QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.

Objectives: Arkansas COVID-19 vaccine uptake has been lower than the national average. This study examined associations between sociodemographic factors and COVID-19 vaccine hesitancy, fear of infection, and protection self-efficacy. Methods: Adults either residing, having employment, or receiving health care in Arkansas (n = 754) participated in an online survey between October 30, 2020 and January 16, 2021. Participants were recruited in both rural and urban areas from 6 Arkansas primary care clinics. Survey questions addressed sociodemographic factors, COVID-19 infection fear, protection self-efficacy, and COVID-19 vaccine attitudes. Bivariate and multivariable logistic regression models were used to assess associations between dependent variables and respondents’ sociodemographic characteristics, COVID-19 infection fear, and COVID-19 protection self-efficacy. Results: About 38% of participants reported COVID-19 vaccine hesitancy. Age, sex, race, and education were significantly associated with COVID-19 and general vaccine attitudes. Odds of COVID-19 vaccine hesitancy decreased as age increased (OR = 0.98; P < .01). Women had higher odds of COVID-19 vaccine hesitancy than men (OR = 1.52; P < .05). Respondents with a high school diploma and below and respondents with some college or a technical degree had greater odds of COVID-19 vaccine hesitancy (OR = 2.58; P < .001; and OR = 1.97; P < .01, respectively) compared to respondents with a 4-year college degree. Black/African American respondents had greater odds of COVID-19 vaccine hesitancy compared to White respondents (OR = 3.08; P < .001). No significant difference was observed among rural and urban respondents regarding COVID-19 vaccine hesitancy; however, respondents in rural areas were more likely to report low general vaccine trust compared to those in urban areas (OR = 1.87; P < .01). Respondents reporting no fear (OR = 5.51; P < .001) and very little fear (OR = 1.95; P < .05) of COVID-19 had greater odds of COVID-19 vaccine hesitancy compared to respondents who feared COVID-19 infection to a great extent. Conclusions: COVID-19 vaccine hesitancy and general trust in vaccines differ significantly among age, sex, race, and education. These trust and hesitancy patterns are challenges for achieving population immunity and follow similar patterns of vulnerability to COVID-19. Vaccination programs and interventions must consider these differences in COVID-19 vaccine hesitancy and general vaccine trust to alleviate COVID-19 disparities. Findings make a significant contribution in evaluating vaccine hesitancy among a large, diverse sample from a rural state.

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Exposure of cells to ionizing radiation (IR) generates reactive oxygen species (ROS). This results in increased oxidative stress and DNA double strand breaks (DSBs) which are the two underlying mechanisms by which IR causes cell/tissue injury. Cells that are deficient or impaired in the cellular antioxidant response are susceptible to IR-induced apoptosis. The transcription factor CCAAT enhancer binding protein delta (Cebpd, C/EBPδ) has been implicated in the regulation of oxidative stress, DNA damage response, genomic stability and inflammation. We previously reported that Cebpd-deficient mice are sensitive to IR and display intestinal and hematopoietic injury, however the underlying mechanism is not known. In this study, we investigated whether an impaired ability to detoxify IR-induced ROS was the underlying cause of the increased radiosensitivity of Cebpd-deficient cells. We found that Cebpd-knockout (KO) mouse embryonic fibroblasts (MEFs) expressed elevated levels of ROS, both at basal levels and after exposure to gamma radiation which correlated with increased apoptosis, and decreased clonogenic survival. Pre-treatment of wild type (WT) and KO MEFs with polyethylene glycol-conjugated Cu-Zn superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) combination prior to irradiation showed a partial rescue of clonogenic survival, thus demonstrating a role for increased intracellular oxidants in promoting IR-induced cell death. Analysis of mitochondrial bioenergetics revealed that irradiated KO MEFs showed significant reductions in basal, adenosine triphosphate (ATP)-linked, maximal respiration and reserved respiratory capacity and decrease in intracellular ATP levels compared to WT MEFs indicating they display mitochondrial dysfunction. KO MEFs expressed significantly lower levels of the cellular antioxidant glutathione (GSH) and its precursor- cysteine as well as methionine. In addition to its antioxidant function, GSH plays an important role in detoxification of lipid peroxidation products such as 4-hydroxynonenal (4-HNE). The reduced GSH levels observed in KO MEFs correlated with elevated levels of 4-HNE protein adducts in irradiated KO MEFs compared to respective WT MEFs. We further showed that pre-treatment with the GSH precursor, N-acetyl L-cysteine (NAC) prior to irradiation showed a significant reduction of IR-induced cell death and increases in GSH levels, which contributed to the overall increase in clonogenic survival of KO MEFs. In contrast, pre-treatment with the GSH synthesis inhibitor- buthionine sulfoximine (BSO) further reduced the clonogenic survival of irradiated KO MEFs. This study demonstrates a novel role for C/EBPδ in protection from basal as well as IR-induced oxidative stress and mitochondrial dysfunction thus promoting post-radiation survival.