National and regional trends in fentanyl seizures in the United States, 2017-2023.

BACKGROUND: Rates of synthetic opioid-related deaths over time and across regions have been compared within the US, but other indicator data could help inform prevention and harm reduction as well. We compared regional trends in fentanyl seizures to examine potential shifts in illicit fentanyl availability. METHODS: Annual trends in fentanyl seizures were examined using data from High Intensity Drug Trafficking Areas for the US overall and by region from 2017 through 2023. Multiple measures included the number of seizures, the number of powder seizures, the number of pill seizures, the total weight of seizures, the number of pills seized, and the percentage of the number of pill seizures relative to the number of total seizures. RESULTS: The percentage of seizures in pill form in the US increased from 10.3 % in 2017 to 49.0 % in 2023 (adjusted annual percentage change [AAPC]=25.2, 95 % CI: 17.6, 33.2), with 115.6 million individual pills seized in 2023. Pill weight related to total seizure weight also increased from 0.4 % to 54.5 % (AAPC=112.6, 95 % CI: 78.6, 153.2). In 2023, the plurality of seizures was in the West, in seven out of eight of our measures, with 77.8 % of seizures in the West being in pill form. Although the Midwest had lower prevalence of seizures than the West, there were notable increases in the Midwest in the number of pill seizures (AAPC=142.2, 95 % CI: 91.9, 205.8) and number of pills seized (AAPC=421.0, 95 % CI: 272.7, 628.4). Total weight of fentanyl seized increased the most in the West (AAPC=84.6, 95 % CI: 72.3, 97.8). CONCLUSIONS: The number and size of fentanyl seizures is increasing in the US, with the majority of seizures, especially in pill form, in the West. Continued monitoring of regional shifts in the fentanyl supply can help inform targeted prevention and public health response.

How smart was T. rex? Testing claims of exceptional cognition in dinosaurs and the application of neuron count estimates in palaeontological research.

Recent years have seen increasing scientific interest in whether neuron counts can act as correlates of diverse biological phenomena. Lately, Herculano-Houzel (2023) argued that fossil endocasts and comparative neurological data from extant sauropsids allow to reconstruct telencephalic neuron counts in Mesozoic dinosaurs and pterosaurs, which might act as proxies for behaviors and life history traits in these animals. According to this analysis, large theropods such as Tyrannosaurus rex were long-lived, exceptionally intelligent animals equipped with "macaque- or baboon-like cognition", whereas sauropods and most ornithischian dinosaurs would have displayed significantly smaller brains and an ectothermic physiology. Besides challenging established views on Mesozoic dinosaur biology, these claims raise questions on whether neuron count estimates could benefit research on fossil animals in general. Here, we address these findings by revisiting Herculano-Houzel's (2023) work, identifying several crucial shortcomings regarding analysis and interpretation. We present revised estimates of encephalization and telencephalic neuron counts in dinosaurs, which we derive from phylogenetically informed modeling and an amended dataset of endocranial measurements. For large-bodied theropods in particular, we recover significantly lower neuron counts than previously proposed. Furthermore, we review the suitability of neurological variables such as neuron numbers and relative brain size to predict cognitive complexity, metabolic rate and life history traits in dinosaurs, coming to the conclusion that they are flawed proxies for these biological phenomena. Instead of relying on such neurological estimates when reconstructing Mesozoic dinosaur biology, we argue that integrative studies are needed to approach this complex subject.

National and regional trends in seizures of shrooms (psilocybin) in the United States, 2017-2022.

BACKGROUND: Psilocybin, the principle psychoactive component in "shrooms", is regaining acceptance in therapeutic settings, leading to media coverage of medical benefits associated with use. Possession is also becoming increasingly decriminalized throughout the United States. There is a lack of data on prevalence of shroom use, but trends in law enforcement seizure data can provide one indicator of shroom availability in US communities. We determined whether seizures of shrooms have shifted between 2017 and 2022. METHODS: This study examined national and regional trends in counts and total weight of shroom seizures reported to High Intensity Drug Trafficking Areas in the US between 2017 and 2022 (N=4526). RESULTS: There were 402 seizures in 2017 compared to 1396 in 2022 with the plurality occurring in the Midwest (36.0%), followed by the West (33.5%). Between 2017 Quarter 1 (Q1) and 2022 Quarter 4 (Q4), the number of seizures increased by 368.9% (AQPC=7.0; 95 CI: 5.9-8.1) and there were significant increases in all four regions. In terms of weight, 226.0kg was seized in 2017 vs. 844.0kg in 2022, and the greatest total weight in seizures was in the West (1864.2kg, 42.6%), followed by the South (1831.9kg, 41.8%). Between 2017 Q1 and 2022 Q4, the total weight seized in the US increased by 2749.7% (AQPC=6.2, 95% CI: 0.3-12.4) and there were significant increases in all four regions. CONCLUSIONS: Seizures of shrooms have increased, suggesting that availability may be escalating; thus, increases in prevention efforts and harm reduction education are warranted.

Integrating cognition in the laboratory with cognition in the real world: the time cognition takes, task fidelity, and finding tasks when they are mixed together.

It is now possible for real-life activities, unfolding over their natural range of temporal and spatial scales, to become the primary targets of cognitive studies. Movement toward this type of research will require an integrated methodological approach currently uncommon in the field. When executed hand in hand with thorough and ecologically valid empirical description, properly developed laboratory tasks can serve as model systems to capture the essentials of a targeted real-life activity. When integrated together, data from these two kinds of studies can facilitate causal analysis and modeling of the mental and neural processes that govern that activity, enabling a fuller account than either method can provide on its own. The resulting account, situated in the activity's natural environmental, social, and motivational context, can then enable effective and efficient development of interventions to support and improve the activity as it actually unfolds in real time. We believe that such an integrated multi-level research program should be common rather than rare and is necessary to achieve scientifically and societally important goals. The time is right to finally abandon the boundaries that separate the laboratory from the outside world.

Trends in Illicit Ketamine Seizures in the US From 2017 to 2022.

This cross-sectional study evaluates trends in the number and weight of illicit ketamine seizures in the US from 2017 to 2022.

Supply-side predictors of fatal drug overdose in the Washington/Baltimore HIDTA region: 2016-2020.

BACKGROUND: Rising rates of fentanyl- and polydrug-involved drug overdose deaths have prompted inquiry into the role of drug supply in fatal overdose outcomes in the United States. To date, however, there have been few empirical investigations of drug enforcement strategies on fatal overdose rates, despite knowledge that both drug use and supply are often geographically distributed. To address this limitation, we examined measures of drug enforcement as predictors of next-year fatal overdose rates in the Washington/Baltimore High Intensity Drug Trafficking Area (W/B HIDTA). METHODS: We conducted mixed-effects models to examine the role of drug seizures and disruption in drug trafficking organizations (DTOs) and money laundering organizations (MLOs) on fatal overdose rates over a 5-year period (2016-2020) across 45 local jurisdictions in the W/B HIDTA region. Outcomes included any, opioid-involved, and fentanyl-involved fatal overdose. RESULTS: Adjusting for covariates, both the total number of drug seizures and amount of cocaine seized (in dosage units per capita) positively predicted next-year opioid- and fentanyl-involved fatal overdose rates. Disruption to DTO and MLO operations did not significantly predict next-year fatal overdose rates for any outcome. CONCLUSION: Supply-side enforcement activities alone may have limited impact on reducing fatal overdose rates, but may serve as important markers to identify communities at high risk of fatal overdose and facilitate targeted intervention. Our findings underscore the importance of comprehensive law enforcement approaches that extend beyond drug enforcement to integrate prevention, linkage to treatment, and harm reduction strategies as needed to address the overdose epidemic.

Repeated mild traumatic brain injuries in mice cause age- and sex-specific alterations in dendritic spine density.

Mild traumatic brain injuries (mTBI) plague the human population and their prevalence is increasing annually. More so, repeated mTBIs (RmTBI) are known to manifest and compound neurological deficits in vulnerable populations. Age at injury and sex are two important factors influencing RmTBI pathophysiology, but we continue to know little about the specific effects of RmTBI in youth and females. In this study, we directly quantified the effects of RmTBI on adolescent and adult, male and female mice, with a closed-head lateral impact model. We report age- and sex-specific neurobehavioural deficits in motor function and working memory, microglia responses to injury, and the subsequent changes in dendritic spine density in select brain regions. Specifically, RmTBI caused increased footslips in adult male mice as assessed in a beam walk assay and significantly reduced the time spent with a novel object in adolescent male and female mice. RmTBIs caused a significant reduction in microglia density in male mice in the motor cortex, but not female mice. Finally, RmTBI significantly reduced dendritic spine density in the agranular insular cortex (a region of the prefrontal cortex in mice) and increased dendritic spine density in the adolescent male motor cortex. Together, the data provided in this study sheds new light on the heterogeneity in RmTBI-induced behavioural, glial, and neuronal architecture changes dependent on age and sex.

Trends in seizures of powders and pills containing illicit fentanyl in the United States, 2018 through 2021.

BACKGROUND: Prevalence of fentanyl-laced counterfeit prescription pills has been increasing in the US, possibly placing a wider population at risk for unintentional exposure. We aimed to determine whether there have been shifts in the number of fentanyl seizures and in the form of fentanyl seized in the US. METHODS: We examined quarterly national seizure data from High Intensity Drug Trafficking Areas to determine the number of drug seizures in the US containing fentanyl from January 2018 through December 2021. Generalized additive models were used to estimate trends in the number and weight of pill and powder seizures containing fentanyl. RESULTS: There was an increase both in the number of fentanyl-containing powder seizures (from 424 in 2018 Quarter 1 [Q1] to 1539 in 2021 Quarter 4 [Q4], ß = 0.94, p < 0.001) and in the number of pill seizures (from 68 to 635, ß = 0.96, p < 0.01). The proportion of pills to total seizures more than doubled from 13.8% in 2018 Q1 to 29.2% in 2021 Q4 (ß = 0.92, p < 0.001). Weight of powder fentanyl seizures increased from 298.2 kg in 2018 Q1 to 2416.0 kg in 2021 Q4 (ß = 1.12, p = 0.01); the number of pills seized increased from 42,202 in 2018 Q1 to 2,089,186 in 2021 Q4 (ß = 0.90, p < 0.001). CONCLUSIONS: Seizures of drugs containing fentanyl have been increasing in the US. Given that over a quarter of fentanyl seizures are now in pill form, people who obtain counterfeit pills such as those disguised as oxycodone or alprazolam are at risk for unintentional exposure to fentanyl.

Uses of Personal Health Records for Communication Among Colorectal Cancer Survivors, Caregivers, and Providers: Interview and Observational Study in a Human-Computer Interaction Laboratory.

BACKGROUND: Personal health records (PHRs) may be useful for patient self-management and participation in communication with their caregivers and health care providers. As each potential participant's role is different, their perception of the best uses of a PHR may vary. OBJECTIVE: The perspectives of patients, caregivers, and providers were all evaluated concurrently in relation to a PHR developed for colorectal cancer (CRC) survivors. METHODS: We explored group perceptions of a CRC PHR prototype. Scenario-based testing across eight use cases, with semistructured follow-up interviews, was videotaped in a human-computer interaction laboratory with patients, caregivers, and health care providers. Providers included oncologists, gastroenterologists, and primary care physicians. Discrete observations underwent grounded theory visual affinity analysis to identify emergent themes. RESULTS: Observations fell into three major themes: the network (who should be granted access to the PHR by the patient), functions (helpful activities the PHR enabled), and implementation (how to adopt the PHR into workflow). Patients wanted physician access to their PHR, as well as family member access, especially when they lived at a distance. All groups noted the added value of linking the PHR to an electronic health record, self-tracking, self-management, and secure messaging. Patients and caregivers also saw information in the PHR as a useful memory tool given their visits to multiple doctors. Providers had reservations about patients viewing raw data, which they were not prepared to interpret or might be inaccurate; patients and caregivers did not express any reservations about having access to more information. Patients saw PHR communication functions as a potential tool for relationship building. Patients and caregivers valued the journal as a tool for reflection and delivery of emotional support. Providers felt the PHR would facilitate patient-physician communication but worried that sharing journal access would make the doctor-patient relationship less professional and had reservations about the time burden of reviewing. Strategies suggested for efficient adoption into workflow included team delegation. Establishment of parameters for patient uses and provider responses was perceived as good standard practice. CONCLUSIONS: PHR perceptions differed by role, with providers seeing the PHR as informational, while patients and caregivers viewed the tool as more relational. Personal health records should be linked to electronic health records for ease of use. Tailoring access, content, and implementation of the PHR is essential. Technology changes have the potential to change the nature of the patient-physician relationship. Patients and providers should establish shared expectations about the optimal use of the PHR and explore how emerging patient-centered technologies can be successfully implemented in modern medical practice to improve the relational quality of care.

Ensuring Access to Albuterol in Schools: From Policy to Implementation. An Official ATS/AANMA/ALA/NASN Policy Statement.

Rationale: For children with asthma, access to quick-relief medications is critical to minimizing morbidity and mortality. An innovative and practical approach to ensure access at school is to maintain a supply of stock albuterol that can be used by any student who experiences respiratory distress. To make this possible, state laws allowing for stock albuterol are needed to improve medication access.Objectives: To provide policy recommendations and outline steps for passing and implementing stock albuterol laws.Methods: We assembled a diverse stakeholder group and reviewed guidelines, literature, statutes, regulations, and implementation documents related to school-based medication access. Stakeholders were divided into two groups-legislation and implementation-on the basis of expertise. Each group met virtually to review documents and draft recommendations. Recommendations were compiled and revised in iterative remote meetings with all stakeholders.Main Results: We offer several recommendations for crafting state legislation and facilitating program implementation. 1) Create a coalition of stakeholders to champion legislation and implement stock albuterol programs. The coalition should include school administrators, school nurses and health personnel, parents, or caregivers of children with asthma, pediatric primary care and subspecialty providers (e.g., pulmonologists/allergists), pharmacists, health department staff, and local/regional/national advocacy organizations. 2) Legislative components critical for effective implementation of stock albuterol programs include specifying that medication can be administered in good faith to any child in respiratory distress, establishing training requirements for school staff, providing immunity from civil liability for staff and prescribers, ensuring pharmacy laws allow prescriptions to be dispensed to schools, and suggesting inhalers with valved holding chambers/spacers for administration. 3) Select an experienced and committed legislator to sponsor legislation and guide revisions as needed during passage and implementation. This person should be from the majority party and serve on the legislature's health or education committee. 4) Develop plans to disseminate legislation and regulations/policies to affected groups, including school administrators, school nurses, pharmacists, emergency responders, and primary/subspecialty clinicians. Periodically evaluate implementation effectiveness and need for adjustments.Conclusions: Stock albuterol in schools is a safe, practical, and potentially life-saving option for children with asthma, whether asthma is diagnosed or undiagnosed, who lack access to their personal quick-relief medication. Legislation is imperative for aiding in the adoption and implementation of school stock albuterol policies, and key policy inclusions can lay the groundwork for success. Future work should focus on passing legislation in all states, implementing policy in schools, and evaluating the impact of such programs on academic and health outcomes.

Pannexin 1 as a driver of inflammation and ischemia-reperfusion injury.

Pannexin 1 (Panx1) is a ubiquitously expressed protein forming large conductance channels that are central to many distinct inflammation and injury responses. There is accumulating evidence showing ATP released from Panx1 channels, as well as metabolites, provide effective paracrine and autocrine signaling molecules that regulate different elements of the injury response. As channels with a broad range of permselectivity, Panx1 channels mediate the secretion and uptake of multiple solutes, ranging from calcium to bacterial derived molecules. In this review, we describe how Panx1 functions in response to different pro-inflammatory stimuli, focusing mainly on signaling coordinated by the vasculature. How Panx1 mediates ATP release by injured cells is also discussed. The ability of Panx1 to serve as a central component of many diverse physiologic responses has proven to be critically dependent on the context of expression, post-translational modification, interacting partners, and the mode of stimulation.

Shifts in drug seizures in the United States during the COVID-19 pandemic.

BACKGROUND: Little is known regarding how the COVID-19 pandemic has affected patterns of drug use in the United States. Because drug seizures can serve as a proxy for drug availability, we examined shifts in drug seizures in the US during the pandemic. METHODS: We examined trends in seizures of marijuana, cocaine, methamphetamine, heroin, and fentanyl within five High Intensity Drug Trafficking Areas-Washington/Baltimore, Chicago, Ohio, New Mexico, and North Florida. Trends were examined for number and total weight of seizures from March 2019 through September 2020 using Joinpoint regression. RESULTS: Significant decreases in seizures involving marijuana (ß = -0.03, P = 0.005) and methamphetamine (ß = -0.02, P = 0.026) were detected through April 2020, and then seizures of marijuana (ß = 0.10, P = 0.028) and methamphetamine (ß = 0.11, P = 0.010) significantly increased through September 2020. The number of seizures involving marijuana and methamphetamine peaked in August 2020, exceeding the highest pre-COVID-19 number of seizures. Fentanyl seizures increased overall (ß = 0.05, P < .001), but did not significantly drop during the start of COVID-19, and significant changes were not detected for cocaine or heroin. We also detected a significant increase in weight of marijuana seized from April through September 2020 (ß = 0.40, P = .001). The weight of marijuana seized in August 2020 exceeded the highest pre-COVID-19 weight. CONCLUSION: The COVID-19 pandemic was associated with an immediate decrease in marijuana and methamphetamine seizures, and then increases throughout 2020 with some months exceeding the number (and weights) of seizures from the previous year. More research is warranted to determine the extent to which these seizures reflect changes in drug use.

HCV eradication in veterans with underlying mental health disorders and substance use.

OBJECTIVE: Hepatitis C virus (HCV) disproportionately affects those with mental health disorders and those with substance use, and the increasing HCV transmission in the United States is driven by the opioid epidemic. However, patients with a mental health disorder, substance use, or combination of both historically have had limited access to HCV treatment. The goal of our study was to compare sustained virologic response (SVR) rates of HCV treatment with direct-acting antivirals (DAAs) between subjects with and without a mental health disorder, substance use, or combination of both. METHODS: We performed a retrospective chart review at 1 Veterans affairs medical center of patients enrolled in the hepatitis C pharmacy clinic who completed DAA treatment from August 17, 2013 to August 17, 2017. The participants (N = 833 patients) were categorized into 2 groups: those with at least 1 mental health disorder, substance use, or combination of both and those without. Baseline variables relevant to HCV treatment, DAA regimen, number of documented efforts to engage patients, and SVR data were collected. RESULTS: Of the 833 study participants, 579 patients had a mental health disorder, substance use, or combination of both. The 3 most prevalent disorders were patient-reported substance use (n = 333), substance-related and addictive disorders (n = 176), and depressive disorders (n = 159). The SVR rates and number of documented efforts to engage patients before and during treatment through SVR laboratory completion between those with a mental health disorder, substance use, or combination of both and those without were not statically significant. CONCLUSION: DAA-based HCV treatment is highly effective with SVR rates exceeding 95% in the entire study cohort, including patients with or without mental health disorders, substance use, or combination of both.

Repetitive Mild Traumatic Brain Injuries in Mice during Adolescence Cause Sexually Dimorphic Behavioral Deficits and Neuroinflammatory Dynamics.

Adolescent brain injuries have devastating impacts on lifelong health given that adolescence is a critical period for brain development. Adolescents are susceptible to mild traumatic brain injuries (mTBIs) acquired from collisions in contact sports, which are often sustained in a repetitive nature (repetitive mild traumatic brain injuries; RmTBIs), and cause compounding, sexually dimorphic neurological deficits. Neuroinflammation accompanies RmTBIs and may be a central driving force for chronic neurological decline. To date, the impact of neuroinflammation and sex-specific dynamics during adolescent RmTBIs has been understudied. A lateral impact model (LIM) was developed that mimics the biomechanical forces commonly experienced in human mTBIs. Here, we report novel sexually dimorphic neurobehavioral and -inflammatory responses using LIM to model adolescent RmTBIs. We first subjected adolescent male C57Bl/6 mice to one, three, or five RmTBIs at 24-h intervals and quantified neurobehavioral deficits, and brain volumetric and structural changes by magnetic resonance imaging. Five RmTBIs caused significant motor deficits, increased brain volume in cortex, hippocampus, and corpus callosum, and reduced white matter integrity in the corpus callosum. We then compared neurobehavioral deficits in adolescent male and female mice and observed sex-specific deficits in motor function, whereas both sexes had dysfunction in learning and memory. Flow cytometric quantification of neuroinflammatory responses revealed time- and sex-dependent infiltration of peripheral macrophages and T cells and male-specific decreases in microglia number. Using immunohistochemistry, we report specific microglia density decreases in male mice in the motor cortex and thalamus. We show novel neuroinflammatory responses after adolescent brain injuries that expands the current understanding of RmTBI pathophysiology in this critical neurodevelopmental period.

Stokesosauridae clade nov., a new family name for a branch of basal tyrannosauroids.

The majority of tyrannosauroid phylogenies published in the last 10 years have recovered a clade of basal tyrannosauroids that include Stokesosaurus clevelandi Madsen, 1974, Eotyrannus lengi Hutt et al., 2001 and Juratyrant langhami (Benson, 2008), which is positioned between Dilong Xu et al., 2004 and more derived tyrannosauroids such as Xiongguanlong Li et al., 2010 (e.g., Brusatte et al., 2010, 2011; Brusatte and Benson, 2013; Lü et al., 2014; Brusatte and Carr, 2016; Yun, 2016; Carr et al., 2017; Delcourt and Grillo, 2018; Nesbitt et al., 2019; Zanno et al., 2019; Wu et al., 2020). Carr et al. (2017) first called this clade as "Stokesosauridae", but did not define or diagnose this clade; but later the name was adopted and  used as valid by Wu et al. (2020).

Research methods and baseline findings of the improving the safety of opioid therapy (ISOT) cluster-randomized trial.

There are adverse effects associated with long-term opioid therapy (LTOT) for chronic pain and clinicians infrequently adhere to opioid treatment guideline recommendations for reducing risk and mitigating opioid-related harms. The primary goal of the Improving the Safety of Opioid Therapy (ISOT) intervention is to reduce harms related to prescription opioids. Secondary aims focus on enhancing the clinician-patient relationship and not having a negative impact on pain-related outcomes (to be examined through a non-inferiority analysis). The study is a cluster-randomized trial and the 44 primary care providers (PCPs) who enrolled were randomized to receive either (1) a two-hour educational workshop about a patient-centered approach to opioid therapy or (2) the educational workshop plus a collaborative care intervention delivered by a nurse care manager (NCM). Patients were assigned to the same condition as their treating PCP. ISOT was based on the chronic care model and includes patient and provider activation, outcomes monitoring, and feedback to the PCP over 12 months. The NCM conducted a baseline assessment with intervention patients, tracked opioid-related behaviors and outcomes, and provided decision support to the opioid-prescribing clinician about opioid safety. Between June 2016 and October 2018, 293 veterans who were prescribed LTOT for chronic pain were enrolled, completed a baseline assessment, and assigned to a treatment condition. Participants were enrolled for 12 months. Masked assessments were conducted with participants at baseline, 6-months, and 12-months. This manuscript describes study rationale, research methods, and baseline findings.

Neurosensory and Sinus Evolution as Tyrannosauroid Dinosaurs Developed Giant Size: Insight from the Endocranial Anatomy of Bistahieversor sealeyi.

Tyrannosaurus rex and other tyrannosaurid dinosaurs were apex predators during the latest Cretaceous, which combined giant size and advanced neurosensory systems. Computed tomography (CT) data have shown that tyrannosaurids had a trademark system of a large brain, large olfactory bulbs, elongate cochlear ducts, and expansive endocranial sinuses surrounding the brain and sense organs. Older, smaller tyrannosauroid relatives of tyrannosaurids developed some, but not all, of these features, raising the hypothesis that tyrannosaurid-style brains evolved before the enlarged tyrannosaurid-style sinuses, which might have developed only with large body size. This has been difficult to test, however, because little is known about the brains and sinuses of the first large-bodied tyrannosauroids, which evolved prior to Tyrannosauridae. We here present the first CT data for one of these species, Bistahieversor sealeyi from New Mexico. Bistahieversor had a nearly identical brain and sinus system as tyrannosaurids like Tyrannosaurus, including a large brain, large olfactory bulbs, reduced cerebral hemispheres, and optic lobes, a small tab-like flocculus, long and straight cochlear ducts, and voluminous sinuses that include a supraocciptal recess, subcondyar sinus, and an anterior tympanic recess that exits the braincase via a prootic fossa. When characters are plotted onto tyrannosauroid phylogeny, there is a two-stage sequence in which features of the tyrannosaurid-style brain evolved first (in smaller, nontyrannosaurid species like Timurlengia), followed by features of the tyrannosaurid-style sinuses (in the first large-bodied nontyrannosaurid tyrannosauroids like Bistahieversor). This suggests that the signature tyrannosaurid sinus system evolved in concert with large size, whereas the brain did not. Anat Rec, 303:1043-1059, 2020. © 2020 American Association for Anatomy.

Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats.

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.