The majority of cases of community-acquired pneumonia are caused by Streptococcus pneumoniae and most studies on pneumococcal host interaction are based on cell culture or animal experiments. Thus, little is known about infections in human lung tissue.Cyclooxygenase-2 and its metabolites play an important regulatory role in lung inflammation. Therefore, we established a pneumococcal infection model on human lung tissue demonstrating mitogen-activated protein kinase (MAPK)-dependent induction of cyclooxygenase-2 and its related metabolites.In addition to alveolar macrophages and the vascular endothelium, cyclooxygenase-2 was upregulated in alveolar type II but not type I epithelial cells, which was confirmed in lungs of patients suffering from acute pneumonia. Moreover, we demonstrated the expression profile of all four E prostanoid receptors at the mRNA level and showed functionality of the E prostanoid 4 receptor by cyclic adenosine monophosphate production. Additionally, in comparison to previous studies, cyclooxygenase-2/prostaglandin E 2 related pro-and anti-inflammatory mediator regulation was partly confirmed in human lung tissue after pneumococcal infection.Overall, cell type-specific and MAPK-dependent cyclooxygenase-2 expression and prostaglandin E 2 formation in human lung tissue may play an important role in the early phase of pneumococcal infections.
A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients.
ObjectivesVeterinary practitioners’ working situation is both challenging and changing. They have higher levels of work-related stress and suicide risk than the general population. The proportion of women is increasing, and in Germany especially women and employed veterinarians are reported to be less satisfied than comparable subgroups of the general population. In this study we identified key factors associated with work and life satisfaction among veterinary practitioners in Germany.DesignQuestionnaire-based cross-sectional survey.SettingAll veterinary practitioners registered in Germany in 2016.ParticipantsThere were 2549 respondents, of whom 1930 met the inclusion criteria for further analysis. They had a median age of 37 and the majority of respondents were women (79.3 per cent). Almost two-thirds (63.8 per cent) worked as employed veterinarian.Primary outcomesImportance of different job characteristics measured in 5-point Likert items, work satisfaction measured on a 5-point Likert item and life satisfaction measured in 11-point Likert items.Secondary outcomesFacets such as satisfaction with leisure time, family life, health and standard of living, information on working conditions such as working time, income, as well as year of birth and other demographic data.ResultsA ‘good working atmosphere’ was the most relevant job characteristic for all veterinary practitioners. Work satisfaction of employed practitioners is closely linked to satisfaction with their colleagues. This link is less pronounced for self-employed practitioners. A ‘reasonable salary’ was the second and ‘holidays and leisure time’ was the third most important job characteristics for employed practitioners. A ‘good working atmosphere’ and ‘family friendly arrangements’ were statistically significantly more important for women than for men, while a ‘reasonable salary’ was more important for men.ConclusionsOur results indicate strong associations between levels of work satisfaction and various work-related factors in subgroups of veterinary practitioners in Germany that reduce life satisfaction. The strength of some associations differs between men and women, as well as between self-employed and employed veterinarians. Outgoing students should be better prepared for the challenging working conditions that they face in veterinary practice. Salary levels should be improved and the working conditions adapted to the respective subgroups in order to increase work and life satisfaction.
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