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BACKGROUND: Severe maternal morbidity is increasing in the United States. Black women experience the highest rates of severe maternal morbidity and also of preterm births, which are associated with severe maternal morbidity. The racial disparity of severe maternal morbidity across weeks of gestation has not been well-studied. OBJECTIVE: This study aimed to evaluate differences in severe maternal morbidity between Black and White birthing people by week of gestation. Differences may indicate periods of pregnancy when Black women are particularly vulnerable to severe maternal morbidity and may require additional interventions. STUDY DESIGN: This was a cross-sectional study using the National Inpatient Sample from 2019. We used International Classification of Diseases codes from Centers for Disease Control and Prevention guidelines to identify severe maternal morbidity from delivery hospitalizations. We examined the rates of severe maternal morbidity in Black vs White women by week of gestation to evaluate periods of pregnancy when Black women experience additional risks of severe maternal morbidity while adjusting for age, region, medical comorbidities, and Medicaid enrollment. Severe maternal morbidity was analyzed while both including and excluding cases for which blood transfusion was the only indicator of severe maternal morbidity. RESULTS: Overall, Black birthing people had twice the rate of severe maternal morbidity births compared with White birthing people (2.7% vs 1.3%; P<.0001) and were more likely to deliver preterm (14.7% vs 9.4%; P<.0001). The racial disparity of severe maternal morbidity was present throughout all weeks of gestation, with the largest gap observed at extremely and moderately preterm gestations (22-33 weeks). Rates of severe maternal morbidity for Black women peaked at 22 to 33 weeks' gestation and were lowest at term (≥37 weeks). Black women had a greater proportion of severe maternal morbidity cases due to blood transfusion (68.3% vs 64.5%; P<.01) and acute renal failure (11.1% vs 8.5%; P<.001). CONCLUSION: Black women experience a substantially higher rate of severe maternal morbidity at preterm gestations (22-36 weeks) in addition to higher rates of preterm delivery. Even when accounting for age, medical comorbidities, and social determinants, Black birthing people have higher odds of severe maternal morbidity throughout pregnancy.
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Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8+ T cell responses mediate disease. Although these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8+ T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8+ T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce ROS and ultimately increased the hypoxic state and granzyme B expression in CD8+ T cells. Importantly, lesions from patients with cutaneous leishmaniasis exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8+ T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as for other inflammatory skin diseases in which cytolytic CD8+ T cells contribute to pathogenesis.
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Linfocitos T CD8-positivos , Leishmaniasis Cutánea , Neutrófilos , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Animales , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Leishmaniasis Cutánea/parasitología , Ratones , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Neutrófilos/inmunología , Neutrófilos/patología , Neutrófilos/metabolismo , Humanos , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Factor 1 de Unión al Dominio 1 de Regulación Positiva/inmunología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/metabolismo , Granzimas/metabolismo , Granzimas/inmunología , Granzimas/genética , Hipoxia de la Célula/inmunología , FemeninoRESUMEN
Using data from the 2018 National Financial Capability Study (NFCS), this study examined the relationships between poor financial behaviors, receiving government assistance, and financial satisfaction while accounting for adverse financial experiences. The logistic regression results showed that both poor financial behaviors and adverse financial experiences increased the likelihood of receiving government assistance. The OLS results indicated that receiving government assistance significantly increased levels of financial satisfaction, whereas poor financial behaviors significantly decreased levels of financial satisfaction. While the magnitude of these associations for both receiving government assistance and poor financial behaviors was small, adverse financial experiences had a stronger influence on the levels of financial satisfaction. When we combined poor financial behaviors and receiving government assistance into a categorical variable, we gained additional insights into the connections between these constructs that warrants further research.
RESUMEN
Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in Leishmania - infected mice, suggesting that local cues within inflamed skin induce cytolytic function. Expression of Blimp-1 ( Prdm1 ), a transcription factor necessary for cytolytic CD8 T cell differentiation, is driven by hypoxia within the inflamed skin. Hypoxia is further enhanced by the recruitment of neutrophils that consume oxygen to produce reactive oxygen species, ultimately increasing granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibit hypoxia transcription signatures that correlate with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.
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During intracellular infection, T follicular helper (TFH) and T helper 1 (TH1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8+ T cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL programming. We find that Aiolos deficiency results in downregulation of key TFH transcription factors, and consequently reduced TFH differentiation and antibody production, during influenza virus infection. Conversely, CD4-CTL programming is elevated, including enhanced Eomes and cytolytic molecule expression. We further demonstrate that Aiolos deficiency allows for enhanced IL-2 sensitivity and increased STAT5 association with CD4-CTL gene targets, including Eomes, effector molecules, and IL2Ra. Thus, our collective findings identify Aiolos as a pivotal regulator of CD4-CTL and TFH programming and highlight its potential as a target for manipulating CD4+ T cell responses.
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Linfocitos T Colaboradores-Inductores , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Interleucina-2/genética , Interleucina-2/metabolismo , Linfocitos T CD8-positivos , Linfocitos T CD4-Positivos , Diferenciación CelularRESUMEN
BACKGROUND: Nucleosome-mediated chromatin compaction has a direct effect on the accessibility of trans-acting activators and repressors to DNA targets and serves as a primary regulatory agent of genetic expression. Understanding the nature and dynamics of chromatin is fundamental to elucidating the mechanisms and factors that epigenetically regulate gene expression. Previous work has shown that there are three types of canonical sequences that strongly regulate nucleosome positioning and thus chromatin accessibility: putative nucleosome-positioning elements, putative nucleosome-repelling sequences, and homopolymeric runs of A/T. It is postulated that these elements can be used to remodel chromatin in C. elegans. Here we show the utility of such elements in vivo, and the extreme efficacy of a newly discovered repelling sequence, PRS-322. RESULTS: In this work, we show that it is possible to manipulate nucleosome positioning in C. elegans solely using canonical and putative positioning sequences. We have not only tested previously described sequences such as the Widom 601, but also have tested additional nucleosome-positioning sequences: the Trifonov sequence, putative repelling sequence-322 (PRS-322), and various homopolymeric runs of A and T nucleotides. CONCLUSIONS: Using each of these types of putative nucleosome-positioning sequences, we demonstrate their ability to alter the nucleosome profile in C. elegans as evidenced by altered nucleosome occupancy and positioning in vivo. Additionally, we show the effect that PRS-322 has on nucleosome-repelling and chromatin remodeling.