bluuebunny/crossref_metadata_2025 huggingface dataset:
79664 Complement Driven Auto-Reactive Antibodies in Lung Transplantation
Authors: McQuiston Alexander , Li Changhai , Patel Kunal , Tu Zhenxiao , Nord Dianna , Nadig Satish , Tomlinson Stephen , Atkinson Carl
Published: March 2021

ABSTRACT IMPACT: Our work unveils a novel mechanism of ischemia repurfusion injury driven by pre-existing autoimmunity following lung transplant and a potential therapeutic strategy for blocking complement-dependent injury thereby reducing risk of lung transplant rejection. OBJECTIVES/GOALS: Our goal was to determine if pre-existing autoimmune autoantibodies, such as those resulting from cigarette smoke (CS), contribute to graft rejection in lung transplantation (LTx) and if autoreactive-mediated graft injury is complement-dependent. METHODS/STUDY POPULATION: For in vivo experiments, we utilized our emphysema mouse model. Briefly, eight-week-old C57BL/6J mice are exposed to 3R4F reference cigarette smoke 5 hours per day, 5 days a week for 6 months. Upon completion, cigarette smoked (CS) mice and control (NS) mice received syngeneic orthotopic left-lung transplant from age-matched C57BL/6J donors. To determine if pre-existing autoreactivity mediated graft injury was complement-dependent we treated CS-LTx mice with a novel, bifunctional complement inhibitor. Autoantibody levels were measured by ELISA and lung injury was assessed by blinded histopathological analyses. Complement inhibition was verified by immunofluorescence. RESULTS/ANTICIPATED RESULTS: We found that CS-exposure leads to production of autoreactive antibodies towards extracellular matrix (ECM) components and contributes to graft injury. Interestingly, LTx into CS exposed mice further increased de-novo ECM autoantibody development. Lastly, treatment with our novel, bifunctional complement inhibitor blocked autoantibody spreading and significantly reduced graft rejection. DISCUSSION/SIGNIFICANCE OF FINDINGS: These data demonstrate that smoking induces pre-LTx autoreactivity to ECM proteins that promotes graft injury following LTx. Furthermore, complement inhibition reduces autoantibody production and protects the graft from injury.
16886 Moyamoya-Like Vasculopathies Observed In a Novel Mouse Surgical Model
Authors: Fraser Justin F. , Whitnel Laura , Roberts Jill
Published: March 2021

ABSTRACT IMPACT: Development of our animal model of moyamoya will provide a meaningful assessment of therapeutic efficacy of interventions applicable to the clinical setting. OBJECTIVES/GOALS: Moyamoya is a cerebrovascular condition with progressive stenosis of the internal carotid arteries (ICA) and formation of abnormal vascular collaterals at the base of the brain, all of which result in ischemic and hemorrhagic strokes. We aim to develop a needed animal model of this condition in order to develop new therapeutics. METHODS/STUDY POPULATION: Male and female C57Bl/6J mice (4 months old) underwent surgery for the unilateral placement of a microcoil (0.16 mm ID) onto the proximal ICA or sham control. After 30 and 60 days (N = 6-8/time point), the brain blood vessels were examined for changes in diameter, number of anastomoses, and development of new collaterals using DiI stain. Brain tissue was examined for micro-hemorrhages using Prussian blue stain, and cross-sections of blood vessels were examined for intimal thickening using H&E and smooth muscle actin. Expression of vascular endothelial growth factor (VEGF), which is associated with angiogenesis and moyamoya syndrome, was quantified by qPCR. Blood samples were also analyzed for inflammatory biomarkers using ELISA. RESULTS/ANTICIPATED RESULTS: Within 30 days, the distal ICA and anterior cerebral artery (ACA) had significantly decreased diameters at the Circle of Willis, with an initial decrease in the number of cortical anastomoses. Histology demonstrated smaller lumen diameter and alterations to in the various layers of the blood vessels, indicating intimal thickening and stenosis of the affected blood vessels. There was also a significant increase in the number of intracranial micro-bleeds, suggesting a compromised vascular integrity. This may be due, in part, to a significant upregulation in VEGF gene expression within the striatum, a region of hemorrhagic occurrence in moyamoya patients. DISCUSSION/SIGNIFICANCE OF FINDINGS: We report the development of an animal model with vasculopathies that mimic those observed in patients with moyamoya syndrome. With further characterization, this animal model will have a positive impact as a meaningful assessment of therapeutic efficacy of interventions applicable to the clinical setting.
38227 Specific and highly potent human monoclonal antibodies against SARS-CoV-2
Authors: de Mattos Barbosa Mayara Garcia , Liu Hui , Huynh Daniel , Platt Jeffrey L. , Cascalho Marilia
Published: March 2021

ABSTRACT IMPACT: We devised a new method to produce highly potent SARS-CoV2-specific that can be used to treat severely ill patients with Covid-19. OBJECTIVES/GOALS: Neutralizing antibodies against SARS-CoV-2 are thought to offer the most immediate and effective treatment for those severely afflicted by Covid-19. We devised an approach for rapid and efficient generation of human monoclonal antibodies with neutralizing activity against SARS-CoV-2. METHODS/STUDY POPULATION: SARS-CoV-2 S1 spike protein-specific memory B cells were isolated from 12 subjects recovering from infection with that virus. Paired end single index sequencing was performed using up to 10,000 antigen-specific B cells per subject. Antigen-specific B cell clones were identified by unique diversity and joining gene V(D)J rearrangements and the CDR3 regions. VH and VL regions were cloned and the products expressed in 293T/17 cells to generate spike-specific human monoclonal antibodies. RESULTS/ANTICIPATED RESULTS: Forty-three human monoclonal antibodies were produced. Every monoclonal antibody so generated neutralized viruses pseudotyped with Spike protein of the Wuhan-1 strain. Eighteen monoclonal antibodies neutralized pseudotyped viruses with half-maximal inhibitory concentration (IC50s) between 1 pg/mL and 1 ng/mL (6.7 x 10E-15 M to 6.7 x 10E-12 M), exceeding by 10-100-fold the potency of previously reported anti-SARS-CoV-2-neutralizing monoclonal antibodies. Eight monoclonal antibodies neutralized viruses pseudotyped with mutant spike proteins previously identified in clinical isolates, including receptor binding domain mutants and the C-terminal D614G mutant with IC50<6.7 x10E-12M. DISCUSSION/SIGNIFICANCE OF FINDINGS: We show that SARS-CoV-2 evokes high affinity B cell responses. Some B cells produce antibodies that are broadly neutralizing; others produce strain-specific antibodies. However, antigenic variants that would potentially escape control by immunity or vaccination were nonetheless identified.
67553 Exoskeleton dynamics alter upper-limb coordination in a virtual reality reaching task
Authors: Brunfeldt Alexander , Dromerick Alexander , Bregman Barbara , Lum Peter
Published: March 2021

ABSTRACT IMPACT: This proof-of-concept study demonstrates that systematically altering limb dynamics with two exoskeleton devices alters ingrained, bilateral upper-limb coordination with the potential to rehabilitate functional reaching in chronic stroke survivors OBJECTIVES/GOALS: Advances in virtual reality and exoskeleton technologies have allowed researchers to alter upper limb coordination with more precision than ever before. The goal of this study was to systematically enhance the use of the nondominant limb during a bimanual reaching task, with an eye towards improving rehabilitative strategies post stroke. METHODS/STUDY POPULATION: Healthy, right-handed volunteers performed a bimanual reaching task in virtual reality (VR) space while simultaneously moving under the influence of two exoskeleton devices. The VR task had participants move a shared cursor, displayed at the midpoint between the hands, to targets arranged at shoulder and eye levels and located at 70% of full arm extension. Two exoskeleton devices applied either resistive torque to the dominant limb or assistive torque to the non-dominant limb. Three-dimensional hand position data were recorded at 50 Hz and analyzed offline. The primary outcome measure was relative contribution, calculated as the ratio of dominant/non-dominant displacement. RESULTS/ANTICIPATED RESULTS: Preliminary results from 3 participants showed that during baseline trials, when no torque was applied by the exoskeletons, relative contribution was 50.6% in favor of the dominant hand, with the dominant hand reaching on average 1.1cm farther than the left. When the exoskeletons resisted movement in the dominant limb while simultaneously assisting movement in the non-dominant limb, relative contribution was 49.7% indicating an increase in non-dominant limb usage. Further analysis showed that this effect was driven by one participant who reached 3.7cm farther with her non-dominant hand compared to baseline. DISCUSSION/SIGNIFICANCE OF FINDINGS: These pilot data suggest our testing platform is capable of altering normal coordination patterns and is likely the result of participants adopting an optimal control strategy imposed by the shared cursor. These findings will form the basis for a rehabilitation intervention to promote the use of the paretic limb in chronic stroke survivors.
68415 Neural Impact of Neighborhood Disadvantage in Traumatically-Injured Adults: a Multi-Modal Investigation
Authors: Webb E. Kate , Weis Carissa , Bennett Ken , Huggins Ashley , Parisi Elizabeth , Krukowski Jessica , deRoon-Cassini Terri , Larson Christine
Published: March 2021

ABSTRACT IMPACT: Neighborhood disadvantage was significantly associated with brain structure and function in trauma-exposed adults, providing evidence that contextual factors should be assessed in mental health research, particularly in high-risk populations. OBJECTIVES/GOALS: Over 13 percent of Americans live in a socioeconomically disadvantaged neighborhood. Previous work has linked lower individual socioeconomic position to alterations in brain structure and function. However, the neural effects of area-level socioeconomic factors, such as neighborhood disadvantage, are unclear. METHODS/STUDY POPULATION: We recruited two-hundred and fifteen traumatically-injured participants from an Emergency Department in southeastern Wisconsin. An Area Deprivation Index (ADI) score, a national measure of neighborhood socioeconomic disadvantage, was derived from each participant’s home address. Two-weeks post-trauma, participants underwent a battery of self-report measures and functional magnetic resonance imaging (fMRI) scans. Using a multi-modal approach, we investigated the impact of ADI on brain structure as well as neural activation during rest and during an emotional uncertainty task. We sought to disentangle the relationship between neighborhood and individual socioeconomic position and neural activity in the context of trauma. RESULTS/ANTICIPATED RESULTS: We demonstrated that neighborhood disadvantage is associated with decreased volume and alterations of resting state functional connectivity of structures implicated in affect processing, including the hippocampus, amygdala, and ventromedial prefrontal cortex. These results held even after controlling for relevant individual variables, including acute post-traumatic stress symptoms and years of education. Moreover, individuals from disadvantaged neighborhoods exhibited heighted activation of these same structures in response to aversive stimuli. Thus, brain regions critical for recognizing and processing negative stimuli are susceptible to the effects of area-level socioeconomic factors. DISCUSSION/SIGNIFICANCE OF FINDINGS: The results offer additional evidence that neurobiological mechanisms clarify how stress ‘gets under the skin’. Changes to key brain regions may explain why those living in disadvantaged neighborhoods are at a heighted risk of PTSD. Broadly, these findings should inform future policies and community-driven interventions aimed at reducing poverty.
77822 PSD95-nNOS interaction alters the basolateral amygdala transcriptome following fear conditioning: implications for molecular mechanisms underlying PTSD
Authors: Patel Jheel , Haulcomb Melissa , Li Liangping , Jiang Guanglong , Dustrude Erik , Liu Yunlong , Lai Yvonne , Molosh Andrei , Shekhar Anantha
Published: March 2021

ABSTRACT IMPACT: This research takes a transcriptomic approach to parse genes and molecular pathways that underlie the fear memory circuitry and, in doing so, identifies therapeutic targets that can further be developed into treatments for fear disorders, such as post-traumatic stress disorder. OBJECTIVES/GOALS: Normal fear learning produces avoidance behavior that promotes survival, but excessive and persistent fear after trauma can lead to development of phobias and post-traumatic stress disorder (PTSD). Our goal is to understand the mechanism and identify novel genetic targets underlying fear responses. METHODS/STUDY POPULATION: Involvement of the basolateral amygdala (BLA) in fear acquisition is well established and requires activation of N-methyl-D-aspartic acid receptors (NMDARs). At a cellular level, NMDAR activation leads to production of nitric oxide (NO) by a process mediated by interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS). To elucidate mechanisms underlying the role of the PSD95-nNOS-NO pathway in conditioned fear, here we use rodent behavioral paradigms, pharmacological treatment with a small molecule PSD95-nNOS inhibitor, RNA-sequencing, and an AAV-mediated knockdown of the nNOS gene in the BLA. RESULTS/ANTICIPATED RESULTS: We show that treatment with ZL006 attenuates rodent cued-fear consolidation. Additionally, with RNA-sequencing, expression of 516 genes was altered in the BLA following fear expression; of these genes, 83 were restored with systemic ZL006 treatment. Network data and gene ontology enrichment analyses further revealed that cGMP effects, insulin-like growth factor binding, and cognition-related pathways were significantly altered. Finally, we show that a BLA-specific knockdown of nNOS attenuates cued fear consolidation, without adverse effects on other memory and motor behaviors. DISCUSSION/SIGNIFICANCE OF FINDINGS: Via a model of NMDAR-mediated fear consolidation, our results reveal novel pathways and genetic targets that underlie plasticity of fear memory circuitry. Importantly, these results will inform future therapeutic strategies for targeting fear related disorders like PTSD.
96101 Temporal Evolution of Neural Activity in Human Brain Organoids
Authors: Mensah-Brown Kobina G. , Lim James , Jgamadze Dennis , Ming Guo-li , Song Hongjun , Wolf John A. , Chen Han-Chiao I.
Published: March 2021

ABSTRACT IMPACT: This study will provide the essential characterization of intrinsic neural activity in human brain organoids, both at the single cell and network levels, to harness for translational purposes. OBJECTIVES/GOALS: Brain organoids are 3D, stem cell-derived neural tissues that recapitulate neurodevelopment. However, to levy their full translational potential, a deeper understanding of their intrinsic neural activity is essential. Here, we present our preliminary analysis of maturing neural activity in human forebrain organoids. METHODS/STUDY POPULATION: Forebrain organoids were generated from human iPSC lines derived from healthy volunteers. Linear microelectrode probes were employed to record spontaneous electrical activity from day 77, 100, and 130 organoids. Single unit recordings were collected during hour-long recordings, involving baseline recordings followed by glutamatergic blockade. Subsequently, tetrodotoxin, was used to abolish action potential firing. Single units were identified via spike sorting, and the spatiotemporal evolution of baseline neural properties and network dynamics was characterized. RESULTS/ANTICIPATED RESULTS: Nine organoids were recorded successfully (n=3 per timepoint). A significant difference in number of units was seen across age groups (F (2,6) = 6.4178, p = 0.0323). Post hoc comparisons by the Tukey HSD test showed significantly more units in day 130 (51.67 ±14.15) than day 77 (16.33 ±14.98) organoids. Mean firing rates were significantly different in organoids based on age, with drug condition also trending toward significance (F (6,12) = 9.97; p = 0.0028 and p = 0.08 respectively). Post hoc comparisons showed a higher baseline firing rate in day 130 (0.99Hz ±0.30) organoids than their day 77 counterparts at baseline (0.31Hz ±0.066) and glutamate blockade (0.31Hz ±0.045). Preliminary network analysis showed no modularity or small-world features; however, these features are expected to emerge as organoids mature. DISCUSSION/SIGNIFICANCE OF FINDINGS: Initial analysis of brain organoid activity demonstrates changes in single unit properties as they mature. Additional work in this area, as well as further network analyses, will confer better sense of how to rationally utilize brain organoids for translational purposes.
60941 Vaginal pH predicts cervical intraepithelial neoplasia-2 regression in women living with human immunodeficiency virus
Authors: Michel Katherine , Colie Christine , Burk Robert D. , Massad L. Stewart , Wang Cuiwei , Hebron Michaeline , Moussa Charbel , D’Souza Gypsyamber , Rahangdale Lisa , Flowers Lisa , Milam Joel , Palefsky Joel M. , Minkoff Howard , Strickler Howard D. , Kassaye Seble G.
Published: March 2021

ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.
91726 Screening for Obesity related renal damage in adolescent women - Body Surface area matters
Authors: Bielopolski D. , Singh N. , Bentur O.S. , Renert-Yuval Y. , MacArthur R. , Vasquez K. , Moftah D.S. , Vaughan R.D. , Kost R.G. , Tobin J.N.
Published: March 2021

ABSTRACT IMPACT: This change will improve primary care physicians and pediatrics ability to identify, intervene and prevent obesity related renal damage in the vulnerable population of young adults OBJECTIVES/GOALS: Obesity related glomerulopathy has a reversible stage manifested as hyperfiltration. Early intervention depends on the ability to identify hyperfiltration. Hyperfiltration prevalence is underestimated using the currently recommended formula We investigated whether calculating BSA-adjusted GFR will more readily identify hyperfiltration. METHODS/STUDY POPULATION: We extracted data from a large urban, multi-institutional Electronic Health Records (EHR) clinical data research network to construct an EHR data base of 60,549 women and girls ages 12-21 years from the New York metropolitan area. EGFR was calculated in two ways, 1) according to age appropriate formula, and 2) according to age appropriate formula and adjusted to body surface area (BSA). BMI-for-age values were classified according to the World Health Organization schema and grouped according to the CDC definitions. BSA was calculated according to the Du-Bois formula. Hyperfiltration was defined by a threshold of 135ml/min. The Bland Altman method assessed the agreement between formulas across the different BMI groups. RESULTS/ANTICIPATED RESULTS: Serum creatinine values were similar across different BMI groups. Comparing eGFR values, hyperfiltration rates were similar across BMI groups, ranging between 4%-6.6%. BSA-adjusted GFR was different across BMI groups: hyperfiltration rates were 0.81% for the underweight group, 2.56% for the normal weight, 12.18% for the overweight and 39% in the obese group. This trend of hyperfiltration paralleled the the rise in urine creatinine across BMI groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: BSA-adjusted GFR more sensitively detects hyperfiltration due to obesity than does eGFR. Calculating BSA-adjusted GFR will improve primary care and pediatric physicians’ ability to identify, intervene and prevent early ORG. Changes in body composition may account for the increasing discordance between BSA-adjusted and eGFR as BMI rises.
10351 Antibiotic Use for Respiratory Syncytial Virus in the Middle East: A Surveillance Study in Hospitalized Jordanian Children
Authors: Rankin Danielle A. , Khankari Nikhil K. , Haddadin Zaid , Hamdan Olla , Faouri Samir , Shehabi Asem , Williams John V. , Khuri-Bulos Najwa , Halasa Natasha B.
Published: March 2021

ABSTRACT IMPACT: Antibiotic stewardship guidelines should consider the barriers clinicians in low- and middle-income countries face due to limited biomarkers for determining the etiologic pathogen for viral infections like respiratory syncytial virus (RSV) that have a similar presentation to bacterial infections. OBJECTIVES/GOALS: We aimed to evaluate antibiotic administration practices in children who were hospitalized at a government-run hospital in Amman, Jordan, where point-of-care testing is limited. We hypothesized those with RSV are more likely to be administered antibiotics during their hospitalization than children without RSV. METHODS/STUDY POPULATION: We conducted a cross-sectional cohort study in Jordanian children hospitalized with history of acute respiratory symptoms and/or fever from 2010 to 2013. Admitting diagnoses were dichotomized into suspected viral- (e.g., bronchiolitis) and bacterial-like infection (e.g., sepsis, pneumonia). Stratifying by sex, we performed a polytomous logistic regression adjusting for age, underlying medical condition, maternal education, and region of residence to estimate prevalence odds ratios (PORs) and 95% confidence intervals for macrolides, broad-, and narrow-spectrum antibiotics during hospitalization. Sensitivity and specificity of admission diagnoses and laboratory results were compared. RESULTS/ANTICIPATED RESULTS: Children with a suspected viral-like admission diagnosis, compared to those with suspected bacterial-like, were 89% less likely to be administered a narrow-spectrum antibiotic (POR: 0.11; p<0.001). There were slight differences by sex with males having a lower prevalence than females of narrow-spectrum or broad-spectrum antibiotic administration; but they had a higher prevalence of macrolide administration. Overall, children with RSV had a 30% probability (sensitivity) of being assigned to a suspected viral infection; whereas RSV-negative children had an 85% probability (specificity) of being assigned to a suspected bacterial infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: Children with a suspected viral-like infection were less likely to receive an antibiotic; however, when evaluating the accuracy of admission diagnosis to RSV-laboratory results there were considerable misclassifications. These results highlight the need for developing antibiotic interventions for Jordan and the rest of the Middle East.
61586 Impact of Diabetes and Pre-diabetes on Prevalence of Infection with Mycobacterium tuberculosis among Household Contacts of Active Tuberculosis Cases in Ethiopia
Authors: Smith Alison G.C.S. , Kempker Russell R. , Wassie Liya , Bobosha Kidist , Nizam Azhar , Gandhi Neel , Magee Matthew J. , Blumberg Henry M.
Published: March 2021

ABSTRACT IMPACT: This work examines the association between diabetes mellitus and latent tuberculosis infection among a cohort of household contacts exposed to active tuberculosis in Ethiopia, focusing attention on the need for further translational research to determine the mechanisms of susceptibility to Mycobacterium tuberculosis infection among individuals with diabetes and pre-diabetes. OBJECTIVES/GOALS: Diabetes mellitus (DM) is an established risk factor for active TB disease, but there is limited understanding of the relationship of DM and latent tuberculosis (LTBI). We sought to determine the relationship between DM or pre-DM with LTBI among household or close contacts (HHCs) of active TB cases in Ethiopia. METHODS/STUDY POPULATION: We conducted a cross-sectional study of the HHCs of index active TB cases enrolled in an ongoing TB Research Unit (TBRU) study in Addis Ababa, Ethiopia. HHCs of individuals with laboratory-confirmed TB had QuantiFERON ®-TB Gold Plus (QFT) and glycated hemoglobin (HbA1c) tests performed. LTBI was defined as a positive QFT and lack of symptoms. HbA1C results were used to define no DM (HbA1c <5.7), pre-DM (HbA1c 5.7-6.5%), and DM (HbA1c >6.5% or prior history of diabetes). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) after adjustment for age, sex and HIV status as potential confounders. RESULTS/ANTICIPATED RESULTS: Among 466 HHCs, the median age was 29 years (IQR 23-38), 58.8% were female, 3.4% were HIV-positive, and median BMI was 20.9 kg/m^2 (IQR 18.9-23.8). Overall, 329 HHCs (70.6%) had LTBI, 26 (5.6%) had DM and 73 (15.7%) had pre-DM. Compared to HHC without DM, the prevalence of LTBI was higher in those with pre-DM (68.9% vs. 72.6%; OR 1.19, 95% CI 0.69-2.13) and those with DM (88.5%; OR 3.45, 95% CI 1.17-14.77). In multivariable analysis, there was a trend towards increased LTBI risk among HHCs with DM vs. without DM (OR 2.16, 95% CI 0.67-9.70) but the difference was not statistically significant. Among HHCs with LTBI, the median IFN-? response to TB1 antigen was modestly greater in those with DM (5.3 IU/mL; IQR 3.0-7.8) and pre-DM (5.4 IU/mL; IQR 2.0-8.4) compared to HHCs without DM (4.3 IU/mL; IQR 1.4-7.7). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results suggest that DM may increase the risk of LTBI among HHCs recently exposed to active TB. Among those with LTBI, increased IFN-? antigen response in the presence of DM and pre-DM may indicate an exaggerated but ineffectual response to TB. Further investigation is needed to assess how dysglycemia impacts susceptibility to M. tuberculosis.
75561 Association of childhood hypertension with early adulthood obesity and hypertension
Authors: Pike Mindy , Ikizler T. Alp , Lipworth Loren , Robinson-Cohen Cassianne
Published: March 2021

ABSTRACT IMPACT: This study establishes the association between childhood hypertension and health outcomes in early adulthood, identifying the need to understand blood pressure during early life for primary prevention of hypertension and cardiovascular disease. OBJECTIVES/GOALS: There is evidence that blood pressure level in early life can influence hypertension and other cardiovascular risk factors later in life. We examined whether hypertension before the age of 18 is associated with higher odds of obesity and hypertension after the age of 18. METHODS/STUDY POPULATION: We studied 19,367 children and adolescents from the Vanderbilt University Medical Center’s Synthetic Derivative, a de-identified version of the electronic medical record. Childhood hypertension was defined as systolic blood pressure (SBP) ≥130 mmHg or diastolic blood pressure (DBP) ≥80 mmHg at three or more outpatient visits before the age of 18. Obesity and hypertension in early adulthood were the primary outcomes. Obesity was defined as being above normal weight for adulthood height at age 30 based on the NIH’s body mass index tables. Hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg at three or more outpatient visits after the age of 18. Odds ratios and 95% confidence intervals (CIs) were computed from logistic regression models adjusted for demographics, medication use, and childhood weight. RESULTS/ANTICIPATED RESULTS: Most subjects were female (63%) and white (80%). During childhood, 17% of participants had hypertension. Approximately 58% of this group were obese at age 30, and 38% had hypertension as adults. Compared to females with no childhood hypertension, females with childhood hypertension had 1.35 times higher odds of being obese at age 30 (95% CI: 1.15, 1.58) and 3.56 times higher odds of having hypertension over the age of 18 (95% CI: 3.09, 4.09). Males with childhood hypertension, compared to males without, had 1.28 times higher odds of being obese at age 30 (95% CI: 1.08, 1.52) and 2.74 times higher odds of having hypertension over the age of 18 (95% CI: 2.35, 3.20). Associations between childhood hypertension, early adulthood obesity, and hypertension significantly differed by gender (p-for-interaction for both: <0.01). DISCUSSION/SIGNIFICANCE OF FINDINGS: Childhood hypertension is associated with obesity and hypertension in early adulthood. Understanding blood pressure levels in childhood and adolescence may help target efforts to reduce early adulthood cardiovascular risk factors.
84617 Prevalence and Co-prevalence of Comorbidities among Patients with Type 2 Diabetes Mellitus living in Puerto Rico, USA
Authors: Garcia-Rivera Enid , Ruiz Krystel , Miranda Edgar , Mejã Luis , Marques Cecile , Quijada José , Monsanto Homero , Orengo Juan , Pinzón Adolfo
Published: March 2021

ABSTRACT IMPACT: Summarize the burden of diabetes comorbidities and its impact in healthcare utilization in Puerto Rico OBJECTIVES/GOALS: To estimate the prevalence of common comorbidities and describe the healthcare utilization patterns in patients with type 2 diabetes mellitus (T2DM) in Puerto Rico. METHODS/STUDY POPULATION: This is a descriptive study using healthcare claims data from patients with T2DM (based on ICD-9 diagnosis code) from most public and private healthcare insurance companies providing services in Puerto Rico in 2013 (representing more than 90% of insured population). Descriptive analyses by age, sex, type of insurance, health region, and type of medical encounter were done using frequency and percent for categorical data or means or median (with corresponding standard deviation or interquartile range) for continuous variables RESULTS/ANTICIPATED RESULTS: A total of 3,100,636 claims were identified from 485,866 adult patients with T2DM. Most patients were women (276,400; 57%), older than 65 years (235,390; 48%), from the Puerto Rico health regions of Caguas (79,604; 16%), Metro (66,280; 14%), or Bayamon (62,673; 13%) with private health insurance (371,806; 77%). The number of claims per patient ranged from 1 to 339. A mean of 6.3 claims (SD ±9.99) and a median of 3 claims (Q1 1- Q3 8) per subject were identified. Most (74%) were related to the diagnosis of diabetes (1,829,2015; 59%) or to cardiovascular diseases (458,219; 15%) and associated to outpatient services (2,722,727; 88%). The most prevalent comorbidities were hypertension (235,277; 48%), hyperlipidemia (197,449; 41%), neuropathy (100,471; 21%); renal disease (71,517; 15%), and retinopathy (61,837; 13%) DISCUSSION/SIGNIFICANCE OF FINDINGS: A high prevalence of comorbidities and use of healthcare services were identified in patients with T2DM, especially in older adults. Most comorbidities were due to diabetes-related conditions, highlighting the importance of early diagnosis and adequate management of T2DM patients to avoid preventable burden to the patient and the healthcare system
86808 Adverse Childhood Experiences are associated with a higher prevalence of asthma among adolescents with sickle cell disease
Authors: Pernell Brandi , Nagalapuram Vishnu , Lin Chee Paul
Published: March 2021

ABSTRACT IMPACT: This research highlights Adverse Childhood Experiences as a potential risk factor and intervention target contributing to the disproportionate number of individuals with sickle cell disease affected by asthma, a well-established catalyst to the increased morbidity and mortality impacting this high-risk population. OBJECTIVES/GOALS: Adverse Childhood Experiences (ACEs) are strongly associated with asthma. A disproportionate number of individuals with sickle cell disease (SCD) also have asthma. Asthma is strongly associated with increased SCD morbidity and mortality. This study compared the prevalence of asthma among children and adolescents with SCD with and without ACEs. METHODS/STUDY POPULATION: This retrospective cohort study involved 45 children and 30 adolescents with SCD. ACEs were captured using the Center for Youth Wellness Adverse Childhood Experiences Child and Teen Questionnaires, which encompass the original 10 ACEs as well as 7 (child) and 9 (teen) expert-recommended ('expanded') ACEs. ACE exposures were categorized as: Original 0-1 vs. ≥2; Original + Expanded 0-1 vs. ≥2. Asthma prevalence was compared among ≥2 and 0-1 ACE groups using the chi-square (or Fisher’s exact) test. A binary logistic regression was performed to predict the likelihood of asthma while adjusting for characteristics (age, household income and gender) that were statistically different among ACE comparison groups at baseline. RESULTS/ANTICIPATED RESULTS: Among the 45 child participants, 64% had a history of asthma; whereas 50% of teens had a history of asthma. Asthma prevalence was higher among teens with ≥2 vs. 0-1 Original ACEs (89% v. 33%, p=0.014). A history of ≥2 ACEs remained significant (p=0.024) among teens after adjusting for age, household income and gender. There was no significance in asthma prevalence among child ACE comparison groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adolescents with ≥2 ACEs had a higher prevalence of asthma compared to subjects with 0-1 ACE. This study, coupled with the cumulative nature of ACEs and the graded-dose response relationship between ACEs and poor health outcomes, highlight the need for larger, longitudinal studies examining the relationship between ACEs, asthma and SCD outcomes.
70400 Collaborative Care for Opioid Dependence And Pain (CCODAP): A Pilot Randomized Control Trial of an Opioid Tapering Intervention
Authors: Bushey Michael , Kroenke Kurt
Published: March 2021

ABSTRACT IMPACT: If successful, this program can provide a scalable, patient-centered intervention to help patients taper off opioid medications in primary care settings. OBJECTIVES/GOALS: Tapering of chronic opioid therapy is often desirable but challenging in primary care and specialty clinics that lack behavioral health expertise. The objective of this pilot study is to determine the feasibility of testing a peer-delivered pain self-management program to assist primary care patients through an opioid taper. METHODS/STUDY POPULATION: To provide critical support to patients and providers during opioid medication tapering, we propose to conduct a 40 patient randomized controlled pilot of a 12-week telecare collaborative care program administered by a psychiatrist and peer recovery specialist team. The intervention will incorporate a validated positive psychology intervention for treating chronic pain. Additionally, participants will be invited to participate in semi-structured individual interviews to discuss their experience in the trial, what worked well, what could be improved, and potential strategies to bolster recruitment of additional patients in future studies. RESULTS/ANTICIPATED RESULTS: Our primary aim is to determine the effectiveness of our intervention in facilitating opioid medication weaning, with reduction in opioid dose as the primary outcome. Our secondary aims will be to assess pain outcomes, adherence to tapering, patient satisfaction, and barriers to adherence as described by patients. DISCUSSION/SIGNIFICANCE OF FINDINGS: This trial proposes a novel collaborative care approach for opioid weaning using proven, easy-to-deliver positive psychology tools for pain management that, if successful, could be implemented broadly in many clinics struggling to safely reduce opioid prescribing.
21968 Adapting a global telehealth model to solve U.S. healthcare needs: age-related hearing loss as a test market
Authors: Weinreb Samuel , Samuel Izabella , Zhang Kai , Hall Mackenzie , Bendavit Mariana , Archer Adler , Verma Neha
Published: March 2021

ABSTRACT IMPACT: We are adapting a global telehealth platform and model of care to the U.S. context in order to solve the problem of undertreatment of age-related hearing loss and, in turn, facilitate healthy aging and social engagement among older adults. OBJECTIVES/GOALS: Intelehealth is a nonprofit startup that provides medical care to last-mile populations in India by equipping frontline health workers with an open-source digital assistant and telemedicine platform. Here, we explore how this technology and model of care might be adapted to address health inequities in the context of the U.S. healthcare system. METHODS/STUDY POPULATION: We first sought to identify a specific healthcare need that we could address as a case study on applying the Intelehealth model more broadly in the U.S. context. We began with a needs assessment, wherein we conducted primary ethnographic research, expert interviews, and literature review to identify problems in the general areas of health disparities, community health workers, and telemedicine accessibility. We then scored each need on clinical impact, feasibility, business potential, and strategic fit. After a top need was selected, a root cause analysis was performed. Brainstorming and solution concepting will be followed by prototyping, iterative design with primary stakeholder feedback, usability testing, and finally implementation and validation of the solution. RESULTS/ANTICIPATED RESULTS: Of 106 needs, the most highly scored was undertreatment of age-related hearing loss (ARHL). The third most common chronic condition in the U.S., ARHL presents a significant barrier to healthy aging and the single largest modifiable risk factor for dementia; yet only 15% of those with ARHL regularly use hearing aids. Thus, a large market segment - nearly 30 million Americans - is underserved by the current hearing care paradigm. Root cause analysis revealed that the primary reasons for hearing aid non-use include stigma around aging, denial of hearing loss, poor awareness of resources, and insufficient education around proper use and maintenance. These barriers, being primarily sociocultural in nature, may be optimally addressed by community health workers, making ARHL an ideal fit for the Intelehealth model. DISCUSSION/SIGNIFICANCE OF FINDINGS: We have identified ARHL as an optimal test market for Intelehealth in the U.S. By developing a targeted intervention to improve hearing aid access and acceptability among older adults, we will create a generalizable model for delivering care through community health workers equipped with a decision support and telemedicine platform.
55256 ReacStick: From Conception to Commercialization
Authors: Bernard Alec , Richarson Ian , Richardson James
Published: March 2021

ABSTRACT IMPACT: ReacStick concussion testing and monitoring can serve as a 'vital sign for the brain', allowing for an immediate, objective assessment on the field or at the bedside. This project examines the entrepreneuship process from invention to commercialization. OBJECTIVES/GOALS: ReacStick is the first objective, portable, measure of concussion likelihood and severity and uses simple and complex reaction time testing. We detail the entrepreneurship process from product invention through its current mid-stage (patented, 20+ publications, etc.) to future commercialization for diverse applications. METHODS/STUDY POPULATION: ReacStick was invented in 2010 and underwent extensive testing and validation of the underlying innovations. The regulatory landscape of the product was examined, and 510(k) was found to be the best pathway. Competitive analysis was done examining alternative products and comparing against the current gold standards. A customer discovery process was undertaken, and stakeholders were interviewed for feedback and iteration. Testing and validation were completed with athletes, older adults, and people taking medications. An overview of the necessary commercialization concepts is: market opportunity/monetization, intellectual property considerations, regulatory processes, commercialization plan. RESULTS/ANTICIPATED RESULTS: ReacStick accurately predicts concussion and time to recovery and was patented through UM Tech Transfer in 2010, with 10 years currently remaining on the patent. Through customer discovery processes, athletics was determined to be the most viable first market to enter. Next steps include seeking additional patent protection, capital investors, delivery of minimum viable product followed by iteration and improvement for military, emergency medicine and acute care use. The current remaining timeline involves 12-18 months to commercialization and includes regulatory approval, additional patent protection, collaboration with regulatory consultants, capital fundraising and product production. DISCUSSION/SIGNIFICANCE OF FINDINGS: The research team has gone through a lengthy process toward commercialization of ReacStick. Proof of concept and extensive validation of the underlying technology have been completed and the regulatory process has been mapped. Our experience can serve as a model of many of the steps and challenges that lie on the path from lab to sale to end users.
00002 Translational Fellows as a mechanism to improve throughput of university technology commercialization
Authors: Hall Everett G. , Krenning Tom M. , Kinch Michael S.
Published: March 2021

ABSTRACT IMPACT: This work aims to identify best practices for university-based asset development programs to improve commercialization throughput, which in turn will drive innovation in the biomedical space and directly contribute to improved human health. OBJECTIVES/GOALS: University technology transfer exhibits a high rate of failure, often due to a lack of researcher experience or early-stage financial capital. The LEAP program at Washington University (WUSTL) was created to address these needs. The goal of this study is to assess the performance of LEAP against similar gap funds and further improve program operations. METHODS/STUDY POPULATION: The goals of LEAP are achieved by providing university inventors with individualized consulting and feedback from industry experts, as well as awarding funding to the most promising projects. To determine whether these activities are impactful, we distributed an awardee report form to collect data on all funded LEAP projects, and then combined the results with project registration information. We also collected records Office of Technology Management, including invention disclosures, licenses, and startup creations. The resulting dataset was used to calculate program metrics and then evaluated against comparable gap funds. Sentiment data from participant surveys were also analyzed to assess perceived program value and knowledge transfer. RESULTS/ANTICIPATED RESULTS: As of the Sp2020 cycle, LEAP has funded 76 projects. Resubmitted projects had a funding rate of 52%, vs. 34% for new projects. Of the startups founded off of WUSTL intellectual property since 2016, nearly two-thirds had previously participated in LEAP. Funded LEAP projects also had a 29% licensing rate, which is comparable to similar gap funds. Lastly, participants self-reported an increase in knowledge across a range of commercialization areas. DISCUSSION/SIGNIFICANCE OF FINDINGS: The increased repeat funding rate and self-reported knowledge suggest that LEAP is impactful in building commercialization proficiency. The licensing rate and prevalence of LEAP projects in WUSTL startups also indicate that LEAP is indeed promoting tech transfer. Together, these results suggest that LEAP could be a model for other institutions.
26600 HiTech and Health Interest Trends in Rural Neighborhoods are Associated with COVID-19
Authors: Greer Melody
Published: March 2021

ABSTRACT IMPACT: Current, complete, unbiased, and accurate information, which includes patient social and environmental context, is necessary to understand health outcomes. OBJECTIVES/GOALS: Literacy in technology empowers patients in improving their health. We hypothesize that by integrating this information into clinical information, obfuscated relationships may become apparent. To test this, we have combined technological literacy elements with clinical data and test results from patients at risk for severe COVID-19 reactions. METHODS/STUDY POPULATION: Zip level data was appended to approximately 55,000 clinical records of COVID-19 positive and negative patients with comorbidities linked to high illness severity (e.g., diabetes, heart disease). The patient zip code was matched to zip code level health and technology interest indicators. Health interest indicates the level of interest in health such as research, exercising, better dieting, preventive care, etc., and is ranked from 0 to 9. The technology interest indicator is a binary flag indicating technology adopters. These lifestyle factor data points were obtained from survey data and purchasing patterns using transactional and response information from self-reported sources. For each zip code, the index values were represented by a percentage of that population. RESULTS/ANTICIPATED RESULTS: There is a pronounced difference between urban and rural areas with respect to interest in health and technology. In neighborhoods where most residents are interested in both health and technology, the percentage of COVID-19 cases was smaller. A Wilcoxon signed-rank test indicated that the distributions were statistically different (p-value = 4.606e-06) when evaluating the low interest values for health and technology, and (p-value = 1.069e-09) when there was high interest in health and technology against COVID-19 results. In addition, the health and technology indicator variables are not correlated with income at the zip code level. At the low index values, interest in health and technology, the correlation was -0.0856, and at the high end, the correlation was -0.0436. DISCUSSION/SIGNIFICANCE OF FINDINGS: This result is significant for COVID-19 research because it describes a methodology for identifying patients who may be at higher risk for contracting the disease. This relationship was reflected in electronic health record data only after zip-level information was added. Moreover, this was true at across income levels.