Rationale for the Development of a Traumatic Brain Injury Case Definition for the Pilot National Concussion Surveillance System.

BACKGROUND: Current methods of traumatic brain injury (TBI) morbidity surveillance in the United States have primarily relied on hospital-based data sets. However, these methods undercount TBIs as they do not include TBIs seen in outpatient settings and those that are untreated and undiagnosed. A 2014 National Academy of Science Engineering and Medicine report recommended that the Centers for Disease Control and Prevention (CDC) establish and manage a national surveillance system to better describe the burden of sports- and recreation-related TBI, including concussion, among youth. Given the limitations of TBI surveillance in general, CDC took this recommendation as a call to action to formulate and implement a robust pilot National Concussion Surveillance System that could estimate the public health burden of concussion and TBI among Americans from all causes of brain injury. Because of the constraints of identifying TBI in clinical settings, an alternative surveillance approach is to collect TBI data via a self-report survey. Before such a survey was piloted, it was necessary for CDC to develop a case definition for self-reported TBI. OBJECTIVE: This article outlines the rationale and process the CDC used to develop a tiered case definition for self-reported TBI to be used for surveillance purposes. CONCLUSION: A tiered TBI case definition is proposed with tiers based on the type of sign/symptom(s) reported the number of symptoms reported, and the timing of symptom onset.

Refinement of a Preliminary Case Definition for Use in Traumatic Brain Injury Surveillance.

OBJECTIVE: Current methods used to measure incidence of traumatic brain injury (TBI) underestimate its true public health burden. The use of self-report surveys may be an approach to improve these estimates. An important step in public health surveillance is to define a public health problem using a case definition. The purpose of this article is to outline the process that the Centers for Disease Control and Prevention undertook to refine a TBI case definition to be used in surveillance using a self-report survey. SETTING: Survey. PARTICIPANTS: A total of 10 030 adults participated via a random digit-dial telephone survey from September 2018 to September 2019. MAIN MEASURES: Respondents were asked whether they had sustained a hit to the head in the preceding 12 months and whether they experienced a series of 12 signs and symptoms as a result of this injury. DESIGN: Head injuries with 1 or more signs/symptoms reported were initially categorized into a 3-tiered TBI case definition (probable TBI, possible TBI, and delayed possible TBI), corresponding to the level of certainty that a TBI occurred. Placement in a tier was compared with a range of severity measures (whether medical evaluation was sought, time to symptom resolution, self-rated social and work functioning); case definition tiers were then modified in a stepwise fashion to maximize differences in severity between tiers. RESULTS: There were statistically significant differences in the severity measure between cases in the probable and possible TBI tiers but not between other tiers. Timing of symptom onset did not meaningfully differentiate between cases on severity measures; therefore, the delayed possible tier was eliminated, resulting in 2 tiers: probable and possible TBI. CONCLUSION: The 2-tiered TBI case definition that was derived from this analysis can be used in future surveillance efforts to differentiate cases by certainty and from noncases for the purpose of reporting TBI prevalence and incidence estimates. The refined case definition can help researchers increase the confidence they have in reporting survey respondents' self-reported TBIs as well as provide them with the flexibility to report an expansive (probable + possible TBI) or more conservative (probable TBI only) estimate of TBI prevalence.

Using machine learning to discover traumatic brain injury patient phenotypes: national concussion surveillance system Pilot.

OBJECTIVE: The objective is to determine whether unsupervised machine learning identifies traumatic brain injury (TBI) phenotypes with unique clinical profiles. METHODS: Pilot self-reported survey data of over 10,000 adults were collected from the Centers for Disease Control and Prevention (CDC)'s National Concussion Surveillance System (NCSS). Respondents who self-reported a head injury in the past 12 months (n = 1,364) were retained and queried for injury, outcome, and clinical characteristics. An unsupervised machine learning algorithm, partitioning around medoids (PAM), that employed Gower's dissimilarity matrix, was used to conduct a cluster analysis. RESULTS: PAM grouped respondents into five TBI clusters (phenotypes A-E). Phenotype C represented more clinically severe TBIs with a higher prevalence of symptoms and association with worse outcomes. When compared to individuals in Phenotype A, a group with few TBI-related symptoms, individuals in Phenotype C were more likely to undergo medical evaluation (odds ratio [OR] = 9.8, 95% confidence interval[CI] = 5.8-16.6), have symptoms that were not currently resolved or resolved in 8+ days (OR = 10.6, 95%CI = 6.2-18.1), and more likely to report at least moderate impact on social (OR = 54.7, 95%CI = 22.4-133.4) and work (OR = 25.4, 95%CI = 11.2-57.2) functioning. CONCLUSION: Machine learning can be used to classify patients into unique TBI phenotypes. Further research might examine the utility of such classifications in supporting clinical diagnosis and patient recovery for this complex health condition.

Nonfatal Emergency Department Visits Associated with Fall-Related Fractured Skulls of Infants Aged 0-4 Months.

BACKGROUND: Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall. OBJECTIVE: This study examined caregiver actions and products associated with ED visits for fall-related fractured skulls in infants aged 0-4 months. METHODS: Data were analyzed from the 2001-2017 National Electronic Injury Surveillance System-All Injury Program. Case narratives of infants aged 0-4 months who visited an ED for a fall-related skull fracture were examined to code caregiver actions preceding the fall. Product codes determined fall location and product type involved (e.g., flooring, bed, or stairs). All national estimates were weighted. RESULTS: There were more than 27,000 ED visits (weighted estimate) of infants aged 0-4 months for a nonfatal fall-related fractured skull between 2001 and 2017. Most were younger than 2 months (46.7%) and male (54.4%). Falls occurred primarily in the home (69.9%) and required hospitalization (76.4%). Primary caregiver actions coded involved placing (58.6%), dropping (22.7%), and carrying an infant (16.6%). Floor surfaces were the most common product (mentioned in 24.0% of the cases). CONCLUSIONS: Fall-related fractured skulls are a health and developmental concern for infants, highlighting the importance of a comprehensive assessment at the time of the injury to better understand adult actions. Findings indicated the need to develop prevention messages that include safe carrying and placement of infants.

Association between traumatic brain injury and suicidality using a mediation approach and MarketScan.

INTRODUCTION: Negative outcomes, including suicidal ideation/attempts, are a major public health concern, particularly among individuals who sustain a traumatic brain injury (TBI). TBI is associated with high rates of postinjury substance use, psychiatric disorders, post-traumatic stress disorder and sleep disturbances. This study examines the mediation effects of substance use, psychiatric disorder and sleep disorder on the associations between TBI and suicidal ideation/attempts. METHODS: A matched case-control study using data from MarketScan databases for private health insurance and Medicaid from October 2015 to December 2018 estimated the association between TBI and suicidal ideation/attempts using a mediation approach. Individuals less than 65 years of age were included. RESULTS: In the Medicaid sample, psychiatric disorders mediated 22.4% of the total effect between TBI and suicidal ideation/attempt, while substance use disorders other than opioid use disorder mediated 7.47%. In the private health insurance sample, psychiatric disorders mediated 3.97% of the total effect, opioid use disorders mediated 2.08% of the total effect and sleep disorder mediated 1.25% of the total effect. CONCLUSIONS: Mediators explained less than 30% of the relationship between TBI and suicidal ideation/attempt. Findings reinforce the importance of primary prevention of TBI and monitoring patients with a TBI for risk of suicide in the first 6-12 months following injury.

Concussion education for youth athletes using Pre-Game Safety Huddles: a cluster-randomised controlled trial.

OBJECTIVES: Determine whether Pre-Game Safety Huddles, a novel and low-resource approach to concussion education, increase the expected likelihood of concussion reporting for youth athletes. METHODS: A cluster-randomised trial compared Safety Huddles to usual care. Safety Huddles bring together athletes and coaches from both teams before the start of each game for coaches to briefly affirm the importance of speaking up if a concussion is suspected. Participants were athletes from 22 competitive community-based American football and girls and boys soccer teams (ages 9-14), and randomisation into intervention or control occurred at the level of the bracket (group of teams that compete against each other during the regular season). The primary outcome was expected likelihood of reporting concussion symptoms to the coach, measured via validated athlete survey at the beginning and end of the season. RESULTS: Of 343 eligible participants, 339 (99%) completed baseline surveys and 303 (88%) completed surveys at season end. The mean (SD) age was 11.4 (1.1) years, 26% were female soccer athletes, 27% were male soccer athletes and 47% were football athletes. In adjusted analyses accounting for baseline values and clustering by sport and team via random effects, expected likelihood of concussion reporting at the end of the season was significantly higher in the intervention group compared to controls (mean difference=0.49, 95% CI 0.11 to 0.88; Cohen's d=0.35). CONCLUSIONS AND RELEVANCE: Pre-Game Safety Huddles increased the expected likelihood of athletes reporting concussion symptoms. While further study is warranted, sport organisations should consider this approach a promising low-resource option for improving concussion safety in their setting. TRIAL REGISTRATION NUMBER: NCT04099329.

Incidence of Nonfatal Traumatic Brain Injury-Related Hospitalizations - United States, 2018.

Traumatic brain injury (TBI), which can disrupt normal brain function and result in short- and long-term adverse clinical outcomes, including disability and death, is preventable. To describe the 2018 incidence of nonfatal TBI-related hospitalizations in the United States by sociodemographic characteristics, injury intent, and mechanism of injury, CDC analyzed data from the Healthcare Cost and Utilization Project (HCUP) National (Nationwide) Inpatient Sample. During 2018, there were 223,050 nonfatal TBI-related hospitalizations; rates among persons aged ≥75 years were approximately three times higher than those among persons aged 65-74 years, and the age-adjusted rate among males was approximately double that among females. Unintentional falls were the most common mechanism of injury leading to nonfatal TBI-related hospitalization, followed by motor vehicle crashes. Proper and consistent use of recommended restraints (i.e., seatbelts, car seats, and booster seats) and, particularly for persons aged ≥75 years, learning about individual fall risk from health care providers are two steps the public can take to prevent the most common injuries leading to nonfatal TBIs. The findings in this report could be used by public health officials and clinicians to identify priority areas for prevention programs.

Multisite medical record review of emergency department visits for unspecified injury of head following the ICD-10-CM coding transition.

INTRODUCTION: In 2016, a proposed International Classification of Diseases, Tenth Edition, Clinical Modification surveillance definition for traumatic brain injury (TBI) morbidity was introduced that excluded the unspecified injury of head (S09.90) diagnosis code. This study assessed emergency department (ED) medical records containing S09.90 for evidence of TBI based on medical documentation. METHODS: State health department representatives in Maryland, Kentucky, Colorado and Massachusetts reviewed a target of 385 randomly sampled ED records uniquely assigned the S09.90 diagnosis code (without proposed TBI codes), which were initial medical encounters among state residents discharged home during October 2015-December 2018. Using standardised abstraction procedures, reviewers recorded signs and symptoms of TBI, and head imaging results. A tiered case confirmation strategy was applied that assigned a level of certainty (high, medium, low, none) to each record based on the number and type of symptoms and imaging results present in the record. Positive predictive value (PPV) of S09.90 by level of TBI certainty was calculated by state. RESULTS: Wide variation in PPV of sampled ED records assigned S09.90: 36%-52% had medium or high evidence of TBI, while 48%-64% contained low or no evidence of a TBI. Loss of consciousness was mentioned in 8%-24% of sampled medical records. DISCUSSION: Exclusion of the S09.90 code in surveillance estimates may result in many missed TBI cases; inclusion may result in counting many false positives. Further, missed TBI cases influenced by incidence estimates, based on the TBI surveillance definition, may lead to inadequate allocation of public health resources.

Deaths from Fall-Related Traumatic Brain Injury - United States, 2008-2017.

One in 10 U.S. residents aged ≥18 years reports falling each year (1). Among all age groups, falls can cause serious injury and are the second leading cause of traumatic brain injury (TBI)-related deaths (2). TBI is a head injury caused by a bump, blow, or jolt to the head or body or a penetrating head injury that results in disruption of normal brain function.* CDC estimated national and state-specific rates and trends for TBI-related deaths (TBI deaths) caused by unintentional falls (fall-related TBI deaths) among U.S. residents during 2008-2017, by selected decedent characteristics. The national age-adjusted rate of fall-related TBI deaths increased by 17% from 2008 to 2017. Rate trends at the national level increased significantly for nearly all decedent characteristics, with the most notable increases observed among persons living in noncore (i.e., most rural), nonmetropolitan counties and those aged ≥75 years. Analysis of state-specific rate trends determined that rates of fall-related TBI deaths increased significantly in 29 states over the 10-year study period. A fall can happen to anyone of any age, but falls are preventable. Health care providers and the public need to be aware of evidence-based strategies to prevent falls, given that rates of fall-related TBI deaths are increasing. Health care providers can educate patients on fall and TBI prevention, assess their risk for falls, and when needed, encourage participation in appropriate evidence-based fall prevention programs.†.

Traumatic Brain Injury-Related Emergency Department Visits Among American Indian and Alaska Native Persons-National Patient Information Reporting System, 2005-2014.

OBJECTIVE: The American Indian/Alaska Native (AI/AN) population has a disproportionately high rate of traumatic brain injuries (TBIs). However, there is little known about incidence and common mechanisms of injury among AI/AN persons who seek care in an Indian Health Service (IHS) or tribally managed facility. METHODS: Using the IHS National Patient Information Reporting System, we assessed the incidence of TBI-related emergency department visits among AI/AN children and adults seen in IHS or tribally managed facilities over a 10-year period (2005-2014). RESULTS: There were 44 918 TBI-related emergency department visits during the study period. Males and persons aged 18 to 34 years and 75 years and older had the highest rates of TBI-related emergency department visits. Unintentional falls and assaults contributed to the highest number and proportion of TBI-related emergency department visits. The number and age-adjusted rate of emergency department visits for TBI were highest among persons living in the Southwest and Northern Plains when compared with other IHS regions. CONCLUSION: Thousands of AI/AN children and adults are seen each year in emergency departments for TBI and the numbers increased over the 10-year period examined. Evidence-based interventions to prevent TBI-related emergency department visits, such as programs to reduce the risk for older adult falls and assault, are warranted.

Emergency Department Visits for Sports- and Recreation-Related Traumatic Brain Injuries Among Children - United States, 2010-2016.

Traumatic brain injuries (TBIs), including concussions, are at the forefront of public concern about athletic injuries sustained by children. Caused by an impact to the head or body, a TBI can lead to emotional, physiologic, and cognitive sequelae in children (1). Physiologic factors (such as a child's developing nervous system and thinner cranial bones) might place children at increased risk for TBI (2,3). A previous study demonstrated that 70% of emergency department (ED) visits for sports- and recreation-related TBIs (SRR-TBIs) were among children (4). Because surveillance data can help develop prevention efforts, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP)* by examining SRR-TBI ED visits during 2010-2016. An average of 283,000 children aged <18 years sought care in EDs each year for SRR-TBIs, with overall rates leveling off in recent years. The highest rates were among males and children aged 10-14 and 15-17 years. TBIs sustained in contact sports accounted for approximately 45% of all SRR-TBI ED visits. Activities associated with the highest number of ED visits were football, bicycling, basketball, playground activities, and soccer. Limiting player-to-player contact and rule changes that reduce risk for collisions are critical to preventing TBI in contact and limited-contact sports. If a TBI does occur, effective diagnosis and management can promote positive health outcomes among children.

Self-Reported Concussions from Playing a Sport or Being Physically Active Among High School Students - United States, 2017.

Increased susceptibility to concussions and longer recovery times among high school athletes compared with older athletes (1) make concussions among youths playing a sport or being physically active an area of concern. Short-term and long-term sequelae of concussions can include cognitive, affective, and behavioral changes (1). Surveillance methods used to monitor concussions among youths likely underestimate the prevalence. Estimates assessed from emergency departments miss concussions treated outside hospitals, those generated using high school athletic trainer reports miss concussions sustained outside of school-based sports (2), and both sources miss medically untreated concussions. To estimate the prevalence of concussions among U.S. high school students related to playing a sport or being physically active, CDC analyzed data from the 2017 national Youth Risk Behavior Survey (YRBS). Overall, 15.1% of students (approximately 2.5 million*) reported having at least one of these concussions during the 12 months before the survey, and 6.0% reported two or more concussions. Concussion prevalence was significantly higher among male students than among female students and among students who played on a sports team than among students who did not. Among all sex, grade, and racial/ethnic subgroups, the odds of reporting a concussion increased significantly with the number of sports teams on which students played. These findings underscore the need to 1) foster a culture of safety in which concussion prevention and management is explicitly addressed; 2) expand efforts to educate students, parents, coaches, and health care providers regarding the risk for concussion; and 3) identify programs, policies, and practices that prevent concussions.

Increases in Fentanyl-Related Overdose Deaths - Florida and Ohio, 2013-2015.

In March and October 2015, the Drug Enforcement Administration (DEA) and CDC issued nationwide alerts identifying fentanyl, particularly illicitly manufactured fentanyl (IMF), as a threat to public health and safety (1,2). IMF is pharmacologically similar to pharmaceutical fentanyl (PF), but is unlawfully produced in clandestine laboratories, obtained via illicit drug markets, and includes fentanyl analogs. Fentanyl is a synthetic opioid 50-100 times more potent than morphine and approved for the management of surgical/postoperative pain, severe chronic pain, and breakthrough cancer pain.* DEA's National Forensic Laboratory Information System (NFLIS) collects drug identification results from drug cases analyzed by federal, state, and local forensic laboratories throughout the United States.(†) In 2014, 80% of fentanyl submissions (i.e., drug products obtained by law enforcement that tested positive for fentanyl) in NFLIS were identified from 10 states, including Florida and Ohio (2), and seven of these 10 states reported sharp increases in fentanyl-related overdose deaths (fentanyl deaths) (3). This report presents findings of increased fentanyl deaths during 2013-2015 from investigations conducted by the University of Florida and the Ohio Department of Public Health, in collaboration with CDC. Analyses examined the association between trends in fentanyl-related law enforcement submissions and fentanyl deaths and describes groups at risk for fentanyl death using medical examiner and coroner reports. The marked increases in fentanyl death in Florida and Ohio during 2013-2015 were closely associated with parallel increases in fentanyl submissions, with the largest impact on persons who use heroin, consistent with reports that IMF is commonly mixed with or sold as heroin (1,4). In Ohio, circumstances associated with fentanyl deaths included a current diagnosed mental health disorder(§) and recent release from an institution such as a jail, rehabilitation facility, or hospital.

Sport and Recreation Related Concussion in Children: National Concussion Surveillance System.

INTRODUCTION: Concussions sustained during sports and recreational activities are a concern for young athletes. The purpose of this study was to estimate past 12-month sport- and recreation-related (SRR) traumatic brain injuries (TBIs) among a sample of children. METHODS: Pilot data from the Centers for Disease Control and Prevention's National Concussion Surveillance System were analyzed. National Concussion Surveillance System utilized a cross-sectional random-digit-dial telephone survey using computer-assisted telephone interviewing to collect self/proxy-reported data from 2018 to 2019. Adults with children aged 5-17 in the household were asked about head injuries sustained by their children. Estimates were stratified by sociodemographic and injury circumstance characteristics. Data analysis occurred from April 2022 to July 2023. RESULTS: Utilizing a tiered case definition developed by the Centers for Disease Control and Prevention, an estimated 6.9% (95% confidence interval [CI], 6.0%-7.8%) of the sample's 5-17-year-old children sustained at least one probable or possible SRR-TBI in the previous 12 months; 3.3% (95% CI, 2.7%-4.0%) of the children sustained at least one probable SRR-TBI. An estimated 63.6% (95% CI, 58.1%-69.0%) of all reported TBIs were attributed to SRR activities. Of the SRR-TBIs reported, 41.1% (95% CI, 33.0%-49.2%) were experienced while playing contact sports. Symptoms did not resolve for 8 or more days or had not resolved at the time of the interview for 18.1% (95% CI, 13.0%-23.1%) of the children's most recent SRR-TBI. CONCLUSIONS: Many proxy-reported TBIs among children aged 5-17 years were due to sports and recreational activities. Athletic trainers and healthcare providers can play a role in the prevention, identification, and management of SRR-TBIs in their respective environments.

Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment.

Cancer cells show altered antioxidant defense systems, dysregulated redox signaling, and increased generation of reactive oxygen species (ROS). Targeting cancer cells through ROS-mediated mechanisms has emerged as a significant therapeutic strategy due to its implications in cancer progression, survival, and resistance. Extensive research has focused on selective generation of H2O2 in cancer cells for selective cancer cell killing by employing various strategies such as metal-based prodrugs, photodynamic therapy, enzyme-based systems, nano-particle mediated approaches, chemical modulators, and combination therapies. Many of these H2O2-amplifying approaches have demonstrated promising anticancer effects and selectivity in preclinical investigations. They selectively induce cytotoxicity in cancer cells while sparing normal cells, sensitize resistant cells, and modulate the tumor microenvironment. However, challenges remain in achieving selectivity, addressing tumor heterogeneity, ensuring efficient delivery, and managing safety and toxicity. To address those issues, H2O2-generating agents have been combined with other treatments leading to optimized combination therapies. This review focuses on various chemical agents/approaches that kill cancer cells via H2O2-mediated mechanisms. Different categories of compounds that selectively generate H2O2 in cancer cells are summarized, their underlying mechanisms and function are elucidated, preclinical and clinical studies as well as recent advancements are discussed, and their prospects as targeted therapeutic agents and their therapeutic utility in combination with other treatments are explored. By understanding the potential of these compounds, researchers can pave the way for the development of effective and personalized cancer treatments.

New paradigm for allosteric regulation of Escherichia coli aspartate transcarbamoylase.

For nearly 60 years, the ATP activation and the CTP inhibition of Escherichia coli aspartate transcarbamoylase (ATCase) has been the textbook example of allosteric regulation. We present kinetic data and five X-ray structures determined in the absence and presence of a Mg(2+) concentration within the physiological range. In the presence of 2 mM divalent cations (Mg(2+), Ca(2+), Zn(2+)), CTP does not significantly inhibit the enzyme, while the allosteric activation by ATP is enhanced. The data suggest that the actual allosteric inhibitor of ATCase in vivo is the combination of CTP, UTP, and a divalent cation, and the actual allosteric activator is a divalent cation with ATP or ATP and GTP. The structural data reveals that two NTPs can bind to each allosteric site with a divalent cation acting as a bridge between the triphosphates. Thus, the regulation of ATCase is far more complex than previously believed and calls many previous studies into question. The X-ray structures reveal that the catalytic chains undergo essentially no alternations; however, several regions of the regulatory chains undergo significant structural changes. Most significant is that the N-terminal region of the regulatory chains exists in different conformations in the allosterically activated and inhibited forms of the enzyme. Here, a new model of allosteric regulation is proposed.

A synthesis of carcass decomposition studies conducted at a tropical (Aw) taphonomy facility: 2013-2022.

Decomposition studies have been conducted in several regions of the world, but relatively few have investigated taphonomy in tropical environments. Even fewer have explored carcass decomposition during multiple tropical seasons, leaving the relationships between season and decomposition in tropical environments poorly understood. Ten decomposition studies using 30 carcasses were conducted in Honolulu, Hawaii, USA to start addressing this knowledge gap. These studies show that some postmortem processes were observed regardless of season. Carcass temperature and chemistry were spatiotemporally variable. Fly larval masses were consistently observed within 3 days (∼75 ADD) postmortem and carcasses lost 60%-90% of mass by 10 days (∼250 ADD) postmortem (Total Body Score ∼26). Season had a significant effect on decomposition, yet the warmest and most humid seasons did not always result in the most rapid and extensive decomposition. Seasonal variation appears to be less pronounced than at other tropical decomposition sites.

A second allosteric site in Escherichia coli aspartate transcarbamoylase.

Escherichia coli aspartate transcarbamoylase is feedback inhibited by CTP and UTP in the presence of CTP. Here, we show by X-ray crystallography that UTP binds to a unique site on each regulatory chain of the enzyme that is near but not overlapping with the known CTP site. These results bring into question all of the previously proposed mechanisms of allosteric regulation in aspartate transcarbamoylase.

Matrix composition regulates three-dimensional network formation by endothelial cells and mesenchymal stem cells in collagen/fibrin materials.

Co-cultures of endothelial cells (EC) and mesenchymal stem cells (MSC) in three-dimensional (3D) protein hydrogels can be used to recapitulate aspects of vasculogenesis in vitro. MSC provide paracrine signals that stimulate EC to form vessel-like structures, which mature as the MSC transition to the role of mural cells. In this study, vessel-like network formation was studied using 3D collagen/fibrin (COL/FIB) matrices seeded with embedded EC and MSC and cultured for 7 days. The EC:MSC ratio was varied from 5:1, 3:2, 1:1, 2:3 and 1:5. The matrix composition was varied at COL/FIB compositions of 100/0 (pure COL), 60/40, 50/50, 40/60 and 0/100 (pure FIB). Vasculogenesis was markedly decreased in the highest EC:MSC ratio, relative to the other cell ratios. Network formation increased with increasing fibrin content in composite materials, although the 40/60 COL/FIB and pure fibrin materials exhibited the same degree of vasculogenesis. EC and MSC were co-localized in vessel-like structures after 7 days and total cell number increased by approximately 70%. Mechanical property measurements showed an inverse correlation between matrix stiffness and network formation. The effect of matrix stiffness was further investigated using gels made with varying total protein content and by crosslinking the matrix using the dialdehyde glyoxal. This systematic series of studies demonstrates that matrix composition regulates vasculogenesis in 3D protein hydrogels, and further suggests that this effect may be caused by matrix mechanical properties. These findings have relevance to the study of neovessel formation and the development of strategies to promote vascularization in transplanted tissues.

Disparities in traumatic brain injury-related deaths-United States, 2020.

INTRODUCTION: Traumatic brain injury (TBI) affects how the brain functions and remains a prominent cause of death in the United States. Although preventable, anyone can experience a TBI and epidemiological research suggests some groups have worse health outcomes following the injury. METHODS: We analyzed 2020 multiple-cause-of-death data from the National Vital Statistics System to describe TBI mortality by geography, sociodemographic characteristics, mechanism of injury (MOI), and injury intent. Deaths were included if they listed an injury International Classification of Diseases, Tenth Revision (ICD-10) underlying cause of death code and a TBI-related ICD-10 code in one of the multiple-cause-of-death fields. RESULTS: During 2020, 64,362 TBI-related deaths occurred and age-adjusted rates, per 100,000 population, were highest among persons residing in the South (20.2). Older adults (≥75) displayed the highest number and rate of TBI-related deaths compared with other age groups and unintentional falls and suicide were the leading external causes among this older age group. The age-adjusted rate of TBI-related deaths in males was more than three times the rate of females (28.3 versus 8.4, respectively); further, males displayed higher numbers and age-adjusted rates compared with females for all the principal MOIs that contributed to a TBI-related death. American Indian or Alaska Native, Non-Hispanic (AI/AN) persons had the highest age-adjusted rate (29.0) of TBI-related deaths when compared with other racial and ethnic groups. Suicide was the leading external cause of injury contributing to a TBI-related death among AI/AN persons. PRACTICAL APPLICATION: Prevention efforts targeting older adult falls and suicide are warranted to reduce disparities in TBI mortality among older adults and AI/AN persons. Effective strategies are described in CDC's Stopping Elderly Accidents, Deaths, & Injuries (STEADI) initiative to reduce older adult falls and CDC's Preventing Suicide: A Technical Package of Policy, Programs, and Practices for the best available evidence in suicide prevention.