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The main objective of this study was to assess whether hesitancy toward receiving the initial COVID-19 vaccine was associated with uptake of the COVID-19 booster several months after it became available to all US adults. We ask whether hesitancy toward the initial COVID-19 vaccine was significantly associated with lower odds of COVID-19 booster uptake among adults. We test this association within the context of the highly rural state of Arkansas. By January 2022, the US had set a global record of nearly 1 million daily cases. The purpose of this study was to advance our understanding of vaccine hesitancy among those who have already received a dose of the COVID-19 vaccine and how that hesitancy may shape COVID-19 booster uptake. We analyzed data from a random sample survey of Arkansan adults (N = 2,201) between March 1 and March 28, 2022 and constrained our analytical sample to those who had received a vaccine (N = 1,649). Nearly two-thirds of vaccinated Arkansas residents had received a COVID-19 booster. Hesitancy was common even among vaccinated individuals and was significantly associated with reduced odds of COVID-19 booster uptake, even after controlling for other factors. Findings provide further support for conceptualizing vaccine hesitancy as an attitude related to—but separate from—the behavior of vaccination, as opposed to conflating vaccination with being nonhesitant. Public health interventions aimed at increasing COVID-19 booster uptake should pay attention to vaccine hesitancy indicated at the initiation of the series and should not ignore the vaccinated as an important population to target for intervention. [ABSTRACT FROM AUTHOR]

Asthma is a disease characterized by reversible airway obstruction. An additional hallmark of chronic asthma is altered wound healing that leads to airway remodeling. Although [beta]-agonists are effective in treating the bronchospasm associated with asthma, their effects on airway wound healing, which are related to airway remodeling, are unknown. It has been demonstrated that [beta]-agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the [beta]-agonist isoproterenol would affect wound healing. Using an in vitro scrape wound assay, we demonstrated that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing [[beta].sub.2]-adrenergic receptor-yellow fluorescent protein, we show that attenuation is due to the accumulation of cAMP and the involvement of at least one additional pathway. Furthermore, attenuation is not due to a direct effect on the EGF receptor or tO an alteration of the ERK/ MAPK signaling cascade. Based on these results, we propose that isoproterenol may exert its effects through other MAPK signaling pathways (JNK and/or p38) or through parallel mechanisms. These results also demonstrate a problem of potential therapeutic relevance in which a commonly prescribed medication may alter wound healing and contribute to the remodeling of asthmatic airways. [[beta].sub.2]-adrenergic receptor; epidermal growth factor receptor; asthma; bronchospasm

Abstract Background The β2-adrenergic receptor (β2AR) is a primary target for medications used to treat asthma. Due to the low abundance of β2AR, very few studies have reported its localization in tissues. However, the intracellular location of β2AR in lung tissue, especially in airway smooth muscle cells, is very likely to have a significant impact on how the airways respond to β-agonist medications. Thus, a method for visualizing β2AR in tissues would be of utility. The purpose of this study was to develop an immunofluorescent labeling technique for localizing native and recombinant β2AR in primary cell cultures. Methods A panel of six different antibodies were evaluated in indirect immunofluorescence assays for their ability to recognize human and rat β2AR expressed in HEK 293 cells. Antibodies capable of recognizing rat β2AR were identified and used to localize native β2AR in primary cultures of rat airway smooth muscle and epithelial cells. β2AR expression was confirmed by performing ligand binding assays using the β-adrenergic antagonist [3H] dihydroalprenolol ([3H]DHA). Results Among the six antibodies tested, we identified three of interest. An antibody developed against the C-terminal 15 amino acids of the human β2AR (Ab-Bethyl) specifically recognized human but not rat β2AR. An antibody developed against the C-terminal domain of the mouse β2AR (Ab-sc570) specifically recognized rat but not human β2AR. An antibody developed against 78 amino acids of the C-terminus of the human β2AR (Ab-13989) was capable of recognizing both rat and human β2ARs. In HEK 293 cells, the receptors were predominantly localized to the cell surface. By contrast, about half of the native rat β2AR that we visualized in primary cultures of rat airway epithelial and smooth muscle cells using Ab-sc570 and Ab-13989 was found inside cells rather than on their surface. Conclusion Antibodies have been identified that recognize human β2AR, rat β2AR or both rat and human β2AR. Interestingly, the pattern of expression in transfected cells expressing millions of receptors was dramatically different from that in primary cell cultures expressing only a few thousand native receptors. We anticipate that these antibodies will provide a valuable tool for evaluating the expression and trafficking of β2AR in tissues.

The β2-AR (β2-adrenergic receptor) is an important target for respiratory and CVD (cardiovascular disease) medications. Clinical studies suggest that N-terminal polymorphisms of β2-AR may act as disease modifiers. We hypothesized that polymorphisms at amino acids 16 and 27 result in differential trafficking and down-regulation of β2-AR variants following β-agonist exposure. The functional consequences of the four possible combinations of these polymorphisms in the human β2-AR (designated β2-AR-RE, β2-AR-GE, β2-AR-RQ and β2-AR-GQ) were studied using site-directed mutagenesis and recombinant expression in HEK-293 cells (human embryonic kidney cells). Ligand-binding assays demonstrated that after 24 h exposure to 1 μM isoprenaline, isoforms with Arg16 (β2-AR-RE and β2-AR-RQ) underwent increased down-regulation compared with isoforms with Gly16 (β2-AR-GE and β2-AR-GQ). Consistent with these differences in down-regulation between isoforms, prolonged isoprenaline treatment resulted in diminished cAMP response to subsequent isoprenaline challenge in β2-AR-RE relative to β2-AR-GE. Confocal microscopy revealed that the receptor isoforms had similar co-localization with the early endosomal marker EEA1 following isoprenaline treatment, suggesting that they had similar patterns of internalization. None of the isoforms exhibited significant co-localization with the recycling endosome marker Rab11 in response to isoprenaline treatment. Furthermore, we found that prolonged isoprenaline treatment led to a higher degree of co-localization of β2-AR-RE with the lysosomal marker LAMP1 (lysosome-associated membrane protein 1) compared with that of β2-AR-GE. Taken together, these results indicate that a mechanism responsible for differential responses of these receptor isoforms to the β-agonist involves differences in the efficiency with which agonist-activated receptors are trafficked to the lysosomes for degradation, or differences in degradation in the lysosomes. [ABSTRACT FROM AUTHOR]