Comparative Toxicogenomics Database (CTD): update 2023.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions by manually curating and interrelating chemical, gene, phenotype, anatomy, disease, taxa, and exposure content from the published literature. This curated information is integrated to generate inferences, providing potential molecular mediators to develop testable hypotheses and fill in knowledge gaps for environmental health. This dual nature, acting as both a knowledgebase and a discoverybase, makes CTD a unique resource for the scientific community. Here, we report a 20% increase in overall CTD content for 17 100 chemicals, 54 300 genes, 6100 phenotypes, 7270 diseases and 202 000 exposure statements. We also present CTD Tetramers, a novel tool that computationally generates four-unit information blocks connecting a chemical, gene, phenotype, and disease to construct potential molecular mechanistic pathways. Finally, we integrate terms for human biological media used in the CTD Exposure module to corresponding CTD Anatomy pages, allowing users to survey the chemical profiles for any tissue-of-interest and see how these environmental biomarkers are related to phenotypes for any anatomical site. These, and other webpage visual enhancements, continue to promote CTD as a practical, user-friendly, and innovative resource for finding information and generating testable hypotheses about environmental health.

Comparative Toxicogenomics Database (CTD): update 2021.

The public Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is an innovative digital ecosystem that relates toxicological information for chemicals, genes, phenotypes, diseases, and exposures to advance understanding about human health. Literature-based, manually curated interactions are integrated to create a knowledgebase that harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions. In this biennial update, we report a 20% increase in CTD curated content and now provide 45 million toxicogenomic relationships for over 16 300 chemicals, 51 300 genes, 5500 phenotypes, 7200 diseases and 163 000 exposure events, from 600 comparative species. Furthermore, we increase the functionality of chemical-phenotype content with new data-tabs on CTD Disease pages (to help fill in knowledge gaps for environmental health) and new phenotype search parameters (for Batch Query and Venn analysis tools). As well, we introduce new CTD Anatomy pages that allow users to uniquely explore and analyze chemical-phenotype interactions from an anatomical perspective. Finally, we have enhanced CTD Chemical pages with new literature-based chemical synonyms (to improve querying) and added 1600 amino acid-based compounds (to increase chemical landscape). Together, these updates continue to augment CTD as a powerful resource for generating testable hypotheses about the etiologies and molecular mechanisms underlying environmentally influenced diseases.

Evaluating sources of bias in pedigree-based estimates of breeding population size.

Applications of genetic-based estimates of population size are expanding, especially for species for which traditional demographic estimation methods are intractable due to the rarity of adult encounters. Estimates of breeding population size (NS ) are particularly amenable to genetic-based approaches as the parameter can be estimated using pedigrees reconstructed from genetic data gathered from discrete juvenile cohorts, therefore eliminating the need to sample adults in the population. However, a critical evaluation of how genotyping and sampling effort influence bias in pedigree reconstruction, and how these biases subsequently influence estimates of NS , is needed to evaluate the efficacy of the approach under a range of scenarios. We simulated a model system to understand the interactive effects of genotyping and sampling effort on error in genetic pedigrees reconstructed from the program COLONY. We then evaluated how errors in pedigree reconstruction influenced bias and precision in estimates of NS using three different rarefaction estimators. Results indicated that pedigree error can be minimal when adequate genetic data are available, such as when juvenile sample sizes are large and/or individuals are genotyped at many informative loci. However, even in cases for which data are limited, using results of the simulation analysis to understand the magnitude and sources of bias in reconstructed pedigrees can still be informative when estimating NS . We applied results of the simulation analysis to evaluate N ̂ $$ \hat{N} $$ S for a population of federally endangered Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) in the Delaware River, USA. Our results indicated that NS is likely to be three orders of magnitude lower compared with historic breeding population sizes, which is a considerable advancement in our understanding of the population status of Atlantic sturgeon in the Delaware River. Our analyses are broadly applicable in the design and interpretation of studies seeking to estimate NS and can help to guide conservation decisions when ecological uncertainty is high. The utility of these results is expected to grow as rapid advances in genetic technologies increase the popularity of genetic population monitoring and estimation.

Outbreak of Foodborne Botulism Associated with a Commercially Produced Multipack Potato Product, Colorado: September 2019.

During September 2019, public health authorities in El Paso County, Colorado, were notified of four patients who had presented to nearby hospitals with clinical features consistent with botulism, a paralytic illness caused by botulinum neurotoxin. One patient died soon after presentation; the other three patients required intensive care but recovered after receiving botulism antitoxin. Botulinum toxin type A was detected in serum from all patients. On further investigation, all four patients had shared a meal that included commercially prepared roasted potatoes from an individual package without refrigeration instructions that had been left unrefrigerated for 15 d. Storage of the product at ambient temperature likely allowed botulism spores to produce botulinum toxin, resulting in severe illness and death. The manufacturer improved labeling in response to this outbreak. Public health officials should consider unrefrigerated potato products as a potential source of botulism; clinicians should consider botulism as a possible cause of paralytic illness.

The Comparative Toxicogenomics Database: update 2019.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a premier public resource for literature-based, manually curated associations between chemicals, gene products, phenotypes, diseases, and environmental exposures. In this biennial update, we present our new chemical-phenotype module that codes chemical-induced effects on phenotypes, curated using controlled vocabularies for chemicals, phenotypes, taxa, and anatomical descriptors; this module provides unique opportunities to explore cellular and system-level phenotypes of the pre-disease state and allows users to construct predictive adverse outcome pathways (linking chemical-gene molecular initiating events with phenotypic key events, diseases, and population-level health outcomes). We also report a 46% increase in CTD manually curated content, which when integrated with other datasets yields more than 38 million toxicogenomic relationships. We describe new querying and display features for our enhanced chemical-exposure science module, providing greater scope of content and utility. As well, we discuss an updated MEDIC disease vocabulary with over 1700 new terms and accession identifiers. To accommodate these increases in data content and functionality, CTD has upgraded its computational infrastructure. These updates continue to improve CTD and help inform new testable hypotheses about the etiology and mechanisms underlying environmentally influenced diseases.

The Comparative Toxicogenomics Database: update 2017.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between chemicals and gene products, and their relationships to diseases. Core CTD content (chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature) are integrated with each other as well as with select external datasets to generate expanded networks and predict novel associations. Today, core CTD includes more than 30.5 million toxicogenomic connections relating chemicals/drugs, genes/proteins, diseases, taxa, Gene Ontology (GO) annotations, pathways, and gene interaction modules. In this update, we report a 33% increase in our core data content since 2015, describe our new exposure module (that harmonizes exposure science information with core toxicogenomic data) and introduce a novel dataset of GO-disease inferences (that identify common molecular underpinnings for seemingly unrelated pathologies). These advancements centralize and contextualize real-world chemical exposures with molecular pathways to help scientists generate testable hypotheses in an effort to understand the etiology and mechanisms underlying environmentally influenced diseases.

Progression of Lung Disease in Preschool Patients with Cystic Fibrosis.

RATIONALE: Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES: To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progression in preschool children with CF. METHODS: Children with CF between the ages of 2.5 and 6 years with a confirmed diagnosis of CF and age-matched healthy control subjects were enrolled at three North American CF centers. Multiple breath washout tests were performed at baseline, 1, 3, 6, and 12 months to mimic time points chosen in clinical care and interventional trials; spirometry was also conducted. A generalized linear mixed-effects model was used to distinguish LCI changes associated with normal growth and development (i.e., healthy children) from the progression of CF lung disease. MEASUREMENTS AND MAIN RESULTS: Data were collected on 156 participants with 800 LCI measurements. Although both LCI and spirometry discriminated health from disease, only the LCI identified significant deterioration of lung function in CF over time. The LCI worsened during cough episodes and pulmonary exacerbations, whereas similar symptoms in healthy children were not associated with increased LCI values. CONCLUSIONS: LCI is a useful marker to track early disease progression and may serve as a tool to guide therapies in young patients with CF.

CARES: A Community-wide Collaboration Identifies Super-utilizers and Reduces Their 9-1-1 Call, Emergency Department, and Hospital Visit Rates.

BACKGROUND: A subset of individuals who inefficiently and frequently use emergency department (ED) services are called "super-utilizers." Our healthcare system is fragmented and complex, making it difficult for providers to identify super-utilizers and address their wide range of health issues. OBJECTIVE: The objective of our study was to evaluate a novel community-wide collaboration program called CARES (Community Assistance Referral and Education Services) designed to identify super-utilizers through local partnering organizations. CARES assists patients in developing their personal health and wellness goals, and navigates them away from 9-1-1 calls, emergency room visits, and hospital admissions, and toward more appropriate resources over 90 days. METHODS: This was a retrospective observational analysis of the CARES program. Data were collected from March 2013 to December 2015. The study population included: enrolled adults with non-compliance of medication or treatment; behavioral health problems; multiple 9-1-1 responses in a short period of time; three or more ED visits within six months; patients with multiple hospital admissions. Adults who were outside of the study period or had missing outcome information were excluded. The primary outcomes of this study were the median rate of 9-1-1 calls/month/person, ED and hospital visits/month/person. Wilcoxon rank-sum tests were used to compare changes between pre- vs. post-enrollment for each subject. RESULTS: A total of 441 subjects were included in this study. The majority of patients (64%) were female, 64% were white, and the median (IQR) age was 48 (35-62) years old. A total of 51% were on Medicaid and 69% identified behavioral health issues as their barriers to optimal health care. Between pre- and post-enrollment periods, the median (IQR) monthly rate of 9-1-1 calls, ED visits, and hospital admissions significantly decreased by 0.26 (-0.06, 0.90), 0.25 (-0.08, 0.71), and 0.18 (0.04, 0.53) (p < 0.001 for all). CONCLUSIONS: When health systems in a geographic area share data, they are better able to recognize patterns of overuse, and address them properly. This study demonstrated that a collaborative 90-day intervention identifying super-utilizers reduced the monthly rate of 9-1-1 calls, ED visits, and hospital admissions.

The Comparative Toxicogenomics Database: update 2013.

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) provides information about interactions between environmental chemicals and gene products and their relationships to diseases. Chemical-gene, chemical-disease and gene-disease interactions manually curated from the literature are integrated to generate expanded networks and predict many novel associations between different data types. CTD now contains over 15 million toxicogenomic relationships. To navigate this sea of data, we added several new features, including DiseaseComps (which finds comparable diseases that share toxicogenomic profiles), statistical scoring for inferred gene-disease and pathway-chemical relationships, filtering options for several tools to refine user analysis and our new Gene Set Enricher (which provides biological annotations that are enriched for gene sets). To improve data visualization, we added a Cytoscape Web view to our ChemComps feature, included color-coded interactions and created a 'slim list' for our MEDIC disease vocabulary (allowing diseases to be grouped for meta-analysis, visualization and better data management). CTD continues to promote interoperability with external databases by providing content and cross-links to their sites. Together, this wealth of expanded chemical-gene-disease data, combined with novel ways to analyze and view content, continues to help users generate testable hypotheses about the molecular mechanisms of environmental diseases.

Single-molecule imaging reveals aß42:aß40 ratio-dependent oligomer growth on neuronal processes.

Soluble oligomers of the amyloid-ß peptide have been implicated as proximal neurotoxins in Alzheimer's disease. However, the identity of the neurotoxic aggregate(s) and the mechanisms by which these species induce neuronal dysfunction remain uncertain. Physiologically relevant experimentation is hindered by the low endogenous concentrations of the peptide, the metastability of Aß oligomers, and the wide range of observed interactions between Aß and biological membranes. Single-molecule microscopy represents one avenue for overcoming these challenges. Using this technique, we find that Aß binds to primary rat hippocampal neurons at physiological concentrations. Although amyloid-ß(1-40) as well as amyloid-ß(1-42) initially form larger oligomers on neurites than on glass slides, a 1:1 mix of the two peptides result in smaller neurite-bound oligomers than those detected on-slide or for either peptide alone. With 1 nM peptide in solution, Aß40 oligomers do not grow over the course of 48 h, Aß42 oligomers grow slightly, and oligomers of a 1:1 mix grow substantially. Evidently, small Aß oligomers are capable of binding to neurons at physiological concentrations and grow at rates dependent on local Aß42:Aß40 ratios. These results are intriguing in light of the increased Aß42:Aß40 ratios shown to correlate with familial Alzheimer's disease mutations.

Lung function from infancy to preschool in a cohort of children with cystic fibrosis.

This study aimed to describe lung function in a cohort of children with cystic fibrosis (CF) who underwent infant pulmonary function tests (IPFTs) and preschool spirometry. Children performed up to four IPFTs (raised volume rapid thoracic compression technique) over 1 yr and five preschool spirometry tests over up to 2 yrs during participation in prospective, multicentre studies of infant and preschool lung function. All lung function data were reviewed centrally for measurement acceptability. 45 children had 252 acceptable measurements (137 IPFTs and 115 preschool spirometries) at ages 0.3-6.5 yrs. The median number of measurements per participant was 6 (range 3-9). Recent Pseudomonas aeruginosa infection was associated with 5.1% (95% CI 0.01-9.9%) lower forced expiratory volume in 0.5 s (FEV(0.5)) and 16.4% (95% CI 7.0-24.9%) lower forced expiratory flow at 25-25% of forced vital capacity (FEF(25-75%)), after adjustment for length, test type and centre. Recent cough was associated with 5.7% (95% CI 1.1-10.1%) lower FEV(0.5) and 10.1% (95% CI 0.6-18.7%) lower FEF(25-75%). Even after accounting for infection status, cough, sex, length, test type and centre, there was significant inter-individual variability in lung function (p<0.01 for each of FEV(0.5), FEF(25-75%) and forced vital capacity). Recent P. aeruginosa infection and cough are associated with lower lung function in children with CF. Significant inter-individual variability in lung function remains to be explained.

Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis.

The optimal strategy for monitoring cystic fibrosis lung disease in infancy remains unclear. Our objective was to describe longitudinal associations between infant pulmonary function tests, chest radiograph scores and other characteristics. Cystic fibrosis patients aged ≤24 months were enrolled in a 10-centre study evaluating infant pulmonary function tests four times over a year. Chest radiographs ∼1 year apart were scored using the Wisconsin and Brasfield systems. Associations of infant pulmonary function tests with clinical characteristics were evaluated with mixed effects models. The 100 participants contributed 246 acceptable flow/volume (forced expiratory volume in 0.5 s (FEV0.5) and forced expiratory flow at 75% of the forced vital capacity (FEF75%)), 303 functional residual capacity measurements and 171 chest radiographs. Both Brasfield and Wisconsin chest radiograph scores worsened significantly over the 1-year interval. Worse Wisconsin chest radiograph scores and Staphylococcus aureus were both associated with hyperinflation (significantly increased functional residual capacity), but not with diminished FEV0.5 or FEF75%. Parent-reported cough was associated with significantly diminished forced expiratory flow at 75% but not with hyperinflation. In this infant cohort in whom we previously reported worsening in average lung function, chest radiograph scores also worsened over a year. The significant associations detected between both Wisconsin chest radiograph score and S. aureus and hyperinflation, as well as between cough and diminished flows, reinforce the ability of infant pulmonary function tests and chest radiographs to detect early cystic fibrosis lung disease.

Health Professionals Working With First Nations, Inuit, and Métis Consensus Guideline.

OBJECTIVE: Our aim is to provide health care professionals in Canada with the knowledge and tools to provide culturally safe care to First Nations, Inuit, and Métis women and through them, to their families, in order to improve the health of First Nations, Inuit, and Métis. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane Library in 2011 using appropriate controlled vocabulary (e.g., cultural competency, health services, indigenous, transcultural nursing) and key words (e.g, indigenous health services, transcultural health care, cultural safety). Targeted searches on subtopics (e.g, ceremonial rites and sexual coming of age) were also performed. The PubMed search was restricted to the years 2005 and later because of the large number of records retrieved on this topic. Searches were updated on a regular basis and incorporated in the guideline to May 2012. Grey (unpublished) literature was identified through searching the websites of selected related agencies (e.g, Campbell Collaboration, Social Care Online, Institute for Healthcare Improvement) VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task force on Preventive Health Care (Table). SPONSORS: This consensus guideline was supported by the First Nations and Inuit Health Branch, Health Canada.

RETIRED: Health Professionals Working With First Nations, Inuit, and Métis Consensus Guideline.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Health professionals working with First Nations, Inuit, and Métis consensus guideline.

OBJECTIVE: Our aim is to provide health care professionals in Canada with the knowledge and tools to provide culturally safe care to First Nations, Inuit, and Métis women and through them, to their families, in order to improve the health of First Nations, Inuit, and Métis. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, Sociological Abstracts, and The Cochrane Library in 2011 using appropriate controlled vocabulary (e.g.,cultural competency, health services, indigenous, transcultural nursing) and key words (e.g., indigenous health services, transcultural health care, cultural safety). Targeted searches on subtopics (e.g., ceremonial rites and sexual coming of age) were also performed. The PubMed search was restricted to the years 2005 and later because of the large number of records retrieved on this topic. Searches were updated on a regular basis and incorporated in the guideline to May 2012. Grey (unpublished) literature was identified through searching the websites of selected related agencies (e.g., Campbell Collaboration, Social Care Online, Institute for Healthcare Improvement). VALUES: The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task force on Preventive Health Care (Table).

Objectif : Nous avons pour objectif de fournir aux professionnels de la santé du Canada les connaissances et les outils qui leur permettront d'offrir des soins sûrs sur le plan culturel aux Inuites, aux Métisses et aux femmes des Premières Nations, et par leur intermédiaire, à leur famille, en vue d'améliorer la santé au sein de ces peuples. Résultats : La littérature publiée a été récupérée par l'intermédiaire de recherches menées dans PubMed, CINAHL, Sociological Abstracts et The Cochrane Library en 2011, au moyen d'un vocabulaire contrôlé (p. ex. « Health Services ¼, « Indigenous ¼, « Transcultural Nursing ¼, « Cultural Competence ¼) et de mots clés (p. ex. « indigenous health services ¼, « transcultural health care ¼, « cultural safety ¼) appropriés. Des recherches ciblées sur des sous-sujets (p. ex. « ceremonial rites ¼ et « sexual coming of age ¼) ont également été menées. Les recherches menées dans PubMed ont été restreintes à l'année 2005 et aux années suivantes, en raison du nombre important de dossiers récupérés sur le sujet. Les recherches ont été mises à jour de façon régulière et intégrées à la directive clinique jusqu'en mai 2012. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes connexes sélectionnés (p.ex. Campbell Collaboration, Social Care Online, Institute for Healthcare Improvement). Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Commanditaires : La présente directive clinique de consensus a été soutenue par la Direction générale de la santé des Premières nations et des Inuits, Santé Canada. Déclarations sommaires 1. Sur le plan démographique, les peuples inuits, métis et des Premières Nations sont plus jeunes et plus mobiles que les peuples non autochtones. Cela nécessite donc, de la part des professionnels de la santé, la mise en œuvre d'efforts supplémentaires en vue d'établir un environnement de confiance et de sûreté culturelle au sein de leurs lieux de travail, et ce, car les occasions d'offrir des soins pourraient être brèves. (III) 2. Selon l'indice du développement humain de l'Organisation mondiale de la santé, le Canada se classe au 6e rang mondial; les Premières Nations, quant à elles, se classent au 68e rang. (II-3) 3. Des ententes officielles ont été conclues pendant des siècles entre les gouvernements européens et les Premières Nations. Elles ont, à l'origine, été conclues dans un esprit d'amitié et de coopération; toutefois, elles en sont plus tard venues à être centrées sur la propriété des terres et l'extraction des ressources. Puisque ces ententes ont été bafouées à répétition, les Premières Nations entretiennent une attitude de méfiance à l'endroit du gouvernement, de ses représentants, de ses politiques et de quiconque étant perçu comme exerçant une quelconque autorité. (III) 4. La Loi sur les Indiens et ses amendements subséquents ont été conçus pour assurer le contrôle de tous les aspects de la vie des Indiens inscrits et pour promouvoir l'assimilation. Il s'agissait également d'un outil dont s'est servi le gouvernement pour obtenir accès aux terres et aux ressources des Premières Nations. (III) 5. Les traumatismes intergénérationnels qui ont été infligés aux Inuits, aux Métis et aux Premières Nations, sont le produit du colonialisme. Les pensionnats, la relocalisation forcée, la stérilisation involontaire, l'adoption forcée, la conversion religieuse et l'émancipation sont quelques exemples des politiques du gouvernement à l'endroit des Inuits, des Métis et des Premières Nations qui ont généré un stress et un dysfonctionnement post-traumatiques intergénérationnels. Quoi qu'il en soit, ces peuples continuent d'être résilients. (III) 6. La plupart des Canadiens ne savent pas qu'une forte proportion du produit intérieur brut du Canada repose sur des ressources naturelles extraites de terres autochtones, tandis que les Inuits et les Premières Nations doivent dépendre de transferts monétaires insuffisants de la part du gouvernement fédéral. (III) 7. Certaines sociétés multinationales procèdent à l'extraction de ressources se trouvant dans des terres qui se situent souvent dans des communautés autochtones ou dans les environs de celles-ci, ou encore dans des terres étant visées par des revendications territoriales. Le fait que la gestion des terres et des ressources soit assurée par les provinces, dans certaines régions, et par les gouvernements fédéral et territoriaux, dans d'autres régions, complique la communication entre les sociétés multinationales et les communautés inuites, métisses et des Premières Nations, particulièrement dans les cas où des revendications territoriales sont en cours de négociation ou dans ceux où de telles négociations n'ont toujours pas été entreprises. Ces sociétés multinationales ne fournissent pas de revenus à ces communautés. La plupart des communautés autochtones sont pauvres, ne disposent pas d'une infrastructure de santé publique adéquate et n'ont pas les moyens économiques d'améliorer leur condition. (III) 8. De nos jours, des problèmes de nature juridictionnelle rendent difficile l'offre de soins de santé, la bonne gestion des terres et la promotion de la santé au sein des communautés. (III) 9. Bien que la consommation d'aliments traditionnels contribue à la préservation de l'identité culturelle, la présence croissante de contaminants environnementaux (tels que le plomb, l'arsenic, le mercure et les polluants organiques persistants [POP]) pourrait compromettre la sécurité de ces aliments. (II-3) 10. Compte tenu des changements démographiques (population en croissance rapide comptant une importante composante jeunesse) et de l'urbanisation croissante que connaissent les Inuits, les Métis et les Premières Nations au Canada, force est de constater que la plupart des cliniciens en viendront à compter des Inuites, des Métisses et des femmes des Premières Nations parmi leurs patientes. (II-3) 11. Traditionnellement, les hommes et les femmes des peuples inuits, métis et des Premières Nations tenaient des rôles égaux et complémentaires. Le colonialisme s'est généralement affairer à mépriser et à ignorer les Inuites et les femmes des Premières Nations, et à les réduire au statut d'objet. Par l'intermédiaire de lois spécifiques, les femmes des Premières Nations (en particulier) ont perdu leurs droits et leurs pouvoirs au sein de leurs communautés, y compris leur rôle en matière de promotion de la santé et de l'éducation traditionnelles. (III) 12. Au sein des communautés autochtones, le taux de chômage est beaucoup plus élevé que celui qui est constaté chez les Canadiens non autochtones. Il contribue de façon importante aux écarts socioéconomiques et aux lacunes en matière d'accès à des soins de santé équitables et de qualité. (II-3) 13. La terminologie de la mesure des issues de santé a souvent pour effet de perpétuer des stéréotypes négatifs envers les Inuits, les Métis et les Premières Nations, puisque les données générées sont souvent signalées sans tenir du contexte social, politique et économique des communautés visées. (III) 14. Les conflits juridictionnels entre les gouvernements fédéral, provinciaux, territoriaux et de bande rendent difficile l'offre de services de santé et de santé publique exhaustifs aux Premières Nations. (III) 15. L'harmonie des sociétés inuites, métisses et des Premières Nations a été troublée par le colonialisme européen à la fin du 18e siècle, lequel est à l'origine d'effets à grande échelle sur la santé sexuelle des femmes et des hommes des communautés inuites, métisses et des Premières Nations. (III) 16. La recherche a démontré que la mise en œuvre de stratégies visant la compétence culturelle menait à l'amélioration des issues de santé et à celle de la satisfaction de la patiente. (II-3) 17. Une forme insidieuse de racisme peut se manifester de façon non intentionnelle; ceux qui en font l'objet sont donc les mieux à même de définir ce qui constitue une telle manifestation de racisme et d'en identifier la présence. (III) Recommandations 1. Les professionnels de la santé devraient disposer d'une compréhension des termes qu'utilisent les Inuits, les Métis et les Premières Nations pour s'identifier. (III-A) 2. Les professionnels de la santé devraient disposer d'une compréhension des termes « sensibilisation culturelle ¼, « compétence culturelle ¼, « sûreté culturelle ¼ et « humilité culturelle ¼. Les professionnels de la santé devraient reconnaître que les Inuits, les Métis et les Premières Nations pourraient avoir des points de vue différents quant à ce qui constitue des soins sûrs sur le plan culturel; ils devraient donc chercher à en savoir plus sur les valeurs propres à la communauté desservie. (III-A) 3. Les professionnels de la santé devraient être conscients des limites des statistiques recueillies au sujet des Inuits, des Métis et des Premières Nations, et devraient éviter d'avoir recours à des généralisations au sujet des risques de mortalité et de morbidité, au moment de comparer les populations inuites, métisses et des Premières Nations les unes aux autres et aux populations non autochtones. (III-A) 4. Les professionnels de la santé qui souhaitent mener des recherches auprès des Inuits, des Métis et des Premières Nations doivent utiliser des cadres éthiques reconnus qui tiennent compte des principes PCAP (propriété, contrôle, accès et possession), de l'Énoncé de politique des trois conseils et des lignes directrices propres aux communautés visées. (II-2A) 5. Les professionnels de la santé devraient reconnaître les effets intergénérationnels des pensionnats comme étant l'une des causes fondamentales des inégalités sociales et en matière de santé qui affectent les Inuits, les Métis et les Premières Nations, ces effets ayant des implications importantes sur les expériences et les pratiquesentourant la grossesse et l'éducation des enfants. (II-3A) 6. Les professionnels de la santé devraient savoir que le discours sur les politiques de santé et les négociations quant aux revendications territoriales perpétue souvent des stéréotypes négatifs, sans adéquatement faire mention des effets du colonialisme. (III-L) 7. Les professionnels de la santé devraient connaître le Principe de Jordan (un principe qui place l'enfant au premier plan et qui exhorte l'agence gouvernementale auxquels les parents se sont d'abord adressés d'assumer les frais des services prodigués à l'enfant, pour ensuite entreprendre des démarches de remboursement, et ce, en vue d'assurer l'offre de soins adéquats en temps opportun) et être au courant des débats en cours (en ce qui concerne les responsabilités juridictionnelles) qui nuisent à l'offre de soins de santé de qualité, opportuns et sûrs sur le plan culturel aux Inuits et aux Premières Nations. (III-A) 8. Les professionnels de la santé qui offrent des soins aux Inuits et aux Premières Nations devraient connaître le programme de services de santé non assurés (SSNA), les critères d'admissibilité de ce dernier et la couverture qu'il offre, ainsi que les exceptions et les permissions spéciales qui sont requises dans certains cas. Les professionnels de la santé devraient reconnaître qu'ils ont un rôle crucial à jouer dans la défense des droits de leurs patientes inuites et des Premières Nations, en vue de les aider à obtenir accès à ces prestations. Les professionnels de la santé devraient savoir que leurs patientes métisses n'ont pas accès au programme SSNA et qu'elles pourraient faire face à des difficultés particulières au moment de chercher à obtenir des soins de santé. (III-A) 9. Tous les professionnels de la santé devraient reconnaître et respecter le rôle des sages-femmes autochtones et traditionnelles dans la promotion de la santé sexuelle et génésique des femmes, et devraient savoir que ce rôle ne se limite pas à la grossesse et à l'accouchement, mais bien qu'il se prolonge souvent au-delà de l'année de la naissance. (II-2A) 10. Dans le cadre des consultations régulières (y compris celles qui visent les soins prénataux), les professionnels de la santé devraient se renseigner au sujet de l'utilisation de pratiques médicales et de médicaments traditionnels par leurs patientes. (III-A) 11. Les professionnels de la santé devraient savoir que chaque communauté inuite, métisse et des Premières Nations compte ses propres traditions, valeurs et pratiques de communication; ils devraient donc participer aux activités de la communauté en question de façon à se familiariser avec ces traditions, valeurs et pratiques. (III-A) 12. Les professionnels de la santé devraient être au courant des lois du Code criminel canadien qui traitent des activités sexuelles chez les mineurs (y compris les enfants de moins de 12 ans et les enfants dont l'âge se situe entre 12 et 16 ans) et de la différence d'âge entre les partenaires. (III-A) 13. Compte tenu de la prévalence de l'exploitation et des sévices sexuels, les professionnels de la santé doivent, après avoir établi une relation de confiance avec la patiente, se pencher sur la présence possible de tels méfaits. Tous les examens gynécologiques et obstétricaux doivent être abordés avec sensibilité, de façon à permettre à la patiente de déterminer elle-même le moment où elle est prête à s'y soumettre. (III-A) 14. Les professionnels de la santé devraient être avisés de la prévalence accrue du VIH/sida chez les Inuits, les Métis et les Premières Nations, et devraient offrir des services de counseling et de dépistage du VIH aux femmes enceintes ou en âge de procréer. La mise en œuvre d'approches sûres sur le plan culturel envers le counseling, le dépistage, le diagnostic et le traitement en présence du VIH et d'autres maladies transmissibles par le sang devrait être soutenue et adoptée. (III-A) 15. Les professionnels de la santé devraient être avisés des taux élevés de cancer du col utérin que l'on constate chez les patientes inuites et des Premières Nations, ainsi que des piètres issues qu'elles connaissent à la suite du diagnostic d'un tel cancer. Les professionnels de la santé devraient s'efforcer de limiter les disparités entre leurs patientes autochtones et leurs patientes non autochtones, en faisant la promotion d'options de dépistage sûres sur le plan culturel. (I-A) 16. Les professionnels de la santé doivent s'assurer que les Inuites, les Métisses et les femmes des Premières Nations ont accès à des services pouvant répondre à tous leurs besoins de santé génésique, y compris l'interruption de grossesse, sans préjugés. Les professionnels de la santé devraient s'efforcer d'assurer la confidentialité, particulièrement dans les petites communautés et dans celles qui ne sont accessibles que par avion. (III-A) 17. Les professionnels de la santé devraient considérer la grossesse comme étant une occasion en or de s'engager envers les droits sexuels et génésiques, les valeurs et les croyances des Inuites, des Métisses et des femmes des Premières Nations, et de prendre position en leur faveur. (III-L) 18. Les fournisseurs de soins de santé devraient s'enquérir des souhaits de la patiente et de sa famille à l'égard de l'élimination ou de la préservation des tissus provenant de la conception, de la grossesse, de la fausse couche, de l'interruption de grossesse, de l'hystérectomie et d'autres interventions, les respecter et plaider en faveur de la mise en œuvre de politiques et de protocoles institutionnels permettant de les soutenir.(III-A) 19. Les professionnels de la santé devraient reconnaître que des troubles mentaux tels que les troubles de l'humeur, l'anxiété et l'assuétude à des substances psychotropes constituent d'importants problèmes de santé publique pour de nombreuses communautés inuites, métisses et des Premières Nations. (II-3B) L'utilisation de substances psychotropes qui mènent à l'assuétude constitue souvent un mécanisme d'adaptation à la douleur causée par les traumatismes intergénérationnels. Les professionnels de la santé devraient se familiariser avec des stratégies de réduction des dommages sûres sur le plan culturel pouvant être utilisées pour soutenir les Inuites, les Métisses et les femmes des Premières Nations (et leur famille) qui sont aux prises avec une telle assuétude. (II-2A) 20. Les professionnels de la santé devraient soutenir et promouvoir le retour de l'accouchement au sein des communautés rurales et éloignées pour ce qui est des femmes qui ne sont exposées qu'à de faibles risques de complications. La participation nécessaire de la communauté à la prise de décisions au sujet de la distribution et de l'affectation des ressources destinées aux soins de maternité devrait être reconnue et facilitée. (III-A) 21. Les professionnels de la santé devraient prendre conscience du fait que très peu de recherches, de ressources et de programmes visent particulièrement la santé des femmes d'âge mûr (y compris la ménopause) au sein des communautés inuites, métisses et des Premières Nations. Les professionnels de la santé devraient plaider en faveur de la tenue de plus amples recherches dans ce domaine. (III-A) 22. Les professionnels de la santé devraient chercher à en savoir plus au sujet des pratiques de communication adaptées à la culture et devraient adapter leurs communications aux situations et aux antécédents particuliers que présentent leurs patientes. (III-A) 23. Les professionnels de la santé pourraient exprimer à leurs patientes qu'ils souhaitent établir avec elles une relation respectueuse marquée par l'écoute, la reconnaissance des différences et la sollicitation de leurs commentaires. (III-L) 24. Les Inuites, les Métisses et les femmes des Premières Nations devraient recevoir des soins prodigués dans leur propre langue, dans la mesure du possible. Les programmes et les établissements de santé offrant des services à un nombre important de patientes inuites, métisses et des Premières Nations devraient compter des interprètes et des défenseurs de la santé inuits, métis et des Premières Nations parmi leurs employés. (III-A).

CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health.

The molecular mechanisms connecting environmental exposures to adverse endpoints are often unknown, reflecting knowledge gaps. At the Comparative Toxicogenomics Database (CTD), we developed a bioinformatics approach that integrates manually curated, literature-based interactions from CTD to generate a "CGPD-tetramer": a 4-unit block of information organized as a step-wise molecular mechanism linking an initiating Chemical, an interacting Gene, a Phenotype, and a Disease outcome. Here, we describe a novel, user-friendly tool called CTD Tetramers that generates these evidence-based CGPD-tetramers for any curated chemical, gene, phenotype, or disease of interest. Tetramers offer potential solutions for the unknown underlying mechanisms and intermediary phenotypes connecting a chemical exposure to a disease. Additionally, multiple tetramers can be assembled to construct detailed modes-of-action for chemical-induced disease pathways. As well, tetramers can help inform environmental influences on adverse outcome pathways (AOPs). We demonstrate the tool's utility with relevant use cases for a variety of environmental chemicals (eg, perfluoroalkyl substances, bisphenol A), phenotypes (eg, apoptosis, spermatogenesis, inflammatory response), and diseases (eg, asthma, obesity, male infertility). Finally, we map AOP adverse outcome terms to corresponding CTD terms, allowing users to query for tetramers that can help augment AOP pathways with additional stressors, genes, and phenotypes, as well as formulate potential AOP disease networks (eg, liver cirrhosis and prostate cancer). This novel tool, as part of the complete suite of tools offered at CTD, provides users with computational datasets and their supporting evidence to potentially fill exposure knowledge gaps and develop testable hypotheses about environmental health.

When Stigma, Disclosure, and Access to Care Collide: An Ethical Reflection of Mpox Vaccination Outreach.

Experiences of stigma in health care encounters among LGBTQ+ populations (lesbian, gay, bisexual, transgender, and queer and questioning) have long been a barrier to care. Marginalization and historically grounded fears of stigmatization have contributed to a reluctance to disclose sexual behavior and/or gender identity to health care providers. We reflect on how student nurses grappled with the ethics of patient disclosure while providing mobile outreach in Chicago for mpox (formerly monkeypox) from fall 2022 to spring 2023. Student nurses addressed how requiring disclosure of sexual behavior or sexual orientation may serve as a barrier to accessing preventive care, such as mpox vaccination. Accounts of stigma and criminalization experienced by LGBTQ+ people provide insight on challenges historically associated with disclosure in health care.

Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial.

CONTEXT: Inhaled hypertonic saline is recommended as therapy for patients 6 years or older with cystic fibrosis (CF), but its efficacy has never been evaluated in patients younger than 6 years with CF. OBJECTIVE: To determine if hypertonic saline reduces the rate of protocol-defined pulmonary exacerbations in patients younger than 6 years with CF. DESIGN, SETTING, AND PARTICIPANTS: The Infant Study of Inhaled Saline in Cystic Fibrosis (ISIS), a multicenter, randomized, double-blind, placebo-controlled trial conducted from April 2009 to October 2011 at 30 CF care centers in the United States and Canada. Participants were aged 4 to 60 months and had an established diagnosis of CF. A total of 344 patients were assessed for eligibility; 321 participants were randomized; 29 (9%) withdrew prematurely. INTERVENTION: The active treatment group (n = 158) received 7% hypertonic saline and the control group (n = 163) received 0.9% isotonic saline, nebulized twice daily for 48 weeks. Both groups received albuterol or levalbuterol prior to each study drug dose. MAIN OUTCOME MEASURES: Rate during the 48-week treatment period of protocol-defined pulmonary exacerbations treated with oral, inhaled, or intravenous antibiotics. RESULTS: The mean pulmonary exacerbation rate (events per person-year) was 2.3 (95% CI, 2.0-2.5) in the active treatment group and 2.3 (95% CI, 2.1-2.6) in the control group; the adjusted rate ratio was 0.98 (95% CI, 0.84-1.15). Among participants with pulmonary exacerbations, the mean number of total antibiotic treatment days for a pulmonary exacerbation was 60 (95% CI, 49-70) in the active treatment group and 52 (95% CI, 43-61) in the control group. There was no significant difference in secondary end points including height, weight, respiratory rate, oxygen saturation, cough, or respiratory symptom scores. Infant pulmonary function testing performed as an exploratory outcome in a subgroup (n = 73, with acceptable measurements at 2 visits in 45 participants) did not demonstrate significant differences between groups except for the mean change in forced expiratory volume in 0.5 seconds, which was 38 mL (95% CI, 1-76) greater in the active treatment group. Adherence determined by returned study drug ampoules was at least 75% in each group. Adverse event profiles were also similar, with the most common adverse event of moderate or severe severity in each group being cough (39% of active treatment group, 38% of control group). CONCLUSION: Among infants and children younger than 6 years with cystic fibrosis, the use of inhaled hypertonic saline compared with isotonic saline did not reduce the rate of pulmonary exacerbations over the course of 48 weeks of treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00709280.

Nurse consultant to day/child care centers.

PURPOSE: Approximately 23.2 million children in the United States attend day care; however, many of these children often lack access to health care. Given the potential for advanced practice nurses to address this gap in health care, the authors sought to gain a better understanding of healthcare consulting provided by nurses to day/child care centers. The purpose of this scoping review is to examine the extent, range, and nature of evidence regarding the role of nurse consultants in day and childcare settings. DESIGN AND METHODS: A scoping review was conducted in CINAHL and PubMed, to report and summarize relevant literature published before 2020. Search terms included day or child care, nurse consultants, healthcare consultants, and day or child care health consultants. RESULTS: The search produced 92 publications; 21 publications met the inclusion criteria and are included in the review. After independently reading the publications, the authors identified and agreed upon seven central themes. Themes included an analysis of the consulting process, description of the nurse consulting role in individual and large day and childcare settings, director's perceptions of health consultants, impact of nurse consultants, education and training, barriers to the healthcare consultant role, and political advocacy. PRACTICE IMPLICATIONS: Advanced nurse practitioner, particularly pediatric nurse practitioners (PNPs), possess the skill set in acute and chronic conditions, as well as health maintenance and promotion that can be translated and used in the role of the nurse consultant to day and child care centers. Having PNPs in this role may help to address primary healthcare needs of children.

Care providers' experiences with and attitudes towards virtual antenatal care: Findings from a qualitative study in British Columbia.

Background: Virtual care has emerged as an adjunctive response to challenges in rural health care, including maternity care, and use has accelerated during the coronavirus disease 2019 (COVID-19) pandemic. This gives rise to the need for a strategic plan for post-COVID-19 virtual maternity care in rural communities. To date, no provincial initiative has focused on understanding and documenting the needs of maternity care practitioners to provide virtual care. Methods: Qualitative study, including virtual interviews and focus groups with rural primary maternity care providers and urban and rural specialists on perceptions of the utility of virtual maternity care pre- and post-COVID-19, and benefits and barriers of virtual care. Data were thematically analysed. Results: In total, 82 health care providers participated in the study. Health care provider responses fell into three categories: Attributes of virtual care, barriers to virtual care and system interventions needed to optimize the provision of virtual perinatal care. Participants expressed a desire for use of virtual communication tools post-COVID-19, continued ability to use fee codes for virtual care and a need for more secure texting options. The benefits of tripartite consultations were noted by many participants; impacts of the transition to virtual care included additional workload and interrupted workflow. Concerns over the lack of physical examinations and challenges in building relationships with patients when providing virtual care were frequently noted. Conclusion: Adapting the current implementation of virtual maternity care in British Columbia may be enhanced through several provider- and evidence-derived strategies, many of which are currently underway in BC. The results from this provincial survey will be used to focus further discussion on the characteristics of an optimal system to meet patient and provider needs within a rural context.