Vaccine Attitudes and Uptake Among Latino Residents of a Former COVID-19 Hotspot.

Early in the COVID-19 pandemic, the Centers for Disease Control and Prevention identified Prince William County (PWC), Va. as a hotspot with a high disease rate among Latinos. This study uses spatial, survey, and qualitative data to understand attitudes towards vaccine uptake among PWC Latinos. A quantitative analysis (n=266) estimates the association for vaccine acceptance among Latinos. Next, qualitative interviews with Latinos (n=37) examine vaccine attitudes. Finally, a spatial analysis identifies clusters of social vulnerability and low vaccine uptake in PWC and adjacent counties. Our findings show that a substantial proportion of PWC Latinos had low vaccination rates as of December 2022, two years after the vaccine's release. Side effects and safety and approval concerns were cited in both the quantitative and qualitative studies. Persistent vaccine disparities are concerning given the high hospitalization and mortality rates that prevailed among Latinos early in the pandemic.

Diversity, Equity, and Inclusion Lessons From Developing Stroke Education Programs for West Michigan Asian Communities.

BACKGROUND: Asians in the United States, facing health care disparities, have increased stroke risk. Multiple subgroups, with distinct cultures and languages, add complexity to caring for Asian American (AsA) communities. We developed a tailored stroke education program for underserved West Michigan AsA communities. Methodology, lessons learned, and diversity, equity, and inclusion insights are described. METHODS: Neurology residents and faculty, in collaboration with trained community-specific navigators, developed culturally resonant stroke education that was tailored to meet the needs of specific self-identified West Michigan AsA communities. Educational and debriefing sessions were delivered over 6 months, following the Plan-Do-Study-Act model, to elucidate diversity, equity, and inclusion insights and improve materials and delivery methods. RESULTS: Eighty-six non-English-speaking participants from 5 self-identified AsA communities (Burmese, Buddhist Vietnamese, Catholic Vietnamese, Chinese, and Nepali) attended educational stroke sessions. The average age of attendees was 57.6±13.2 years; most were females (70%). Diversity, equity, and inclusion insights included identification of Asian cultural beliefs about acute stroke treatment (eg, bloodletting), investigator insights (eg, need for kitchen-table programs), systemic barriers (eg, language), and mitigation strategies. CONCLUSIONS: Institutions should consider the integration of equity-focused, trainee-influenced quality improvement projects, such as this culturally resonant stroke educational program for AsA, to enhance stroke care in these vulnerable communities.

Detection of trait donors and QTL boundaries for early blight resistance using local ancestry inference in a library of genomic sequences for tomato.

By conducting hierarchical clustering along a sliding window, we generated haplotypes across hundreds of re-sequenced genomes in a few hours. We leveraged our method to define cryptic introgressions underlying disease resistance in tomato (Solanum lycopersicum L.) and to discover resistant germplasm in the tomato seed bank. The genomes of 9 accessions with early blight (Alternaria linariae) disease resistance were newly sequenced and analyzed together with published sequences for 770 tomato and wild species accessions, most of which are available in germplasm collections. Identification of common ancestral haplotypes among resistant germplasm enabled rapid fine mapping of recently discovered quantitative trait loci (QTL) conferring resistance and the identification of possible causal variants. The source of the early blight QTL EB-9 was traced to a vintage tomato named 'Devon Surprise'. Another QTL, EB-5, as well as resistance to bacterial spot disease (Xanthomonas spp.), was traced to Hawaii 7998. A genomic survey of all accessions forecasted EB-9-derived resistance in several heirloom tomatoes, accessions of S. lycopersicum var. cerasiforme, and S. pimpinellifolium PI 37009. Our haplotype-based predictions were validated by screening the accessions against the causal pathogen. There was little evidence of EB-5 prevalence in surveyed contemporary germplasm, presenting an opportunity to bolster tomato disease resistance by adding this rare locus. Our work demonstrates practical insights that can be derived from the efficient processing of large genome-scale datasets, including rapid functional prediction of disease resistance QTL in diverse genetic backgrounds. Finally, our work finds more efficient ways to leverage public genetic resources for crop improvement.

Geographical Variation in Social Determinants of Female Breast Cancer Mortality Across US Counties.

Importance: Breast cancer mortality is complex and traditional approaches that seek to identify determinants of mortality assume that their effects on mortality are stationary across geographic space and scales. Objective: To identify geographic variation in the associations of population demographics, environmental, lifestyle, and health care access with breast cancer mortality at the US county-level. Design, Setting, and Participants: This geospatial cross-sectional study used data from the Surveillance, Epidemiology, and End Results (SEER) database on adult female patients with breast cancer. Statistical and spatial analysis was completed using adjusted mortality rates from 2015 to 2019 for 2176 counties in the US. Data were analyzed July 2022. Exposures: County-level population demographics, environmental, lifestyle, and health care access variables were obtained from open data sources. Main Outcomes and Measures: Model coefficients describing the association between 18 variables and age-adjusted breast cancer mortality rate. Compared with a multivariable linear regression (OLS), multiscale geographically weighted regression (MGWR) relaxed the assumption of spatial stationarity and allowed for the magnitude, direction, and significance of coefficients to change across geographic space. Results: Both OLS and MGWR models agreed that county-level age-adjusted breast cancer mortality rates were significantly positively associated with obesity (OLS: ß, 1.21; 95% CI, 0.88 to 1.54; mean [SD] MGWR: ß, 0.72 [0.02]) and negatively associated with proportion of adults screened via mammograms (OLS: ß, -1.27; 95% CI, -1.70 to -0.84; mean [SD] MGWR: ß, -1.07 [0.16]). Furthermore, the MGWR model revealed that these 2 determinants were associated with a stationary effect on mortality across the US. However, the MGWR model provided important insights on other county-level factors differentially associated with breast cancer mortality across the US. Both models agreed that smoking (OLS: ß, -0.65; 95% CI, -0.98 to -0.32; mean [SD] MGWR: ß, -0.75 [0.92]), food environment index (OLS: ß, -1.35; 95% CI, -1.72 to -0.98; mean [SD] MGWR: ß, -1.69 [0.70]), exercise opportunities (OLS: ß, -0.56; 95% CI, -0.91 to -0.21; mean [SD] MGWR: ß, -0.59 [0.81]), racial segregation (OLS: ß, -0.60; 95% CI, -0.89 to -0.31; mean [SD] MGWR: ß, -0.47 [0.41]), mental health care physician ratio (OLS: ß, -0.93; 95% CI, -1.44 to -0.42; mean [SD] MGWR: ß, -0.48 [0.92]), and primary care physician ratio (OLS: ß, -1.46; 95% CI, -2.13 to -0.79; mean [SD] MGWR: ß, -1.06 [0.57]) were negatively associated with breast cancer mortality, and that light pollution was positively associated (OLS: ß, 0.48; 95% CI, 0.24 to 0.72; mean [SD] MGWR: ß, 0.27 [0.04]). But in the MGWR model, the magnitude of effect sizes and significance varied across geographical regions. Inversely, the OLS model found that disability was not a significant variable for breast cancer mortality, yet the MGWR model found that it was significantly positively associated in some geographical locations. Conclusions and Relevance: This cross-sectional study found that not all social determinants associated with breast cancer mortality are spatially stationary and provides spatially explicit insights for public health practitioners to guide geographically targeted interventions.

Barriers and facilitators to effective cervical cancer screening in Belize: a qualitative analysis.

PURPOSE: Belize has among the highest cervical cancer incidence and mortality rates of Latin American and Caribbean countries. This study evaluates the perspectives of key stakeholders for cervical cancer screening in Belize and identifies the barriers and facilitators for providing equitable access to prevention services. METHODS: Semi-structured interviews discussing cervical cancer screening were conducted with key stakeholders across the six districts of Belize in 2018. Interviews were transcribed, coded, and analyzed thematically; themes were organized by levels of the social-ecological model. RESULTS: We conducted 47 interviews with health care providers (45%), administrators (17%), government officials (25%), and other stakeholders (13%). Majority (78%) of interviews were from the public sector. Perceived barriers to cervical cancer screening were identified across multiple levels: (1) Individual Patient: potential delays in Pap smear results and fear of a cancer diagnosis; (2) Provider: competing clinician responsibilities; (3) Organizational: insufficient space and training; (4) Community: reduced accessibility in rural areas; and (5) Policy: equipment and staffing budget limitations. The main facilitators we identified included the following: (1) at the Community level: resource-sharing between public and private sectors and dedicated rural outreach personnel; (2) at the Policy level: free public screening services and the establishment of population-based screening. CONCLUSION: Despite free, publicly available cervical cancer screening in Belize, complex barriers affect access and completion of management when abnormal screening tests are identified. Provider workload, education outreach, and additional funding for training and facilities are potential areas for strengthening this program and increasing detection and management for cervical cancer control.

Scoping review of disease-modifying effect of drugs in experimental epilepsy.

Objective: Epilepsy affects ~50 million people worldwide causing significant medical, financial, and sociologic concerns for affected patients and their families. To date, treatment of epilepsy is primarily symptomatic management because few effective preventative or disease-modifying interventions exist. However, recent research has identified neurobiological mechanisms of epileptogenesis, providing new pharmacologic targets to investigate. The current scientific evidence remains scattered across multiple studies using different model and experimental designs. The review compiles different models of anti-epileptogenic investigation and highlights specific compounds with potential epileptogenesis-modifying experimental drugs. It provides a platform for standardization of future epilepsy research to allow a more robust compound analysis of compounds with potential for epilepsy prevention. Methods: PubMed, Ovid MEDLINE, and Web of Science were searched from 2007 to 2021. Studies with murine models of epileptogenesis and explicitly detailed experimental procedures were included in the scoping review. In total, 51 articles were selected from 14,983 and then grouped by five core variables: (1) seizure frequency, (2) seizure severity, (3) spontaneous recurrent seizures (SRS), (4) seizure duration, and (5) mossy fiber sprouting (MFS). The variables were differentiated based on experimental models including methods of seizure induction, treatment schedule and timeline of data collection. Data was categorized by the five core variables and analyzed by converting original treatment values to units of percent of its respective control. Results: Discrepancies in current epileptogenesis models significantly complicate inter-study comparison of potential anti-epileptogenic interventions. With our analysis, many compounds showed a potential to reduce epileptogenic characteristics defined by the five core variables. WIN55,212-2, aspirin, rapamycin, 1400W, and LEV + BQ788 were identified compounds with the potential of effective anti-epileptic properties. Significance: Our review highlights the need for consistent methodology in epilepsy research and provides a novel approach for future research. Inconsistent experimental designs hinder study comparison, slowing the progression of treatments for epilepsy. If the research community can optimize and standardize parameters such as methods of seizure induction, administration schedule, sampling time, and aniMal models, more robust meta-analysis and collaborative research would follow. Additionally, some compounds such as rapamycin, WIN 55,212-2, aspirin, 1400W, and LEV + BQ788 showed anti-epileptogenic modulation across multiple variables. We believe they warrant further study both individually and synergistically.

Sonodynamic Therapy for the Treatment of Glioblastoma Multiforme in a Mouse Model Using a Portable Benchtop Focused Ultrasound System.

Sonodynamic therapy (SDT) is an application of focused ultrasound (FUS) that enables a sonosensitizing agent to prime tumors for increased sensitivity during sonication. Unfortunately, current clinical treatments for glioblastoma (GBM) are lacking, leading to low long-term survival rates among patients. SDT is a promising method for treating GBM in an effective, noninvasive, and tumor-specific manner. Sonosensitizers preferentially enter tumor cells compared to the surrounding brain parenchyma. The application of FUS in the presence of a sonosensitizing agent generates reactive oxidative species resulting in apoptosis. Although this therapy has been shown previously to be effective in preclinical studies, there is a lack of established standardized parameters. Standardized methods are necessary to optimize this therapeutic strategy for preclinical and clinical use. In this paper, we detail the protocol to perform SDT in a preclinical GBM rodent model using magnetic resonance-guided FUS (MRgFUS). MRgFUS is an important feature of this protocol, as it allows for specific targeting of a brain tumor without the need for invasive surgeries (e.g., craniotomy). The benchtop device used here can focus on a specific location in three dimensions by clicking on a target on an MRI image, making target selection a straightforward process. This protocol will provide researchers with a standardized preclinical method for MRgFUS SDT, with the added flexibility to change and optimize parameters for translational research.

Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes.

Tissue-resident memory CD8+ T (TRM) cells are a subset of memory T cells that play a critical role in limiting early pathogen spread and controlling infection. TRM cells exhibit differences across tissues, but their potential heterogeneity among distinct anatomic compartments within the small intestine and colon has not been well recognized. Here, by analyzing TRM cells from the lamina propria and epithelial compartments of the small intestine and colon, we showed that intestinal TRM cells exhibited distinctive patterns of cytokine and granzyme expression along with substantial transcriptional, epigenetic, and functional heterogeneity. The T-box transcription factor Eomes, which represses TRM cell formation in some tissues, exhibited unexpected context-specific regulatory roles in supporting the maintenance of established TRM cells in the small intestine, but not in the colon. Taken together, these data provide previously unappreciated insights into the heterogeneity and differential requirements for the formation vs. maintenance of intestinal TRM cells.

Explainable Machine Learning to Bring Database to the Bedside: Development and Validation of the TROUT (Trauma fRailty OUTcomes) Index, a Point-of-Care Tool to Prognosticate Outcomes After Traumatic Injury Based on Frailty.

OBJECTIVE: Exemplify an explainable machine learning framework to bring database to the bedside; develop and validate a point-of-care frailty assessment tool to prognosticate outcomes after injury. BACKGROUND: A geriatric trauma frailty index that captures only baseline conditions, is readily-implementable, and validated nationwide remains underexplored. We hypothesized Trauma fRailty OUTcomes (TROUT) Index could prognosticate major adverse outcomes with minimal implementation barriers. METHODS: We developed TROUT index according to Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis guidelines. Using nationwide US admission encounters of patients aged ≥65 years (2016-2017; 10% development, 90% validation cohorts), unsupervised and supervised machine learning algorithms identified baseline conditions that contribute most to adverse outcomes. These conditions were aggregated into TROUT Index scores (0-100) that delineate 3 frailty risk strata. After associative [between frailty risk strata and outcomes, adjusted for age, sex, and injury severity (as effect modifier)] and calibration analysis, we designed a mobile application to facilitate point-of-care implementation. RESULTS: Our study population comprised 1.6 million survey-weighted admission encounters. Fourteen baseline conditions and 1 mechanism of injury constituted the TROUT Index. Among the validation cohort, increasing frailty risk (low=reference group, moderate, high) was associated with stepwise increased adjusted odds of mortality {odds ratio [OR] [95% confidence interval (CI)]: 2.6 [2.4-2.8], 4.3 [4.0-4.7]}, prolonged hospitalization [OR (95% CI)]: 1.4 (1.4-1.5), 1.8 (1.8-1.9)], disposition to a facility [OR (95% CI): 1.49 (1.4-1.5), 1.8 (1.7-1.8)], and mechanical ventilation [OR (95% CI): 2.3 (1.9-2.7), 3.6 (3.0-4.5)]. Calibration analysis found positive correlations between higher TROUT Index scores and all adverse outcomes. We built a mobile application ("TROUT Index") and shared code publicly. CONCLUSION: The TROUT Index is an interpretable, point-of-care tool to quantify and integrate frailty within clinical decision-making among injured patients. The TROUT Index is not a stand-alone tool to predict outcomes after injury; our tool should be considered in conjunction with injury pattern, clinical management, and within institution-specific workflows. A practical mobile application and publicly available code can facilitate future implementation and external validation studies.

Predicting building types using OpenStreetMap.

Having accurate building information is paramount for a plethora of applications, including humanitarian efforts, city planning, scientific studies, and navigation systems. While volunteered geographic information from sources such as OpenStreetMap (OSM) has good building geometry coverage, descriptive attributes such as the type of a building are sparse. To fill this gap, this study proposes a supervised learning-based approach to provide meaningful, semantic information for OSM data without manual intervention. We present a basic demonstration of our approach that classifies buildings into either residential or non-residential types for three study areas: Fairfax County in Virginia (VA), Mecklenburg County in North Carolina (NC), and the City of Boulder in Colorado (CO). The model leverages (i) available OSM tags capturing non-spatial attributes, (ii) geometric and topological properties of the building footprints including adjacent types of roads, proximity to parking lots, and building size. The model is trained and tested using ground truth data available for the three study areas. The results show that our approach achieves high accuracy in predicting building types for the selected areas. Additionally, a trained model is transferable with high accuracy to other regions where ground truth data is unavailable. The OSM and data science community are invited to build upon our approach to further enrich the volunteered geographic information in an automated manner.

The Need to Routinely Convert Emergency Cricothyroidotomy to Tracheostomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Traditional surgical teaching advocates converting emergency cricothyroidotomies to tracheostomies to mitigate the risk of subglottic stenosis. A conversion procedure that may risk losing a tenuous airway should have clear benefits over risks. We aimed to evaluate the necessity of routine cricothyroidotomy to tracheostomy conversion by conducting a systematic review and meta-analysis of contemporary literature. STUDY DESIGN: We performed a systematic review of experimental and observational studies (published between January 1, 2008, and March 1, 2021) reporting hospital outcomes of adults aged ≥18 years who underwent emergency cricothyroidotomies or tracheostomies. We followed PRISMA guidelines and assessed quality of data using GRADE methodology. Meta-analysis pooled incidence of procedure-specific complications (bleeding, subglottic stenosis, and others) using Freeman-Tukey double arcsine transformation and sensitivity analysis addressed survival bias. RESULTS: A total of 18 studies including 1246 patients were analyzed. Incidence of bleeding (5 [1 to 11]% vs 3 [1 to 7]%), subglottic stenosis (0 [0 to 3]% vs 0 [0 to 0]%) and other complications (12 [8 to 16]% vs 13 [5 to 23]%) were similar among patients undergoing emergency cricothyroidotomy or tracheostomy. Sensitivity analysis evaluating the incidence of complications among only survivors found similar results. Only one study reported complications attributable to cricothyroidotomy to tracheostomy conversion. CONCLUSIONS: Subglottic stenosis, the main harm conversion seeks to avoid, appears to be a rare complication after cricothyroidotomy. We did not find evidence supporting routine need to convert cricothyroidotomies to tracheostomies; for many patients, conversion is unlikely to rectify complications attributable to emergency cricothyroidotomy. However, our findings cannot be generalized to patients who require prolonged or permanent airway cannulation. Providers should consider performing cricothyroidotomy to tracheostomy selectively when the benefits clearly outweigh the risks of disrupting a secured airway.

Trans and Gender Diverse People's Experience Wearing Face Masks During the COVID-19 Pandemic: Findings from Data Across 4 States in the USA.

Introduction: Social isolation and reduced access to public life in response to SARS-CoV-2 (COVID-19) challenges health and well-being for many. Marginalized communities, including transgender and gender diverse (TGD) people, have been disproportionally impacted. Experiences of TGD people should be centered in pandemic-related research to better inform policy. Methods: A diverse sample of TGD people (N = 158) were recruited from Michigan, Nebraska, Oregon, and Tennessee to participate in the Trans Resilience and Health Study. Participants ranged from 19 to 70 years old (M = 33.06; SD = 12.88) with 27.2% identifying as trans men/men, 26% identifying as trans women/women, and remaining identifying with terms like genderqueer and nonbinary. Thirty percent identified as people of color. Participants completed a monthly COVID-19-related questionnaire April 2020-March 2021 including open-ended questions to learn what contributed to resilience during this time. Thematic analyses of responses enabled identification of salient themes. Results: Analyses revealed pandemic-related changes in social experiences of marginalization and mask-wearing. Twenty-six participants mentioned face masks as contributing to resilience while also elaborating the influence of masks on experiences of misgendering. Participants identifying as trans women reported decreased misgendering while trans men and nonbinary participants reported increased misgendering. Conclusions and Policy Implications: Mask-wearing helps reduce transmission of COVID-19. For some trans women, masks also reduce the threat of misgendering and possibly other forms of enacted stigma. However, increased risk for misgendering, as noted by trans men in our study, should be considered and increased supports should be provided.

Improving sexually transmitted infection screening, testing, and treatment among people with HIV: A mixed method needs assessment to inform a multi-site, multi-level intervention and evaluation plan.

Bacterial sexually transmitted infections (STIs) continue to be a worsening public health concern in the United States (US). Though the national incidence of HIV infection has decreased over recent years, that of chlamydia, gonorrhea, and syphilis have not. Despite national recommendations on prevention, screening, and treatment of these STIs, these practices have not been standardized. Nine Health Resources and Services Administration Ryan White HIV/AIDS Program funded clinics across 3 US jurisdictions (Florida, Louisiana, and Washington, DC), were selected as clinical demonstration sites to be evaluated in this mixed method needs assessment to inform a multi-site, multi-level intervention to evaluate evidence-based interventions to improve STI screening and testing of bacterial STIs among people with or at risk for HIV. These 3 US jurisdictions were selected due to having higher than national average incidence rates of HIV and bacterial STIs. Descriptive statistics and deductive analysis were used to assess quantitative and qualitative needs assessment data. Results indicate the following needs across participating sites: inconsistent and irregular comprehensive sexual behavior history taking within and among sites, limited routine bacterial STI testing (once/year and if symptomatic) not in accordance with CDC recommendations, limited extragenital site gonorrhea/chlamydia testing, limited annual training on STI-related topics including LGBTQ health and adolescent/young adult sexual health, and limited efforts for making high-STI incidence individuals feel welcome in the clinic (primarily LGBTQ individuals and adolescents/young adults). These findings were used to identify interventions to be used to increase routine screenings and testing for bacterial STIs.

Change of human mobility during COVID-19: A United States case study.

With the onset of COVID-19 and the resulting shelter in place guidelines combined with remote working practices, human mobility in 2020 has been dramatically impacted. Existing studies typically examine whether mobility in specific localities increases or decreases at specific points in time and relate these changes to certain pandemic and policy events. However, a more comprehensive analysis of mobility change over time is needed. In this paper, we study mobility change in the US through a five-step process using mobility footprint data. (Step 1) Propose the Delta Time Spent in Public Places (ΔTSPP) as a measure to quantify daily changes in mobility for each US county from 2019-2020. (Step 2) Conduct Principal Component Analysis (PCA) to reduce the ΔTSPP time series of each county to lower-dimensional latent components of change in mobility. (Step 3) Conduct clustering analysis to find counties that exhibit similar latent components. (Step 4) Investigate local and global spatial autocorrelation for each component. (Step 5) Conduct correlation analysis to investigate how various population characteristics and behavior correlate with mobility patterns. Results show that by describing each county as a linear combination of the three latent components, we can explain 59% of the variation in mobility trends across all US counties. Specifically, change in mobility in 2020 for US counties can be explained as a combination of three latent components: 1) long-term reduction in mobility, 2) no change in mobility, and 3) short-term reduction in mobility. Furthermore, we find that US counties that are geographically close are more likely to exhibit a similar change in mobility. Finally, we observe significant correlations between the three latent components of mobility change and various population characteristics, including political leaning, population, COVID-19 cases and deaths, and unemployment. We find that our analysis provides a comprehensive understanding of mobility change in response to the COVID-19 pandemic.

Viscoelastic Testing in Traumatic Brain Injury: Key Research Insights.

The role of viscoelastic testing in the evaluation and management of traumatic brain injury (TBI) remains a subject of ongoing exploration. This review highlights four key publications that provide significant insights into this subject. Holcomb et al. provided early evidence of the relationship between thromboelastography (TEG) and conventional coagulation tests (CCTs). Later, Samuels et al. used TEG to identify a unique coagulopathy phenotype in TBI characterized by a notable absence of fibrinolytic abnormalities. Dixon et al. built upon these findings by exploring the application of TEG in the context of antifibrinolytic administration, noting a similar lack of effect on LY30. Finally, Guillotte et al. demonstrated the utility of TEG-PM in assessing platelet dysfunction in TBI. While these studies provide key early support for the utility of viscoelastic testing in the TBI, further exploration is needed to define evidence-based guidelines for clinical application.

Downregulation of CD40L-CD40 attenuates seizure susceptibility and severity of seizures.

Unregulated neuro-inflammation mediates seizures in temporal lobe epilepsy (TLE). Our aim was to determine the effect of CD40-CD40L activation in experimental seizures. CD40 deficient mice (CD40KO) and control mice (wild type, WT) received pentenyltetrazole (PTZ) or pilocarpine to evaluate seizures and status epilepticus (SE) respectively. In mice, anti-CD40L antibody was administered intranasally before PTZ. Brain samples from human TLE and post-seizure mice were processed to determine CD40-CD40L expression using histological and molecular techniques. CD40 expression was higher in hippocampus from human TLE and in cortical neurons and hippocampal neural terminals after experimental seizures. CD40-CD40L levels increased after seizures in the hippocampus and in the cortex. After SE, CD40L/CD40 levels increased in cortex and showed an upward trend in the hippocampus. CD40KO mice demonstrated reduction in seizure severity and in latency compared to WT mice. Anti-CD40L antibody limited seizure susceptibility and seizure severity. CD40L-CD40 interaction can serve as a target for an immuno-therapy for TLE.