The role of ILâ 5 in bleomycinâ induced pulmonary fibrosis

Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukinâ 5 (ILâ 5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung ILâ 5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of ILâ 5 in pulmonary fibrosis, the effects of antiâ ILâ 5 antibody were investigated in a model of bleomycinâ induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either antiâ ILâ 5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is ILâ 5. Furthermore, antiâ ILâ 5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for ILâ 5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophilâ dependent fibrogenic cytokine production. J. Leukoc. Biol. 64: 657â 666; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141191/1/jlb0657.pd

Experts� perspectives on the application of public-private partnership policy in prevention of road traffic injuries

Purpose: Successful application experiences on public-private partnership (PPP) in different countries, suggest that PPP could be an option in road traffic injury (RTI) prevention. The present study aims at investigating the applicability of PPP policy in RTI prevention in Iran based on the experts� perspectives. Methods: This is a qualitative study with grounded theory approach which has been conducted in Tabriz University of Medical Sciences, Iran in 2018. The participants were 22 experts in the field of RTIs selected using purposive sampling method. Data were collected by semi-structured interviews and analyzed with content-analysis method. Results: The results were classified under 5 main themes (applicability, scopes and services, challenges, advantages, and strategies) for applying PPP policy and 37 sub-themes. Due to the prevalence of RTIs, the present challenges in public sector, existence of qualified private sector, and successful experiences in other areas, there are opportunities for private sector partnership in prevention of RTIs. Private sector could participate in different scopes and services regarding RTI prevention, including road construction and maintenance, maintenance and provision of vehicles safety and public education. The main challenges including legislation issues, ambiguities in collaboration, political and organizational unsustainability, government's financial hardship and lack of experienced experts in the field of RTI. However, there are significant advantages including high efficiency in program implementation, covering the weaknesses of public sector, effective and efficient management on application of PPP in RTI prevention. The strategies include identifying and prioritizing the assignable activities, identifying the qualified private sector, developing PPP policies and legal frameworks, creating a common language between public and private parties, trying to meet the expectations of the private sector by public sector, developing a comprehensive and sound contract, and cultivating public culture to accept private sector in the field of RTI prevention. Conclusion: This study sought to determine whether PPP could be used as strategy to reduce the burden of RTIs in Iran. But it requires a lot of preliminary studies to provide the context and conditions for applying this policy. © 2020 Chinese Medical Associatio

Nurses� perception of patient safety culture and its relationship with adverse events: a national questionnaire survey in Iran

Background: Patient safety culture is an important factor in determining hospitals� ability to address and reduce the occurrence of adverse events (AEs). However, few studies have reported on the impact of nurses� perceptions of patient safety culture on the occurrence of AEs. Our study aimed to assess the association between nurses� perception of patient safety culture and their perceived proportion of adverse events. Methods: A cross-sectional survey was carried out among 2295 nurses employed in thirty-two teaching hospitals in Iran. Nurses completed the Persian version of the hospital survey of patients� safety culture between October 2018 and September 2019. Results: Positive Response Rates of overall patient safety culture was 34.1 and dimensions of patient safety culture varied from 20.9 to 43.8. Also, nurses estimated that the occurrence of six adverse events varied from 51.2�63.0 in the past year. The higher nurses� perceptions of �Staffing�, �Hospital handoffs and transitions�, �Frequency of event reporting�, �Non-punitive response to error�, �Supervisor expectation and actions promoting safety�, �Communication openness�, �Organizational learning continuous improvement�, �Teamwork within units�, and �Hospital management support patient safety� were significantly related to lower the perceived occurrence at least two out of six AEs (OR = 0.69 to 1.46). Conclusions: Our findings demonstrated that nurses� perception regarding patient safety culture was low and the perceived occurrence of adverse events was high. The research has also shown that the higher level of nurses� perception of patient safety culture was associated with lowered occurrence of AEs. Hence, managers could provide prerequisites to improve patient safety culture and reduce adverse events through different strategies, such as encouraging adverse events� reporting and holding training courses for nurses. However, further research is needed to assess how interventions addressing patient safety culture might reduce the occurrence of adverse events. © 2021, The Author(s)

Development of quality indicators to measure pre-hospital emergency medical services for road traffic injury

Background: Pre-Hospital Emergency Care (PEC) is a fundamental property of prevention of Road Traffic Injuries (RTIs). Thus, this sector requires a system for evaluation and performance improvement. This study aimed to develop quality indicators to measure PEC for RTIs. Methods: Following the related literature review, 14 experts were interviewed through semi-structured interviews to identify Quality Measurement Indicators (QMIs). The extracted indicators were then categorized into three domains: structure, performance, and management. Finally, the identified QMIs were confirmed through two rounds of the Delphi technique. Results: Using literature review 11 structural, 13 performance, and four managerial indicators (A total of 28 indicators) were identified. Also, four structural, four performance, and three managerial indicators (A total of 11indicators) were extracted from interviews with experts. Two indicators were excluded after two rounds of Delphi�s technics. Finally, 14 structural, 16 performance and, seven managerial indicators (A total of 37indicators) were finalized. Conclusion: Due to the importance and high proportion of RTIs compared to other types of injuries, this study set out to design and evaluate the QMIs of PEC delivered for RTIs. The findings of this research contribute to measuring and planning aimed at improving the performance of PEC. © 2021, The Author(s)

Electronic and optical spectra in a diluted magnetic semiconductor multilayer

The effects of random distribution of magnetic impurities with concentration $x$ in a semiconductor alloy multilayer at a paramagnetic temperature are investigated by means of coherent potential approximation and tight-binding model. The change in the electronic states and the optical absorption spectrum with $x$ is calculated for weak and strong exchange interactions between carrier spins and localized spin moments on magnetic ions. We find that the density of states and optical absorption are strongly layer-dependent due to the quantum size effects. The electronic and optical spectra are broadened due to the spin fluctuations of magnetic ions and in the case of strong exchange interaction, an energy gap appears in both spectra. Furthermore, the interior layers show higher contribution in the optical absorption of the system. The results can be helpful for magneto-optical devices at a paramagnetic temperature.Comment: 7 pages, 5 figure

Antisense oligonucleotide inhibition of Heat Shock Protein (HSP) 47 improves bleomycin-induced pulmonary fibrosis in rats

<p>Abstract</p> <p>Background</p> <p>The most common pathologic form of pulmonary fibrosis arises from excessive deposition of extracellular matrix proteins such as collagen. The 47 kDa heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been shown to play a major role during the processing and/or secretion of procollagen.</p> <p>Objectives</p> <p>To determine whether inhibition of HSP47 could have beneficial effects in mitigating bleomycin-induced pulmonary fibrosis in rats.</p> <p>Methods</p> <p>All experiments were performed with 250–300 g male Wistar rats. Animals were randomly divided into five experimental groups that were administered: 1) saline alone, 2) bleomycin alone, 3) antisense HSP47 oligonucleotides alone, 4) bleomycin + antisense HSP47 oligonucleotides, and 5) bleomycin + sense control oligonucleotides. We investigated lung histopathology and performed immunoblot and immunohistochemistry analyses.</p> <p>Results</p> <p>In rats treated with HSP47 antisense oligonucleotides, pulmonary fibrosis was significantly reduced. In addition, treatment with HSP47 antisense oligonucleotides significantly improved bleomycin-induced morphological changes. Treatment with HSP47 antisense oligonucleotides alone did not produce any significant changes to lung morphology. Immunoblot analyses of lung homogenates confirmed the inhibition of HSP47 protein by antisense oligonucleotides. The bleo + sense group, however, did not exhibit any improvement in lung pathology compared to bleomycin alone groups, and also had no effect on HSP47 expression.</p> <p>Conclusion</p> <p>These findings suggest that HSP47 antisense oligonucleotide inhibition of HSP47 improves bleomycin-induced pulmonary fibrosis pathology in rats.</p

Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.</p

Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.</p

Aspergillus antigen induces robust Th2 cytokine production, inflammation, airway hyperreactivity and fibrosis in the absence of MCP-1 or CCR2

BACKGROUND: Asthma is characterized by type 2 T-helper cell (Th2) inflammation, goblet cell hyperplasia, airway hyperreactivity, and airway fibrosis. Monocyte chemoattractant protein-1 (MCP-1 or CCL2) and its receptor, CCR2, have been shown to play important roles in the development of Th2 inflammation. CCR2-deficient mice have been found to have altered inflammatory and physiologic responses in some models of experimental allergic asthma, but the role of CCR2 in contributing to inflammation and airway hyperreactivity appears to vary considerably between models. Furthermore, MCP-1-deficient mice have not previously been studied in models of experimental allergic asthma. METHODS: To test whether MCP-1 and CCR2 are each required for the development of experimental allergic asthma, we applied an Aspergillus antigen-induced model of Th2 cytokine-driven allergic asthma associated with airway fibrosis to mice deficient in either MCP-1 or CCR2. Previous studies with live Aspergillus conidia instilled into the lung revealed that MCP-1 and CCR2 play a role in anti-fungal responses; in contrast, we used a non-viable Aspergillus antigen preparation known to induce a robust eosinophilic inflammatory response. RESULTS: We found that wild-type C57BL/6 mice developed eosinophilic airway inflammation, goblet cell hyperplasia, airway hyperreactivity, elevations in serum IgE, and airway fibrosis in response to airway challenge with Aspergillus antigen. Surprisingly, mice deficient in either MCP-1 or CCR2 had responses to Aspergillus antigen similar to those seen in wild-type mice, including production of Th2 cytokines. CONCLUSION: We conclude that robust Th2-mediated lung pathology can occur even in the complete absence of MCP-1 or CCR2