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Objectives This study aimed to explore the views of breast cancer (BC) specialists as to their role in the return-to-work (RTW) process of their BC patients. Methods A qualitative study using semi-structured interviews was conducted in a sample of 20 BC specialists selected according to age, gender, medical specialty (medical oncology, radiation oncology, gynecological surgery), and healthcare organization (regional cancer center, university or private hospital). All interviews were audiotaped and transcribed for qualitative thematic content analysis. Results BC specialists had heterogeneous representations and practices regarding their role in their patients` RTW process, ranging from non-involvement to frequent discussion. Most BC specialists had concerns regarding the "right time and right way" to address patient`s RTW. They hardly mentioned workplace and job factors as potential barriers but rather stressed motivation. The main reported barriers to involvement in the RTW process were lack of time, lack of knowledge, lack of skills, and a professional attitude exclusively focused on cancer care issues. Conclusion While our study showed varying representations and practices among BC specialists, participants consistently identified barriers in supporting BC survivors` RTW. The results will guide the development of an intervention to facilitate the role of BC specialists in the RTW process as part of a multicomponent intervention to facilitate BC survivors` RTW.

Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease., eLife digest The deadliest form of lung cancer is called lung adenocarcinoma, or LUAD. Tobacco chemicals often cause the disease by damaging the genetic information of lung cells. The damage leads to harmful changes in the DNA sequence which prompt the cells to form tumors. For instance, the most common of these changes takes place in a gene called KRAS. However, it is still unclear exactly which type of lung cells are more likely to develop into a tumor. In the lungs, airway epithelial cells cover the inside of the passages that bring the air inside little sacks called alveoli, which are lined by alveolar cells. Previous studies have used genetic methods to switch on the KRAS mutation in different compartments of the mouse lung. This showed that groups of airway cells, of alveolar cells, and of a class of cells located at the junction between airways and alveoli could all give rise to cancer. However, these experiments did not examine how tobacco chemicals could give rise to tumors in different groups of lung cells. Here, Spella et al. triggered LUAD in adult mice by exposing them to the toxic chemicals found in tobacco smoke, but without making any change to the KRAS gene. These mice also had genetically engineered reporters that could be used to deduce where the resulting tumors came from. DNA sequencing showed that the airway epithelial cells gained KRAS mutations after the chemical treatment. When the airway epithelial cells were experimentally removed before the treatments with tobacco chemicals, these mice did not get LUAD tumors. Spella et al. also observed that the tobacco-induced tumors came from the epithelial cells in the airways, and not from the cells in the alveoli. Moreover, when the lung was damaged, airway cells could move to the alveoli and start adopting the identity of alveolar cells, thereby replenishing this population. Together, these experiments imply that tobacco-induced LUAD starts in the airway epithelial cells. These findings suggest that airway epithelial cells could be targeted to stop lung cancer early on. Further studies should also examine how airway epithelial cells can transition to look more like alveolar cells when the lungs get harmed.

KRAS inhibitors perform inferior to other targeted drugs. To investigate a possible reason for this, we treated cancer cells with KRAS inhibitors deltarasin (targeting phosphodiesterase-δ), cysmethynil (targeting isoprenylcysteine carboxylmethyltransferase), and AA12 (targeting KRASG12C), and silenced/overexpressed mutant KRAS using custom vectors. We show that KRAS-mutant tumor cells exclusively respond to KRAS blockade in vivo, because the oncogene co-opts host myeloid cells via a C-C-motif chemokine ligand 2/interleukin-1β signaling loop for sustained tumorigenicity. Indeed, KRAS-mutant tumors did not respond to deltarasin in Ccr2 and Il1b gene-deficient mice, but were deltarasin-sensitive in wild-type and Ccr2-deficient mice adoptively transplanted with wild-type murine bone marrow. A KRAS-dependent pro-inflammatory transcriptome was prominent in human cancers with high KRAS mutation prevalence and predicted poor survival. Hence the findings support that in vitro systems are suboptimal for anti-KRAS drug screens, and suggest that interleukin-1β blockade might be specific for KRAS-mutant cancers.

Après un rappel des objectifs, du fonctionnement et de la méthode d’interprétation des résultats du réseau de contrôle microbiologique REMI et du réseau de surveillance chimique ROCCH, ce rapport décrit le programme annuel des départements du Calvados, de la Manche et de la Seine Maritime. Il présente l’ensemble des résultats obtenus de 2016 à 2018, en particulier l’estimation de la qualité microbiologique et chimique des zones de production de coquillages classées. Ce rapport intègre également les résultats du réseau « Coquillages » de l’Agence Régionale de Santé de Normandie dans le cadre de la surveillance de la qualité des zones de pêche à pied récréative.

Increased expression of osteopontin (secreted phosphoprotein 1, SPP1) is associated with aggressive human lung adenocarcinoma (LADC), but its function remains unknown. Our aim was to determine the role of SPP1 in smoking-induced LADC. We combined mouse models of tobacco carcinogen-induced LADC, of deficiency of endogenous Spp1 alleles, and of adoptive pulmonary macrophage reconstitution to map the expression of SPP1 and its receptors and determine its impact during carcinogenesis. Co-expression of Spp1 and mutant KrasG12C in benign cells was employed to investigate SPP1/KRAS interactions in oncogenesis. Finally, intratracheal adenovirus encoding Cre recombinase was delivered to LSL.KRASG12D mice lacking endogenous or overexpressing transgenic Spp1 alleles. SPP1 was overexpressed in experimental and human LADC and portended poor survival. In response to two different smoke carcinogens, Spp1-deficient mice developed fewer and smaller LADC with decreased cellular survival and angiogenesis. Both lung epithelial- and macrophage-secreted SPP1 drove tumor-associated inflammation, while epithelial SPP1 promoted early tumorigenesis by fostering the survival of KRAS-mutated cells. Finally, loss and overexpression of Spp1 was, respectively, protective and deleterious for mice harboring KRASG12D-driven LADC. Our data support that SPP1 is functionally involved in early stages of airway epithelial carcinogenesis driven by smoking and mutant KRAS and may present an important therapeutic target.

Lung adenocarcinoma (LUAD) and chronic lung diseases caused by smoking and environmental noxious agents are the deadliest diseases worldwide, sharing a partially charted pathobiology of dysfunctional alveolar repair. Here we sought to identify the respiratory epithelial dynamics and molecular signatures participating in adult lung maintenance and chemical carcinogenesis. We employed novel mouse models of respiratory epithelial marking and ablation, a battery of pulmonary toxins and carcinogens, experimental protocols of carcinogen-induced LUAD, tobacco carcinogen-induced LUAD cell lines, and human transcriptomic data and identified a prominent involvement of airway molecular programs in alveolar maintenance and carcinogen-induced LUAD. The airway-specific transcriptomic signature was redistributed to the alveoli after toxic and carcinogenic insults and resulted in marked contributions of airway-labeled cells to injury-recovered alveoli and LUAD. Airway cells maintained Kras mutations and therefore possibly contributed to lung cancer initiation, while LUAD were spatially linked to neighboring airways. Transcriptomic profiling of carcinogen-induced murine and human LUAD revealed enrichment in airway signatures, while ablation of airway cells distorted alveolar structure and function and protected mice from LUAD development. Collectively, these results indicate that airway cells and/or transcriptomic signatures are essential for alveolar maintenance and LUAD development.

Purposes Intervention mapping (IM) is a protocol for developing effective behavior change interventions. It has been used for 10 years to develop work disability prevention (WDP) interventions, but it is not known to what extent and with what success. The main objective of this study was to review the effectiveness of these interventions. Secondary objectives were to review their fidelity to the IM protocol, their theoretical frameworks and their content. Methods A search strategy was conducted in MEDLINE, Web of Science, PsycINFO, Pascal, Francis, and BDSP. All titles and abstracts were reviewed. A standardized extraction form was developed. All included studies were reviewed by two reviewers blinded to each other. Results Eight WDP interventions were identified aimed at return to work (RTW; n = 6) and self-management at work (n = 2). RTW interventions targeted workers with stress-related mental disorders (n = 1), low back pain (n = 1), musculoskeletal disorders (n = 1), cancer (n = 2) and gynecological surgery (n = 1). The fidelity to the IM protocol was weaker for the participatory planning group. Matrices of change, change methods, and applications were systematically reported. The main theoretical frameworks used were the attitude-social influence-self efficacy model (n = 4) and the theory of planned behavior (n = 2). Half of the interventions included a workplace component (n = 4). Two interventions were reported as effective, and one partially effective. Conclusion The IM protocol is used in WDP since 2007. The participative dimension appears underused. Few theoretical frameworks were used. Implications are to better consider the stakeholders involvement, and mobilize theoretical frameworks with greater attempts to intervene on the work environment.

Lung cancer and chronic lung diseases impose major disease burdens worldwide and are caused by inhaled noxious agents including tobacco smoke. The cellular origins of environmental-induced lung tumors and of the dysfunctional airway and alveolar epithelial turnover observed with chronic lung diseases are unknown. To address this, we combined mouse models of genetic labeling and ablation of airway (club) and alveolar cells with exposure to environmental noxious and carcinogenic agents. Club cells are shown to survive KRAS mutations and to form lung tumors after tobacco carcinogen exposure. Increasing numbers of club cells are found in the alveoli with aging and after lung injury, but go undetected since they express alveolar proteins. Ablation of club cells prevents chemical lung tumors and causes alveolar destruction in adult mice. Hence club cells are important in alveolar maintenance and carcinogenesis and may be a therapeutic target against premalignancy and chronic lung disease. © eLife Sciences Publications Ltd. All rights reserved.

OBJECTIVES: This study aimed to explore the views of breast cancer (BC) specialists as to their role in the return-to-work (RTW) process of their BC patients. METHODS: A qualitative study using semi-structured interviews was conducted in a sample of 20 BC specialists selected according to age, gender, medical specialty (medical oncology, radiation oncology, gynecological surgery), and healthcare organization (regional cancer center, university or private hospital). All interviews were audiotaped and transcribed for qualitative thematic content analysis. RESULTS: BC specialists had heterogeneous representations and practices regarding their role in their patients` RTW process, ranging from non-involvement to frequent discussion. Most BC specialists had concerns regarding the ?right time and right way? to address patient`s RTW. They hardly mentioned workplace and job factors as potential barriers but rather stressed motivation. The main reported barriers to involvement in the RTW process were lack of time, lack of knowledge, lack of skills, and a professional attitude exclusively focused on cancer care issues. CONCLUSION: While our study showed varying representations and practices among BC specialists, participants consistently identified barriers in supporting BC survivors` RTW. The results will guide the development of an intervention to facilitate the role of BC specialists in the RTW process as part of a multicomponent intervention to facilitate BC survivors` RTW.

The glycoprotein osteopontin (OPN) possesses multiple functions in health and disease. To this end, osteopontin has beneficial roles in wound healing, bone homeostasis, and extracellular matrix (ECM) function. On the contrary, osteopontin can be deleterious for the human body during disease. Indeed, osteopontin is a cardinal mediator of tumor-associated inflammation and facilitates metastasis. The purpose of this review is to highlight the importance of osteopontin in malignant processes, focusing on lung and pleural tumors as examples.

Macrophage elastase, or MMP-12, is mainly produced by alveolar macrophages and is believed to play a major role in the development of chronic obstructive pulmonary disease (COPD). The catalytic domain of MMP-12 is unique among MMPs in that it is very highly active on numerous substrates including elastin. However, measuring MMP-12 activity in biological fluids has been hampered by the lack of highly selective substrates. We therefore synthesized four series of fluorogenic peptide substrates based on the sequences of MMP-12 cleavage sites in its known substrates. Human MMP-12 efficiently cleaved peptide substrates containing a Pro at P3 in the sequence Pro-X-X↓Leu but lacked selectivity towards these substrates compared to other MMPs, including MMP-2, MMP-7, MMP-9 and MMP-13. On the contrary, the substrate Abz-RNALAVERTAS-EDDnp derived from the CXCR5 chemokine was the most selective substrate for MMP-12 ever reported. All substrates were cleaved more efficiently by full-length MMP-12 than by its catalytic domain alone, indicating that the C-terminal hemopexin domain influences substrate binding and/or catalysis. Docking experiments revealed unexpected interactions between the peptide substrate Abz-RNALAVERTAS-EDDn and MMP-12 residues. Most of our substrates were poorly cleaved by murine MMP-12 suggesting that human and murine MMP-12 have different substrate specificities despite their structural similarity.

Après un rappel des objectifs, du fonctionnement et de la méthode d'interprétation des résultats du réseau de contrôle microbiologique REMI et deu réseau de surveillance chimique ROCCH, ce rapport décrit le programme annuel des départements du Calvados, de la Manche et de la Seine Maritime. Il présente l 'ensemble des résultats obtenus de 2015 à 2017, en particulier l'estimation de la qualité microbiologique et chimique des zones de production de coquillages classées. Ce rapport intègre également les résultats du réseau "Coquillages" de l'Agence Régional de Santé de Normandie dans le cadre de la surveillance de la qualité des zones de pêche à pied récréative.

Monitoring n° 30 of PENLY nuclear power - plant takes into account studies between March and September 2017. Hydrology, microbiology, phytoplankton, zooplankton and fishing are studied. This power-plant has been in operation for twenty-eight years., La surveillance n° 30 sur le site de PENLY couvre la période de mars à septembre 2017. Les domaines étudiés sont l'hydrologie, la microbiologie, le plancton végétal et animal et le domaine halieutique. L’année 2017 est la vingt huitième année de fonctionnement de la centrale.

La vente de deux fragments de minutes autographes d’Aloysius Bertrand, partiellement connues depuis la dispersion de la bibliothèque de Jules Claretie en 1918, permet de mieux connaître la manière dont Bertrand a refusé une place en Suède ou au Danemark en 1834 et les circonstances dans lesquelles il a sollicité Harel pour faire jouer Daniel en 1837., The sale of two fragments of records written in the hand of Aloysius Bertrand, partially known since the scattering of the Jules Claretie library in 1918, allows us to gain a better understanding of the way Bertrand refused a place in Sweden or Denmark in 1834 and the circumstances in which he asked Harel to have Daniel performed in 1837.

Objectives The Intervention Mapping (IM) protocol provides a structured framework to develop, implement, and evaluate complex interventions. The main objective of this review was to identify and describe the content of the interventions developed in the field of cancer with the IM protocol. Secondary objectives were to assess their fidelity to the IM protocol and to review their theoretical frameworks. Methods Medline, Web of Science, PsycINFO, PASCAL, FRANCIS, and BDSP databases were searched. All titles and abstracts were reviewed. A standardized extraction form was developed. All included studies were reviewed by 2 reviewers blinded to each other. Results Sixteen studies were identified, and these reported 15 interventions. The objectives were to increase cancer screening participation (n = 7), early consultation (n = 1), and aftercare/quality of life among cancer survivors (n = 7). Six reported a complete participatory planning group, and 7 described a complete logic model of the problem. Ten studies described a complete logic model of change. The main theoretical frameworks used were the theory of planned behaviour (n = 8), the transtheoretical model (n = 6), the health belief model (n = 6), and the social cognitive theory (n = 6). The environment was rarely integrated in the interventions (n = 4). Five interventions were reported as effective. Conclusions Culturally relevant interventions were developed with the IM protocol that were effective to increase cancer screening and reduce social disparities, particularly when they were developed through a participative approach and integrated the environment. Stakeholders' involvement and the role of the environment were heterogeneously integrated in the interventions.

Contexte : La loi HPST (2009) introduit le suivi gynecologique de prevention et la prescription de contraception en dehors de la grossesse dans les competences des sages-femmes. Medecins generalistes et sages-femmes ont des competences communes decrites pour chaque profession dans un referentiel metier et competences. Il convient de connaitre et d’articuler ces competences des la formation initiale pour exercer ensuite en cooperation. But : Recueillir les propositions des enseignants et enseignes de maieutique et de medecine generale de l’universite de Lyon a propos d’un futur enseignement commun entre etudiants des deux filieres. Methodes : Une etude qualitative exploratrice dans le champ de la planification pedagogique a ete conduite a l’aide de groupes de discussion focalisee et d’entretiens individuels semi-structures. Les participants etaient respectivement des enseignants et des enseignes des deux filieres de l’universite. Les themes explores etaient les etudiants concernes, le moment pour le realiser, le contenu, la forme pedagogique, l’encadrement, la frequence et l’objectif attendu. Resultats : Cet enseignement interprofessionnel se baserait sur des cas cliniques inspires de familles de situations cliniques issus des referentiels metiers et competences. Il concernerait les etudiants en fin de cursus. Le travail s’effectuerait en petits groupes encadres par un binome medecin generaliste et sage-femme, formes a la pedagogie et ayant une activite clinique. L’enseignement comprendrait : la presentation des deux professions, une analyse de pratiques a partir de cas cliniques rapportes et une synthese. L’interet serait de mieux connaitre le champ de competences des deux professions. Conclusion : Cette etude definit les caracteristiques d’un enseignement interprofessionnel de maieutique et medecine generale, qui puisse repondre aux attentes de chacune des filieres qui se connaissent peu.