OBJECTIVES/GOALS: Patients who have experienced conjunctive mild traumatic brain injuries (mTBIs) suffer from a number of comorbidities, including chronic pain. Despite extensive studies investigating the underlying mechanisms of mTBI-associated chronic pain, the role of inflammation after mTBI and its contribution to long-term pain are still poorly understood. METHODS/STUDY POPULATION: Given the shifting dynamics of inflammation, it is important to understand the spatial-longitudinal changes and their effects on TBI-related pain. Utilizing a recently developed transgenic caspase-1 luciferase reporter mouse, we characterized the bioluminescence signal evident in both in vivo and ex vivo tissues following repetitive closed head mTBIs. This allowed us to reveal the spatiotemporal dynamics of caspase-1 activation in individual animals over time. Furthermore, we utilize various proteomic and behavioral assays to evaluate the role of caspase-1 mediated inflammation in the development and progression of injury-associated chronic pain. Lastly, by blocking inflammasome caspase-1 activation with a specific inhibitor, we assess its clinical potential as the next therapeutic approach to pain. RESULTS/ANTICIPATED RESULTS: We established that there were significant increases in bioluminescent signals upon protease cleavage in the brain, thorax, abdomen, and paws in vivo, which lasted for at least one week after each injury. Enhanced inflammation was also observed in ex vivo brain slice preparations following injury events that lasted for at least 3 days. Concurrent with the in vivo detection of the bioluminescent signal were persistent decreases in mouse hind paw withdrawal thresholds that lasted for more than two months postinjury. Using MCC950, a potent small molecule inhibitor of NLRP3 inflammasome-caspase 1 activity, we observed reductions in both caspase-1 bioluminescent signals in vivo and caspase-1 p45 expression by immunoblotting and an increase in hind paw withdrawal thresholds. DISCUSSION/SIGNIFICANCE: Overall, these findings suggest that neuroinflammation in the brain following repeated mTBIs is coincidental with a chronic nociplastic pain state, and repeated mTBI-associated events can be ameliorated by a highly specific small molecule inhibitor of NLRP3 inflammasome activation.

A crucial reckoning was initiated when the COVID-19 pandemic began to expose and intensify long-standing racial/ethnic health inequities, all while various sectors of society pursued racial justice reform. As a result, there has been a contextual shift towards broader recognition of systemic racism, and not race, as the shared foundational driver of both societal maladies. This confluence of issues is of particular relevance to Black populations disproportionately affected by the pandemic and racial injustice. In response, institutions have initiated diversity, equity, and inclusion (DEI) efforts as a way forward. This article considers how the dual pandemic climate of COVID-19-related health inequities and the racial justice movement could exacerbate the “time and effort tax” on Black faculty to engage in DEI efforts in academia and biomedicine. We discuss the impact of this “tax” on career advancement and well-being, and introduce an operational framework for considering the interconnected influence of systemic racism, the dual pandemics, and DEI work on the experience of Black faculty. If not meaningfully addressed, the “time and effort tax” could contribute to Black and other underrepresented minority faculty leaving academia and biomedicine – consequently, the very diversity, equity, and inclusion work meant to increase representation could decrease it.

Infants with critical CHD have abnormal neurobehavior assessed by the Neonatal ICU Network Neurobehavioral Scales. This retrospective cohort study hypothesized associations between abnormal infant neurobehavior in the first month of life and later neurodevelopmental outcomes at 1−2 years of age. Associations between abnormal infant attention (orienting to and tracking stimuli) on the Neonatal ICU Network Neurobehavioral Scales and later motor, cognitive, and language neurodevelopmental outcomes on the Bayley Scales of Infant Development-III at follow-up were examined with descriptive statistics and univariable and multivariable regression. Multiple imputation was used to account for missing outcome data. 189 infants with critical CHD were included, and 69% had abnormal neurobehavioral attention scores. 58 (31%) returned as toddlers for neurodevelopmental follow-up, of which 23% had motor delay. Abnormal infant attention had high sensitivity (92%, 95% CI 60−100%) but low specificity (36%, 95% CI 23−52%) for later motor delay. Higher infant attention scores were associated with higher later motor scores in univariable analysis (coefficient 3.49, 95% CI 0.52,6.46, p = 0.025), but not in multivariable analyses. Neither cognitive nor language scores were associated with infant attention scores. Lower birth weight and male sex were significantly associated with lower motor scores in multivariable analysis (p = 0.048, 0.007). Although impaired infant attention is interdependent with other clinical and demographic risk factors, it may be a sensitive clinical marker of risk for later motor delay. In children with critical CHD, impaired infant attention may be capturing early signs of abnormal visual-motor neurodevelopment.

Background: Racial and ethnic disparities in healthcare access, medical treatment, and outcomes have been extensively reported. However, the impact of racial and ethnic differences in patient safety, including healthcare-associated infections, has not been well described. Methods: We performed a retrospective review analyzing prospectively collected data on central-line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) rates per 1,000 device days. Data for adult patients admitted to an academic medical center between 2018 and 2021 were stratified by 7 racial and ethnic groups: non-Hispanic White, non-Hispanic Black, Hispanic/Latino, Asian, American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and othe. The “other” group was composed of bi- or multiracial patients, or those for whom no data were reported. We compared the CLABSI and CAUTI rates between the different racial and ethnic groups using Poisson regression. Results: Compared to non-Hispanic White patients, the rate of CLABSI was significantly higher in non-Hispanic Black patients (1.27; 95% CI, 1.02–1.58; P < .03) and those in the “other” race category (1.79; 95% CI, 1.39–2.30; P < .001, respectively), and these trends increased in Hispanic/Latino patients (Table 1). Similarly, Black patients had higher rates of CAUTI (1.42; 95% CI, 1.05–1.92; P < .02), as did Asian patients (2.49; 95% CI, 1.16–5.36; P < .02), and patients in the “other” category (1.52; 95% CI, 1.06–2.18; P < .02) (Table 2). Conclusions: Racial and ethnic minorities may be vulnerable to a higher rate of patient safety events, including CLABSIs and CAUTIs. Additional analyses controlling for potential confounding factors are needed to better understand the relationship between race or ethnicity, clinical management, and healthcare-associated infections. This evaluation is essential to inform mitigation strategies and to provide optimum, equitable care for all.

Funding: None

Disclosures: None

Glass bangles are found in southern England and Wales from the mid-first century ad and become common in the north of England and southern Scotland in the late first century, before their numbers decline a century later. British bangles develop at a time of change, as Roman glassmaking practices were introduced across large areas of Britain, and as blown, transparent, colourless and naturally-coloured glassware became increasingly popular. In many communities, however, there was still a demand for strongly coloured opaque glass, including for bangles, and glassworkers devised ways of extending their supplies of opaque coloured glass. This study is based on over one hundred and fifty analyses of bangle fragments from sites in Wales, northern England and southern Scotland, spanning this transitional period. The bangle makers recycled coloured glass from imported vessels, and probably beads and bangle-making waste, to supplement supplies of fresh coloured glass. The novel methods used to modify and extend the coloured glass may derive from pre-Roman bead-making industries, and made use of widely available materials, including smithing hammerscale and possibly plant ashes. The results show the shifting balance of indigenous and Roman influences on different bangle types, depending on when and where they were made, and by whom.

ABSTRACT IMPACT: This study evaluates the long term effects of pharmacologic weaning therapy for opiate exposed infants. OBJECTIVES/GOALS: Infants born to chronic opioid users often suffer from neonatal abstinence syndrome (NAS), a condition characterized by tremors, diarrhea, hyperirritability and an inconsolable high-pitched cry. Symptoms are treated with pharmacologic weaning therapy, but long-term effects of this treatment have not been established. METHODS/STUDY POPULATION: A sample of infants born between 2011-2017 was obtained from a large metropolitan hospital system. All infants who were exposed to opioids and received a Finnegan score were included in the sample (N=1,807). The analysis utilizes three dependent variables to measure developmental delay: motor delay, language delay or any delay, which includes general/non-specific delay in addition to motor and language delay. The treatment is defined as receipt of pharmacologic therapy with methadone or morphine. Maximum Finnegan score was also included as a continuous measure of the extent of the infant’s withdrawal symptoms. Linear models were utilized to determine a relationship between pharmacologic therapy and developmental delay with Maximum Finnegan score as an interaction term. RESULTS/ANTICIPATED RESULTS: In the linear models examining the main effects of weaning therapy on developmental delay, there was no relationship between pharmacologic therapy and motor delay (p=.260), language delay (p=.542) or any developmental delay (p=.176). When maximum Finnegan score was entered into the model as an interaction term the relationships were not significant. DISCUSSION/SIGNIFICANCE OF FINDINGS: These results suggest that while pharmacologic weaning is an appropriate treatment for withdrawal symptoms in infants, it is not a deterrent against developmental delays associated with NAS. This provides support suggest an increased focus on non-pharmacologic interventions such as breastfeeding as the first line of treatment for NAS infants.

ABSTRACT IMPACT: Congregations’ support for social, emotional, mental and spiritual wellness is foundational to human health and their community knowledge and presence can improve resilience and health in socially vulnerable neighborhoods. OBJECTIVES/GOALS: The Indiana CTSI Monon Collaborative is listening and understanding the most pressing health issues in the community and are working together to design and deliver community health solutions. We worked with our community ambassador to launch a health and wellness learning community for ten congregations seeking to build a health-connector network. METHODS/STUDY POPULATION: Study team used qualitative (interviews, focus groups, listening sessions, learning management system, participatory-design research) and quantitative (surveys) data collection methods in the development and ongoing implementation of the learning community. Study Population: Based on initial assessment of health and social vulnerability data within the Marion County neighborhoods in Indianapolis, community ambassador engaged congregations in more vulnerable neighborhoods to seek participation in learning community. Ten congregations signed a covenant of participation; learning community includes 10 clergy and 8 health advocates. RESULTS/ANTICIPATED RESULTS: Since the inception of the Learning Community in May 2020, we have developed a better understanding of the assets and barriers of LC participants around health and well-being. Through ongoing virtual gatherings (facilitated by community ambassador Good to the Soul), sharing of resources through our online modules on Canvas (LMS), and synthesis of data captured throughout our time together, LC participants have developed SMART goals which will inform priority setting for congregations to assist them in identifying the resources and connections necessary to drive forward solutions together as they seek out funding opportunities to support health improvement. DISCUSSION/SIGNIFICANCE OF FINDINGS: The learning community has provided a space and structure for congregations to align around a shared goal focused on health and wellness. Through regular gatherings we were able to connect people, organizations, and systems who were all eager to learn and work across boundaries leading to greater resilience in vulnerable communities.

‘Dementia-friendly communities’ herald a shift toward the neighbourhood as a locus for the care and support of people with dementia, sparking growing interest in the geographies of dementia care and raising questions over the shifting spatial and social experience of the condition. Existing research claims that many people with dementia experience a ‘shrinking world’ whereby the boundaries to their social and physical worlds gradually constrict over time, leading to a loss of control and independence. This paper reports a five-year, international study that investigated the neighbourhood experience of people with dementia and those who care for and support them. We interrogate the notion of a shrinking world and in so doing highlight an absence of attention paid to the agency and actions of people with dementia themselves. The paper draws together a socio-relational and embodied-material approach to question the adequacy of the shrinking world concept as an explanatory framework and to challenge reliance within policy and practice upon notions of place as fixed or stable. We argue instead for the importance of foregrounding ‘lived place’ and attending to social practices and the networks in which such practices evolve. Our findings have implications for policy and practice, emphasising the need to bolster the agency of people living with dementia as a route to fostering accessible and inclusive neighbourhoods.