OX40 signaling favors the induction of T(H)9 cells and airway inflammation.

The mechanisms that regulate the T(H)9 subset of helper T cells and diseases mediated by T(H)9 cells remain poorly defined. Here we found that the costimulatory receptor OX40 was a powerful inducer of T(H)9 cells in vitro and T(H)9 cell-dependent airway inflammation in vivo. In polarizing conditions based on transforming growth factor-ß (TGF-ß), ligation of OX40 inhibited the production of induced regulatory T cells and the T(H)17 subset of helper T cells and diverted CD4(+)Foxp3(-) T cells to a T(H)9 phenotype. Mechanistically, OX40 activated the ubiquitin ligase TRAF6, which triggered induction of the kinase NIK in CD4(+) T cells and the noncanonical transcription factor NF-κB pathway; this subsequently led to the generation of T(H)9 cells. Thus, our study identifies a previously unknown mechanism for the induction of T(H)9 cells and may have important clinical implications in allergic inflammation.

Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance.

The intracellular signaling molecule TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). We now report that DC-specific deletion of TRAF6 (TRAF6ΔDC) resulted, unexpectedly, in loss of mucosal tolerance, characterized by spontaneous development of T helper 2 (Th2) cells in the lamina propria and eosinophilic enteritis and fibrosis in the small intestine. Loss of tolerance required the presence of gut commensal microbiota but was independent of DC-expressed MyD88. Further, TRAF6ΔDC mice exhibited decreased regulatory T (Treg) cell numbers in the small intestine and diminished induction of iTreg cells in response to model antigen. Evidence suggested that this defect was associated with diminished DC expression of interleukin-2 (IL-2). Finally, we demonstrate that aberrant Th2 cell-associated responses in TRAF6ΔDC mice could be mitigated via restoration of Treg cell activity. Collectively, our findings reveal a role for TRAF6 in directing DC maintenance of intestinal immune tolerance through balanced induction of Treg versus Th2 cell immunity.

Mice Lacking the Purinergic Receptor P2X5 Exhibit Defective Inflammasome Activation and Early Susceptibility to Listeria monocytogenes.

P2X5 is a member of the P2X purinergic receptor family of ligand-gated cation channels and has recently been shown to regulate inflammatory bone loss. In this study, we report that P2X5 is a protective immune regulator during Listeria monocytogenes infection, as P2X5-deficient mice exhibit increased bacterial loads in the spleen and liver, increased tissue damage, and early (within 3-6 d) susceptibility to systemic L. monocytogenes infection. Whereas P2X5-deficient mice experience normal monocyte recruitment in response to L. monocytogenes, P2X5-deficient bone marrow-derived macrophages (BMMs) exhibit defective cytosolic killing of L. monocytogenes We further showed that P2X5 is required for L. monocytogenes-induced inflammasome activation and IL-1ß production and that defective L. monocytogenes killing in P2X5-deficient BMMs is substantially rescued by exogenous IL-1ß or IL-18. Finally, in vitro BMM killing and in vivo L. monocytogenes infection experiments employing either P2X7 deficiency or extracellular ATP depletion suggest that P2X5-dependent anti-L. monocytogenes immunity is independent of the ATP-P2X7 inflammasome activation pathway. Together, our findings elucidate a novel and specific role for P2X5 as a critical mediator of protective immunity.

Regulation of T cell-associated tissues and T cell activation by RANKL-RANK-OPG.

The receptor activator of nuclear factor kappa-B ligand (RANKL)-RANK-osteoprotegerin (OPG) system is critical to bone homeostasis, but genetically deficient mouse models have revealed important roles in the immune system as well. RANKL-RANK-OPG is particularly important to T cell biology because of its organogenic control of thymic development and secondary lymphoid tissues influence central T cell tolerance and peripheral T cell function. RANKL-RANK-OPG cytokine-receptor interactions are often controlled by regulation of expression of RANKL on developing T cells, which interacts with RANK expressed on some lymphoid tissue cells to stimulate key downstream signaling pathways that affect critical tuning functions of the T cell compartment, like cell survival and antigen presentation. Activation of peripheral T cells is regulated by RANKL-enhanced dendritic cell survival, and dysregulation of the RANKL-RANK-OPG system in this context is associated with loss of T cell tolerance and autoimmune disease. Given its broader implications for immune homeostasis and osteoimmunology, it is critical to further understand how the RANKL-RANK-OPG system operates in T cell biology.

CD44 Can Compensate for IgSF11 Deficiency by Associating with the Scaffold Protein PSD-95 during Osteoclast Differentiation.

Differentiation of osteoclasts, which are specialized multinucleated macrophages capable of bone resorption, is driven primarily by receptor activator of NF-κB ligand (RANKL). Additional signaling from cell surface receptors, such as cell adhesion molecules (CAMs), is also required for osteoclast maturation. Previously, we have demonstrated that immunoglobulin superfamily 11 (IgSF11), a member of the immunoglobulin-CAM (IgCAM) family, plays an important role in osteoclast differentiation through association with the scaffold protein postsynaptic density protein 95 (PSD-95). Here, we demonstrate that the osteoclast-expressed CAM CD44 can compensate for IgSF11 deficiency when cell-cell interaction conditions are suboptimal by associating with PSD-95. Impaired osteoclast differentiation in IgSF11-deficient (IgSF11-/-) cultures was rescued by antibody-mediated stimulation of CD44 or by treatment with low-molecular-weight hyaluronan (LMW-HA), a CD44 ligand. Biochemical analysis revealed that PSD-95, which is required for osteoclast differentiation, associates with CD44 in osteoclasts regardless of the presence or absence of IgSF11. RNAi-mediated knockdown of PSD-95 abrogated the effects of either CD44 stimulation or LMW-HA treatment on osteoclast differentiation, suggesting that CD44, similar to IgSF11, is functionally associated with PSD-95 during osteoclast differentiation. Taken together, these results reveal that CD44 can compensate for IgSF11 deficiency in osteoclasts through association with PSD-95.

Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-ß receptors (TGFßR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs.

Dendritic cell expression of the signaling molecule TRAF6 is required for immune tolerance in the lung.

Immune tolerance in the lung is important for preventing hypersensitivity, such as allergic asthma. Maintenance of tolerance in the lung is established by coordinated activities of poorly understood cellular and molecular mechanisms, including participation of dendritic cells (DCs). We have previously identified DC expression of the signaling molecule TRAF6 as a non-redundant requirement for the maintenance of immune tolerance in the small intestine of mice. Because mucosal tissues share similarities in how they interact with exogenous antigens, we examined the role of DC-expressed TRAF6 in the lung. As with the intestine, we found that the absence TRAF6 expression by DCs led to spontaneous generation of Th2-associated immune responses and increased susceptibility to model antigen-induced asthma. To examine the role of commensal microbiota, mice deficient in TRAF6 in DCs were treated with broad-spectrum antibiotics and/or re-derived on a germ-free (GF) background. Interestingly, we found that antibiotics-treated specific pathogen-free, but not GF, mice showed restored immune tolerance in the absence of DC-expressed TRAF6. We further found that antibiotics mediate microbiota-independent effects on lung T cells to promote immune tolerance in the lung. This work provides both a novel tool for studying immune tolerance in the lung and an advance in our conceptual understanding of potentially common molecular mechanisms of immune tolerance in both the intestine and the lung.

Interaction of Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) and Vav3 in the Receptor Activator of Nuclear Factor κB (RANK) Signaling Complex Enhances Osteoclastogenesis.

The signaling pathway downstream of stimulation of receptor activator of nuclear factor κB (RANK) by RANK ligand is crucial for osteoclastogenesis. RANK recruits TNF receptor-associated factor 6 (TRAF6) to TRAF6-binding sites (T6BSs) in the RANK cytoplasmic tail (RANKcyto) to trigger downstream osteoclastogenic signaling cascades. RANKcyto harbors an additional highly conserved domain (HCR) that also activates crucial signaling during RANK-mediated osteoclastogenesis. However, the functional cross-talk between T6BSs and the HCR in the RANK signaling complex remains unclear. To characterize the cross-talk between T6BSs and the HCR, we screened TRAF6-interacting proteins using a proteomics approach. We identified Vav3 as a novel TRAF6 binding partner and evaluated the functional importance of the TRAF6-Vav3 interaction in the RANK signaling complex. We demonstrated that the coiled-coil domain of TRAF6 interacts directly with the Dbl homology domain of Vav3 to form the RANK signaling complex independent of the TRAF6 ubiquitination pathway. TRAF6 is recruited to the RANKcyto mutant, which lacks T6BSs, via the Vav3 interaction; conversely, Vav3 is recruited to the RANKcyto mutant, which lacks the IVVY motif, via the TRAF6 interaction. Finally, we determined that the TRAF6-Vav3 interaction resulting from cross-talk between T6BSs and the IVVY motif in RANKcyto enhances downstream NF-κB, MAPK, and NFATc1 activation by further strengthening TRAF6 signaling, thereby inducing RANK-mediated osteoclastogenesis. Thus, Vav3 is a novel TRAF6 interaction partner that functions in the activation of cooperative signaling between T6BSs and the IVVY motif in the RANK signaling complex.

TLR signalling augments macrophage bactericidal activity through mitochondrial ROS.

Reactive oxygen species (ROS) are essential components of the innate immune response against intracellular bacteria and it is thought that professional phagocytes generate ROS primarily via the phagosomal NADPH oxidase machinery. However, recent studies have suggested that mitochondrial ROS (mROS) also contribute to mouse macrophage bactericidal activity, although the mechanisms linking innate immune signalling to mitochondria for mROS generation remain unclear. Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation. ECSIT- and TRAF6-depleted macrophages have decreased levels of TLR-induced ROS and are significantly impaired in their ability to kill intracellular bacteria. Additionally, reducing macrophage mROS levels by expressing catalase in mitochondria results in defective bacterial killing, confirming the role of mROS in bactericidal activity. These results reveal a novel pathway linking innate immune signalling to mitochondria, implicate mROS as an important component of antibacterial responses and further establish mitochondria as hubs for innate immune signalling.

Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity.

Fatty acids (FAs) are essential constituents of cell membranes, signaling molecules, and bioenergetic substrates. Because CD8(+) T cells undergo both functional and metabolic changes during activation and differentiation, dynamic changes in FA metabolism also occur. However, the contributions of de novo lipogenesis to acquisition and maintenance of CD8(+) T cell function are unclear. In this article, we demonstrate the role of FA synthesis in CD8(+) T cell immunity. T cell-specific deletion of acetyl coenzyme A carboxylase 1 (ACC1), an enzyme that catalyzes conversion of acetyl coenzyme A to malonyl coenzyme A, a carbon donor for long-chain FA synthesis, resulted in impaired peripheral persistence and homeostatic proliferation of CD8(+) T cells in naive mice. Loss of ACC1 did not compromise effector CD8(+) T cell differentiation upon listeria infection but did result in a severe defect in Ag-specific CD8(+) T cell accumulation because of increased death of proliferating cells. Furthermore, in vitro mitogenic stimulation demonstrated that defective blasting and survival of ACC1-deficient CD8(+) T cells could be rescued by provision of exogenous FA. These results suggest an essential role for ACC1-mediated de novo lipogenesis as a regulator of CD8(+) T cell expansion, and may provide insights for therapeutic targets for interventions in autoimmune diseases, cancer, and chronic infections.

IL-18 synergizes with IL-7 to drive slow proliferation of naive CD8 T cells by costimulating self-peptide-mediated TCR signals.

Naive T cell populations are maintained in the periphery at relatively constant levels via mechanisms that control expansion and contraction and are associated with competition for homeostatic cytokines. It has been shown that in a lymphopenic environment naive T cells undergo expansion due, at least in part, to additional availability of IL-7. We have previously found that T cell-intrinsic deletion of TNFR-associated factor (TRAF) 6 (TRAF6ΔT) in mice results in diminished peripheral CD8 T cell numbers. In this study, we report that whereas naive TRAF6ΔT CD8 T cells exhibit normal survival when transferred into a normal T cell pool, proliferation of naive TRAF6ΔT CD8 T cells under lymphopenic conditions is defective. We identified IL-18 as a TRAF6-activating factor capable of enhancing lymphopenia-induced proliferation (LIP) in vivo, and that IL-18 synergizes with high-dose IL-7 in a TRAF6-dependent manner to induce slow, LIP/homeostatic-like proliferation of naive CD8 T cells in vitro. IL-7 and IL-18 act synergistically to upregulate expression of IL-18R genes, thereby enhancing IL-18 activity. In this context, IL-18R signaling increases PI3K activation and was found to sensitize naive CD8 T cells to a model noncognate self-peptide ligand in a way that conventional costimulation via CD28 could not. We propose that synergistic sensitization by IL-7 and IL-18 to self-peptide ligand may represent a novel costimulatory pathway for LIP.

Food insecurity and dyslipidemia in a representative population-based sample in the US.

OBJECTIVE: The association of food insecurity with dyslipidemia has not been firmly established. The main objective of this study was to assess whether food insecurity was associated with dyslipidemia. METHOD: A population-based sample of 1,663 adults from the 2008-2011 Survey of the Health of Wisconsin was used. Food insecurity was defined as an affirmative response to either of the questions: (1) "In the last 12months, have you been concerned about having enough food for you or your family?" (2) "In the last 12months, have your food choices been limited because there wasn't enough money?" High total cholesterol was defined as total cholesterol (TC) >240mg/dL or taking prescribed lipid-lowering medication. Low high-density lipoprotein cholesterol (HDL-C) was defined as <40mg/dL in men and <50mg/dL in women. RESULTS: Food insecurity was not associated with high TC either among men or women. Food insecurity was associated with a higher likelihood of low HDL-C among women (adjusted odds ratio [AOR]: 2.31 {95% confidence interval [CI]: 1.42, 3.76}), but not among men. Obesity appears to be a partial mediator of the association among women (P from the Sobel test=0.01). CONCLUSION: These findings suggest that food insecurity may contribute to an increased risk of low HDL-C in women.

Enhancing CD8 T-cell memory by modulating fatty acid metabolism.

CD8 T cells, which have a crucial role in immunity to infection and cancer, are maintained in constant numbers, but on antigen stimulation undergo a developmental program characterized by distinct phases encompassing the expansion and then contraction of antigen-specific effector (T(E)) populations, followed by the persistence of long-lived memory (T(M)) cells. Although this predictable pattern of CD8 T-cell responses is well established, the underlying cellular mechanisms regulating the transition to T(M) cells remain undefined. Here we show that tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an adaptor protein in the TNF-receptor and interleukin-1R/Toll-like receptor superfamily, regulates CD8 T(M)-cell development after infection by modulating fatty acid metabolism. We show that mice with a T-cell-specific deletion of TRAF6 mount robust CD8 T(E)-cell responses, but have a profound defect in their ability to generate T(M) cells that is characterized by the disappearance of antigen-specific cells in the weeks after primary immunization. Microarray analyses revealed that TRAF6-deficient CD8 T cells exhibit altered expression of genes that regulate fatty acid metabolism. Consistent with this, activated CD8 T cells lacking TRAF6 display defective AMP-activated kinase activation and mitochondrial fatty acid oxidation (FAO) in response to growth factor withdrawal. Administration of the anti-diabetic drug metformin restored FAO and CD8 T(M)-cell generation in the absence of TRAF6. This treatment also increased CD8 T(M) cells in wild-type mice, and consequently was able to considerably improve the efficacy of an experimental anti-cancer vaccine.

The association between neighborhood economic hardship, the retail food environment, fast food intake, and obesity: findings from the Survey of the Health of Wisconsin.

BACKGROUND: Neighborhood-level characteristics such as economic hardship and the retail food environment are assumed to be correlated and to influence consumers' dietary behavior and health status, but few studies have investigated these different relationships comprehensively in a single study. This work aims to investigate the association between neighborhood-level economic hardship, the retail food environment, fast food consumption, and obesity prevalence. METHODS: Linking data from the population-based Survey of the Health of Wisconsin (SHOW, n = 1,570, 2008-10) and a commercially available business database, the Wisconsin Retail Food Environment Index (WRFEI) was defined as the mean distance from each participating household to the three closest supermarkets divided by the mean distance to the three closest convenience stores or fast food restaurants. Based on US census data, neighborhood-level economic hardship was defined by the Economic Hardship Index (EHI). Relationships were analyzed using multivariate linear and logistic regression models. RESULTS: SHOW residents living in neighborhoods with the highest economic hardship faced a less favorable retail food environment (WRFEI = 2.53) than residents from neighborhoods with the lowest economic hardship (WRFEI = 1.77; p-trend < 0.01). We found no consistent or significant associations between the WRFEI and obesity and only a weak borderline-significant association between access to fast food restaurants and self-reported fast food consumption (≥ 2 times/week, OR = 0.59-0.62, p = 0.05-0.09) in urban residents. Participants reporting higher frequency of fast food consumption (≥ 2 times vs. <2 times per week) were more likely to be obese (OR = 1.35, p = 0.06). CONCLUSION: This study indicates that neighborhood-level economic hardship is associated with an unfavorable retail food environment. However inconsistent or non-significant relationships between the retail food environment, fast food consumption, and obesity were observed. More research is needed to enhance methodological approaches to assess the retail food environment and to understand the complex relationship between neighborhood characteristics, health behaviors, and health outcomes.

Health Literacy and Health-Related Quality of Life Among a Population-Based Sample of Cancer Patients.

Health-related quality of life is an important outcome in cancer care. A few studies indicate that health literacy influences cancer patients' health-related quality of life, but additional investigation is needed. The authors examined the relation between health literacy and health-related quality of life among cancer patients. A cross-sectional survey was conducted with cancer patients in Wisconsin during 2006-2007. Data on sociodemographics, clinical characteristics, health-related quality of life, and health literacy were obtained from the state's cancer registry and a mailed questionnaire. Regression analyses were used to characterize the association between health-related quality of life and health literacy. The study sample included 1,841 adults, newly diagnosed with lung, breast, colorectal, or prostate cancer in 2004 (response rate = 68%). Health-related quality of life was measured with the Functional Assessment of Cancer Therapy-General. Adjusting for confounders, higher health literacy was associated with greater health-related quality of life (p < .0001). Controlling for covariates, we found significant differences between those in the highest and lowest health literacy categories (p < .0001) and in the physical (p < .0001), functional (p < .0001), emotional (p < .0001), and social (p = .0007) well-being subscales. These associations exceeded the minimally important difference threshold for overall health-related quality of life and functional well-being. Health literacy is positively and independently associated with health-related quality of life among cancer patients. These findings support adoption of health literacy best practices by cancer care systems.

The Wisconsin Assessment of the Social and Built Environment (WASABE): a multi-dimensional objective audit instrument for examining neighborhood effects on health.

BACKGROUND: Growing evidence suggests that mixed methods approaches to measuring neighborhood effects on health are needed. The Wisconsin Assessment of the Social and Built Environment (WASABE) is an objective audit tool designed as an addition to a statewide household-based health examination survey, the Survey of the Health of Wisconsin (SHOW), to objectively measure participant's neighborhoods. METHODS: This paper describes the development and implementation of the WASABE and examines the instrument's ability to capture a range of social and built environment features in urban and rural communities. A systematic literature review and formative research were used to create the tool. Inter-rater reliability parameters across items were calculated. Prevalence and density of features were estimated for strata formed according to several sociodemographic and urbanicity factors. RESULTS: The tool is highly reliable with over 81% of 115 derived items having percent agreement above 95%. It captured variance in neighborhood features in for a diverse sample of SHOW participants. Sidewalk density in neighborhoods surrounding households of participants living at less than 100% of the poverty level was 67% (95% confidence interval, 55-80%) compared to 34% (25-44%) for those living at greater than 400% of the poverty level. Walking and biking trails were present in 29% (19-39%) of participant buffer in urban areas compared to only 7% (2-12%) in rural communities. Significant environmental differences were also observed for white versus non-white, high versus low income, and college graduates versus individuals with lower level of education. CONCLUSIONS: The WASABE has strong inter-rater reliability and validity properties. It builds on previous work to provide a rigorous and standardized method for systematically gathering objective built and social environmental data in a number of geographic settings. Findings illustrate the complex milieu of built environment features found in participants neighborhoods and have relevance for future research, policy, and community engagement purposes.

Urban-rural and regional variability in the prevalence of food insecurity: the survey of the health of Wisconsin.

BACKGROUND: Food insecurity is a public health concern estimated to affect 18 million American households nationally, which can result in chronic nutritional deficiencies and other health risks. The relationships between food insecurity and specific demographic and geographic factors in Wisconsin are not well documented. The goals of this paper are to investigate sociodemographic and geographic features associated with food insecurity in a representative sample of Wisconsin adults. METHODS: This study used data from the Survey of the Health of Wisconsin (SHOW). SHOW annually collects health-related data on a representative sample of Wisconsin residents. Between 2008-2012, 2,947 participants were enrolled in the SHOW study. The presence of food insecurity was defined based on the participant's affirmative answer to the question "In the last 12 months, have you been concerned about having enough food for you or your family?" RESULTS: After adjustment for age, race, and gender, 13.2% (95% CI, 10.8%-15.1%) of participants reported food insecurity, 56.7% (95% CI, 50.6%-62.7%) of whom were female. Food insecurity did not statistically differ by region (P = 0.30). The adjusted prevalence of food insecurity in the urban core, other urban, and rural areas was 14.1%, 6.5%, and 10.5%, respectively. These differences were not statistically significant (P = 0.13) and, for urban core and rural areas, persisted even when accounting for level of economic hardship in the community. CONCLUSIONS: The prevalence of food insecurity is substantial, affecting an estimated 740,000 or more Wisconsin residents. The prevalence was similarly high in all urbanicity levels and across all state public health regions in Wisconsin. Food insecurity is a common problem with potentially serious health consequences affecting populations across the entire state.

Overall prescription medication use among adults: findings from the Survey of the Health of Wisconsin.

PURPOSE: To analyze overall prescription medication use patterns among study participants in a representative statewide sample of Wisconsin adults. METHODS: We analyzed data on 1572 participants from the 2008-2010 cycles of the Survey of the Health of Wisconsin (SHOW). SHOW is a statewide population-based survey that collects health information, including prescription medications, from 21 to 74 year olds. Prescription medication use was examined according to demographic and socioeconomic characteristics. RESULT: Almost 55% of participants reported using at least 1 medication in the past month and 14% reported using at least 5 medications. The top 5 medications reported were lisinopril, hydrochlorothiazide, simvastatin, levothyroxine, and metoprolol. Overall prescription medication use increased significantly with age. Medication use was greater among females, former smokers, adults with body mass index (BMI) ≥ 30, or with low family income, and non-hispanic blacks. Adults having health insurance, drug coverage, or a regular source of care were more likely to report medication use. CONCLUSION: The prevalence of prescription medication use in a general population sample in Wisconsin was high. Age, gender, race, BMI, family income, smoking history, health insurance, prescription drug coverage, and having a regular source of health care were associated with prescription medication use.

Participant attrition from statewide, population-based Survey of the Health of Wisconsin into the longitudinal SHOW COVID-19 cohort.

PURPOSE: Longitudinal studies are essential for examining how social and institutional determinants of health, historical and contemporary, affect disparities in COVID-19 related outcomes. The unequal impacts of COVID-19 likely exacerbated selected attrition in longitudinal research. This study examines attrition and survey mode effects in the SHOW COVID-19 study which recruited from a statewide, representative cohort. MATERIALS & METHODS: Participants were recruited from the Survey of the Health of Wisconsin (SHOW) cohort. Online surveys, or phone interviews, were administered at three timepoints during 2020-2021. The surveys captured social, behavioral, and structural determinants of health and the lived experience. Univariate and multivariate logistic regression was used to examine predictors of participation and survey mode effects. RESULTS: A total of 2304 adults completed at least one COVID-19 online survey. Participants were more educated, older, and more likely to be female, married, non-Hispanic, and White compared to non-participants. Phone participants were older, less educated, and more likely be non-White, food insecure, and have co-morbidities compared to online participants. Mode effects were seen with reporting COVID-19 beliefs, loneliness, and anxiety. CONCLUSION: The SHOW COVID-19 cohort offers unique longitudinal data but suffered from selected attrition. Phone interview is an important mode for retention and representation.