Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have ...shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C-deficient (IL-17C
) mice infected with P. aeruginosa at 24 h. Systemic concentrations of interleukin-6 (IL-6) were significantly decreased in infected IL-17C
mice at 24 h and the survival of IL-17C
mice was significantly increased at 48 h. The expression of IL-17C was reduced in infected mice deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL-17A were not affected by the deficiency for IL-17C. Stimulation of primary alveolar epithelial cells with IL-17A resulted in a significantly increased expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression of epithelial IL-17C amplifies the release of chemokines by epithelial cells and thereby contributes to the recruitment of neutrophils and systemic inflammation during acute P. aeruginosa pneumonia.
Women-identifying emergency physicians face gender-based discrimination throughout their careers. The purpose of this study was to explore emergency physician's perceptions and experiences of gender ...equity in emergency medicine.
We conducted a secondary analysis of data from a previously conducted survey of Canadian emergency physicians on barriers to gender equity in emergency medicine. Survey responses were analyzed using logistic regression to determine the impact that gender, practice setting, years since graduation, race, equity-seeking status, and parental status had on agreement about gender equity in emergency medicine and five of the problem statements.
A total of 710 participants completed the survey. Most identified as women (58.8%), white (77.4%), graduated between 2010 and 2019 (40%), had CCFP (Emergency Medicine) designation (47.9%), an urban practice (84.4%), were parents (62.4%) and did not identify as equity-seeking (79.9%). Women-identifying physicians were less likely to perceive gender equity in emergency medicine, OR 0.52, CI 0.38, 0.73. Women-identifying physicians were more likely to agree with statements about microaggressions, OR 4.39, CI 2.66, 7.23; barriers to leadership, OR 3.51, CI 2.25, 5.50; gender wage gap, OR 13.46, CI 8.27, 21.91; lack of support for parental leave, OR 2.85, CI 1.82, 4.44; and education on allyship, OR 2.23 CI 1.44, 3.45 than men-identifying physicians.
In this study, women-identifying physicians were less likely to perceive that there was gender equity in emergency medicine than men-identifying physicians. Women-identifying physicians agreed that there are greater barriers for career advancement including fewer opportunities for leadership, a gender wage gap, a lack of parental leave policies to support a return to work and a lack of education for men to become allies. Men-identifying physicians were less aware of these inequities. Health systems must work to improve gender equity in emergency medicine and this will require education and allyship from men-identifying physicians.
Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. ...depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom.
The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up.
From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors.
This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.
Seasonality is a key aspect for the performance of the majority of tourism enterprises and a central theme for policy makers. The usual practice of strategy formulation in this area, whilst often ...involving a sound analysis of objective performance data, largely ignores the perceptions which the businesses concerned have of the seasonality issue. This paper demonstrates that the heterogeneity of attitudes and perceptions in the sector need to be recognised when developing effective strategies for tackling seasonality. An empirical quantitative approach is applied using occupancy data of the serviced accommodation sector in addition to a survey of owner/managers. The findings indicate that an insufficiently detailed level of segmentation of the business sector concerned may lead to ill-focused broad-brush strategies and consequent misallocations of resources. The paper contends that policy makers in this area need information beyond what can be obtained from the usual performance measurement systems.
Class 3 semaphorins were discovered as a family of axon guidance molecules, but are now known to be involved in diverse biologic processes. In this study, we investigated the anti-angiogenic ...potential of SEMA3E and SEMA3F (SEMA3E&F) in infantile hemangioma (IH). IH is a common vascular tumor that involves both vasculogenesis and angiogenesis. Our lab has identified and isolated hemangioma stem cells (HemSC), glucose transporter 1 positive (GLUT1+) endothelial cells (designated as GLUT1sel cells) based on anti-GLUT1 magnetic beads selection and GLUT1-negative endothelial cells (named HemEC). We have shown that these types of cells play important roles in hemangiogenesis. We report here that SEMA3E inhibited HemEC migration and proliferation while SEMA3F was able to suppress the migration and proliferation in all three types of cells. Confocal microscopy showed that stress fibers in HemEC were reduced by SEMA3E&F and that stress fibers in HemSC were decreased by SEMA3F, which led to cytoskeletal collapse and loss of cell motility in both cell types. Additionally, SEMA3E&F were able to inhibit vascular endothelial growth factor (VEGF)-induced sprouts in all three types of cells. Further, SEMA3E&F reduced the level of p-VEGFR2 and its downstream p-ERK in HemEC. These results demonstrate that SEMA3E&F inhibit IH cell proliferation and suppress the angiogenic activities of migration and sprout formation. SEMA3E&F may have therapeutic potential to treat or prevent growth of highly proliferative IH.
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•SEMA3E&F reduce actin stress fibers and induce cytoskeletal collapse in HemEC.•SEMA3E&F inhibit angiogenic activities of HemEC.•SEMA3E&F can interrupt the VEGF-A-VEGFR2-ERK signaling pathway in HemEC.•Plexin D1 and NRP2 are induced during HemSC/GLUT1sel-to-EC differentiation.
We assessed the occurrence and aetiology of chest pain in primary care practice. These features differ between primary and emergency care settings, where most previous studies have been performed.
59 ...GPs in western Switzerland recorded all consecutive cases presenting with chest pain. Clinical characteristics, laboratory tests and other investigations as well as the diagnoses remaining after 12 months of follow-up were systematically registered.
Among 24,620 patients examined during a total duration of 300 weeks of observation, 672 (2.7%) presented with chest pain (52% female, mean age 55 +/- 19(SD)). Most cases, 442 (1.8%), presented new symptoms and in 356 (1.4%) it was the reason for consulting. Over 40 ailments were diagnosed: musculoskeletal chest pain (including chest wall syndrome) (49%), cardiovascular (16%), psychogenic (11%), respiratory (10%), digestive (8%), miscellaneous (2%) and without diagnosis (3%). The three most prevalent diseases were: chest wall syndrome (43%), coronary artery disease (12%) and anxiety (7%). Unstable angina (6), myocardial infarction (4) and pulmonary embolism (2) were uncommon (1.8%). Potentially serious conditions including cardiac, respiratory and neoplasic diseases accounted for 20% of cases. A large number of laboratory tests (42%), referral to a specialist (16%) or hospitalisation (5%) were performed. Twentyfive patients died during follow-up, of which twelve were for a reason directly associated with thoracic pain cancer (7) and cardiac causes (5).
Thoracic pain was present in 2.7% of primary care consultations. Chest wall syndrome pain was the main aetiology. Cardio - vascular emergencies were uncommon. However chest pain deserves full consideration because of the occurrence of potentially serious conditions.
This paper analyzes the seasonal variations in occupancy rates for the accommodation sector in Wales over the period 1998 to 2000. The approach is based on a combination of principal components and ...cluster analysis. The results are used to group establishments with similar performance profiles. Some general relationships between occupancy performance and the characteristics of the accommodation businesses in Wales are identified. The analysis extends to the hotel and other parts of the serviced accommodation sector allowing comparisons to be drawn. Several concrete pointers for tailoring marketing strategies to the requirements of different accommodation segments are discussed.
Une analyse de la saisonnalité dans les données des taux d’occupation des chambres au pays de Galles. Cet article analyse les variations saisonnières des taux d’occupation pour le secteur du logement au pays de Galles pour la période 1998 à 2000. On utilise une approche basée sur une combinaison des composants principaux et l’analyse de groupement. Les résultats sont utilisés pour grouper des établissements avec des profils de rendement similaires. On identifie quelques liens généraux entre le rendement d’occupation et les caractéristiques des entreprises de logement au pays de Galles. L’analyse s’étend aux hôtels et aux autres parties du secteur du logement avec services, ce qui permet de tirer des conclusions. On discute de plusieurs indications concrètes pour adapter des stratégies de marketing aux exigences des différentes parties du secteur du logement.
This paper examines the seasonal pattern for different types of domestic tourism demand in the UK during 1994–2000. The focus is on Wales, a region with a particularly pronounced tourism seasonality. ...The characteristics of the Welsh seasonal pattern are identified and compared with other UK regions, notably Scotland. An overview of various different methods for quantifying these seasonal variations is presented. Various scalar measures are used to evaluate the inequality of the distribution of tourism trips within a year. The stability of seasonal patterns between the years is also examined and more complex methodologies, such as Seasonal Decomposition, are applied in order to assess in detail the differences in the seasonal behaviour of demand among the UK home nations. On the basis of the analysis, policy implications for tackling the seasonality problem are discussed.
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