9 research outputs found
Pulmonary lipid homeostasis in cigarette smoke-associated lung diseases
Introduction. Les effets du tabagisme demeurent problĂ©matiques dans notre sociĂ©tĂ©. Les mĂ©canismes initiateurs de la rĂ©ponse immunitaire pulmonaire induits par la fumĂ©e de cigarette sont peu caractĂ©risĂ©s. Un des phĂ©nomĂšnes dominants en contexte tabagique est lâaugmentation de la taille des macrophages alvĂ©olaires. Ce changement phĂ©notypique se distingue par une accumulation intracellulaire de lipides suggĂ©rant que le transport lipidique pulmonaire des macrophages alvĂ©olaires est modifiĂ© en contexte tabagique. Le transport lipidique pulmonaire est composĂ© de plusieurs Ă©tapes, dont la capture, le remaniement et lâexport de lipides par les macrophages alvĂ©olaires. Les impacts du tabagisme sur le transport lipidique pulmonaire sont actuellement inconnus. HypothĂšse. Le tabagisme altĂšre le transport lipidique pulmonaire. Objectifs : Chapitre 1) Investiguer lâimpact de lâexposition Ă la fumĂ©e de cigarette sur le transport lipidique pulmonaire dans un modĂšle murin et chez lâhumain ainsi quâĂ©valuer lâimpact dâune thĂ©rapie dâaugmentation des high-density lipoproteins (HDLs) dans un modĂšle murin. Chapitre 2) Investiguer les effets dâune thĂ©rapie avec un agoniste du rĂ©cepteur nuclĂ©aire liver X receptor (LXR) activant lâexport lipidique dans un modĂšle murin. Chapitre 3) CaractĂ©riser les rĂ©percussions dâune carence alimentaire sur la santĂ© pulmonaire et sur la rĂ©ponse pulmonaire en contexte tabagique dans un modĂšle murin. MĂ©thodes. 1. Le transcriptome pulmonaire de souris exposĂ©es Ă la fumĂ©e de cigarette et de sujets non-fumeurs, fumeurs et ex-fumeurs a Ă©tĂ© Ă©tudiĂ©. La capacitĂ© dâefflux de cholestĂ©rol a Ă©tĂ© mesurĂ©e dans le sĂ©rum et dans le lavage bronchoalvĂ©olaire (LBA) de souris fumeuses et non fumeuses. Une HDL recombinante, le MDCO-216, a Ă©tĂ© administrĂ©e Ă des souris fumeuses et non-fumeuses et leurs rĂ©ponses immunitaires, leurs fonctions pulmonaires et leurs compositions corporelles ont Ă©tĂ© analysĂ©es. 2. Un agoniste du LXR, le T0901317, a Ă©tĂ© administrĂ© Ă des souris en contexte tabagique. Le transcriptome pulmonaire reliĂ© au transport lipidique, la rĂ©ponse immunitaire pulmonaire et du macrophage alvĂ©olaire ainsi que les impacts sur le surfactant pulmonaire ont Ă©tĂ© investiguĂ©s. 3. Des souris fumeuses et non fumeuses ont Ă©tĂ© nourries avec des diĂštes dĂ©ficientes en mĂ©thionine (MD), choline (CD) et mĂ©thionine et choline (MCD) et leurs fonctions pulmonaires, leurs rĂ©ponses immunitaires pulmonaires et leurs expressions gĂ©niques pulmonaires ont Ă©tĂ© caractĂ©risĂ©es. RĂ©sultats. Chapitre 1. Lâexpression des gĂšnes impliquĂ©s dans le transport lipidique pulmonaire murin et humain est modifiĂ©e en contexte tabagique. La capacitĂ© du sĂ©rum et du LBA Ă promouvoir la sortie de cholestĂ©rol est augmentĂ©e aprĂšs une seule exposition Ă la fumĂ©e de cigarette. Lâadministration du MDCO-216 rĂ©duit la rĂ©ponse inflammatoire pulmonaire et la taille des macrophages alvĂ©olaires dans un modĂšle dâexposition aiguĂ« Ă la fumĂ©e de cigarette. Le MDCO-216 semble protĂ©ger les fonctions pulmonaires et induit une augmentation de la quantitĂ© de masse maigre chez les souris fumeuses. Chapitre 2. Lâagoniste du LXR augmente lâexpression des gĂšnes de transport lipidique pulmonaire, cependant il exacerbe la rĂ©ponse immunitaire pulmonaire en contexte tabagique. Les macrophages alvĂ©olaires ont aussi un phĂ©notype inflammatoire exacerbĂ© et ont davantage de stress au rĂ©ticulum endoplasmique lorsquâils sont traitĂ©s en contexte tabagique. Lâactivation de LXR mĂšne Ă une rĂ©duction des niveaux de surfactant pulmonaire. Chapitre 3. La diĂšte MCD altĂšre les fonctions pulmonaires en induisant un profil restrictif pulmonaire et abolit la rĂ©ponse immunitaire pulmonaire Ă la fumĂ©e de cigarette. En histologie, ces souris nourries avec la diĂšte MCD nâont toutefois aucun foyer fibrotique pulmonaire. Lâexpression gĂ©nique de plusieurs gĂšnes associĂ©s Ă la matrice extracellulaire et les niveaux de surfactant pulmonaire sont rĂ©duits chez les souris nourries avec la diĂšte MCD. Les phĂ©notypes pulmonaires de la diĂšte MCD sont toutefois rĂ©versibles aprĂšs un retour dâune semaine sur la diĂšte contrĂŽle. La diĂšte CD induit un profil pulmonaire de type emphysĂ©mateux et la diĂšte MD mĂšne Ă un profil restrictif. Conclusions. Ces travaux dĂ©montrent que le transport lipidique pulmonaire a un rĂŽle majeur en contexte tabagique et quâil est modulĂ© rapidement. La thĂ©rapie dâaugmentation des HDLs, avec le MDCO-216, propose une nouvelle voie de traitement envisageable pour les ex-fumeurs. La thĂ©rapie ciblant LXR suggĂšre quâil pourrait y avoir des effets dĂ©lĂ©tĂšres chez les sujets fumeurs actifs. Les carences alimentaires en mĂ©thionine et en choline dĂ©montrent dâimportants changements sur la physiologie pulmonaire. Ce tout nouveau domaine de recherche, le nutri-respiratoire, requiert davantage dâĂ©tudes afin de mieux comprendre lâimpact dâune mauvaise nutrition sur la santĂ© pulmonaire.Introduction. Cigarette smoking remains a major problem in our society.While a lot of cigarette smoke impacts are actually known, few data are available on initiating mechanisms involved in the pulmonary immune response to cigarette smoke. One of the most intriguing phenomena under cigarette smoke exposure conditions is the presence of enlarged alveolar macrophages. This phenotypic change is characterized by an intracellular lipid accumulation which may be a sign of inadequate lipid export by alveolar macrophages induced by cigarette smoking. Pulmonary lipid transport begins with lipid capture, lipid reorganization and lipid droplet formation followed by lipid export by alveolar macrophages. Cigarette smoke impacts on these steps are actually unknown. Hypothesis. Cigarette smoking alters pulmonary lipid transport. Objectives: Chapter 1) To investigate the effect of cigarette smoke exposure on pulmonary lipid transport in cigarette smoke-exposed mice and in healthy controls, smokers and former smokers. To investigate the impact of high-density lipoprotein (HDLs) therapeutic potential in cigarette smoke-exposed mice. Chapter 2) To investigate, in mice, the therapeutic potential of an agonist activating the nuclear receptor liver X receptor (LXR) involved in the transcription of lipid export genes. Chapter 3) To explore, in mice, if a dietary deficiency alters the pulmonary health and the pulmonary response to cigarette smoke. Methods. 1. The pulmonary transcriptome of cigarette smoke-exposed mice and healthy controls, smokers and former smokers was assessed. Cholesterol efflux capacity of serum and bronchoalveolar lavage (BAL) was measured in unexposed and cigarette smoke-exposed mice. MDCO-216, a recombinant HDL, was administered to unexposed and cigarette smoke-exposed mice and analyzed their pulmonary immune response, lung functions and body composition. 2. T0901317, an LXR agonist, was systemically given to mice under cigarette smoke exposure conditions. Pulmonary genes associated with lipid transport, lungs and alveolar macrophage immune pulmonary response to cigarette smoke and the impact of T0901317 on the pulmonary surfactant were assessed. 3. Unexposed and cigarette smoke-exposed mice were fed with methionine deficient (MD), choline deficient (CD) or methionine and choline deficient (MCD) diet. Diets impact on lung functions, pulmonary immune response to cigarette smoke and pulmonary transcriptome were characterized. Results. Chapter 1. Cigarette smoking altered the expression of pulmonary lipid transport genes in mice and in humans. Serum and BALF cholesterol efflux capacities were increased following a twohour cigarette smoke exposure. MDCO-216 dampened the pulmonary inflammatory response and reduced the size of alveolar macrophages in our acute cigarette smoke exposure model. MDCO-216 also seemed to be beneficial to lung functions and induced an increase in lean mass in cigarette smokeexposed treated mice. Chapter 2. T0901317 treatments led to an increase in the expression of pulmonary lipid transport genes. However, it also induced an exacerbated pulmonary immune response during cigarette smoking. Cigarette smoke-exposed treated-alveolar macrophages displayed an exacerbated inflammatory phenotype and showed an augmented endoplasmic reticulum stress. Furthermore, LXR activation led to pulmonary surfactant depletion under cigarette smoke exposure conditions. Chapter 3. The MCD diet altered lung function displaying a restrictive profile and almost abolished the pulmonary immune response to cigarette smoke. Lung histology showed no signs of fibrosis, a phenotype usually associated with restrictive pulmonary functions. MCD diet led to a dramatic change in the pulmonary expression of extracellular matrix genes and also reduced pulmonary surfactant levels. Nevertheless, these pulmonary phenotypes were reversible within a week when mice were refed a control diet. Interestingly, the CD diet induced an emphysema-like profile, while MD diet showed similar pulmonary functions to the MCD diet. Conclusions. The present thesis adds major data to an underestimated field of research and demonstrates the importance of pulmonary lipid transport, especially during cigarette smoking. Recombinant HDL therapy with MDCO-216 may be a new opportunity to overcome adverse effects of cigarette smoking, while activating LXR seems rather deleterious. Nutrient deficiencies, such as methionine and choline led to unprecedented impacts on the pulmonary health and on the pulmonary response to cigarette smoke. This completely new field of research, ânutri-respiratoryâ, requires additional studies to fully decipher the impact of unhealthy nutrition on the respiratory system
Caractérisation microbiologique des expectorations de patients MPOC en exacerbation
Les patients atteints dâune maladie pulmonaire obstructive chronique (MPOC) ont des exacerbations menant Ă une perte de leur qualitĂ© de vie. La documentation est incomplĂšte quant Ă lâidentitĂ© des microorganismes responsables, due Ă lâutilisation dâapproches classiques, telle la culture de microorganismes. Lâutilisation de nouvelles approches telles les mĂ©thodes dâĂ©cologie microbienne et le sĂ©quençage de nouvelle gĂ©nĂ©ration basĂ©es sur la biologie molĂ©culaire permet lâidentification de microorganismes, et ce, sans culture. Le microbiome de patients MPOC contrĂŽles, stables et exacerbĂ©s ont Ă©tĂ© comparĂ©s. Une diminution de Proteobacteria ou de Firmicutes vers une augmentation de Firmicutes ou de Proteobacteria respectivement a Ă©tĂ© observĂ©e lors des exacerbations. Le microbiome de patients MPOC contrĂŽles a Ă©tĂ© comparĂ© Ă trois mois dâintervalle. Un dĂ©balancement de leur microbiome vers les Proteobacteria a Ă©tĂ© observĂ© aprĂšs trois mois. Ces rĂ©sultats pourront mener Ă des traitements plus appropriĂ©s et plus ciblĂ©s afin dâaccroĂźtre la qualitĂ© de vie des patients.Chronic obstructive pulmonary disease (COPD) patients are often affected with exacerbation lowering their quality of life. The scientific community is unclear on which microorganism is responsible. This confusion is due mostly because of the culture techniques that are used to evaluate the presence of pathogens. The use of new approaches such as microbial ecology techniques and next generation sequencing based on molecular biology can identify the presence of bacteria without the need of culture. The microbiome of control, stable and exacerbated COPD patients was compared. Principal microbiome shift during exacerbation was a proportional reduction in Proteobacteria or Firmicutes and enrichment in Firmicutes or Proteobacteria respectively. The microbiome of control COPD patients was compared at baseline and three months later. Their microbiome shifted over a period of three months towards Proteobacteria. This study could lead to a better understanding of exacerbation and a better quality of life for COPD patients
Performance des établissements de soins de longue durée dans le contexte de la pandémie de la COVID-19
Introduction : Les Ă©tablissements de soins de longue durĂ©e ont Ă©tĂ© durement touchĂ©s par la pandĂ©mie de la COVID-19. Alors que la majoritĂ© dâentre eux ont rapportĂ© un nombre Ă©levĂ© de cas et de dĂ©cĂšs, certains ont Ă©tĂ© plus performants. Le but de lâĂ©tude est dâidentifier les facteurs qui ont Ă©tĂ© associĂ©s Ă la performance de ces Ă©tablissements dans la gestion de la pandĂ©mie de la COVID-19.
Méthode : Une revue de la portée, basée sur un cadre multidimensionnel de la performance, a été utilisée. Les articles, publiés entre le 1er janvier 2020 et le 31 décembre 2021 en français ou anglais dans CINAHL, MEDLINE, CAIRN, Science Direct, Scopus et Web of Science, ont été révisés par trois co-auteurs de maniÚre indépendante.
RĂ©sultats prĂ©liminaires : 6 107 articles ont Ă©tĂ© identifiĂ©s dans les bases de donnĂ©es. Ă la suite de deux Ă©tapes de sĂ©lection, lâanalyse finale porte sur 130 articles. Les facteurs organisationnels, tels que le dĂ©pistage rapide du personnel et des rĂ©sidents, la disponibilitĂ© des ressources humaines et matĂ©rielles sont les facteurs qui semblent avoir Ă©tĂ© associĂ©s Ă la performance des Ă©tablissements de soins de longue durĂ©e. Ces facteurs sont en lien avec une des dimensions de la performance de notre cadre conceptuel- soit lâefficacitĂ©, dĂ©finie comme la capacitĂ© Ă utiliser les ressources disponibles de maniĂšre optimale.
Discussion et conclusion : Cette revue de la portĂ©e pourrait mener Ă une comprĂ©hension globale des facteurs qui contribuent Ă la performance dans les Ă©tablissements de soins de longue durĂ©e et permettrait dâĂ©laborer des interventions efficaces pour la gestion des Ă©closions ainsi que pour les pandĂ©mies actuelles et futures. Introduction : Les Ă©tablissements de soins de longue durĂ©e ont Ă©tĂ© durement touchĂ©s par la pandĂ©mie de la COVID-19. Alors que la majoritĂ© dâentre eux ont rapportĂ© un nombre Ă©levĂ© de cas et de dĂ©cĂšs, certains ont Ă©tĂ© plus performants. Le but de lâĂ©tude est dâidentifier les facteurs qui ont Ă©tĂ© associĂ©s Ă la performance de ces Ă©tablissements dans la gestion de la pandĂ©mie de la COVID-19.
Méthode : Une revue de la portée, basée sur un cadre multidimensionnel de la performance, a été utilisée. Les articles, publiés entre le 1er janvier 2020 et le 31 décembre 2021 en français ou anglais dans CINAHL, MEDLINE, CAIRN, Science Direct, Scopus et Web of Science, ont été révisés par trois co-auteurs de maniÚre indépendante.
RĂ©sultats prĂ©liminaires : 6 107 articles ont Ă©tĂ© identifiĂ©s dans les bases de donnĂ©es. Ă la suite de deux Ă©tapes de sĂ©lection, lâanalyse finale porte sur 130 articles. Les facteurs organisationnels, tels que le dĂ©pistage rapide du personnel et des rĂ©sidents, la disponibilitĂ© des ressources humaines et matĂ©rielles sont les facteurs qui semblent avoir Ă©tĂ© associĂ©s Ă la performance des Ă©tablissements de soins de longue durĂ©e. Ces facteurs sont en lien avec une des dimensions de la performance de notre cadre conceptuel- soit lâefficacitĂ©, dĂ©finie comme la capacitĂ© Ă utiliser les ressources disponibles de maniĂšre optimale.
Discussion et conclusion : Cette revue de la portĂ©e pourrait mener Ă une comprĂ©hension globale des facteurs qui contribuent Ă la performance dans les Ă©tablissements de soins de longue durĂ©e et permettrait dâĂ©laborer des interventions efficaces pour la gestion des Ă©closions ainsi que pour les pandĂ©mies actuelles et futures.  
Identification of dichloroacetic acid degrading Cupriavidus bacteria in a drinking water distribution network model
Aims: Bacterial community structure and composition of a drinking water
network were assessed to better understand this ecosystem in relation to
haloacetic acid (HAA) degradation and to identify new bacterial species having
HAA degradation capacities.
Methods and Results: Biofilm samples were collected from a model system,
simulating the end of the drinking water distribution network and supplied
with different concentrations of dichloroacetic and trichloroacetic acids at
different periods over the course of a year. The samples were analysed by
culturing, denaturing gradient gel electrophoresis (DGGE) and sequencing.
Pipe diameter and HAA ratios did not impact the bacterial community
profiles, but the season had a clear influence. Based on DGGE profiles, it
appeared that a particular biomass has developed during the summer
compared with the other seasons. Among the bacteria isolated in this study,
those from genus Cupriavidus were able to degrade dichloroacetic acid.
Moreover, these bacteria degrade dichloroacetic acid at 18°C but not at 10°C.
Conclusions: The microbial diversity evolved throughout the experiment, but
the bacterial community was distinct during the summer. Results obtained on
the capacity of Cupriavidus to degrade DCAA only at 18°C but not at 10°C
indicate that water temperature is a major element affecting DCAA
degradation and confirming observations made regarding season influence on
HAA degradation in the drinking water distribution network.
Significance and Impact of the Study: This is the first demonstration of the
HAA biodegradation capacity of the genus Cupriavidu
Variants of a genomic island in Aeromonas salmonicida subsp. salmonicida link isolates with their geographical origins
Aeromonas salmonicida subsp. salmonicida is a fish pathogen. Analysis of its genomic characteristics is required to determine the worldwide distribution of the various populations of this bacterium. Genomic alignments between the 01-B526 pathogenic strain and the A449 reference strain have revealed a 51-kb chromosomal insertion in 01-B526. This insertion (AsaGEI1a) has been identified as a new genomic island (GEI) bearing prophage genes. PCR assays were used to detect this GEI in a collection of 139 A. salmonicida subsp. salmonicida isolates. Three forms of this GEI (AsaGEI1a, AsaGEI1b, AsaGEI2a) are now known based on this analysis and the sequencing of the genomes of seven additional isolates. A new prophage (prophage 3) associated with AsaGEI2a was also discovered. Each GEI appeared to be strongly associated with a specific geographic region. AsaGEI1a and AsaGEI2a were exclusively found in North American isolates, except for one European isolate bearing AsaGEI2a. The majority of the isolates bearing AsaGEI1b or no GEI were from Europe. Prophage 3 has also a particular geographic distribution and was found only in North American isolates. We demonstrated that A. salmonicida subsp. salmonicida possesses unsuspected elements of genomic heterogeneity that could be used as indicators to determine the geographic origins of isolates of this bacterium.Keywords : Bacteria, Genomics-functional genomics-comparative genomics; Furunculosis; Aeromonas salmonicida; Fish pathogen; Genomic island; Geographical distributio
The Hepatokine TSK does not affect brown fat thermogenic capacity, body weight gain, and glucose homeostasis
Objectives
Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis.
Methods
We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression.
Results
The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice
Standardized and validated training to support the charge nurse: Research protocol
Abstract Aim To develop a standardized training for charge nurses. Design A developmental research design divided into three parts will be undertaken. Methods (1) A scoping review will be used to develop standardized training focusing on charge nurse skills and subâskills; (2) a Delphi review with nurses, managers and researchers will validate the content of the training; content validity will be assessed over sufficient rounds of review to obtain a content validity index of over 0.7 and (3) a crossâsectional study will pilot test the training with 30 charge nurses. Results This study will describe the development of updated and empirically validated training to be systematically implemented in healthcare institutions and offered to charge nurses when they begin