Association Between Acute Plasma Glial Fibrillary Acidic Protein Levels and White Matter Integrity in Recent Trauma Survivors

https://doi.org/10.1177/08977151251363590Traumatic brain injuries (TBIs) account for over 2.5 million emergency department (ED) visits each year in the United States. The bulk of TBI research in acute care settings has focused exclusively on individuals who receive computed tomography (CT) scanning. Recently, more sensitive TBI assessment tools have been identified, including blood biomarkers such as glial fibrillary acidic protein (GFAP) and magnetic resonance imaging (MRI) of white matter microstructural integrity. These methods can evaluate for evidence of TBI in CT-negative patients. However, limited prior work has investigated the relationship between blood GFAP levels and white matter microstructural integrity. The present study examined the association between acute (≤72 h) GFAP levels and white matter microstructural integrity at 2 weeks post-trauma among ED patients ( = 328) recruited after a qualifying traumatic experience. We hypothesized that acute GFAP concentrations would be associated with disrupted microstructural integrity, quantified with Tract-Based Spatial Statistics-derived diffusion tensor imaging (DTI) metrics (reduced fractional anisotropy and increased axial diffusivity [AD], radial diffusivity, and mean diffusivity), in tracts previously shown to be vulnerable to TBI. Our secondary hypothesis was that there would be a stronger association between GFAP levels and white matter integrity among female relative to male trauma survivors, in line with previous literature suggesting that females' axons are less resilient to stretch injury. To test the primary hypothesis, we fit four sets of linear regression models to assess the association between natural log-transformed acute GFAP concentration and DTI metrics for 15 white matter regions of interest (ROIs). The false discovery rate (FDR) was controlled at 0.05 for each set of models. Models were adjusted for age, sex, neuroimaging site, and a composite lifetime traumatic stress variable. To test the secondary hypotheses, we fit identical sets of linear regression models, with an additional interaction term between sex and ln(GFAP). We followed up all significant results surviving FDR correction with correlational tractography to examine the location and direction of tracts associated with the DTI metric passing through those ROIs. We observed significant and positive associations between acute GFAP and AD in the parahippocampal cingulum ( = 1.416 × 10, standard error [SE] = 4.806 × 10, = 0.003, FDR-corrected = 0.026), and the sagittal stratum ( = 1.012 × 10, SE = 3.438 × 10, = 0.003, FDR-corrected = 0.026), including fibers of the inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus. Furthermore, the association between GFAP and AD of the parahippocampal cingulum was stronger in female trauma survivors compared with male trauma survivors ( = 2.898 × 10, SE = 9.352 × 10, = 0.002, FDR-corrected = 0.032). Our results suggest that among ED patients with low rates of intracranial injuries observed on CT and MRI scans, acute peripheral levels of GFAP may be able to predict later disruption in structural connectivity.No embarg

Mobile applications for atrial fibrillation self-management: a systematic search and evaluation [preprint]

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Atrial fibrillation (AF) is the most common cardiac arrhythmia, increasing the risk of stroke, heart failure, and healthcare costs. Although patient self-management can improve outcomes, sustaining long-term engagement is often difficult. Mobile health applications may help address this gap, but their quality and clinical alignment have not been systematically assessed using a validated framework. A structured search of the Apple App Store and Google Play Store identified free, English-language apps supporting AF self-management. Eligible apps included features such as symptom tracking, medication reminders, or educational content. App quality was assessed using the Mobile Application Rating Scale (MARS), which evaluates engagement, functionality, aesthetics, and information quality. Of 455 apps identified, five met all inclusion criteria. Common features included symptom tracking and medication logging, but coverage of evidence-based care domains varied. Mean MARS scores ranged from 4.07 to 4.53 out of 5. Higher-performing apps excelled in functionality and information quality but often lacked comprehensive integration of guideline-recommended care, such as stroke risk assessment or personalized feedback. These findings highlight a gap in high-quality, clinically grounded digital tools for AF self-care. Improved co-design processes and clearer frameworks for app evaluation may help guide the development and selection of effective tools to support AF self-management. Author summary: We wanted to understand whether smartphone apps can help people manage atrial fibrillation (AF), a common heart rhythm condition that raises the risk of stroke and heart failure. While actively managing AF through lifestyle changes and regular monitoring can reduce health risks, many people find it hard to stay engaged over time. Mobile apps could make self-care more convenient, but their quality and usefulness vary greatly. We searched the two largest app stores for free apps in English that offer tools to help people track symptoms, manage medications, and learn about their condition. Out of more than 450 apps, only five met our criteria. We found that while these apps include helpful features, they often do not cover all aspects of AF care or follow current medical guidelines closely. Our findings show that people with AF have limited trustworthy options to support self-care. We hope our study encourages app developers, healthcare professionals, and patients to work together to create better digital tools that can safely and effectively support people living with AF.No embarg

Computationally designed proteins mimic antibody immune evasion in viral evolution

Recurrent waves of viral infection necessitate vaccines and therapeutics that remain effective against emerging viruses. Our ability to evaluate interventions is currently limited to assessments against past or circulating variants, which likely differ in their immune escape potential compared with future variants. To address this, we developed EVE-Vax, a computational method for designing antigens that foreshadow immune escape observed in future viral variants. We designed 83 SARS-CoV-2 spike proteins that transduced ACE2-positive cells and displayed neutralization resistance comparable to variants that emerged up to 12 months later in the COVID-19 pandemic. Designed spikes foretold antibody escape from B.1-BA.4/5 bivalent booster sera seen in later variants. The designed constructs also highlighted the increased neutralization breadth elicited by nanoparticle-based, compared with mRNA-based, boosters in non-human primates. Our approach offers targeted panels of synthetic proteins that map the immune landscape for early vaccine and therapeutic evaluation against future viral strains.No embarg

Urgent Versus Delayed Surgical Treatment of Open Distal Radius Fractures: A Multicenter Retrospective Study

Purpose: Controversy exists on the urgency of operative treatment for low energy open distal radius fractures. Two medical centers shifted practice and no longer take all open distal radius fractures emergently to the operating for debridement. The purpose of this study is to provide preliminary data to evaluate if this is associated with unacceptably high infection rates. Methods: A retrospective chart review was performed for 55 open distal radius fractures in 54 patients at two level one trauma centers. Patients underwent irrigation and closed reduction in the emergency department followed by definitive closed treatment or operative treatment with surgical irrigation, debridement, and fixation, either within 24 hours or after discharge. The main outcome measure was infection, with secondary outcomes of complications or secondary procedures. Results: In this cohort, 4 of 55 patients experienced infections (7.2%.) There were no infections in low energy injuries. Twenty-four patients went to the operating room 2 or more days from presentation or were treated nonoperatively with only 1 postoperative infection (4.2%). All infections were in high energy mechanism injuries with at least one additional risk factor: smoking, polytrauma, or Gustilo Anderson type 2 injury. Conclusions: These data suggest that in patients with low energy injury mechanisms and type 1 injuries, delay in formal operative debridement is not associated with an elevated infection risk in this small case series. Future prospective studies with larger sample sizes are needed to definitively evaluate whether some open distal radius fracture patterns may not require emergent operative debridement. Type of study/level of evidence: Prognostic IV.No embarg

Defining terminology and outcome measures for evaluating overdose response technology: An international Delphi study

Introduction: Various novel harm reduction services leverage technology to reduce the rising number of drug poisoning deaths, particularly among those who use drugs alone. There is significant variability in terminology and outcome measures in reporting these interventions, complicating efforts to build a comprehensive knowledge base. Thus, we conducted a Delphi study to establish consensus and heterogeneity in these metrics. Methods: Panellists from three stakeholder groups (people who use drugs, virtual harm reduction service operators and academics) participated in a multi-round Delphi study. The first round included open-ended questions to propose items in three categories: terminology, demographic information and outcomes. Subsequent rounds included options from a previously conducted scoping review for consideration. Likert ratings were used to achieve consensus, with a 70% threshold. Final rounds involved ranking terminology that reached a consensus. Results: Of 23 initial participants, 14 completed the fourth survey round. "Overdose response technology" was identified as the most appropriate term for these harm reduction technologies. This definition includes drug contamination alerts, overdose response hotlines and applications, wearable overdose detection technology and overdose detection tools. Fourteen demographic outcomes reached a consensus for data collection, including name or handle, neighbourhood, age, gender, past overdose experience, substance used, amount and route of use. Six service use outcomes were recommended: response type, service outcomes, morbidity and mortality, overdose events, responder arrival time and post-rescue care. Discussion and conclusions: The study results are recommended to standardise terminology and guide future research and knowledge dissemination in the field, ensuring clear communication with a shared language.No embarg

Biological rhythms: Living your life, one half-day at a time

Circadian rhythms play a preeminent role in our life, organizing our physiology and behavior on a daily basis to resonate with our fluctuating environment. However, recent studies reveal that hundreds of mouse and human genes are expressed with a 12-h pattern. We take a close look at mammalian 12-h rhythms, their potential mechanisms and functions, and evidence linking them to circatidal rhythms, which enable marine animals to adapt to tides.No embarg

Impact of ALS-linked Mutations on the Structure and Dynamics of Profilin-1

Dysregulation of proteins involved in the formation and maintenance of the actin cytoskeleton has been implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the actin-binding protein, profilin-1 (PFN1), have been identified and linked to familial ALS. PFN1 is an essential protein that regulates different cellular processes, including membrane trafficking, neurite outgrowth, axonal development, neuronal growth cone formation, and GTPase signaling. Recent studies have shown that different ALS-linked PFN1 mutations can lead to either a gain or loss of function, depending on the stability of the mutant and its propensity for aggregation. In this thesis, I focused on two ALS-linked variants- G118V and M114T which exhibit a gain of function in formin-mediated actin dynamics. To understand the biophysical differences between these two mutants and WT PFN1, I investigated how these mutations impact PFN1 binding affinity to its ligands using fluorescence and NMR spectroscopic methods. Reduced chemical shift perturbations observed in the β-strand containing the mutation site in M114T PFN1, compared to WT PFN1 suggest that the mutation impacts allosteric communication. In addition, I characterized the effects of the M114T mutation on PFN1 dynamics across fast and slow time scales. This dissertation represents the first study to examine conformational dynamics changes in ALS-linked PFN1 variants, providing insights into their functional impact and elucidating the role of cytoskeletal perturbation in disease.Biochemistry and Molecular Biotechnology2 years2027-05-2

POCUS Standoff: Comparing Ultrasound Interfaces for Soft Tissue Foreign Body Imaging

Background: Point-of-care ultrasound can be used to identify foreign bodies (FBs) in soft tissue. Imaging interfaces such as standoff pads and water baths can improve image resolution for superficial soft tissue structures. Our objective was to determine the optimal interface for FB detection. We hypothesized that water baths would be associated with the greatest FB detection accuracy and image quality. Methods: Prospective analysis of ultrasound imaging interfaces to detect FBs. 18 emergency physicians in training were enrolled: 8 interns, 8 senior residents, and 2 fellows. Four imaging interfaces were compared: gel, saline bag standoff, water bath, and a novel proposed interface: water-filled patient belongings bag (PBB). Standardized FBs (wood, plastic, and metal) were inserted into porcine models, which were imaged by participants using the interfaces. The primary outcome was the accuracy of FB detection for the interfaces. Secondary outcomes included time to FB detection, image quality, and impact of training level. Ultrasounds were reviewed by 2 blinded ultrasound fellowship-trained emergency physicians to determine FB visibility and image quality. Data analysis was performed using the χ2 test and Kruskal-Wallis test with GraphPad Prism Software. Results: Eighteen participants completed 16 stations. Two hundred eighty-eight ultrasounds total. Interface types demonstrated a trend of greatest accuracy for PBB, followed by water bath, gel, and saline bag. Gel was significantly more accurate than saline bag (P=0.0120). Gel did not have a significant difference from PBB (P=0.1425) or water bath (P=0.125). As training level increased, time to FB detection significantly decreased (P=0.02), and accuracy increased. Accuracy for fellows was significantly greater than for senior residents (P=0.0473) and interns (P=0.0027). There was a trend of greater accuracy in senior residents from interns.However, there was no significant difference (P=0.0729). Conclusions: PBBs may be a viable alternative interface for soft tissue FB detection. PBBs, water baths, and gel should be considered prior to saline standoffs.No embarg

Evaluation of an Integrated Digital and Mobile Intervention for COPD Exacerbation [preprint]

This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and healthcare utilization, with frequent exacerbations contributing to emergency department visits and hospitalizations. This study evaluates a multimodal, community-based digital health intervention's association with changes in acute care utilization among patients with COPD to develop preliminary estimates of intervention effects. Methods: In this decentralized, nonrandomized pilot clinical trial, participants with moderate to severe COPD were offered biometric monitoring, symptom tracking, on-demand MIH services, and a digital pulmonary rehabilitation program. Outcomes were compared between intervention participants and a weighted synthetic control group using full optimal matching. Weighted odds ratios derived from regression models were used to estimate intervention effect size. The primary outcome was hospitalization during the study period. Secondary outcomes included 30 and 90-day readmission rates, emergency department visits, and hospital length of stay. Results: In total, 88 participants from the intervention arm (mean age 67, 50% female) were compared to a weighted synthetic control of 14,492 participants (weighted mean age 66, 48.7% female). We observed that participants in the intervention arm had a trend toward decreased hospitalization with an OR of 0.69 (CI 0.44-1.03, p=0.066). The intervention was also associated with 61% decreased odds of 30-day readmission after an index admission compared to controls (OR: 0.39, 95% CI: 0.16-0.95, p = 0.04). Trends toward reductions in ED visits and hospital length of stay were also observed. Conclusions: A combined digital and mobile health approach to COPD management was associated with reductions in acute care utilization. These findings support further investigation into hybrid care models to enhance COPD self-management and improve patient outcomes. Future research should evaluate scalability, cost-effectiveness, and long-term clinical impact.No embarg

Central-variant posterior reversible encephalopathy syndrome in association with adrenal insufficiency: A case report

Rationale: Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic condition often linked to hypertension, eclampsia, or renal failure. PRES typically presenting with seizures, headaches, visual disturbances, and altered mental status. A rarer form, the central variant of PRES, involves atypical radiologic findings such as edema in central brain structures. PRES has not been previously associated with adrenal insufficiency, making this case novel and significant. Patient concerns: A 59-year-old woman with a history of hypertension, chronic obstructive pulmonary disease, and previous COVID-19 infection presented to the emergency department with seizures and altered mental status. She exhibited a fluctuating systolic blood pressure (79-195 mm Hg) and had a Glasgow Coma Scale (GCS) score of 7. Diagnoses: Initial imaging and laboratory tests were inconclusive. Continuous electroencephalogram indicated focal cortical irritability, raising concerns about seizures. Brain magnetic resonance imaging revealed increased T2-weighted signals in the bilateral cerebellar hemispheres, consistent with central variant PRES. Endocrine evaluation showed primary adrenal insufficiency, confirmed by low AM cortisol levels and a positive cosyntropin stimulation test. Interventions: The patient was started on levetiracetam for seizure management and hydrocortisone for adrenal insufficiency. She was intubated for airway protection but later extubated as her condition stabilized. Outcomes: Follow-up magnetic resonance imaging showed progressive resolution of the cerebellar T2 hyperintensities. The patient was discharged on day 15 with no residual neurological deficits. At a 3-month follow-up, she remained seizure-free and continued oral hydrocortisone and levetiracetam. Lessons: This case highlights adrenal insufficiency as a possible novel precipitant of the central variant of PRES, emphasizing the need for prompt diagnosis and treatment to prevent serious neurological outcomes. The underlying pathophysiological mechanism of PRES from adrenal insufficiency is most likely labile blood pressure causing rapid alterations in cerebral perfusion pressure (CPP) precipitating PRES.No embarg