Vaccines are effective interventions that can reduce the high burden of diseases globally. However, public vaccine hesitancy is a pressing problem for public health authorities. With the availability of COVID-19 vaccines, little information is available on the public acceptability and attitudes towards the COVID-19 vaccines in Jordan. This study aimed to investigate the acceptability of COVID-19 vaccines and its predictors in addition to the attitudes towards these vaccines among public in Jordan. An online, cross-sectional, and self-administered questionnaire was instrumentalized to survey adult participants from Jordan on the acceptability of COVID-19 vaccines. Logistic regression analysis was used to find the predictors of COVID-19 vaccines’ acceptability. A total of 3,100 participants completed the survey. The public acceptability of COVID-19 vaccines was fairly low (37.4%) in Jordan. Males (OR = 2.488, 95CI% = 1.834–3.375, p < .001) and those who took the seasonal influenza vaccine (OR = 2.036, 95CI% = 1.306–3.174, p = .002) were more likely to accept COVID-19 vaccines. Similarly, participants who believed that vaccines are generally safe (OR = 9.258, 95CI% = 6.020–14.237, p < .001) and those who were willing to pay for vaccines (OR = 19.223, 95CI% = 13.665–27.042, p < .001), once available, were more likely to accept the COVID-19 vaccines. However, those above 35 years old (OR = 0.376, 95CI% = 0.233–0.607, p < .001) and employed participants (OR = 0.542, 95CI% = 0.405–0.725, p < .001) were less likely to accept the COVID-19 vaccines. Moreover, participants who believed that there was a conspiracy behind COVID-19 (OR = 0.502, 95CI% = 0.356–0.709, p < .001) and those who do not trust any source of information on COVID-19 vaccines (OR = 0.271, 95CI% = 0.183–0.400, p < .001), were less likely to have acceptance towards them. The most trusted sources of information on COVID-19 vaccines were healthcare providers. Systematic interventions are required by public health authorities to reduce the levels of vaccines’ hesitancy and improve their acceptance. We believe these results and specifically the low rate of acceptability is alarming to Jordanian health authorities and should stir further studies on the root causes and the need of awareness campaigns. These interventions should take the form of reviving the trust in national health authorities and structured awareness campaigns that offer transparent information about the safety and efficacy of the vaccines and the technology that was utilized in their production.

β(2)-Adrenoceptor (β2AR) agonists are the most effective class of bronchodilators and a mainstay of asthma management. The first potent β2AR agonist discovered and widely used in reversing the airway constriction associated with asthma exacerbation was the endogenous activator of the β2AR, epinephrine. In this study, we demonstrate that activation of the β2AR by epinephrine is paradoxically required for development of the asthma phenotype. In an antigen-driven model, mice sensitized and challenged with ovalbumin showed marked elevations in three cardinal features of the asthma phenotype: inflammatory cells in their bronchoalveolar lavage fluid, mucin over production, and airway hyperresponsiveness. However, genetic depletion of epinephrine using mice lacking the enzyme to synthesize epinephrine, phenylethanolamine N-methyltransferase, or mice that had undergone pharmacological sympathectomy with reserpine to deplete epinephrine, had complete attenuation of these three cardinal features of the asthma phenotype. Furthermore, administration of the long-acting β2AR agonist, formoterol, a drug currently used in asthma treatment, to phenylethanolamine N-methyltransferase-null mice restored the asthma phenotype. We conclude that β2AR agonist-induced activation is needed for pathogenesis of the asthma phenotype. These findings also rule out constitutive signaling by the β2AR as sufficient to drive the asthma phenotype, and may help explain why chronic administration of β2AR agonists, such as formoterol, have been associated with adverse outcomes in asthma. These data further support the hypothesis that chronic asthma management may be better served by treatment with certain "β-blockers."

BackgroundVaccines are effective interventions that can reduce the high burden of diseases globally. However, public vaccine hesitancy is a pressing problem for public health authorities. With the availability of COVID-19 vaccines, little information is available on the public acceptability and attitudes towards the COVID-19 vaccines in Jordan. This study aimed to investigate the acceptability of COVID-19 vaccines and its predictors in addition to the attitudes towards these vaccines among public in Jordan.MethodsAn online, cross-sectional, and self-administered questionnaire was instrumentalized to survey adult participants from Jordan on the acceptability of COVID-19 vaccines. Logistic regression analysis was used to find the predictors of COVID-19 vaccines’ acceptability.ResultsA total of 3,100 participants completed the survey. The public acceptability of COVID-19 vaccines was fairly low (37.4%) in Jordan. Males (OR=2.488, 95CI%=1.834–3.375, p<.001) and those who took the seasonal influenza vaccine (OR=2.036, 95CI%=1.306–3.174, p=.002) were more likely to accept Covid-19 vaccines. Similarly, participants who believed that vaccines are generally safe (OR=9.258, 95CI%=6.020–14.237, p<.001) and those who were willing to pay for vaccines (OR=19.223, 95CI%=13.665–27.042, p<.001), once available, were more likely to accept the COVID-19 vaccines. However, those above 35 years old (OR=0.376, 95CI%=0.233-0.607, p<.001) and employed participants (OR=0.542, 95CI%=0.405-0.725, p<.001) were less likely to accept the COVID-19 vaccines. Moreover, participants who believed that there was a conspiracy behind COVID-19 (OR=0.502, 95CI%=0.356- 0.709, p<.001) and those who do not trust any source of information on COVID-19 vaccines (OR=0.271, 95CI%=0.183 – 0.400, p<.001), were less likely to have acceptance towards them. The most trusted sources of information on COVID-19 vaccines were healthcare providers.ConclusionSystematic interventions are required by public health authorities to reduce the levels of vaccines’ hesitancy and improve their acceptance. We believe these results and specifically the low rate of acceptability is alarming to Jordanian health authorities and should stir further studies on the root causes and the need of awareness campaigns. These interventions should take the form of reviving the trust in national health authorities and structured awareness campaigns that offer transparent information about the safety and efficacy of the vaccines and the technology that was utilized in their production.

The mostly widely used bronchodilators in asthma therapy are β-adrenoreceptor (βAR) agonists, but their chronic use causes paradoxical adverse effects. We have previously determined that βAR activation is required for expression of the asthma phenotype in mice, but the cell types involved are unknown. We now demonstrate that βAR signaling in the airway epithelium is sufficient to mediate key features of the asthmatic responses to IL-13 in murine models. Our data show that inhibition of βAR signaling with an aerosolized antagonist attenuates airway hyperresponsiveness (AHR), eosinophilic inflammation, and mucus-production responses to IL-13, whereas treatment with an aerosolized agonist worsens these phenotypes, suggesting that βAR signaling on resident lung cells modulates the asthma phenotype. Labeling with a fluorescent βAR ligand shows the receptors are highly expressed in airway epithelium. In βAR mice, transgenic expression of βARs only in airway epithelium is sufficient to rescue IL-13-induced AHR, inflammation, and mucus production, and transgenic overexpression in WT mice exacerbates these phenotypes. Knockout of β-arrestin-2 (βarr-2) attenuates the asthma phenotype as in βAR mice. In contrast to eosinophilic inflammation, neutrophilic inflammation was not promoted by βAR signaling. Together, these results suggest βARs on airway epithelial cells promote the asthma phenotype and that the proinflammatory pathway downstream of the βAR involves βarr-2. These results identify βAR signaling in the airway epithelium as capable of controlling integrated responses to IL-13 and affecting the function of other cell types such as airway smooth muscle cells.

Here we report that paclitaxel induces variable degrees of apoptosis in human colorectal cancer cells. Paclitaxel induces multiple arms of the endoplasmic reticulum stress response, including upregulation of the 78-kDa glucose-regulatory protein (GRP78) and eukaryotic initiation factor alpha phosphorylation. Inhibition of the MEK/ERK pathway sensitized colorectal cancer cells to paclitaxel-induced apoptosis. A similar result was obtained by the inhibition of GRP78 using small interfering RNA molecules. Knockdown of MEK resulted in a significant downregulation of paclitaxel-induced upregulation of GRP78 indicating that activation of GRP78 is a downstream event of MEK/ERK pathway activation. These results indicate that GRP78 might be a novel mechanism underlying the resistance of colorectal cancer cells to microtubule-targeting drugs. A combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes.