Natural Killer Cells in Asthma

The worldwide prevalence, morbidity, and mortality of asthma have dramatically increased over the last few decades and there is a clear need to identify new effective therapeutic and prophylactic strategies. Despite high numbers of NK cells in the lung and their ability to generate a variety of immunomodulatory mediators, the potential of NK cells as therapeutic targets in allergic airway disease has been largely overlooked. The fact that IgE, acting through FcγRIII, can activate NK cells resulting in cytokine/chemokine production implies that NK cells may contribute to IgE-mediated allergic responses. Indeed, current evidence suggests that NK cells can promote allergic airway responses during sensitization and ongoing inflammation. In animal models, increased NK cells are observed in the lung following antigen challenge and depletion of the cells before immunization inhibits allergic airway inflammation. Moreover, in asthmatics, NK cell phenotype is altered and may contribute to the promotion of a pro-inflammatory Th2-type environment. Conversely, driving NK cells toward an IFN-γ-secreting phenotype can reduce features of the allergic airway response in animal models. However, we have limited knowledge of the signals that drive the development of distinct subsets and functional phenotypes of NK cells in the lung and thus the role and therapeutic potential of NK cells in the allergic airway remains unclear. Here we review the potentially diverse role of NK cells in allergic airway disease, identify gaps in current knowledge, and discuss the potential of modulating NK cell function as a treatment strategy in asthma

Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines.</p> <p>Methods</p> <p>In this study, we evaluated the effects of cigarette smoke medium (CSM) on TLR4 expression and interleukin (IL)-8 production by human macrophages investigating the involvement of ROS.</p> <p>Results and Discussion</p> <p>TLR4 surface expression was downregulated on short term exposure (1 h) of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH) levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IκB-α degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC).</p> <p>Conclusion</p> <p>TLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.</p

General wellbeing and work impacts among community pharmacists during crisis management

Background: Community pharmacists are highly accessible for advice, as most pharmacies are open long hours and no appointment is needed. Community pharmacists, as essential community health workers, play a critical role in the fight against coronavirus disease 2019 (COVID-19). This study aimed to determine the general wellbeing and work impacts of pharmacists and the factors important for adaptability and resilience during the COVID-19 pandemic. Methods: This study adopted a cross-sectional design. Community pharmacists from various professional networks in Australia were invited through emails and social media posts to complete an anonymous online survey during the second wave of the COVID-19 pandemic in Victoria, Australia. Results: Sixty-five community pharmacists completed the online survey. The respondents reported fair levels of general wellbeing during the COVID-19 pandemic, with a mean self-related health score of 33.57 (s.d. = 13.19) out of a maximal of 96, despite relatively high levels of job stress and emotional labour. Lower levels of general wellbeing were correlated with higher levels of job stress (r = 0.645, P < 0.01) and emotional labour (r = 0.513, P < 0.01), and lower levels of occupational self-efficacy (r = −0.566, P < 0.01). Leader member exchange was negatively correlated with job stress (r = −0.419, P < 0.01) and positively correlated with psychological safety (r = 0.693, P < 0.01). The linear regression models showed that female pharmacists had lower occupational self-efficacy (β = −0.286, P = 0.024), but higher psychological safety (β = 0.234, P = 0.042). Higher work ability was associated with lower job stress (β = −0.529, P < 0.001), higher occupational self-efficacy (β = 0.511, P = 0.001), and poorer self-related health (β = −0.659, P < 0.001). Conclusions: The findings highlight the importance of a supportive work environment in helping community pharmacists to feel psychologically safe and reduce stress during a crisis

Adaptation strategies in transnational education: a case study of an Australian Master of Health Administration Course offered to Chinese managers

Background: Management decisions in health influence patient care outcomes; however, health management development courses in China are rare. This study aims to document and evaluate a transnational Master of Health Administration (MHA) course launched in 2000 for the benefit of Chinese health managers. Methods: A case study of the MHA program jointly run by an Australian university and a Chinese Medical University was conducted. We reviewed the development of the MHA course through a document analysis (key events recorded in achieves, minutes, and audits) followed by reflection (by two course coordinators), extracting key themes related to adaptative strategies. We then conducted a questionnaire survey of 139 graduates seeking their views on relevance, satisfaction and challenges associated with each subject within the course, the relevance of key management skills (as determined by the Australasian College of Health Service Management competency framework), and the impact of the course on their personal career trajectories. Chi-square tests identified differences in the responses by age, gender, pre-training position, and current workplace. Results: The curriculum pedagogy followed the principles of practice-based reflective learning. Research findings and student feedback shaped the curriculum design and subject content, to enhance management practices of the students. Survey participants expressed high levels of satisfaction and confirmed the relevance of all study subjects. Two subjects, health economics and data management, were perceived as being the most challenging. Of the ten management skills we assessed, relatively low self-rated confidence was found in “strategic thinking” and “planning”. Younger and less experienced graduates were more likely to report learning challenges (p < 0.05). Frontline managers were least likely to obtain promotion by changing employers (χ2 = 6.02, p < 0.05) or being seconded to another position (χ2 = 9.41, p < 0.01). Conclusions: This case study illustrates the suitability of cross-country partnerships in health management training, which offers opportunities for managers to systematically explore and acquire a comprehensive set of management skills applicable to their career needs. Opportunities for developing training aligned to career development opportunities are critical for attracting and developing a competent and well-prepared health service management workforce in China

A Comparative Study of the Position of the Contractualization in Iranian and French Family Law

Contractualization is the subject of the current reflection of French law on the rapid evolution of family law. Individualism, fundamentalism, and distancing from institutionalism and imperative rules are at the root of this trend. . It is true that many forbidden things have been broken in this way. Items only Limits such as some elements of personal status and legal parenthood are not . It is true that many forbidden things have been broken in this way. Items only Limits such as some elements of personal status and legal parenthood are not contracted.. The correct understanding of contractualization will be possible by recognizing the relationship of a legal system with contractualism. In French law, there is a serious view that contractualism, although in the service of the individual, will ultimately serve society and shape a kind of social regulation of family relations. In contrast, Iranian family law, given its Islamic origins, has a serious relationship with contracts. But this relationship is organized according to the comprehensiveand definite interest of man, in which no dimension of human existence is ignored and mixed with doubt and there is confidence in it. In this case, the interests of both the individual and society will be served. Proper knowledge of the boundaries of the imperative rules and protection of its capabilities can protect Iranian law from the harms of this trend while benefiting from contractualization

Mucosal exposure to cockroach extract induces allergic sensitization and allergic airway inflammation

<p>Abstract</p> <p>Background</p> <p>Allergic sensitization to aeroallergens develops in response to mucosal exposure to these allergens. Allergic sensitization may lead to the development of asthma, which is characterized by chronic airway inflammation. The objective of this study is to describe in detail a model of mucosal exposure to cockroach allergens in the absence of an exogenous adjuvant.</p> <p>Methods</p> <p>Cockroach extract (CE) was administered to mice intranasally (i.n.) daily for 5 days, and 5 days later mice were challenged with CE for 4 consecutive days. A second group received CE i.n. for 3 weeks. Airway hyperresponsiveness (AHR) was assessed 24 h after the last allergen exposure. Allergic airway inflammation was assessed by BAL and lung histology 48 h after the last allergen exposure. Antigen-specific antibodies were assessed in serum. Lungs were excised from mice from measurement of cytokines and chemokines in whole lung lysate.</p> <p>Results</p> <p>Mucosal exposure of Balb/c mice to cockroach extract induced airway eosinophilic inflammation, AHR and cockroach-specific IgG1; however, AHR to methacholine was absent in the long term group. Lung histology showed patchy, multicentric damage with inflammatory infiltrates at the airways in both groups. Lungs from mice from the short term group showed increased IL-4, CCL11, CXCL1 and CCL2 protein levels. IL4 and CXCL1 were also increased in the BAL of cockroach-sensitized mice in the short-term protocol.</p> <p>Conclusions</p> <p>Mucosal exposure to cockroach extract in the absence of adjuvant induces allergic airway sensitization characterized by AHR, the presence of Th2 cytokines in the lung and eosinophils in the airways.</p

Biodegradable starch-based composites: effect of micro and nanoreinforcements on composite properties

Thermoplastic starch (TPS) matrix was reinforced with various kenaf bast cellulose nanofiber loadings (0–10 wt%). Thin films were prepared by casting and evaporating the mixture of aqueous suspension of nanofibers (NFs), starch, and glycerol which underwent gelatinization process at the same time. Moreover, raw fibers (RFs) reinforced TPS films were prepared with the same contents and conditions. The effects of filler type and loading on different characteristics of prepared materials were studied using transmission and scanning electron microscopies, X-ray diffractometry, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and moisture absorption analysis. Obtained results showed a homogeneous dispersion of NFs within the TPS matrix and strong association between the filler and matrix. Moreover, addition of nanoreinforcements decreased the moisture sensitivity of the TPS film significantly. About 20 % decrease in moisture content at equilibrium was observed with addition of 10 wt% NFs while this value was only 5.7 % for the respective RFs reinforced film

Modulation of embryo-forming capacity in culture through the expression of Brassica genes involved in the regulation of the shoot apical meristem

Somatic embryogenesis in Arabidopsis is achieved by culturing bending-cotyledon embryos on a 2,4-D-containing induction medium for 14 d followed by a transfer on to a hormone-free development medium. Several genes orthologous to Arabidopsis SHOOTMERISTEMLESS (STM), CLAVATA 1 (CLV1), and ZWILLE (ZLL) were isolated from Brassica oleracea (Bo), B. rapa (Br), and B. napus (Bn), and ectopically expressed in Arabidopsis to assess their effects on somatic embryogenesis. Ectopic expression of BoSTM, BrSTM, and BnSTM increased the number of somatic embryos, whereas a different effect was observed in lines overexpressing BnCLV1 in which somatic embryo formation was severely repressed. The introduction of BnZLL did not have any effects on Arabidopsis somatic embryogenesis. The increased embryo-forming capacity observed in lines overexpressing Brassica STM was associated with a lower requirement for the inductive signal 2,4-D, and a higher expression of WUSCHEL (WUS) which demarcates the formation of embryogenic cells. This was in contrast to the 35S::BnCLV1 lines which showed the highest requirement for exogenous 2,4-D and a reduced WUS expression. Microarray studies were conducted to monitor global changes in transcript levels during Arabidopsis somatic embryogenesis between the wild-type (WT) line and a BoSTM-overexpressing line, which showed the most pronounced enhancement of somatic embryo yield. The introduction of BoSTM affected the expression of many genes involved in hormone perception and signalling, as well as genes encoding DNA methyltransferases and enzymes of glutathione metabolism. Pharmacological experiments performed to confirm some of the microarray results showed that Arabidopsis somatic embryogenesis is encouraged by a global hypomethylation of the DNA during the induction phase and by a switch of the glutathione pool towards an oxidized state during the subsequent development phase. Both events occurred in the 35S::BoSTM line, but not in the WT line. Altered expression of Brassica STM also had profound effects on B. napus microspore-derived embryogenesis. The yield of microspore-derived embryos increased in lines overexpressing BnSTM and significantly decreased in antisense lines down-regulating BnSTM