The association of safety-net program participation with government perceptions, welfare stigma, and discrimination.

Safety-net programs in the United States offered critical support to counter food insecurity and poverty during the first year of the COVID-19 pandemic. The Supplemental Nutrition Assistance Program (SNAP) and the Earned Income Tax Credit (EITC) are both means-tested programs with significant benefits. Take-up of SNAP and EITC is lower in California than nationwide and reasons for this difference are unclear. We examined associations of participation in SNAP and receipt of the EITC and perceptions of the US government, 2 types of welfare stigma (program stigma and social stigma), and perceived discrimination. We interviewed a sample of 497 caregivers of young children from families with low income in California during the COVID-19 pandemic (August 2020-May 2021). We found that participation in SNAP (odds ratio [OR] = 1.24 [1.05, 1.47]) and receiving the EITC (OR = 1.39 [1.05, 1.84]) were both associated with greater reported perceptions of social stigma, but not with perceptions of government, program stigma, or discrimination. Among food-insecure respondents, we found that participation in SNAP was additionally associated with program stigma and discrimination. These findings suggest that perceived social stigma may be a reason that people with low income may not participate in programs for which they are eligible.

Understanding Multiprogram Take-Up of Safety Net Programs Among California Families.

Introduction: The U.S. safety net, which provides critical aid to households with low income, is composed of a patchwork of separate programs, and many people with low income benefit from accessing <1 program. However, little is known about multiprogram take-up, that is, participation conditioned on eligibility. This study examined individual and multiprogram take-up patterns and sociodemographic factors associated with multiprogram take-up of U.S. safety net programs. Methods: The Assessing California Communities' Experiences with Safety Net Supports study interviewed Californians and reviewed their 2019 tax forms between August 2020 and May 2021. Take-up of safety net programs was calculated among eligible participants (n=365), including the Earned Income Tax Credit; Supplemental Nutrition Assistance Program; the Special Supplemental Nutrition Program for Women, Infants, and Children; and Medicaid. Multivariable regressions identified sociodemographic factors associated with take-up of multiple programs. Results: Take-up was highest for Medicaid (90.6%) and lowest for Supplemental Nutrition Assistance Program (57.5%). Among people who received benefits from at least 1 other program, take-up ranged from 81.7% to 84.8% for the Earned Income Tax Credit; 54.4%-62.0% for Supplemental Nutrition Assistance Program; 74.3%-80.1% for Special Supplemental Nutrition Program for Women, Infants, and Children; and 89.7%-98.1% for Medicaid. Having a lower income and being younger were associated with concurrent take-up of Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children. Among Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children recipients, having higher income, being older, and being primarily English speaking were associated with Earned Income Tax Credit take-up. Conclusions: Individual and multiprogram take-up vary between programs and by sociodemographic factors. Findings suggest opportunities to increase take-up of potentially synergistic programs by improving cross-program coordination, data sharing, and targeted recruitment of underenrolled subgroups (Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children).

Fluoxetine restrains allergic inflammation by targeting an FcɛRI-ATP positive feedback loop in mast cells.

There is a clinical need for new treatment options addressing allergic disease. Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that have anti-inflammatory properties. We tested the effects of the SSRI fluoxetine on IgE-induced function of mast cells, which are critical effectors of allergic inflammation. We showed that fluoxetine treatment of murine or human mast cells reduced IgE-mediated degranulation, cytokine production, and inflammatory lipid secretion, as well as signaling mediated by the mast cell activator ATP. In a mouse model of systemic anaphylaxis, fluoxetine reduced hypothermia and cytokine production. Fluoxetine was also effective in a model of allergic airway inflammation, where it reduced bronchial responsiveness and inflammation. These data show that fluoxetine suppresses mast cell activation by impeding an FcɛRI-ATP positive feedback loop and support the potential repurposing of this SSRI for use in allergic disease.

Potential mechanisms linking poverty alleviation and health: an analysis of benefit spending among recipients of the U.S. earned income tax credit.

BACKGROUND: The earned income tax credit (EITC) is the largest U.S. poverty alleviation program for low-income families, disbursed annually as a lump-sum tax refund. Despite its well-documented health impacts, the mechanisms through which the EITC affects health are not well understood. The objective of this analysis was to examine self-reported spending patterns of tax refunds among EITC recipients to clarify potential pathways through which income may affect health. METHODS: We first examined spending patterns among 2020-2021 Assessing California Communities' Experiences with Safety Net Supports (ACCESS) study participants (N = 241) and then stratified the analysis by key demographic subgroups. RESULTS: More than half of EITC recipients reported spending their tax refunds on bills and debt (52.3%), followed by 49.4% on housing, and 37.8% on vehicles. Only 3.3% reported spending on healthcare. (Note: respondents could list more than one possible spending category.) Participants ages 30 + were more likely to spend on bills and debt relative to those ages 18-29 (57.6% versus 39.4%, respectively). Other subgroup analyses did not yield significant findings. CONCLUSIONS: Our findings suggest that EITC recipients primarily use their refunds on bills and debt, as well as on household and vehicle expenses. This supports the idea of the EITC as a safety net policy which addresses key social determinants of health.

Experiences of distress and gaps in government safety net supports among parents of young children during the COVID-19 pandemic: a qualitative study.

BACKGROUND: The COVID-19 pandemic prompted rapid federal, state, and local government policymaking to buffer families from the health and economic harms of the pandemic. However, there has been little attention to families' perceptions of whether the pandemic safety net policy response was adequate, and what is needed to alleviate lasting effects on family well-being. This study examines the experiences and challenges of families with low incomes caring for young children during the pandemic. METHODS: Semi-structured qualitative interviews conducted from August 2020 to January 2021 with 34 parents of young children in California were analyzed using thematic analysis. RESULTS: We identified three key themes related to parents' experiences during the pandemic: (1) positive experiences with government support programs, (2) challenging experiences with government support programs, and (3) distress resulting from insufficient support for childcare disruptions. Participants reported that program expansions helped alleviate food insecurity, and those attending community colleges reported accessing a range of supports through supportive counselors. However, many reported gaps in support for childcare and distance learning, pre-existing housing instability, and parenting stressors. With insufficient supports, additional childcare and education workloads resulted in stress and exhaustion, guilt about competing demands, and stagnation of longer-term goals for economic and educational advancement. CONCLUSIONS: Families of young children, already facing housing and economic insecurity prior to the pandemic, experienced parental burnout. To support family well-being, participants endorsed policies to remove housing barriers, and expand childcare options to mitigate job loss and competing demands on parents. Policy responses that either alleviate stressors or bolster supports have the potential to prevent distress catalyzed by future disasters or the more common destabilizing experiences of economic insecurity.

The Pent-Up Demand for Breastfeeding Among US Women: Trends After COVID-19 Shelter-in-Place.

Objectives. To estimate changes in national breastfeeding trends immediately before and after COVID-19‒related workplace closures in early 2020. Methods. The implementation of shelter-in-place policies in early 2020, when 90% of people in the United States were urged to remain at home, represents a unique natural experiment to assess the pent-up demand for breastfeeding among US women that may be stymied by the lack of a national paid leave policy. We used the 2017-2020 Pregnancy Risk Assessment Monitoring System (n = 118 139) to estimate changes in breastfeeding practices for births occurring before and after shelter-in-place policies were implemented in the United States. We did this in the overall sample and by racial/ethnic and income subgroups. Results. There was no change in breastfeeding initiation and a 17.5% increase in breastfeeding duration after shelter-in-place, with lingering effects through late 2020. High-income and White women demonstrated the largest gains. Conclusions. The United States ranks worse than similar countries when it comes to breastfeeding initiation and duration. This study suggests that this is partly attributable to inadequate access to postpartum paid leave. This study also demonstrates inequities introduced by patterns of remote work during the pandemic. (Am J Public Health. 2023;113(8):870-873. https://doi.org/10.2105/AJPH.2023.307313).

The Dynamic Role of Endoplasmic Reticulum Stress in Chronic Liver Disease.

Chronic liver disease (CLD) is a major worldwide public health threat, with an estimated prevalence of 1.5 billion individuals with CLD in 2020. Chronic activation of endoplasmic reticulum (ER) stress-related pathways is recognized as substantially contributing to the pathologic progression of CLD. The ER is an intracellular organelle that folds proteins into their correct three-dimensional shapes. ER-associated enzymes and chaperone proteins highly regulate this process. Perturbations in protein folding lead to misfolded or unfolded protein accumulation in the ER lumen, resulting in ER stress and concomitant activation of the unfolded protein response (UPR). The adaptive UPR is a set of signal transduction pathways evolved in mammalian cells that attempts to reestablish ER protein homeostasis by reducing protein load and increasing ER-associated degradation. However, maladaptive UPR responses in CLD occur due to prolonged UPR activation, leading to concomitant inflammation and cell death. This review assesses the current understanding of the cellular and molecular mechanisms that regulate ER stress and the UPR in the progression of various liver diseases and the potential pharmacologic and biological interventions that target the UPR.

Sugar-Sweetened Beverage Taxes and Perinatal Health: A Quasi-Experimental Study.

INTRODUCTION: One in 5 pregnant individuals report consuming sugar-sweetened beverages at least once per day. Excess sugar consumption during pregnancy is associated with several perinatal complications. As sugar-sweetened beverage taxes become increasingly common public health measures to reduce sugar-sweetened beverage consumption, evidence of the downstream effects of sugar-sweetened beverage taxes on perinatal health remains limited. METHODS: This longitudinal retrospective study examines whether sugar-sweetened beverage taxes in 5 U.S. cities were associated with decreased risk of perinatal complications, leveraging 2013-2019 U.S. national birth certificate data and a quasi-experimental difference-in-differences approach to estimate changes in perinatal outcomes. Analysis occurred from April 2021 through January 2023. RESULTS: The sample included 5,324,548 pregnant individuals and their live singleton births in the U.S. from 2013 through 2019. Sugar-sweetened beverage taxes were associated with a 41.4% decreased risk of gestational diabetes mellitus (-2.2 percentage points; 95% CI= -4.2, -0.2), a -7.9% reduction in weight-gain-for-gestational-age z-score (-0.2 standard deviations; 95% CI= -0.3, -0.01), and decreased risk of infants born small for gestational age (-4.3 percentage points; 95% CI= -6.5, -2.1). There were heterogeneous effects across subgroups, particularly for weight-gain-for-gestational-age z-score. CONCLUSIONS: Sugar-sweetened beverage taxes levied in five U.S. cities were associated with improvements in perinatal health. Sugar-sweetened beverage taxes may be an effective policy instrument for improving health during pregnancy, a critical window during which short-term dietary exposures can have lifelong consequences for the birthing person and child.

Effects Of The 2021 Expanded Child Tax Credit On Adults' Mental Health: A Quasi-Experimental Study.

The US Congress temporarily expanded the Child Tax Credit (CTC) during the COVID-19 pandemic to provide economic assistance for families with children. Although formerly the CTC provided $2,000 per child for mostly middle-income parents, during July-December 2021 it provided up to $3,600 per child. Eligibility criteria were also expanded to reach more economically disadvantaged families. There has been little research evaluating the effect of the policy expansion on mental health. Using data from the Census Bureau's Household Pulse Survey and a quasi-experimental study design, we examined the effects of the expanded CTC on mental health and related outcomes among low-income adults with children, and by racial and ethnic subgroup. We found fewer depressive and anxiety symptoms among low-income adults. Adults of Black, Hispanic, and other racial and ethnic backgrounds demonstrated greater reductions in anxiety symptoms compared to non-Hispanic White adults with children. There were no changes in mental health care use. These findings are important for Congress and state legislators to weigh as they consider making the expanded CTC and other similar tax credits permanent to support economically disadvantaged families.

Understanding Take-Up Of The Earned Income Tax Credit Among Californians With Low Income.

The Earned Income Tax Credit (EITC) is the largest poverty alleviation program for families with children in the US, and it has well-documented health effects. However, not all eligible families receive benefits. The Assessing California Communities' Experiences with Safety Net Supports (ACCESS) Study interviewed 411 EITC-eligible Californians with young children to understand low take-up of the federal EITC and California's supplemental CalEITC. Interviews were conducted in English and Spanish in 2020 and 2021 to gather information on sociodemographic characteristics, tax filing, and EITC receipt (verified via tax forms). Among those eligible for the EITC or CalEITC, 9 percent of participants did not file taxes; among those who did file taxes, about 84 percent received the EITC, and 83 percent received the CalEITC. Lower likelihood of federal EITC receipt among those eligible and filing taxes was associated with being younger, not speaking English, and not having prior knowledge of the EITC. Lower likelihood of CalEITC receipt among those eligible and filing taxes was associated with not speaking English. These findings can inform policies and community interventions to increase EITC take-up and thereby help address health equity.

RNA binding protein HuR protects against NAFLD by suppressing long noncoding RNA H19 expression.

BACKGROUND: NAFLD has become the most common chronic liver disease worldwide. Human antigen R (HuR), an RNA-binding protein, is an important post-transcriptional regulator. HuR has been reported as a key player in regulating lipid homeostasis in the liver and adipose tissues by using tissue-specific HuR knockout mice. However, the underlying mechanism by which hepatocyte-specific HuR regulates hepatic lipid metabolism under metabolic stress remains unclear and is the focus of this study. METHODS: Hepatocyte-specific HuR deficient mice (HuRhKO) and age-/gender-matched control mice, as well as long-noncoding RNA H19 knockout mice (H19-/-), were fed a Western Diet plus sugar water (WDSW). Hepatic lipid accumulation, inflammation and fibrosis were examined by histology, RNA transcriptome analysis, qRT-PCR, and Western blot analysis. Bile acid composition was measured using LC-MS/MS. RESULTS: Hepatocyte-specific deletion of HuR not only significantly increased hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also markedly induced inflammation by increasing immune cell infiltration and neutrophil activation under metabolic stress. In addition, hepatic deficiency of HuR disrupted bile acid homeostasis and enhanced liver fibrosis. Mechanistically, HuR is a repressor of H19 expression. Analysis of a recently published dataset (GSE143358) identified H19 as the top-upregulated gene in liver-specific HuR knockout mice. Similarly, hepatocyte-specific deficiency of HuR dramatically induced the expression of H19 and sphingosine-1 phosphate receptor 2 (S1PR2), but reduced the expression of sphingosine kinase 2 (SphK2). WDSW-induced hepatic lipid accumulation was alleviated in H19-/- mice. Furthermore, the downregulation of H19 alleviated WDSW-induced NAFLD in HuRhKO mice. CONCLUSIONS: HuR not only functions as an RNA binding protein to modulate post-transcriptional gene expression but also regulates H19 promoter activity. Hepatic HuR is an important regulator of hepatic lipid metabolism via modulating H19 expression.

Pandemic-related socioeconomic disruptions and adverse health outcomes: a cross-sectional study of female caregivers.

BACKGROUND: The COVID-19 pandemic and efforts to mitigate transmission resulted in sudden and widespread socioeconomic disruptions including school and child care closures, unemployment and underemployment, and housing precarity. Understanding the extent to which these disruptions may have contributed to adverse health outcomes is critical for establishing policy priorities that can mitigate further harm. METHODS: We explored the associations between pandemic-related child care, employment, and housing disruptions with depressive symptoms, self-rated health, and food security status among a sample of economically disadvantaged and racially diverse female caregivers of young children (n=464). Data were derived from the Assessing California Communities' Experiences with Safety Net Supports (ACCESS) study, which conducted survey-based interviews with California caregivers with low-income from August 2020 - May 2021. We implemented a series of multivariable Poisson regressions with robust standard errors to assess the potency of each exposure, independently and within the context of one another. RESULTS: Most caregivers experienced disruptions to child care (70%) and employment (63%); few experienced major housing disruptions (8%). Women that experienced child care and housing disruptions had greater depressive symptoms, lower self-rated health, and greater food insecurity, although the relationships for housing and depressive symptoms were modified by the timing of participants' interviews. Employment disruptions were not associated with any of the examined adverse health outcomes. CONCLUSION: In the wake of socioeconomic stressors brought about by the COVID-19 pandemic, attending to structural deficits in the child care system and increasing housing supports may be critical for protecting the health of caregivers.

Bile acids and sphingolipids in non-alcoholic fatty liver disease.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

Key Signaling in Alcohol-Associated Liver Disease: The Role of Bile Acids.

Alcohol-associated liver disease (ALD) is a spectrum of diseases, the onset and progression of which are due to chronic alcohol use. ALD ranges, by increasing severity, from hepatic steatosis to alcoholic hepatitis (AH) and alcohol-associated cirrhosis (AC), and in some cases, can lead to the development of hepatocellular carcinoma (HCC). ALD continues to be a significant health burden and is now the main cause of liver transplantations in the United States. ALD leads to biological, microbial, physical, metabolic, and inflammatory changes in patients that vary depending on disease severity. ALD deaths have been increasing in recent years and are projected to continue to increase. Current treatment centers focus on abstinence and symptom management, with little in the way of resolving disease progression. Due to the metabolic disruption and gut dysbiosis in ALD, bile acid (BA) signaling and metabolism are also notably affected and play a prominent role in disease progression in ALD, as well as other liver disease states, such as non-alcoholic fatty liver disease (NAFLD). In this review, we summarize the recent advances in the understanding of the mechanisms by which alcohol consumption induces hepatic injury and the role of BA-mediated signaling in the pathogenesis of ALD.

Characterizing the Landscape of Safety Net Programs and Policies in California during the COVID-19 Pandemic.

The COVID-19 pandemic prompted rapid and innovative policymaking around the world at the national, regional, and local levels. There has been limited work to systematically document and characterize new and expanded local U.S. pandemic-era policies, which is imperative to better understand the policy variation and resulting health impacts during this unprecedented time. California, the most populous U.S. state, provides a case example of a particularly active policy response. The aim of this Brief Report is to summarize the creation and potential areas of application of a newly created publicly available California- and US-based COVID-19 policy database. We generated an extensive list of California and US policies that were modified or created in response to the COVID-19 pandemic. From July-November 2021, we searched current and historical California and federal government websites, press releases, social media, and news sources and recorded detailed information on these policies, including coverage dates, eligibility criteria, and benefit amounts. This comprehensive dataset includes 39 public health, economic, housing, and safety net programs and policies implemented at both federal and state levels and provides details of the complex and multifaceted policy landscape in California from March 2020 to November 2021. Our database is publicly available. Future investigators can leverage the information systematically recorded in this database to rigorously assess the short- and long-term effects of these policies, which will in turn inform future preparedness response plans in California and beyond.

IL-33 priming amplifies ATP-mediated mast cell cytokine production.

Inflammatory responses are required to block pathogen infection but can also lead to hypersensitivity and chronic inflammation. Barrier tissues actively release IL-33, ATP, and other alarmins during cell stress, helping identify pathogenic stimuli. However, it is unclear how these signals are integrated. Mast cells are critical initiators of allergic inflammation and respond to IL-33 and ATP. We found that mouse mast cells had a 3-6-fold increase in ATP-induced cytokine production when pre-treated with IL-33. This effect was observed at ATP concentrations < 100 µM and required < 30-minute IL-33 exposure. ATP-induced degranulation was not enhanced by pretreatment nor was the response to several pathogen molecules. Mechanistic studies implicated the P2X7 receptor and calcineurin/NFAT pathway in the enhanced ATP response. Finally, we found that IL-33 + ATP co-stimulation enhanced peritoneal eosinophil and macrophage recruitment. These results support the hypothesis that alarmins collaborate to surpass a threshold necessary to initiate an inflammatory response.

Fluvastatin enhances IL-33-mediated mast cell IL-6 and TNF production.

Statins are HMG-CoA reductase inhibitors prescribed for lowering cholesterol. They can also inhibit inflammatory responses by suppressing isoprenylation of small G proteins. Consistent with this, we previously found that fluvastatin suppresses IgE-mediated mast cell function. However, some studies have found that statins induced pro-inflammatory cytokines in macrophages and NK cells. In contrast to IgE signaling, we show that fluvastatin augments IL-33-induced TNF and IL-6 production by mast cells. This effect required the key mast cell growth factor, stem cell factor (SCF). Treatment of IL-33-activated mast cells with mevalonic acid or isoprenoids reduced fluvastatin effects, suggesting fluvastatin acts at least partly by reducing isoprenoid production. Fluvastatin also enhanced IL-33-induced NF-κB transcriptional activity and promoted neutrophilic peritonitis in vivo, a response requiring mast cell activation. Other statins tested did not enhance IL-33 responsiveness. Therefore, this work supports observations of unexpected pro-inflammatory effects of some statins and suggests mechanisms by which this may occur. Because statins are candidates for repurposing in inflammatory disorders, our work emphasizes the importance of understanding the pleiotropic and possible unexpected effects of these drugs.

Peptide inhibition of acute lung injury in a novel two-hit rat model.

Acute lung injury (ALI) often causes severe trauma that may progress to significant morbidity and mortality. ALI results from a combination of the underlying clinical condition of the patient (e.g., inflammation) with a secondary insult such as viral pneumonia or a blood transfusion. While the secondary insult may be variable, the rapidly progressive disease process leading to pulmonary failure is typically mediated by an overwhelming innate immunological or inflammatory reaction driven by excessive complement and neutrophil-mediated inflammatory responses. We recently developed a 'two-hit' ALI rat model mediated by lipopolysaccharide followed by transfusion of incompatible human erythrocytes resulting in complement activation, neutrophil-mediated ALI and free DNA in the blood indicative of neutrophil extracellular trap formation. The objective of this study was to evaluate the role of peptide inhibitor of complement C1 (RLS-0071), a classical complement pathway inhibitor and neutrophil modulator in this animal model. Adolescent male Wistar rats were infused with lipopolysaccharide followed by transfusion of incompatible erythrocytes in the presence or absence of RLS-0071. Blood was collected at various time points to assess complement C5a levels, free DNA and cytokines in isolated plasma. Four hours following erythrocyte transfusion, lung tissue was recovered and assayed for ALI by histology. Compared to animals not receiving RLS-0071, lungs of animals treated with a single dose of RLS-0071 showed significant reduction in ALI as well as reduced levels of C5a, free DNA and inflammatory cytokines in the blood. These results demonstrate that RLS-0071 can modulate neutrophil-mediated ALI in this novel rat model.

Effectiveness of the recombinant zoster vaccine among Kaiser Permanente Hawaii enrollees aged 50 and older: A retrospective cohort study.

BACKGROUND: The incidence of herpes zoster (HZ) has been on the rise for decades in the United States. Clinical trials for the recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of over 90% in preventing herpes zoster. However, there is limited information on its effectiveness outside of a clinical trial setting, as well as its effectiveness against herpes zoster ophthalmicus (HZO). METHODS: A de-identified electronic health records database from Kaiser Permanente Hawaii (KPH) was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against HZ and HZO in immunocompetent, vaccine age-eligible individuals without a prior history of HZ, who were continuously enrolled in KPH for ≥365 days prior to becoming age-eligible for RZV between January 1, 2018, through December 31, 2019. RESULTS: A total of 78 356 adults were included in this study, with 11 864 (15.1%) adults receiving two valid doses of the recombinant zoster vaccine. The incidence rate of HZ was 325.6 (95% CI: 217.7 to 464.4) cases per 100 000 person-years in vaccinated persons compared to 1063.3 cases per 100 000 person-years (95% CI: 1006.0 to 1122.8) in the unvaccinated group. The incidence rate of HZO was 11.9 (95% CI: 0.7 to 52.3) cases per 100 000 person-years in the vaccinated group compared to 72.1 (95% CI: 58.0 to 88.3) in the unvaccinated group. RZV was 83.5% (95% CI: 74.9% to 89.2%) effective against HZ and 93.3% (95% CI: 48.7% to 99.1%) effective against HZO. CONCLUSIONS: RZV has demonstrated high effectiveness against both HZ and HZO outside of a clinical trial setting in the United States. Vaccine coverage is low, emphasizing the need for public health efforts to increase vaccination to reduce morbidity from HZ and HZO.

Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.

Mast cells are found primarily at interfaces with the external environment, where they provide protection from pathogens but also elicit allergic inflammation. Mast cell activation by antigen-induced aggregation of IgE bound to the high affinity receptor, FcεRI, is a critical factor leading to inflammation and bronchoconstriction. We previously found that Stat5 is activated by FcεRI and that Stat5B suppression decreased IgE-induced cytokine production in vitro, but in vivo responses have not been assessed. We now show that Stat5B-deficient (KO) mice have reduced responses to IgE-mediated anaphylaxis, despite normal mast cell tissue distribution. Similarly, Stat5B KO mast cells have diminished IgE-induced degranulation and cytokine secretion in vitro. These mice have elevated IgE production that is not correlated with an intrinsic B cell defect. The current work demonstrates that the Stat5B isoform is required for normal mast cell function and suggests it limits IgE production in vivo.