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Pattern recognition receptor-associated immuno-thrombotic transcript changes in platelets and leukocytes with COVID19
Full text linkRespiratory infections are characterized by an increased risk of thrombosis, likely involving platelet-leukocyte crosstalk via pattern recognition receptors (PRRs). Here we characterized COVID19-mediated changes in PRR levels and their associations with thrombotic/coagulation-related transcriptional programs across platelets and leukocytes and assessed their correlation with COVID19 outcomes. Amplicon RNAseq of platelets and leukocytes from COVID19 patients (n = 10) and non-infected donors (n = 15) showed distinct patterns of PRR-expression levels based on cell type. Platelets from non-infected donors expressed TLR9 > RIG-I> CGAS at the highest level while leukocytes expressed TLR4 > TLR8 > RIG-I. COVID19 resulted in increased levels of TLR9, RIG-I, CGAS, and TLR1 in platelets and decreased levels of TLR6 and TLR8 in leukocytes, while the levels of the highest expressed PRRs remained almost unchanged. In platelets from COVID19 patients, MDA5, RIG-I, and LGP2 showed the highest associations with thrombotic-, coagulation-, and thrombolysis-associated transcripts, while in non-infected donors, TLR9 showed the highest associations with those transcripts. In leukocytes, RIG-I and MDA5 also correlated with coagulation-related transcripts when derived from the non-infected donors, but those associations were almost lost with COVID19. Platelet-leukocyte aggregates increased with COVID19 as did extracellular vesicles detected by imaging cytometry, immunofluorescence, or electron microscopy. Platelet-TLR3 and leukocyte-TLR5 positively correlated with severity and survival of the COVID19 patients, while leukocyte-TLR7 showed an inverse correlation. Coagulopathy, measured by INR, was associated with platelet-TLR4 and leukocyte-TLR10. Liver inflammation, assessed by ALT levels, correlated with platelet- and leukocyte-LGP2, in addition to leukocyte-TLR3, -TLR6, -TLR7, and -RIG-I. Analysis of publicly available whole-blood-RNAseq, showed that COVID19 and tuberculosis were more similar than COVID19 and influenza with respect to associations between PRRs and thrombotic/coagulation-related transcripts. Overall, platelets and leukocytes exhibit distinct patterns of PRR expression and correlations with thrombotic/coagulation-related transcripts that change with COVID19, and there are distinct PRRs in each cell population that associate with COVID19 severity, coagulopathy, and liver damage.No embarg
Patients Who Screen Positive for Suicide Risk Incidental to Their Chief Complaint in the Emergency Department: Characteristics and Post-Visit Suicide Outcomes
No full textObjective: Universal screening improves suicide risk detection in individuals presenting to the emergency department (ED) who are not presenting with a psychiatric chief complaint, what we refer to as incidental risk. We sought to better understand characteristics of individuals who present with incidental risk and to evaluate their suicide-related outcomes after the ED visit.
Methods: Two samples (cross-sectional, longitudinal) from the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) study were used. Combined, the samples allowed for comparison of baseline characteristics and suicide-related outcomes for participants with incidental risk compared to those with negligible risk (any kind of chief complaint and negative suicide risk) and clinically congruent risk (psychiatric chief complaint and positive suicide risk). Univariable and multivariable logistic regression analyses were completed.
Results: Universal screening differentially improved the identification of suicide risk among non-white individuals, potentially reducing racial disparities in risk detection. Participants presenting with incidental risk were generally more similar to those with congruent risk than they were to those with negligible risk across demographics and clinical characteristics. Those with incidental suicide risk exhibited similar post-visit suicide-related outcomes compared to those with congruent risk, yet they were far less likely to receive clinical assessments and interventions during the ED visit.
Conclusions: The results of this study highlight an opportunity to broaden evidence-based suicide prevention practices in the ED where logistically possible. EDs may need to consider redesigning their clinical approach to address suicide risk among those who present with medical complaints but screen positive for suicide risk.No embarg
Nidogen/NID-1 Guides Regenerating Motor Axons in the Mature Nervous System Following Injury.
No full textFollowing injury, some neurons are capable of repairing themselves through a process called functional axon regeneration, in which axons regrow and rebuild synapses with the appropriate target cells. To reach the correct location, regenerating growth cones must be guided through a substantially different landscape compared to that which they navigated during development. Errors in post-developmental guidance inhibit functional repair, resulting in permanent neurological deficits. Despite their critical importance to functional repair, our understanding of the molecular and cellular mechanisms that guide regenerating axons in the post-developmental nervous system is limited. Here, I present my finding that the extracellular matrix protein Nidogen guides adult regenerating motor axons in C. elegans. Nidogen guides axons specifically in the mature nervous system through a tripartite interaction with laminin and integrin. Cell specific expression of the three proteins guide regenerating cholinergic motor axons along the dendrites of mechanosensory neuron PVD. Nidogen mediated guidance of individual ACh axons along PVD dendrites to their pre-injury location promotes synapse reformation and restores function. Interestingly, this form of guidance is cell type-specific: injured ACh axons preferentially regenerate along the PVD dendrites compared to other neighboring neurons and injured GABA axons are not prone to being guided along PVD dendrites, despite being as proximal to the PVD as Ach neurons. Significantly, the Nidogen-Laminin-Integrin interaction can be manipulated in GABA neurons to guide them along the PVD by cell-autonomous overexpression of integrin. My finding that nidogen functions specifically in the post-developmental nervous system to direct extension of regenerating ACh motor axons and promotes functional repair significantly adds to our knowledge of the molecular and cellular mechanisms that regulate axon guidance and the injury response. Consequently, it reveals a potential strategy to promote functional repair of injured axons in the mature mammalian nervous system.MD/PhD2 years2027-07-2
PsychENCODE at 10: From genomic maps to mechanistic insights in mental illness
No full textOver the past decade, the PsychENCODE Consortium has transformed psychiatric genomics-from static maps of genetic risk to dynamic, cell-resolved models of the human brain-linking DNA sequence to neural circuitry and behavior and laying the foundation for precision approaches to mental illness.No embarg
Health Concerns of Youths From Historically Marginalized Communities During the Postacute Phase of COVID-19
Full text linkThis survey study uses text message surveys to explore the behaviors, perspectives, and health concerns of youths from historically marginalized racial and ethnic groups in Boston, Massachusetts, during the postacute phase of the COVID-19 pandemic.No embarg
Association Between Acute Plasma Glial Fibrillary Acidic Protein Levels and White Matter Integrity in Recent Trauma Survivors
No full texthttps://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
Effects of Hematoma Block During Ketamine Sedation for Pediatric Forearm Fracture Reductions
No full textBackground
Distal forearm fractures are common in children and require proper analgesia to be reduced appropriately in the pediatric emergency department (PED). While hematoma blocks have become a common form of analgesia for adult patients, few studies have examined the effect of hematoma block for pediatric patients undergoing distal forearm fracture reduction.
Methods
This retrospective cohort study included children between the ages of 3 and 17 years old who were treated in a tertiary care PED between October 2017 and August 2024 with distal forearm fractures who underwent intravenous ketamine sedation for closed reduction. Data were collected from patient’s electronic medical record including pre- and post-procedural pain scores, ketamine dosing, and occurrence of any adverse events.
Results
The mean age of the study population was nine years old, 34% were girls, 84% broke both bones in their forearm, and 38% received pain medication prior to arrival. Patients who received a hematoma block (n=53) had a 53% lower odds (95%CI 0.18-1.26) of having any pain post-procedurally compared with those who did not receive a hematoma block (n=168), and a 68% lower odds (95% CI 0.07-1.52) of reporting severe pain. The total ketamine dose for patients who received a hematoma block was 1.39 milligram per kilogram (mg/kg) compared to 1.5 mg/kg for the patients who did not receive a hematoma block.
Conclusion
For pediatric patients undergoing ketamine sedation for distal forearm fracture reductions, hematoma blocks can provide additional analgesia.Master of Science in Clinical Investigation2 years2027-05-0
ACR Appropriateness Criteria® Hematospermia
No full textHematospermia is an uncommon source of referral for imaging. When considering the adequate modalities for its evaluation, the patient's age, duration, and associated symptomatology need to be taken into consideration. Younger patients with transient hematospermia and without associated signs or symptoms usually require a clinical approach and reassurance. In the setting of symptomatic hematospermia, persistent hematospermia, and in older patients, imaging may be indicated to assess for possible etiologies. However, there are variations on the initial imaging approach for the evaluation of a patient with hematospermia, in which literature data, and clinical consensus provide guidance on the imaging modalities most suitable for the assessment of possible etiologies. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.No embarg
A universally applicable definition for domestication
No full textThe process of domestication is commonly perceived as a human achievement, and domestic species are typically assumed to be those under human control. Domestic species have emerged from a greater diversity of interactions than this perspective allows, and none of the many definitions proposed for domestication can readily, reliably, and consistently distinguish domestic and nondomestic populations. Here, we propose that the process of domestication should instead be defined solely as evolution of a nonhuman population in response to an anthropogenic niche and that a domestic population is one that cannot sustain itself outside of an anthropogenic niche. As a result, this definition does not require comparisons with a presumed and largely unobservable ancestor. Instead, it focuses on the observable relationship between a nonhuman population and humans. It also avoids making assumptions about how domestication happens, thus enabling an exploration of the mechanisms underlying the process of adaptation to an anthropogenic niche. By applying this definition to plants, animals, and microbes, we illustrate its utility for investigating the evolution of the relationship between humans and other species and for anticipating which species are likely to survive in an increasingly human-influenced world. Domestication is simply an evolutionary process resulting from the interaction between two species, one of which is human. As we work to protect Earth's biodiversity, this definition allows us to understand why, in response to the conditions human societies create, some species survive and thrive, while others struggle and go extinct.No embarg
Snowblower Injuries To The Hand: A Longitudinal Study
Full text linkObjectives: The aim of our study is to understand the types of injuries patients experience from snowblowers, along with their treatment, and outcomes.
Methods: Snowblower injuries at a level one trauma center were identified over a 10-year period. Mechanism, injury, treatment, and follow-up were recorded from the medical record, and functional outcomes via QuickDASH were collected when available.
Results: Of 52 patients, 94% were male with an average age of 50 years and 83% of patients sustained the injury by unclogging the machine. All patients required partial revision amputation and/or closure; 43% of patients underwent surgery with 18% requiring reoperation. Seven patients were interviewed and reported varying limitations.
Conclusion: The injuries in our cohort were universally severe, often leading to amputation and surgery. Further studies are needed to better characterize the resulting degree of disability.1 year2026/08/0