Critical Dialogue and Capacity-Building Projects Reduced Alcohol and Substance Use in a Randomized Clinical Trial Among Formerly Incarcerated Men.

Background: Rates of alcohol and/or substance use (ASU) among residents of predominantly Black and marginalized communities are similar to ASU rates in White communities. Yet ASU has worse consequences in predominantly Black and marginalized communities (e.g., higher incarceration). Objective: We randomized participants to one of 16 intervention conditions using a 24 full factorial design to optimize a multilevel intervention reducing ASU among 602 formerly incarcerated men with substance-use-disorders (SUD). Candidate intervention components included (1) critical dialogue (CD; six weekly 2-hour-long group sessions vs. no CD sessions), (2) Quality of Life Wheel (QLW; six weekly 1-hour-long group sessions vs. no QLW sessions), (3) capacity building projects (CBP; six weekly 1-hour-long group sessions vs. no CBP sessions), and (4) delivery by a trained peer versus licensed facilitators. Outcome was percentage of days in which participants used alcohol, cocaine, opioid, and/or cannabis in previous 30 days. Results: Intent-to-treat analysis did not meet a priori component selection criteria due to low intervention attendance. After controlling for intervention group attendance (percentage of sessions attended), peer-delivered CD and CBP produced statistically and clinically significant main and interaction effects in ASU over 5 months. Per the multiphase optimization strategy framework, we selected peer-delivered CD and CBP for inclusion as the optimized version of the intervention with a cost of US$1,380 per 10 individuals. No adverse intervention effects occurred. Conclusion: CD and CBP were identified as the only potentially effective intervention components. Future research will examine strategies to improve attendance and test the optimized intervention against standard of care in a randomized-controlled-trial.

Targeting of nanoparticles to the cerebral vasculature after traumatic brain injury.

Traumatic brain injury has faced numerous challenges in drug development, primarily due to the difficulty of effectively delivering drugs to the brain. However, there is a potential solution in targeted drug delivery methods involving antibody-drug conjugates or nanocarriers conjugated with targeting antibodies. Following a TBI, the blood-brain barrier (BBB) becomes permeable, which can last for years and allow the leakage of harmful plasma proteins. Consequently, an appealing approach for TBI treatment involves using drug delivery systems that utilize targeting antibodies and nanocarriers to help restore BBB integrity. In our investigation of this strategy, we examined the efficacy of free antibodies and nanocarriers targeting a specific endothelial surface marker called vascular cell adhesion molecule-1 (VCAM-1), which is known to be upregulated during inflammation. In a mouse model of TBI utilizing central fluid percussion injury, free VCAM-1 antibody did not demonstrate superior targeting when comparing sham vs. TBI brain. However, the administration of VCAM-1-targeted nanocarriers (liposomes) exhibited a 10-fold higher targeting specificity in TBI brain than in sham control. Flow cytometry and confocal microscopy analysis confirmed that VCAM-1 liposomes were primarily taken up by brain endothelial cells post-TBI. Consequently, VCAM-1 liposomes represent a promising platform for the targeted delivery of therapeutics to the brain following traumatic brain injury.

The lived experience of military beneficiaries with amputations at the hip and pelvic level.

BACKGROUND: Hip- and pelvic-level amputations are devastating injuries that drastically alter patient function and quality of life. This study examined the experience of military beneficiaries with a hip- or pelvic-level amputation to better characterize their challenges and specific needs and to optimize treatment in the future. METHODS: We conducted a retrospective review of the Military Health System and identified 118 patients with a history of one or more amputation(s) at the hip or pelvic level between October 2001 and September 2017. Surviving participants (n = 97) were mailed a letter which explained the details of the study and requested participation in a telephonic interview. A total of six individuals (one female, five males) participated in structured interviews. RESULTS: The study group included four participants with hip disarticulations and two participants with hemipelvectomies (one internal, one external). All six participants reported significant challenges with activities related to prosthetic use, mobility, residual limb health, pain, gastrointestinal and genitourinary function, psychiatric health, and sexual function. CONCLUSIONS: These interviews highlight the unique needs of individuals with hip- and pelvic-level amputations and may improve access to higher echelons of care that would enhance the function and quality of life for these participants.

The LTAR Cropland Common Experiment at the Texas Gulf.

Texas Gulf is one of the 18 regional sites that is part of the USDA-ARS Long-Term Agroecosystem Research (LTAR) Network and focuses on cropland and integrated grazing land research in Central Texas, addressing challenges posed by soil characteristics, climate variability, and urbanization. This paper provides brief site descriptions of the two Cropland Common Experiments being conducted in the Texas Gulf LTAR region, emphasizing conservation tillage practices and precision agriculture techniques. The plot-scale study is located in Temple, TX, at the USDA-ARS Grassland, Soil and Water Research Laboratory and examines conventional tillage, strip tillage, and no tillage practices. The field-scale study, located in Riesel, TX, at the USDA-ARS Riesel Watersheds, assesses the impact of no tillage, cover crops, fertility management, adaptive management, and precision conservation on crop yield, profitability, and environmental footprint. Key measurements include soil and plant analyses, greenhouse gas fluxes, runoff water quantity and quality, and field operations recorded with precision agriculture equipment. Despite challenges posed by urban encroachment, future research aims to incorporate new technologies, such as unmanned ground vehicles, to enhance sustainability and productivity of the agricultural landscape. These experiments provide valuable insights for stakeholders, contributing to the development of sustainable agricultural practices tailored to the unique challenges within the Texas Gulf LTAR region.

Daily quetiapine after severe TBI improves learning and memory.

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

Sex differences in the extent of acute axonal pathologies after experimental concussion.

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.

The LTAR-integrated grazing land common experiment at the Texas Gulf.

Extreme weather and climate events have become more frequent and directly affect the ecological structure and function of integrated grazing lands. While the Great Plains have experienced a long history of regular disturbances from drought and floods, grazing, and fires, the increased frequency and magnitude of these disturbances can reduce ecological resilience, largely depending on management practices. Alternative strategies designed to adaptively manage grazing land resources based on the ecology of the system should increase the resistance and resilience to disturbances when compared to prevailing practices. Determining the ecologic and economic value of alternative strategies will require long-term evaluations across large spatial scales. The Long-Term Agroecosystem Research Network has been established to evaluate the differences between alternative and prevailing practices among 18 strategically located sites and across decadal time scales throughout the continental United States. A key integrated grazing land site within this network is the Texas Gulf located at the Riesel Watersheds in the Blackland Prairie of Central Texas. At this study site, the differences between alternative and prevailing grazing management strategies are now being evaluated. The alternative strategy was designed using a combination of knowledge of the site and species ecology with modern-day tools and technologies. Alternatively, the prevailing practice implements a conventional year-round continuous grazing system with heavy reliance on hay and supplemental protein during winter. Results will provide grazing land managers with economically viable adaptive management choices for increasing ecological resilience following extreme and frequent disturbance events.

Correlation between Lower-body Strength and Performance Tests among Female NCAA Division II Softball Players.

Softball is a sport that requires speed, agility, and lower-body power to be successful. Accordingly, strength and conditioning programs have focused on improving speed and lower-body power, which are beneficial to players performing softball-related tasks. The purpose of this study was to determine the correlation between absolute and relative lower-body strength to performance measures among female collegiate softball players. Archived data collected during pre-season performance testing for twenty-one (n = 21) NCAA Division II collegiate softball players was used for this analysis. Measurements included countermovement jump (CMJ), broad jump (BJ), linear speed (LS), 505 test for change of direction speed (COD), and shuttle runs. Absolute lower body strength (ALBS) was measured using a 3-repetition maximum hex-bar deadlift (HBDL) and body weight was used to calculate relative lower body strength (RLBS) of each player. Pearson's correlation coefficients were used to relate measures of lower body strength to each performance test. Significant (p ≤ 0.05) large to moderate correlations were discovered between RLBS and COD (505L: r = -0.59, 505R: r = -.63), 300 yard (yd) shuttle run time (trial 1: r = -0.47, trial 2: -0.50), and lower-body power (CMJ: r = 0.48, BJ: r = 0.52). ALBS was correlated only to the BJ (r = 0.43). The results suggest that relative strength is related more with COD, shuttle run, and lower-body power when compared to absolute strength. Therefore, strength and conditioning professionals should consider measures of RLBS when administering softball specific tests for developing and implementing a successful strength program in collegiate softball.

Increased Risk of Cryptogenic Stroke Associated with Patent Foramen Ovale in Young Adults.

Ischemic stroke is defined as a reduction in blood flow to brain tissue that results in the deterioration and death of neurons in a matter of minutes. While often seen in older patients with a history of atherosclerosis of the major arteries, a subset of ischemic strokes occur in younger individuals with minimal to no prior risk factors. Further evaluation of these unknown, or cryptogenic, strokes has yielded positive findings of a patent foramen ovale (PFO) in a concerning number of cases. Cryptogenic strokes attributable to PFO present an important clinical occurrence because they do not fit the typical template regarding those most at risk for such acutely devastating outcomes, making their identification uniquely important for both immediate and long-term patient care.  A 20-year-old Hispanic female presented to the emergency department for evaluation of neurological symptoms indicating obstruction of a major cerebral vessel. After being placed on stroke alert and found to have an embolus occluding the left middle cerebral artery (MCA) via non-contrast computed tomography (CT), tissue plasminogen activator (tPA) was administered, and mechanical thrombectomy was performed to restore blood flow. Following stabilization, further testing done on the patient revealed a substantial PFO that likely allowed for the crossing of an embolus from venous blood returning to the heart directly into the arterial circulation. The patient opted for cardiac monitor placement and has remained asymptomatic to this point while awaiting surgical repair. This case demonstrates an unusual presentation of ischemic stroke in a young individual with no reported risk factors and highlights the importance of screening for large PFO in patients prior to a serious cerebrovascular accident. It is our hope that highlighting this case may heighten awareness of this condition and allow for timely recognition from medical personnel who may encounter this same medical emergency in the future.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

From wolves to humans: oral microbiome resistance to transfer across mammalian hosts.

The mammalian mouth is colonized by complex microbial communities, adapted to specific niches, and in homeostasis with the host. Individual microbes interact metabolically and rely primarily on nutrients provided by the host, with which they have potentially co-evolved along the mammalian lineages. The oral environment is similar across mammals, but the diversity, specificity, and evolution of community structure in related or interacting mammals are little understood. Here, we compared the oral microbiomes of dogs with those of wild wolves and humans. In dogs, we found an increased microbial diversity relative to wolves, possibly related to the transition to omnivorous nutrition following domestication. This includes a larger diversity of Patescibacteria than previously reported in any other oral microbiota. The oral microbes are most distinct at bacterial species or strain levels, with few if any shared between humans and canids, while the close evolutionary relationship between wolves and dogs is reflected by numerous shared taxa. More taxa are shared at higher taxonomic levels including with humans, supporting their more ancestral common mammalian colonization followed by diversification. Phylogenies of selected oral bacterial lineages do not support stable human-dog microbial transfers but suggest diversification along mammalian lineages (apes and canids). Therefore, despite millennia of cohabitation and close interaction, the host and its native community controls and limits the assimilation of new microbes, even if closely related. Higher resolution metagenomic and microbial physiological studies, covering a larger mammalian diversity, should help understand how oral communities assemble, adapt, and interact with their hosts.IMPORTANCENumerous types of microbes colonize the mouth after birth and play important roles in maintaining oral health. When the microbiota-host homeostasis is perturbed, proliferation of some bacteria leads to diseases such as caries and periodontitis. Unlike the gut microbiome, the diversity of oral microbes across the mammalian evolutionary space is not understood. Our study compared the oral microbiomes of wild wolves, dogs, and apes (humans, chimpanzees, and bonobos), with the aim of identifying if microbes have been potentially exchanged between humans and dogs as a result of domestication and cohabitation. We found little if any evidence for such exchanges. The significance of our research is in finding that the oral microbiota and/or the host limit the acquisition of exogenous microbes, which is important in the context of natural exclusion of potential novel pathogens. We provide a framework for expanded higher-resolution studies across domestic and wild animals to understand resistance/resilience.

A review of the development and implementation of the critical source area concept: A reflection of Andrew Sharpley's role in improving water quality.

Critical source areas (CSAs) are small areas of a field, farm, or catchment that account for most contaminant loss by having both a high contaminant availability and transport potential. Most work on CSAs has focused on phosphorus (P), largely through the work in the 1990s initiated by Dr. Sharpley and colleagues who recognized the value in targeting mitigation efforts. The CSA concept has been readily grasped by scientists, farmers, and policymakers across the globe. However, experiences and success have been mixed, often caused by the variation in where and how CSAs are defined. For instance, analysis of studies from 1990 to 2023 shows that the proportion of the annual contaminant load coming from a CSA decreases from field to farm to catchment scale. This finding is consistent with increased buffering of CSAs and greater contribution of other sources with scale, or variation in the definition of CSAs. We therefore argue that the best application of CSAs to target mitigation actions should be at small areas that truly account for most contaminant loss. This article sheds light on the development and utilization of CSAs, paying tribute to Dr. Sharpley's remarkable contributions to the improvement of water quality, and reflecting upon where the CSA concept has succeeded or not in reducing contaminant (largely P) loss.

Heavy metals concentration in soils across the conterminous USA: Spatial prediction, model uncertainty, and influencing factors.

Assessment and proper management of sites contaminated with heavy metals require precise information on the spatial distribution of these metals. This study aimed to predict and map the distribution of Cd, Cu, Ni, Pb, and Zn across the conterminous USA using point observations, environmental variables, and Histogram-based Gradient Boosting (HGB) modeling. Over 9180 surficial soil observations from the Soil Geochemistry Spatial Database (SGSD) (n = 1150), the Geochemical and Mineralogical Survey of Soils (GMSS) (n = 4857), and the Holmgren Dataset (HD) (n = 3400), and 28 covariates (100 m × 100 m grid) representing climate, topography, vegetation, soils, and anthropic activity were compiled. Model performance was evaluated on 20 % of the data not used in calibration using the coefficient of determination (R2), concordance correlation coefficient (ρc), and root mean square error (RMSE) indices. Uncertainty of predictions was calculated as the difference between the estimated 95 and 5 % quantiles provided by HGB. The model explained up to 50 % of the variance in the data with RMSE ranging between 0.16 (mg kg-1) for Cu and 23.4 (mg kg-1) for Zn, respectively. Likewise, ρc ranged between 0.55 (Cu) and 0.68 (Zn), respectively, and Zn had the highest R2 (0.50) among all predictions. We observed high Pb concentrations near urban areas. Peak concentrations of all studied metals were found in the Lower Mississippi River Valley. Cu, Ni, and Zn concentrations were higher on the West Coast; Cd concentrations were higher in the central USA. Clay, pH, potential evapotranspiration, temperature, and precipitation were among the model's top five important covariates for spatial predictions of heavy metals. The combined use of point observations and environmental covariates coupled with machine learning provided a reliable prediction of heavy metals distribution in the soils of the conterminous USA. The updated maps could support environmental assessments, monitoring, and decision-making with this methodology applicable to other soil databases, worldwide.

Healthcare Utilization Following Hemipelvectomy or Hip Disarticulation in the Military Health System.

INTRODUCTION: Amputations at the hip and pelvic level are often performed secondary to high-energy trauma or pelvic neoplasms and are frequently associated with a prolonged postoperative rehabilitation course that involves a multitude of health care providers. The purpose of this study was to examine the health care utilization of patients with hip- and pelvic-level amputations that received care in the U.S. Military Health System. MATERIALS AND METHODS: We performed a retrospective review of all patients who underwent a hip- or pelvic-level amputation in the Military Health System between 2001 and 2017. We compiled and reviewed all inpatient and outpatient encounters during three time points: (1) 3 months pre-amputation to 1 day pre-amputation, (2) the day of amputation through 12 months post-amputation, and (3) 13-24 months post-amputation. Health care utilization was defined as the average number of encounter days/admissions for each patient. Concomitant diagnoses following amputation including post-traumatic stress disorder, traumatic brain injury, anxiety, depression, and chronic pain were also recorded. RESULTS: A total of 106 individuals with hip- and pelvic-level amputations were analyzed (69 unilateral hip disarticulation, 6 bilateral hip disarticulations, 27 unilateral hemipelvectomy, 2 bilateral hemipelvectomies, and 2 patients with a hemipelvectomy and contralateral hip disarticulation). Combat trauma contributed to 61.3% (n = 65) of all amputations. During the time period of 3 months pre-amputation, patients had an average of 3.8 encounter days. Following amputation, health care utilization increased in both the year following amputation and the time period of 13-24 months post-amputation, averaging 170.8 and 77.4 encounter days, respectively. Patients with trauma-related amputations averaged more total encounter days compared to patients with disease-related amputations in the time period of 12 months following amputation (203.8 vs.106.7, P < .001) and the time period of 13-24 months post-amputation (92.0 vs. 49.0, P = .005). PTSD (P = .02) and traumatic brain injuries (P < .001) were more common following combat-related amputations. CONCLUSIONS: This study highlights the increased health care resource demand following hip- and pelvic-level amputations in a military population, particularly for those patients who sustained combat-related trauma. Additionally, patients with combat-related amputations had significantly higher rates of concomitant PTSD and traumatic brain injury. Understanding the extensive needs of this unique patient population helps inform providers and policymakers on the requirements for providing high-quality care to combat casualties.

Retrospective chart analysis to determine the impact of a patient-facing digital risk stratification tool combined with a clinical screener for hereditary cancer genetic risk assessment triage in a community oncology clinic.

The purpose of this study was to evaluate the utility of adding a clinical screener to the patient-facing digital risk stratification tool triage process for the identification of patients eligible for a genetic risk assessment for hereditary cancer. Digital risk stratification entries were retrospectively reviewed to determine the overall number of patients eligible for genetic risk assessment. These were also analyzed to determine how many patients were re-contacted by the clinical screener, and how many of those recontacted patients met criteria after their personal and family history was revised by the clinical screener. There was an 89.9% digital risk stratification triage tool completion rate, with 22.6% requiring contact from the clinical screener. Of the 640 patients who completed the digital tool, 5.9% met criteria for testing after their personal and/or family history was revised by the clinical screener. Overall, 51.1% of patients met criteria for a genetic risk assessment. The addition of a clinical screener further increased identification of patients eligible for genetic risk assessment. About half of patients who met criteria after being contacted by the clinical screener met criteria based on their personal diagnosis of cancer alone. Incorporation of a clinical screener to the digital screening process may serve to reduce barriers to patient completion of the tool and increase rates of patient identification for cancer genetic services.

Investigating tritrophic interactions using bioenergetic demographic models.

A central debate in ecology has been the long-running discussion on the role of apex predators in affecting the abundance and dynamics of their prey. In terrestrial systems, research has primarily relied on correlational approaches, due to the challenge of implementing robust experiments with replication and appropriate controls. A consequence of this is that we largely suffer from a lack of mechanistic understanding of the population dynamics of interacting species, which can be surprisingly complex. Mechanistic models offer an opportunity to examine the causes and consequences of some of this complexity. We present a bioenergetic mechanistic model of a tritrophic system where the primary vegetation resource follows a seasonal growth function, and the herbivore and carnivore species are modeled using two integral projection models (IPMs) with body mass as the phenotypic trait. Within each IPM, the demographic functions are structured according to bioenergetic principles, describing how animals acquire and transform resources into body mass, energy reserves, and breeding potential. We parameterize this model to reproduce the population dynamics of grass, elk, and wolves in northern Yellowstone National Park (USA) and investigate the impact of wolf reintroduction on the system. Our model generated predictions that closely matched the observed population sizes of elk and wolf in Yellowstone prior to and following wolf reintroduction. The introduction of wolves into our basal grass-elk bioenergetic model resulted in a population of 99 wolves and a reduction in elk numbers by 61% (from 14,948 to 5823) at equilibrium. In turn, vegetation biomass increased by approximately 25% in the growing season and more than threefold in the nongrowing season. The addition of wolves to the model caused the elk population to switch from being food-limited to being predator-limited and had a stabilizing effect on elk numbers across different years. Wolf predation also led to a shift in the phenotypic composition of the elk population via a small increase in elk average body mass. Our model represents a novel approach to the study of predator-prey interactions, and demonstrates that explicitly considering and linking bioenergetics, population demography and body mass phenotypes can provide novel insights into the mechanisms behind complex ecosystem processes.

Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals.

BACKGROUND: Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days. METHODS: CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days. RESULTS: Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory. CONCLUSION: Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.

Cerebrospinal Fluid Flow Extends to Peripheral Nerves.

Cerebrospinal fluid (CSF) is an aqueous solution responsible for nutrient delivery and waste removal for the central nervous system (CNS). The three-layer meningeal coverings of the CNS support CSF flow. Peripheral nerves have an analogous three-layer covering consisting of the epineurium, perineurium, and endoneurium. Peripheral axons, located in the inner endoneurium, are bathed in "endoneurial fluid" similar to CSF but of undefined origin. CSF flow in the peripheral nervous system has not been demonstrated. Here we show CSF flow extends beyond the CNS to peripheral nerves in a contiguous flowing system. Utilizing gold nanoparticles, we identified that CSF is continuous with the endoneurial fluid and reveal the endoneurial space as the likely site of CSF flow in the periphery. Nanogold distribution along entire peripheral nerves and within their axoplasm suggests CSF plays a role in nutrient delivery and waste clearance, fundamental aspects of peripheral nerve health and disease. One Sentence Summary: Cerebrospinal fluid unites the nervous system by extending beyond the central nervous system into peripheral nerves.

Coming of age in recovery: The prevalence and correlates of substance use recovery status among adolescents and emerging adults.

BACKGROUND AND AIMS: To date, no epidemiological survey has estimated the prevalence of adolescents identifying as being in recovery. This is necessary for planning and identifying the needs of youth with current and remitted substance use disorders. This study estimated the prevalence of recovery status in a large statewide epidemiological survey administered between January and March 2020. PARTICIPANTS: Participants were high school students in 9th through 12th grades throughout Illinois. MEASUREMENTS: Youth were asked if they were in recovery and if they had resolved problems with substances. Youth who reported recovery and problem resolving dual status (DS), recovery only (RO), and problem resolution only (PRO) were compared to propensity score matched control groups who reported neither status (neither/nor; NN). Outcomes included alcohol use, binge alcohol use, cannabis use, and prescription drug use in the past 30 days. FINDINGS: Prevalence estimates were 884 (1.4%) for DS, 1546 (2.5%) for PRO, and 1,811 (2.9%) for RO. Relative to propensity matched control samples, all three groups had significantly lower odds of prescription drug use. The PRO group had lower odds of past month cannabis use. There were no significant differences for either alcohol outcome. CONCLUSIONS: Prevalence estimates of youth in recovery are slightly lower than those of adults in recovery, and estimates should be replicated. Youth in recovery and those resolving problems have numerous behavioral health needs, and relative to matched controls, have even odds for past 30-day alcohol use. These findings compel us to further define recovery for adolescents and emerging adults to allow for improving treatments and epidemiological research.

Clark's nutcracker forest community visitation: Whitebark pine maintains a keystone seed disperser.

Clark's nutcrackers (Nucifraga columbiana) are obligate seed dispersers for whitebark pine (Pinus albicaulis), but they frequently use other conifer seed resources because of annual variability in cone production or geographic variation in whitebark pine availability. Whitebark pine is declining from several threats including white pine blister rust, leading to potential population declines in the nutcracker and the pine. We hypothesize that where there are few additional seed resources, whitebark pine becomes the key and limiting resource supporting nutcracker populations. We investigated how nutcrackers use coniferous forest community types within Yellowstone National Park to determine potential seed resources and the importance of whitebark pine. We established sites representing five forest community types, including whitebark pine, lodgepole pine (P. contorta), Engelmann spruce (Picea engelmannii), limber pine (P. flexilis), and Douglas-fir (Pseudotsuga menziesii). Each transect annually generated nutcracker point counts, conifer cone production indices, community composition data, and seed resource use observations. We compared hierarchical distance sampling models, estimating nutcracker density and its relationship to forest community type, seed harvesting time-period, year, study site, and cone seed energy. We found cone production varied across years indicating annual variability in energy availability. Nutcracker density was best predicted by forest community type and survey time-period and was highest in whitebark pine stands during the mid-harvesting season. Nutcracker density was comparatively low for all other forest community types. This finding underscores the importance of whitebark pine as a key seed resource for Clark's nutcracker in Yellowstone National Park. The decline of whitebark pine potentially leads to a downward spiral in nutcrackers and whitebark pine, arguing for continued monitoring of nutcrackers and implementation of restoration treatments for whitebark pine.