Validating self-reported Toxic Release Inventory data using Benford's Law: investigating toxic chemical release hazards in floodplains.

Introduction: Acute and long-term health impacts from flooding related toxic chemical releases are a significant local health concern and can disproportionately impact communities with vulnerable populations; reliable release data are needed to quantify this hazard. Methods: In this paper, we analyze US Federal Emergency Management Agency designated floodplain data and US Environmental Protection Agency Toxic Release Inventory (TRI) data to determine if geographically manipulated databases adhere to Benford's Law. Results: We investigated multiple variants and discovered pollution releases adhere to Benford's Law and tests which thereby validates the self-reported toxic release dataset. Discussion: We find that Benford's Law applies to self-reported toxic chemical release and disposal data, indicating a lack of widespread data errors or manipulation.

"Ripping Off the Band-Aid": uncovering future health care Professionals' "Fractured Knowledge" about sexual and reproductive health.

Background: Research has shown the role of identity on future health professionals' confidence and competence in addressing the sexual and reproductive health (SRH) needs of their patients. While there has been some work in increasing the sexual health literacy of future providers via various curricular approaches and comprehensive clinical-based training, there are research gaps on how social differences around identity impact future healthcare professionals' knowledge and practices around SRH. Objectives: This article presents research findings on the experiences of US undergraduate students attending a campus that provides training in the health sciences and health professions. Our study aims to understand the perspectives of these students as they pertain to their future career choices in healthcare, with a focus on how their past experiences learning about sex, sexuality, and reproduction impact their current and future professional trajectories. Methods: We present a qualitative analysis from 40 in-depth interviews with U.S. undergraduates. The interview questions were designed in collaboration with undergraduate researchers interested in sexual health education. These student researchers collected all the interview data and worked with senior researchers to analyze some of these data. Results: The themes that emerged from the interviews were around experiences with what students perceived as "fractured" sexual and reproductive health (SRH) knowledge they received as children and adolescents. This knowledge shaped essential aspects of their identity as young adults and future healers. Data indicated unique processes implicated in how past as well as present socialization experiences learning about sex, sexuality, and reproduction positions undergraduates in health professions to see young adulthood as a journey of "catching up" on sexual knowledge but also as an ongoing experience of anticipation and planning influencing their career-building journey. Conclusions: The importance of sexual health literacy among healthcare professionals cannot be overstated, as it is vital in providing patient-centered and non-judgmental sexual and reproductive health (SRH) care and services. To date, there is a shortage of studies looking at the impact of sexual health knowledge on healthcare professionals. More research is needed on educational strategies that could be implemented at the intra-personal level to assist college-aged young adults in healthcare career tracks to "catch up" or "fill in the gaps" in their sexual education journey.

From pandemic to endemic: Divergence of COVID-19 positive-tests and hospitalization numbers from SARS-CoV-2 RNA levels in wastewater of Rochester, Minnesota.

Traditionally, public health surveillance relied on individual-level data but recently wastewater-based epidemiology (WBE) for the detection of infectious diseases including COVID-19 became a valuable tool in the public health arsenal. Here, we use WBE to follow the course of the COVID-19 pandemic in Rochester, Minnesota (population 121,395 at the 2020 census), from February 2021 to December 2022. We monitored the impact of SARS-CoV-2 infections on public health by comparing three sets of data: quantitative measurements of viral RNA in wastewater as an unbiased reporter of virus level in the community, positive results of viral RNA or antigen tests from nasal swabs reflecting community reporting, and hospitalization data. From February 2021 to August 2022 viral RNA levels in wastewater were closely correlated with the oscillating course of COVID-19 case and hospitalization numbers. However, from September 2022 cases remained low and hospitalization numbers dropped, whereas viral RNA levels in wastewater continued to oscillate. The low reported cases may reflect virulence reduction combined with abated inclination to report, and the divergence of virus levels in wastewater from reported cases may reflect COVID-19 shifting from pandemic to endemic. WBE, which also detects asymptomatic infections, can provide an early warning of impending cases, and offers crucial insights during pandemic waves and in the transition to the endemic phase.

Just in case: undergraduate students identifying and mitigating barriers to their sexual and reproductive health needs.

BACKGROUND: Many U.S. colleges and universities offer access to a healthcare center that provides sexual and reproductive health (SRH) resources, services, and products. The importance of health centers in college and university settings in reducing sexual health disparities in student populations cannot be stressed enough. This article evaluates a student-led, mutual-aid, grassroots health promotion strategy for students with limited access to healthcare services, supplies, and tools via an anonymous and discrete distribution of SRH resources without charge. METHODS: In partnership with faculty, undergraduate students worked to address their school's unmet SRH needs by increasing on-campus access to comprehensive, evidence-based, and sex-positive resources. Referred to as Just in Case, this student-led, grassroots health promotion program provided students with supply kits containing contraceptives, sexual health wellness products, basic hygiene supplies, and education materials. Students were surveyed in a pre- (n = 95) post- (n = 73) pilot study to identify contraception acquisition barriers, discern perceptions of on-campus SRH resources, and elucidate trends in this program's use and impact. Chi-square tests of independence were used to compare survey group responses, and association rule mining was employed in tandem to identify SRH items that students requested. RESULTS: Students identified cost and privacy as significant barriers to acquiring sexual health products on campus. Of the 182 Just in Case supply kits requested by students during the 2022-2023 academic year, condoms were requested most frequently in 75% of fulfilled kits, while emergency contraception and pregnancy tests were asked most often in 61% of kits. 50% of students reported access to contraceptives on campus before this program's implementation, growing to 75% (p < 0.001) 1 year later post-implementation. Similar jumps were observed for reported access to sexual health education (30 to 73%, p < 0.001) and services (36 to 73%, p < 0.001). CONCLUSION: A student-led SRH supply and resource delivery strategy may immediately reduce SRH inequities and decrease barriers to contraceptive use for students with limited access to on-site SRH product availability.

Using Artificial Intelligence to Identify Sources and Pathways of Lead Exposure in Children.

CONTEXT: Sources and pathways of lead exposure in young children have not been analyzed using new artificial intelligence methods. OBJECTIVE: To collect environmental, behavioral, and other data on sources and pathways in 17 rural homes to predict at-risk households and to compare urban and rural indicators of exposure. DESIGN: Cross-sectional pilot study. SETTING: Knox County, Illinois, which has a high rate of childhood lead poisoning. PARTICIPANTS: Rural families. METHODS: Neural network and K-means statistical analysis. MAIN OUTCOME MEASURE: Children's blood lead level. RESULTS: Lead paint on doors, lead dust, residential property assessed tax, and median interior paint lead level were the most important predictors of children's blood lead level. CONCLUSIONS: K-means analysis confirmed that settled house dust lead loadings, age of housing, concentration of lead in door paint, and geometric mean of interior lead paint samples were the most important predictors of lead in children's blood. However, assessed property tax also emerged as a new predictor. A sampling strategy that examines these variables can provide lead poisoning prevention professionals with an efficient and cost-effective means of identifying priority homes for lead remediation. The ability to preemptively target remediation efforts can help health, housing, and other agencies to remove lead hazards before children develop irreversible health effects and incur costs associated with lead in their blood.

Creating an Integrated Undergraduate Public Health Curricula: Inspiring the Next Generation to Solve Complex Public Health Issues.

This article takes a novel approach of highlighting the creation and development of an integrated undergraduate public health curricula geared to students in the health sciences. In our practice, undergraduate and public health pedagogy supports innovative and proven approaches of experiential learning in our classrooms. We show how public health faculty take a team approach to teaching which has allowed them to collaborate in and outside of the classroom resulting in inherent knowledge of course materials, student engagement, and outcomes. This evolved to an overall curricula design that involves scaffolded research skills and/or projects within and between the public health courses. In addition, we highlight examples of upperclassmen utilizing these curriculum schemas outside the classroom to engage in faculty research beyond the public health discipline. This narrative describes lessons learned when teaching undergraduate students across public health curricula, how we integrated research skills within each course using pedagogical practices, and why this approach supports student engaged research within directed study and paid undergraduate research opportunities.

A Data Driven Approach for Prioritizing COVID-19 Vaccinations in the Midwestern United States.

Considering the potential for widespread adoption of social vulnerability indices (SVI) to prioritize COVID-19 vaccinations, there is a need to carefully assess them, particularly for correspondence with outcomes (such as loss of life) in the context of the COVID-19 pandemic. The University of Illinois at Chicago School of Public Health Public Health GIS team developed a methodology for assessing and deriving vulnerability indices based on the premise that these indices are, in the final analysis, classifiers. Application of this methodology to several Midwestern states with a commonly used SVI indicates that by using only the SVI rankings there is a risk of assigning a high priority to locations with the lowest mortality rates and low priority to locations with the highest mortality rates. Based on the findings, we propose using a two-dimensional approach to rationalize the distribution of vaccinations. This approach has the potential to account for areas with high vulnerability characteristics as well as to incorporate the areas that were hard hit by the pandemic.

A second wave of COVID-19 in Cook County: What lessons can be applied?

During the ongoing public health crisis, many agencies are reporting COVID-19 health outcome information based on the overall population. This practice can lead to misleading results and underestimation of high risk areas. To gain a better understanding of spatial and temporal distribution of COVID-19 deaths; the long term care facility (LTCF) and household population (HP) deaths must be used. This approach allows us to better discern high risk areas and provides policy makers with reliable information for community engagement and mitigation strategies. By focusing on high-risk LTCFs and residential areas, protective measures can be implemented to minimize COVID-19 spread and subsequent mortality.  These areas should be a high priority target when COVID-19 vaccines become available.

Comprehensive Neighborhood Portraits and Child Asthma Disparities.

Objectives Previous research has established links between child, family, and neighborhood disadvantages and child asthma. We add to this literature by first characterizing neighborhoods in Houston, TX by demographic, economic, and air quality characteristics to establish differences in pediatric asthma diagnoses across neighborhoods. Second, we identify the relative risk of social, economic, and environmental risk factors for child asthma diagnoses. Methods We geocoded and linked electronic pediatric medical records to neighborhood-level social and economic indicators. Using latent profile modeling techniques, we identified Advantaged, Middle-class, and Disadvantaged neighborhoods. We then used a modified version of the Blinder-Oaxaca regression decomposition method to examine differences in asthma diagnoses across children in these different neighborhoods. Results Both compositional (the characteristics of the children and the ambient air quality in the neighborhood) and associational (the relationship between child and air quality characteristics and asthma) differences within the distinctive neighborhood contexts influence asthma outcomes. For example, unequal exposure to PM2.5 and O3 among children in Disadvantaged and Middle-class neighborhoods contribute to asthma diagnosis disparities within these contexts. For children in Disadvantaged and Advantaged neighborhoods, associational differences between racial/ethnic and socioeconomic characteristics and asthma diagnoses explain a significant proportion of the gap. Conclusions for Practice Our results provide evidence that differential exposure to pollution and protective factors associated with non-Hispanic White children and children from affluent families contribute to asthma disparities between neighborhoods. Future researchers should consider social and racial inequalities as more proximate drivers, not merely as associated, with asthma disparities in children.

Does neighborhood social and environmental context impact race/ethnic disparities in childhood asthma?

Utilizing over 140,000 geocoded medical records for a diverse sample of children ages 2-12 living in Houston, Texas, we examine whether a comprehensive set of neighborhood social and environmental characteristics explain racial and ethnic disparities in childhood asthma. Adjusting for all individual risk factors, as well as neighborhood concentrated disadvantage, particulate matter, ozone concentration, and race/ethnic composition, reduced but did not fully attenuate the higher odds of asthma diagnosis among black (OR=2.59, 95% CI=2.39, 2.80), Hispanic (OR=1.22, 95% CI=1.14, 1.32) and Asian (OR=1.18, 95% CI=1.04, 1.33) children relative to whites.

Utilizing Exploratory Spatial Data Analysis to Examine Health and Environmental Disparities in Disadvantaged Neighborhoods.

Health disparities research has focused primarily on racial and socioeconomic differences in health outcomes. Although neighborhood characteristics and the concept of built environment have been shown to affect individual health, measuring the effects of environmental risks on health has been a less developed area of disparities research. To examine spatial associations and the distribution of geographic patterns of sociodemographic characteristics, environmental cancer risk, and cancer rates, we utilized existing data from multiple sources. The findings from our initial analysis, which concerned with proximity to environmental hazards and at-risk communities, were consistent with results of previous studies, which often reported mixed relationships between health disparity indicators and environmental burden. However, further analysis with refined models showed that several key demographic and subdomains of cancer risk measures were shown to have spatial components. With the application of exploratory spatial data analysis, we were able to identify areas with both high rates of poverty and racial minorities to further examine for possible associations to environmental cancer risk. Global spatial autocorrelation found spatial clustering with percent black, percent poverty, point and non-point cancer risks requiring further spatial analysis to determine relationship of significance based on geography. This methodology was based upon particular assumptions associated with data and applications, which needed to be met. We conclude that careful assessment of the data and applications were required to properly interpret the findings in understanding the relationship between vulnerable populations and environmental burden.

Highly active antiretroviral therapy potently suppresses HIV infection in humanized Rag2-/-gammac-/- mice.

Humanized Rag2(-/-)gamma(c)(-/-) mice (Hu-DKO mice) become populated with functional human T cells, B cells, and dendritic cells following transplantation with human hematopoietic stem cells (HSC) and represent an improved model for studying HIV infection in vivo. In the current study we demonstrated that intrasplenic inoculation of hu-DKO mice with HIV-1 initiated a higher level of HIV infection than intravenous or intraperitoneal inoculation, associated with a reciprocal decrease in peripheral CD4(+) T cells and increase in peripheral CD8(+) T cells. HIV infection by intrasplenic injection increased serum levels of human IgG and IgM including human IgM and IgG specific for HIV-1 gp120. There was a significant inverse correlation between the level of HIV-1 infection and the extent of CD4(+) T cell depletion. Highly active antiretroviral therapy (HAART) initiated 1 week after HIV-1 inoculation markedly suppressed HIV-1 infection and prevented CD4(+) T cell depletion. Taken together, these findings demonstrate that intrasplenic injection of hu-DKO mice with HIV is a more efficient route of HIV infection than intravenous or intraperitoneal injection and generates increased infection associated with an increased anti-HIV humoral response. This animal model can serve as a valuable in vivo model to study the efficacy of anti-HIV therapies.

CD4-specific transgenic expression of human cyclin T1 markedly increases human immunodeficiency virus type 1 (HIV-1) production by CD4+ T lymphocytes and myeloid cells in mice transgenic for a provirus encoding a monocyte-tropic HIV-1 isolate.

Human immunodeficiency virus type 1 (HIV-1)-encoded Tat provides transcriptional activation critical for efficient HIV-1 replication by interacting with cyclin T1 and recruiting P-TEFb to efficiently elongate the nascent HIV transcript. Tat-mediated transcriptional activation in mice is precluded by species-specific structural differences that prevent Tat interaction with mouse cyclin T1 and severely compromise HIV-1 replication in mouse cells. We investigated whether transgenic mice expressing human cyclin T1 under the control of a murine CD4 promoter/enhancer cassette that directs gene expression to CD4(+) T lymphocytes and monocytes/macrophages (hu-cycT1 mice) would display Tat responsiveness in their CD4-expressing mouse cells and selectively increase HIV-1 production in this cellular population, which is infected primarily in HIV-1-positive individuals. To this end, we crossed hu-cycT1 mice with JR-CSF transgenic mice carrying the full-length HIV-1(JR-CSF) provirus under the control of the endogenous HIV-1 long terminal repeat and demonstrated that human cyclin T1 expression is sufficient to support Tat-mediated transactivation in primary mouse CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo HIV-1 production by these stimulated cells. Increased HIV-1 production by CD4(+) T lymphocytes was paralleled with their specific depletion in the peripheral blood of the JR-CSF/hu-cycT1 mice, which increased over time. In addition, increased HIV-1 transgene expression due to human cyclin T1 expression was associated with increased lipopolysaccharide-stimulated monocyte chemoattractant protein 1 production by JR-CSF mouse monocytes/macrophages in vitro. Therefore, the JR-CSF/hu-cycT1 mice should provide an improved mouse system for investigating the pathogenesis of various aspects of HIV-1-mediated disease and the efficacies of therapeutic interventions.

CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS.

Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.

Identification of granulocyte-macrophage colony-stimulating factor and lipopolysaccharide-induced signal transduction pathways that synergize to stimulate HIV type 1 production by monocytes from HIV type 1 transgenic mice.

HIV-1-infected monocyte/macrophages located in lymph nodes and tissues are highly productive sources of HIV-1 and may function as a persistent reservoir contributing to the rebound viremia observed after highly active antiretroviral therapy is stopped. Mechanisms activating latently infected, primary monocyte/macrophages to produce HIV-1 were investigated using monocytes isolated from a transgenic mouse line carrying a full-length proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1(JR-CSF), regulated by the endogenous long terminal repeat (LTR) (JR-CSF mice). Granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with lipopolysaccharide (LPS) induced infectious HIV-1 production by JR-CSF mouse monocytes over 10-fold and 100-fold higher than that stimulated by GM-CSF or LPS alone, respectively. We examined mechanisms of GM-CSF synergy with LPS and demonstrated that GM-CSF up-regulated the LPS receptor, TLR-4, and also synergized with LPS to activate mitogen-activated protein (MAP) kinase/ERK kinase and the Sp1 transcription factor. Inhibitors of either MAP kinase/ERK kinase or p38 kinase but not PI 3-kinase potently suppressed GM-CSF and LPS-induced HIV-1 production by JR-CSF mouse monocytes. Because Sp1 is activated by both the MAP kinase/ERK kinase and p38 kinase pathways, we postulate that synergistic activation of these pathways by GM-CSF and LPS induced sufficient levels of Sp1 to activate the HIV-1 LTR in a Tat-independent manner and induced HIV-1 production by JR-CSF mouse monocytes. Thus, our study delineated the pathway of HIV-1 LTR activation by GM-CSF and LPS and indicated that JR-CSF transgenic mice may provide a new in vitro and in vivo system for investigating the mechanism by which inflammatory and infectious stimuli activate HIV-1 production from latently infected monocytes.

Microglia from mice transgenic for a provirus encoding a monocyte-tropic HIV type 1 isolate produce infectious virus and display in vitro and in vivo upregulation of lipopolysaccharide-induced chemokine gene expression.

A large body of evidence has indicated that microglia are the predominant cellular location for HIV-1 in the brains of HIV-1-infected individuals and play a direct role in the development of HIV-1-associated dementia (HAD). Therefore, investigation of the mechanism by which HIV-1-infected microglia contribute to the development of HIV-associated dementia should be facilitated by the creation of a mouse model wherein microglia carry replication-competent HIV-1. To circumvent the inability of HIV-1 to infect mouse cells, we developed a mouse line that is transgenic for a full-length proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1(JR-CSF) (JR-CSF mice), whose T cells and monocytes produce infectious HIV-1. We detected expression of the long terminal repeat-regulated proviral transgene in the microglia of these transgenic mice and demonstrated that it was increased by in vitro and in vivo stimulation with lipopolysaccharide. Furthermore, microglia isolated from JR-CSF mouse brains produced HIV-1 that was infectious in vitro and in vivo. We examined the effect that carriage of the HIV-1 provirus had on chemokine gene regulation in the brains of these mice and demonstrated that MCP-1 gene expression by JR-CSF mouse microglia and brains was more responsive to in vitro and in vivo stimulation with lipopolysaccharide than were microglia and brains from control mice. Thus, this study indicates that the JR-CSF mice may represent a new mouse model to study the effect of HIV-1 replication on microglia function and its contribution to HIV-1-associated neurological disease.

Development of a novel transgenic mouse/SCID-hu mouse system to characterize the in vivo behavior of reservoirs of human immunodeficiency virus type 1-infected cells.

To develop a system in which transgenic and knockout technologies are used to study the in vivo behavior of human immunodeficiency virus type 1 (HIV-1) reservoirs, 2 different mouse models were combined: transgenic mice carrying full-length provirus encoding the monocyte-tropic HIV-1(JR-CSF) isolate (JR-CSF mice) and severe combined immunodeficient mice implanted with human fetal thymus and liver tissues (thy/liv-SCID-hu mice). Extensive HIV-1 infection of human thymic implants occurred after injection of JR-CSF mouse leukocytes into thy/liv-SCID-hu mice, indicating that these cells provide an in vivo source of replication-competent HIV-1. In vivo persistence of transferred JR-CSF mouse leukocytes carrying replication-competent HIV-1 in thy/liv-SCID-hu mice was indicated by the emergence of HIV-1 infection in mice that had no detectable HIV-1 infection until after highly active antiretroviral therapy. Thus, thy/liv-SCID-hu mice populated with JR-CSF mouse leukocytes, a persistent cellular reservoir harboring replication-competent HIV-1, present a new in vivo system for characterizing reservoirs of HIV-1 and evaluating therapeutic strategies designed to eliminate them.