Activation of β2-Adrenoceptors Is Required for Mucin Production in Airway Bronchial Epithelial Cells

Asthma, a chronic inflammatory disease of the airways, is associated with mucus hypersecretion by airway epithelium. Accumulated mucus in the airways contributes to airway obstruction, airway hyperresponsiveness and sometimes death. In a murine model of asthma, chronically blocking β2-adrenoceptors (β2-ARs) or genetic ablation of β2-ARs causes a reduction in mucus secretion, an index of inflammatory responses, in response to allergen. The detailed molecular components of these effects remain to be elucidated. We examined the β2-AR signaling pathways involved in mediating mucin production in response to IL-13 in airway epithelial cells. The expression of MUC5AC, the predominant mucin-producing gene in asthma, and mucin content were induced by IL-13 in normal human bronchial epithelial (NHBE) cells as compared to control cells only in the presence of epinephrine. Blocking β2-ARs, but not β1-ARs, attenuated the IL-13 effect. The three members of MAPK family, ERK1/2, p38 and JNK, were all involved in inducing mucin production in response to IL-13 in the presence of epinephrine. Since β2-ARs signal through the canonical Gs-adenylyl cyclase or β-arrestin signaling cascade, we examined each pathway separately. Elevating intracellular cAMP levels was associated with enhanced IL-13 response, either in the presence or absence of epinephrine and increased epithelial cell number. Moreover, inhibiting the activity of PKA and PDE4 resulted in attenuated IL-13 response. Stimulating β-arrestin-2 signaling did not alter the IL-13 response in NHBE cells, either in the presence or absence of epinephrine. However, the absence of β-arrestin-2 from mouse airway epithelial cells attenuated the response to IL-13 as compared to cells expressing β-arrestin-2. β2-ARs did not seem to affect IL-13 mediated mucuciliary shift from ciliated to goblet cells or cell proliferation. We conclude that, in human bronchial epithelial cells, epinephrine-induced β2-AR signaling is required to enhance mucus production in response to IL-13. Moreover, MAPKs, cAMP and cAMPdependent protein kinases are all involved components of β2-AR signaling in mediating the effect of IL-13 in NHBE cells.Pharmacological and Pharmaceutical Sciences, Department o

Healthcare providers’ attitude and knowledge regarding medication use in breastfeeding women: a Jordanian national questionnaire study

Medication use among women who have recently given birth is unavoidable in some situations. The aim of this study was to assess the attitude and knowledge of healthcare providers (HCPs) in Jordan about the safe use of medications during breastfeeding. The data were collected from HCPs in maternal and children care centres and hospitals from April 2015 to January 2016, using a self-administered questionnaire. A total of 904 HCPs (79.3%) were enrolled in the study. Half of the participants followed the World Health Organisation’s and American Academy of Pediatrics’ recommendations. The awareness of HCPs regarding these recommendations was lower among nurses (OR 0.212, 95%CI 0.132–0.338, p < .001) and pharmacists (OR 0.476, 95%CI 0.297–0.763, p = .002) than physicians. The majority of participants (80%) had low level of knowledge and nurses were more likely to have low knowledge than physicians (OR 0.099, 95%CI 0.050–0.197, p < .001). Professional continuous education programmes were highly encouraged.Impact statement What is already known on this subject: Use of medications among women who have recently given birth is unavoidable in some situations and most of them are safe to be given during breastfeeding. What the results of this study add: Healthcare providers in Jordan have variable attitudes regarding the safety of medication use during breastfeeding. The majority of healthcare providers have a low level of knowledge regarding the safe use of medication during breastfeeding. Nurses are more likely to have low knowledge as compared to physicians. Implications for clinical practice: Healthcare providers should be encouraged to seek information regarding compatibility of medication use during breastfeeding from reliable sources. Professional continuing education programmes concerning the safety of medication use during breastfeeding period are needed to target all involved HCPs. More attention should be directed toward medical schools’ curricula to widen the knowledge of medication use and focus on practice-based clinical experience

The difference in knowledge and concerns between healthcare professionals and patients about genetic-related issues: A questionnaire-based study.

Effective adoption of genetics in clinical practice requires the support of and interaction between the different partners of healthcare system; healthcare professionals (HCPs) and patients. The study aimed to assess and compare the knowledge, factors affecting the knowledge, and concerns of HCPs and patients regarding genetic-related issues such as lack of knowledge about genetics and genetic conditions, awareness of the importance of genetics in clinical practice and genetic services and resources deficits. A cross sectional study was conducted in different areas of Jordan using a convenient sampling approach. An English questionnaire was self-administered to HCPs. Face-to-face interviews were conducted with patients in Arabic by trained researcher. A total of 1000 HCPs and 1448 patients were recruited. There was a significant difference (p<0.001) in the knowledge between HCPs and patients. Among HCPs, physicians (OR = 2.278, 95%CI = 1.410-3.680, p = 0.001) and pharmacists (OR = 2.163, 95%CI = 1.362-3.436, p = 0.001) were more knowledgeable than nurses. In addition, females were more knowledgeable than males (OR = 1.717, 95%CI = 1.203-2.451, p = 0.003). Among patients, participants who had a bachelor degree (OR = 1.579, 95%CI = 1.231-2.025, p<0.001) were more knowledgeable compared to those who only had school education. HCPs appeared to have more concerns than patients (p<0.001) regarding all genetic-related issues. These findings suggested a positive association between education and genetic knowledge as well as concerns; as HCPs were more knowledgeable and concerned than patients. Appropriate integration and expansion of basic genetic knowledge courses and clinical genetic training in the curriculum should be adopted to prepare HCPs to enhance the integration of genetic information in clinical settings

hep-th/0007204 DYNAMICS OF STRINGS IN NONCOMMUTATIVE GAUGE THEORY

a

The attitude of blood donors towards the use of their samples and information in biomedical research

Methods The study is cross-sectional and questionnaire-based and involved 616 blood donors from the Gaza Strip. Results The majority of participants (86%) showed a positive attitude towards donating blood for medical research, including genetic studies. About two-thirds of participants agreed that informed consent should be taken before conducting medical research on the donated blood. A similar percentage also accepted linking of their health information to the donated blood samples. On the other hand, about 38% of participants disapproved of sharing of their data with third parties such as health insurance companies and health authorities. Finally, 10% of participants stated that their future blood donation decision would be affected if they knew that part of their donated blood was to be used in research without taking their permission. Conclusion Blood donors in Gaza Strip have a positive attitude toward using

Acceptance and attitudes toward COVID-19 vaccines: A cross-sectional study from Jordan

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.Scopu

Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78

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