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Exploring Supplemental Nutrition Assistance Program (SNAP) Participation Stigma in the Context of the COVID-19 Pandemic
Get PDFBackground
The Supplemental Nutrition Assistance Program (SNAP) is the largest federal program designed to reduce poverty and related food insecurity. The COVID-19 pandemic increased SNAP eligibility and enrollment and prompted the federal government to allow states to modify SNAP implementation. SNAP is proven to improve food insecurity among participants, but there are still aspects of SNAP which could be improved to enhance program efficacy and the experience of participants. Due to negative societal assumptions about SNAP participants, SNAP participation can be a stigmatized and stigmatizing experience. SNAP participation explicitly requires numerous social interactions during enrollment and benefit use through which stigma is enacted, felt, and iteratively reconstituted.
Methods
Data from a national survey of SNAP participants was used to measure the prevalence of various types of stigma and explore associations between participant characteristics and stigma (Aim 1). Interview data collected from SNAP participants was used to qualitatively explore the role of SNAP-related stigma in participant experiences during the COVID-19 pandemic (Aim 2). Focus group data collected from state-level SNAP administrators was used to qualitatively explore the role of SNAP participation stigma in SNAP administrators’ experience implementing pandemic-related program flexibilities (Aim 3).
Results
Approximately two in five survey respondents reported at least one of six stigma-informed perceptions or behaviors, and these perceptions and behaviors are associated with experiencing food insecurity (Aim 1). The COVID-19 pandemic impacted the stigma experienced by SNAP participants by creating a more socially acceptable context in which more people could relate to needing assistance to meet their basic needs (Aim 2). SNAP administrators explained how SNAP participation stigma informs various program requirements, and the ways that stigma and the fear of federal sanctions influenced if and how state-level SNAP agencies waived interviews during the pandemic (Aim 3).
Discussion
SNAP participation stigma is experienced by many SNAP participants, and it influences SNAP implementation and efficacy. The context in which SNAP is experienced informs how SNAP participation stigma operates and the extent to which it impacts SNAP participants. SNAP policy makers should consider their motivation for program requirements and find ways to reduce or eliminate practices which perpetuate stigmatization
ENGINEERING IODOTYROSINE DEIODINASE FROM THERMOTOGA NEAPOLITANA TO BIOREMEDIATE HALOPHENOLS AND TO ALLEVIATE SUBSTRATE INHIBITION
No full textIodotyrosine deiodinases (IYD) are flavin-dependent reductive dehalogenases with a substrate preference towards halotyrosines. Although IYDs hold great potential for the bioremediation of the environmental pollutants halophenols, their uses are restricted by the drastic decrease in the catalytic efficiency for halophenols compared to halotyrosines. IYD from Thermotoga neapolitana (TnIYD) was engineered to enhance its kcat¬ and decrease its KM¬ for the dehalogenation of bromohydroquinone (BHQ), a model halophenol. Several strategies, including computational redesign by PyRosetta, chimeragenesis and rational mutagenesis, were employed to promote an efficient lid closure and to provide the cationic interactions to flavin. However, the resulting variants did not exhibit the desired enhancements in kcat¬ or KM for BHQ dehalogenation. Notably, the study revealed a critical role of the amino group of substrates in dehalogenation and suggested that lid closure may not be indispensable for efficient dehalogenation.
The application of TnIYD is hindered by several substrate inhibitions. I-Tyr was found to form a dead-end complex with the oxidized TnIYD and inhibit the reduction of its FMN cofactor. To enhance FMN reduction, a split gene approach was developed to split TnIYD lid. Lid splitting alleviated the substrate inhibition in TnIYD with concomitant enhancements in kcat. Notably, facile FMN reduction was observed in these split TnIYDs in the presence of I-Tyr. Additionally, the dehalogenation activity of TnIYD was maintained after the lid splitting, except for TnIYD split at Glu68. This highlights the importance of the positioning of Glu68 over the closed lid for efficient reductive dehalogenation.
The widespread presence of IYD homologs in various invertebrates implies a distinct physiological role beyond iodide homeostasis in Chordata. To continue the function investigation of IYD in Drosophila melanogaster (DmIYD), the transgenic HA3-tagged DmIYD was prepared and characterized in vitro. This HA3-DmIYD efficiently debrominated Br-Tyr, with comparable kcat¬ and KM to wildtype DmIYD. The Br-Tyr quantity in fly food and its differential accumulation in female versus male flies with the deletion of DmIYD gene were examined to support an endogenous production of Br-Tyr. These findings contribute to establishing a physiological role of IYD in maintaining the long-term male fertility in Drosophila melanogaster by eliminating Br-Tyr
GENERATING EPIDEMIOLOGICAL EVIDENCE FOR INNOVATIONS IN MALARIA INTERVENTIONS ACROSS TRANSMISSION STRATA IN ZAMBIA: EXPLORING THE TIMING OF INDOOR RESIDUAL SPRAYING AND IMPLEMENTATION OF ELIMINATION STRATEGIES
No full textMalaria is a vector borne disease that causes over a half a million deaths in young children annually. While disease burden declined precipitously from 2000 - 2016, recent stagnation in global progress, intransigently high transmission in high burden areas, and elimination in low transmission areas require new approaches. While novel tools are in various stages development, innovative approaches to already available interventions should be considered. This work, conducted in Zambia, evaluated a modification to the planning of indoor residual spraying, a long-used intervention for malaria prevention in high transmission settings. It also evaluated an innovative surveillance platform, layered atop a focal reactive strategy in a pre-elimination setting. First, we conducted a comparison-control study of a prospective longitudinal cohort in Nchelenge District, a high transmission area, to determine if a change in indoor residual spraying (IRS) timing to better target the seasonality of the vector population would result in a decrease in malaria prevalence. Second, we conducted a type-two implementation effectiveness study of “1-3-7” surveillance of focus investigation in Choma District, a low transmission area. This included a zonal-randomized trial to measure the impact of 1-3-7 surveillance and a mixed-methods study to assess implementation outcomes. In addition, measures of parasite relatedness were used to explore patterns of local transmission. In Nchelenge, IRS was associated with a reduction in the hazard of infection but was not associated with a change in the prevalence of parasitemia or vector abundance, suggesting IRS may prevent infections but did not interrupt transmission in this setting. In Choma, 1-3-7 was largely accepted and feasible and associated with a decline in clinical incidence. The malaria parasites in this area were highly related, with over two thirds of the cases containing highly related parasites linked in a persistent chain of transmission across the entire study period. Taken together, these finding support the use of and importance of multiple epidemiological outcomes in malaria study design. These findings also suggest that in areas of both high and low transmission, malaria interventions can have difficult to measure individual or very localized population benefits
MYELOID CELL IMMUNE RESPONSES TO SARS-CoV-2: FROM INFLAMMASOME ACTIVATION TO IMMUNE SUPPRESSION
No full textInfection with SARS-CoV-2, the pathogenic agent underlying the COVID-19 pandemic, is characterized by cytokine dysregulation and a simultaneous inflammatory and immunosuppressive phenomenon in effector cells. While mRNA vaccines have demonstrated success in reducing disease severity, the determinants of severe COVID-19 manifest in some individuals, while others remain asymptomatic or exhibit mild symptoms, remain unclear. Understanding the immune responses to this viral infection is crucial for deciphering the pathogenesis of SARS-CoV-2 and for developing effective treatments.
The innate immune response is the host's initial defense against pathogens. In the context of viral infections, early control relies on innate sensing through multiple pathways. Inflammasomes, large multiprotein complexes, play a central role in stimulating host inflammatory response by cleaving pro-forms of IL-1β and IL-18 into active, mature cytokines. Our research revealed significantly elevated plasma IL-18 levels in COVID-19 patients compared to healthy individuals, with IL-18 levels directly correlating with disease severity. Here, we investigate the causal role of the NLRP3 inflammasome in SARS-CoV-2-induced inflammation. THP-1, macrophage-like cell line, activates the inflammasome in response to SARS-CoV-2 via TLR2. Notably, inflammatory cytokines produced by inflammasome activation did not suppress viral replication, suggesting that aberrant inflammasome activation may enhance severity in individuals with high IL-18 levels.
Neutrophils, granulocytes recognized for their role in eliminating bacterial and fungal infections, have been implicated in COVID-19 pathogenesis due to their activation and degranulation signatures. In this study, we discovered a neutrophil subset known as the polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in circulation and in the bronchioalveolar lavage fluid samples of COVID-19 patients. Abundance of PMN-MDSC was a strong predictor of disease severity. Direct sensing of SARS-CoV-2 can lead to induction of PMN-MDSC markers from resting mature neutrophils. These viral-induced PMN-MDSC are functionally suppressive via neutrophil degranulation and programmed death ligand 1 (PD-L1) expression. Our findings identify biologically and clinically relevant factors in SARS-CoV-2 pathogenesis, highlighting a potential detrimental role in severe COVID-19.
Our data support that macrophages and neutrophils are major sources of hyperinflammation and immunosuppression during COVID-19. Inflammatory responses are crucial for the host's defense against pathogens and the development of adaptive immunity, although they are associated with pathogenesis. Thus, a deeper understanding of the balance between beneficial and detrimental inflammatory responses is essential. This work collectively highlights the multifaceted roles of myeloid lineage cells in viral infections and underscores the need for a better understanding of how they contribute to viral diseases
Insights into human genetics and evolution from structurally complex genomic regions
Get PDFThe development of third-generation long-read sequencing technologies has changed the landscape of genomics and the ways that the human genome is studied. In this thesis, we leverage novel computational and sequencing methods to advance our understanding of human genetics and evolution in some of the most challenging areas of the genome. We first describe the generation of a population-wide structural variant callset, which we use to identify structural variants under historical selection in human populations, uncovering evidence of an adaptive Neanderthal- introgressed haplotype. Next, we assess how the complete T2T-CHM13 reference genome improves variant calling and analysis, discovering evidence for evolutionary signatures within previously unresolved genomic regions. We then develop a simulation of somatic cell evolution, which we use to determine that telomere length is a key limiter of clonal expansion. Finally, we apply long-read RNA sequencing to five globally diverse human samples to discover novel RNA isoforms and resolve the complexity of transcription. Together, this work demonstrates the power of modern genomics technologies to advance our knowledge of human genetic variation and evolution — providing valuable insights into the genomic basis of human biology and disease
Data Integration Approaches to Estimate Heterogenous Treatment Effects
Get PDFClinicians and practitioners are often motivated to determine which treatment would work best for a given individual based on their observed characteristics, but doing so can be challenging because sample sizes are typically not large enough, and the variables involved in the true treatment effect heterogeneity are often unknown. To better understand treatment effect heterogeneity, researchers can rely on combining information from multiple sources, e.g., multiple randomized controlled trials (RCTs), or RCTs in conjunction with observational datasets. However, combining data requires taking into account that the data comes from heterogeneous sources, and different sources might have different settings, potential biases, and site-level characteristics that can impact treatment effects. This dissertation discusses approaches for integrating multiple datasets to estimate heterogeneous treatment effects. Previous approaches are outlined, and new methods are developed and introduced to estimate the conditional average treatment effect function across multiple trials and in a target population. The methods used are primarily non-parametric but compared to parametric meta-analysis. Methods are applied to real data comparing treatments for major depression to investigate potential heterogeneity of the treatment effect in this setting
Transport (and other) cocktails for solid tumor alpha-particle radiopharmaceutical therapy to overcome the heterogeneous intratumoral drug microdistributions
No full textHeterogeneous intratumoral drug microdistributions, which are especially pronounced in established solid tumors, are a major reason for treatment failure, since cancer cells not exposed to drugs will likely not be killed. The PhD research project interrogates a novel therapeutic strategy of employing simultaneously more than one, separate, delivery carriers of the same drug, an alpha-particle emitter. The carriers are chosen to deliver their therapeutic cargo in complementary regions of the same solid tumor. Collectively, the alpha particle emitters become well-spread within established, soft-tissue solid tumors. The study outcomes include remarkable improvements in cancer therapy, namely, better tumor growth inhibition and prolonged survival, in tumor bearing mice at low administered activities. This is a tumor agnostic strategy: the applicability of this approach is demonstrated on solid tumors of different origin. The physics, transport considerations, dosimetry and therapeutic effects are investigated and presented at the single-cell scale, the scale of multicellular spheroids and/or the whole-body animal scale
NOVEL INSIGHTS INTO THE ROLE OF GUT MICROBIOTA IN RENAL PHYSIOLOGY
Get PDFGut microbiota are commensal bacteria in the intestinal lumen and play a pivotal role in influencing host health. Previous research from our lab linked gut microbiota to kidney function by elucidating how microbial metabolites activate receptors in the kidney. While protein-level interactions between the host and microbiome have been extensively studied, the impact of intestinal microorganisms on gene expression in the kidney warrants further investigation. To address this, we conducted unbiased bulk RNA sequencing (RNA-Seq) to compare gene expression in germ-free versus conventionalized male and female mice, examining kidney, liver, and large intestine.
Our results reveal a sexually dimorphic, and tissue-specific, influence of microbiota on host gene expression. The pattern of differentially expressed genes (DEGs) were sex-specific: 85%, 90%, and 89% of DEGs changed in kidney, liver, and large intestine, respectively, in either males or females, but not both. Additional RNA-Seq analysis also revealed tissue-specific effects of commensal bacteria on gene expression: the DEGs in the kidney were different from the DEGs in both the liver and the large intestine. Interestingly, a subset of genes including Mt1, Mt2, Per1, and Per2 showed differential regulation across all three tissues and in both sexes, implicating their role in microbiota-mediated mechanisms.
Further investigations focused on metallothioneins (Mt1,Mt2) and circadian genes (Per1,Per2). Utilizing qPCR, we found metallothioneins were upregulated in antibiotic-treated mice in the kidney, and in both sexes examined. Furthermore, based on RNA-Seq analysis, Per1 and Per2 were upregulated in kidney and liver in the absence of gut microbes. Additional qPCR analysis revealed that male mice treated with oral antibiotics had altered rhythmicity in circadian gene in the kidney and liver.
Finally, Per1 is induced by an important hormone implicated in blood pressure regulation, aldosterone. Thus, we also examined the influence of gut microbiota on the renin-angiotensin aldosterone system, revealing elevated aldosterone levels in both plasma and urine in mice with suppressed or absent gut microbiota, particularly significant in males, indicating a potential role of microbiota in blood pressure regulation through aldosterone modulation. These findings suggest new avenues for understanding gut microbiota influences on host kidney, highlighting the therapeutic potential of microbiota-targeted interventions
Addressing Statistical Issues in Aging: Dynamical Systems Modeling and Estimating Age-Related Declines
No full textAs the population of older adults in the United States continues to grow, it is increasingly important that research addresses the health of these individuals. This thesis focuses on addressing statistical issues in modeling physiological changes with age.
We first explore the hypothesis that dysregulation of key physiological systems leads to adverse aging outcomes such as physical frailty and death. We do so by fitting the Ackerman model, a parametric, nonlinear model of the glucose-insulin system, to oral glucose tolerance test (OGTT) data. In Chapter 2, we develop guidelines for researchers looking to fit nonlinear models to individual-level data obtained from a heterogeneous cohort. We also apply functional principal components analysis (fPCA) to the OGTT data. Subsequent analyses suggest fPC summaries of OGTT curves in middle-aged and older adults are associated with survival (Chapter 2), longitudinal gait speeds (Chapter 3), and odds of robustness (Chapter 3); Ackerman model parameters were not associated with any of these outcomes.
In Chapter 4, our focus shifts to estimating physiological changes due to aging in the presence of period and cohort effects. The age-period-cohort (APC) problem refers to the identification problem arising due to period being the sum of age and cohort. In gerontological research, the APC problem is often ignored, resulting in age-related decline estimates which may be confounded by period and/or cohort effects. We conduct a literature survey to understand the scope of the under-representation of the APC problem in age-related decline papers and conduct a simulation study to demonstrate the impact of the problem in different sampling designs.
In this dissertation, we found that Ackerman model parameters were not associated with declines in age-related function. Considerable measurement variability in glucose response and sparse temporal sampling posed major challenges for our dynamical systems modeling framework. We found evidence of associations between fPCA summaries and age-related declines in function. The findings from Chapter 4 indicate the APC can substantially bias age-related change estimates, but careful study design selection can mitigate this issue if only period or cohort effects are suspected