We then conducted a cross-sectional evaluation of publicly available statewide EMS clinical protocols in the US to determine the degree of alignment with national guidelines. We calculated descriptive statistics for each factor in the state protocols. Despite adoption of some evidence-based recommendations for a standard approach to the prehospital management of patients with TBI, we found significant variability in statewide EMS treatment protocols for management of severe TBI, especially in the recommended frequency of patient reassessment and for the management of suspected herniation. Most statewide protocols provided guidance regarding oxygenation, ventilation, and blood pressure management that aligned with evidence-based guidelines. While most protocols did address management of oxygenation and ventilation, one in four protocols had no specific guidance for managing hypoxia and only 31% of protocols recommended avoiding hyperventilation. For the management of suspected cerebral herniation, over half of statewide protocols recommended hyperventilation, whereas only 31% explicitly advised against hyperventilation regardless of TBI severity. Interestingly, 94% of protocols do not mention the use of hyperosmolar therapy for TBI patients, neither recommending use or avoidance of hyperosmolar therapy. In conclusion, we found inconsistent adoption of national recommendations in available statewide protocols for prehospital TBI management. We identified significant gaps and variation in statewide protocols regarding patient monitoring and reassessment, as well as in several key areas of severe TBI management.

Traumatic Brain Injury and Its Risk Factors in a Homeless Population.

OBJECTIVE: To characterize the traumatic brain injury profile and its associated risk factors in homeless individuals in Santa Clara County, CA. DESIGN: Observational cohort study SETTING: : Two homeless shelter health clinics in Santa Clara County, CA PARTICIPANTS: Currently or recently homeless individuals seeking health care at two homeless shelter health clinics between August 2013 and May 2014. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Demographics, traumatic brain injury incidence and characteristics RESULTS: Findings indicate that TBI history in the homeless population is higher (79.7%) than the general population (12%). Almost half of the population (49.2%) reported that their TBI occurred before the age of 18. 68.2% of participants reported sustaining a TBI with loss of consciousness. TBI due to violence (60%) was lower in this cohort compared to other homeless cohorts but was the main cause of injury regardless of age. Alcoholism was a risk factor for having more TBIs. No differences in TBI profile were found between genders. CONCLUSION: Our findings underscore the need for more research on the lifetime risk factors associated with TBI to prevent and reduce the number of brain injuries in homeless populations.

Longitudinal Outcomes of Neurofeedback and Hyperbaric Oxygen Therapy in Treating a Traumatic Brain Injury Patient: A Case Report.

Severe Traumatic Brain Injury (TBI) is a significant health issue, with neurofeedback and Hyperbaric Oxygen Therapy (HBOT) as potentially effective treatments. Neurofeedback uses operant conditioning for real-time psychological and physiological awareness, and HBOT increases blood oxygen levels, potentially enhancing cognitive abilities and the body's innate healing processes and reducing symptoms. On July 30, 2018, a 33-year-old female runner was hit by a car going 40 mph and thrown 30 feet, resulting in a severe TBI and a seven-week coma. After seven months of intensive rehabilitation, she started HBOT and neurofeedback treatments in November 2021, as recommended by her neuropsychiatrist. These treatments led to noticeable improvements in her cognition, sleep, conversation skills, emotional control, and relationships by January 2022. By December 2023, after 195 neurofeedback and over 300 HBOT sessions, she reported further improvements in various cognitive and emotional aspects and daily activities like feeding, toileting, grooming, and communication. Post-treatment quantitative electroencephalogram (qEEG) results in June 2024 showed moderate to large effects on her brain's average frequency band parameters (g = .612) and small to moderate average effects on 19 scalp electrode placement sites outcomes (uV2 g=.339 and Hz g=.333). This indicates significant progress in her recovery journey over a 31-month treatment period. This patient's case demonstrated noteworthy improvements in cognitive variables, namely, feeding (p=0.046), toileting (p=0.046), grooming (p=0.046), and communication abilities (p=0.046) per the objective measures, Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE). Based on the qEEG effect sizes, DRS, and GOSE results from the pretest (2021) and posttest (2024), the patient has made noteworthy gains in brain recovery and overall quality of life.

Endothelin-1 increases Na+-K+-2Cl- cotransporter-1 expression in cultured astrocytes and in traumatic brain injury model: An involvement of HIF1α activation.

Na+-K+-2Cl- cotransporter-1 (NKCC1) is present in brain cells, including astrocytes. The expression of astrocytic NKCC1 increases in the acute phase of traumatic brain injury (TBI), which induces brain edema. Endothelin-1 (ET-1) is a factor that induces brain edema and regulates the expression of several pathology-related genes in astrocytes. In the present study, we investigated the effect of ET-1 on NKCC1 expression in astrocytes. ET-1 (100 nM)-treated cultured astrocytes showed increased NKCC1 mRNA and protein levels. The effect of ET-1 on NKCC1 expression in cultured astrocytes was reduced by BQ788 (1 µM), an ETB antagonist, but not by FR139317 (1 µM), an ETA antagonist. The involvement of ET-1 in NKCC1 expression in TBI was examined using a fluid percussion injury (FPI) mouse model that replicates the pathology of TBI with high reproducibility. Administration of BQ788 (15 nmol/day) decreased FPI-induced expressions of NKCC1 mRNA and protein, accompanied with a reduction of astrocytic activation. FPI-induced brain edema was attenuated by BQ788 and NKCC1 inhibitors (azosemide and bumetanide). ET-1-treated cultured astrocytes showed increased mRNA and protein expression of hypoxia-inducible factor-1α (HIF1α). Immunohistochemical observations of mouse cerebrum after FPI showed co-localization of HIF1α with GFAP-positive astrocytes. Increased HIF1α expression in the TBI model was reversed by BQ788. FM19G11 (an HIF inhibitor, 1 µM) and HIF1α siRNA suppressed ET-induced increase in NKCC1 expression in cultured astrocytes. These results indicate that ET-1 increases NKCC1 expression in astrocytes through the activation of HIF1α.

Anti-inflammatory and anti-apoptotic activity of synaptamide improves the morphological state of neurons in traumatic brain injury.

Traumatic brain injuries (TBI) of varying severity are becoming more frequent all over the world. The process of neuroinflammation, in which macrophages and microglia are key players, underlies all types of brain damage. The present study focuses on evaluating the therapeutic potential of N-docosahexaenoylethanolamine (DHEA, synaptamide), which is an endogenous metabolite of docosahexaenoic acid in traumatic brain injury. Previously, several in vitro and in vivo models have shown significant anti-neuroinflammatory and synaptogenic activity of synaptamide. The results of the present study show that synaptamide by subcutaneous administration (10 mg/kg/day, 7 days) exerts anti-inflammatory and anti-apoptotic effects in the thalamus and cerebral cortex of experimental animals (male C57BL/6 mice). Were analyzed the dynamics of changes in the activity of Iba-1- and CD68-positive microglia/macrophages, the level of production of pro-inflammatory cytokines (IL1ß, IL6, TNFα) and pro-apoptotic proteins (Bad, Bax), the expression of pro- and anti-inflammatory markers (CD68, CD206, arg-1). ATF3 transcription factor distribution and neuronal state in the thalamus and cerebral cortex of animals with craniotomy, traumatic brain injury, and therapy are quantitatively assessed. The obtained data showed that synaptamide: (1) has no effect on the total pool of microglia/macrophages; (2) inhibits the activity of pro-inflammatory microglia/macrophages and cytokines they produce; (3) increases the expression of CD206 but not arg-1; (4) has anti-apoptotic effect and (5) improves the morphological state of neurons. The results obtained confirm the high therapeutic potential of synaptamide in the therapy of traumatic brain injury.

Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries in mice.

Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5-3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.

Probiotics in Traumatic Brain Injury: New Insights into Mechanisms and Future Perspectives.

Traumatic brain injury (TBI) is a serious global public health issue, recognized as a chronic and progressive disease that can affect multiple organs, including the gastrointestinal (GI) tract. Research shows that there is a specific link between the GI tract and the central nervous system, termed the gut-brain axis, which consists of bidirectional exchange between these two. Several preclinical and clinical studies have demonstrated intestinal barrier dysfunction, intestinal inflammation and gut dysbiosis in patients with TBI. It is proven that probiotics can modulate the inflammatory process and modify gut microbiota. Numerous animal studies and human clinical trials have proven the effectiveness of selected bacterial strains as an adjuvant treatment in reducing inflammation, infection rates and time spent in intensive care of hospitalized patients suffering from brain injury. Thus, this review summarizes the current evidence regarding the beneficial effects of probiotic administration in patients suffering from TBI-related complications. This review will help identify novel therapeutic strategies in the future as probiotics have an extensive history of apparently safe use.

Exploring the Role of Neuropeptide PACAP in Cytoskeletal Function Using Spectroscopic Methods.

The behavior and presence of actin-regulating proteins are characteristic of various clinical diseases. Changes in these proteins significantly impact the cytoskeletal and regenerative processes underlying pathological changes. Pituitary adenylate cyclase-activating polypeptide (PACAP), a cytoprotective neuropeptide abundant in the nervous system and endocrine organs, plays a key role in neuron differentiation and migration by influencing actin. This study aims to elucidate the role of PACAP as an actin-regulating polypeptide, its effect on actin filament formation, and the underlying regulatory mechanisms. We examined PACAP27, PACAP38, and PACAP6-38, measuring their binding to actin monomers via fluorescence spectroscopy and steady-state anisotropy. Functional polymerization tests were used to track changes in fluorescent intensity over time. Unlike PACAP27, PACAP38 and PACAP6-38 significantly reduced the fluorescence emission of Alexa488-labeled actin monomers and increased their anisotropy, showing nearly identical dissociation equilibrium constants. PACAP27 showed weak binding to globular actin (G-actin), while PACAP38 and PACAP6-38 exhibited robust interactions. PACAP27 did not affect actin polymerization, but PACAP38 and PACAP6-38 accelerated actin incorporation kinetics. Fluorescence quenching experiments confirmed structural changes upon PACAP binding; however, all studied PACAP fragments exhibited the same effect. Our findings indicate that PACAP38 and PACAP6-38 strongly bind to G-actin and significantly influence actin polymerization. Further studies are needed to fully understand the biological significance of these interactions.

Single-Task and Dual-Task Gait Performance After Sport-Related Concussion: A Machine Learning Statistical Approach.

BACKGROUND: This study evaluated 2 different dual-task (DT) conditions during tandem gait (TG) to predict sport-related concussion (SRC) diagnosis. HYPOTHESIS: The best (fastest) single-task (ST) gait will differ between groups (controls vs SRC; baseline vs SRC), with auditory pure switching task (APST) response rate being the most important behavioral variable to aid prediction of SRC. STUDY DESIGN: Cohort design. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 409 National Collegiate Athletic Association Division I student-athlete controls and 21 team-physician-diagnosed SRC participated. All data were collected at preseason physicals (baseline) and within 7 days of injury for SRC. Each participant completed 3 conditions of TG in a pseudorandomized order: (1) ST, (2) DT with serial-7s (SS) subtractions, and (3) DT with APST. Outcomes of time-to-complete for TG and behavioral (eg, responses per second) for SS and APST were recorded for each trial. RESULTS: ST Trials 2 (P = 0.03) and 3 (P = 0.01) were significantly different between controls and SRC. ST Trial 3 (P = 0.04) was significantly different between baseline and SRC. Average responses per second for APST were significantly different between- (P < 0.01) and within- (P = 0.01) group. CONCLUSION: The results suggest that ST is significantly slower after SRC. However, DT (both SS and APST) time-to-complete are also important variables when predicting the SRC diagnosis. It is advised that both ST and DT be administered when making clinical decisions regarding postural instability after SRC. CLINICAL RELEVANCE: The best ST TG time to complete gait is an important objective marker of concussion while DT paradigms, specifically SS and APST, are highly variable. DT may be more useful for clinical observable signs of SRC. Both SS and APST have unique usefulness, but APST response rate per second can be relied upon numerically for clinical decisions.

An observational cohort study of alcohol use and cognitive difficulties among post-9/11 veterans with and without TBI and PTSD.

BACKGROUND: Traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and alcohol use are highly prevalent among military Veterans and independently associated with cognitive difficulties; less is known about the combined effects. This study aimed to investigate the association between alcohol use patterns and cognitive diagnoses in Veterans with TBI and/or PTSD. METHODS: Using electronic health record data,193,663 Veterans were classified into three alcohol use trajectory groups (consistently low, initially high transitioning to low, initially moderate transitioning to high) based on self-reported Alcohol Use Disorders Identification Test-C (AUDIT-C) scores. Cox proportional hazards models were used to examine the association between alcohol use patterns, TBI, PTSD, and the risk of cognitive diagnosis, while adjusting for demographic factors and comorbidities. RESULTS: Veterans with initially high transitioning to low (HR = 1.21, 95 % CI: 1.11-1.31) and initially moderate transitioning to high (HR = 1.42, 95 % CI: 1.33-1.51) alcohol use patterns had a significantly greater risk of cognitive diagnosis compared to those with consistently low alcohol use when accounting for TBI, PTSD, and comorbidities. TBI (HR = 5.40, 95 % CI: 5.06-5.76) and PTSD (HR = 2.42, 95 % CI: 2.25-2.61) were also independently associated with an elevated risk of cognitive diagnosis. CONCLUSIONS: Findings suggest that Higher levels of alcohol consumption, even if decreasing over time, may confer an increased risk of cognitive diagnosis for Veterans with TBI and/or PTSD. Long-term alcohol use patterns should be considered in clinical assessments and interventions to identify individuals at greater risk for experiencing cognitive difficulties.