Effect of heavy metal cations on the activity of cathepsin D (in vitro study)

We studied the effect of heavy metal cations: Fe 2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+ on the activity ofcathepsin D in human aorta homogenate and blood serum. The concentration of cations was 1 mmol/l. Hemoglobinwas the cathepsin D substrate. The activity of cathepsin D was determined at pH 3.5. Only Hg2+ cationsinhibit the activity of cathepsin D. Cations Hg2+ damage lysosomes and release cathepsin D from these organelles.We studied the effect of heavy metal cations: Fe 2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+ on the activity ofcathepsin D in human aorta homogenate and blood serum. The concentration of cations was 1 mmol/l. Hemoglobinwas the cathepsin D substrate. The activity of cathepsin D was determined at pH 3.5. Only Hg2+ cationsinhibit the activity of cathepsin D. Cations Hg2+ damage lysosomes and release cathepsin D from these organelles

Inter-agency coordination of services for children and families - initial literature review

Disadvantaged families living in poverty, especially those living in deprived neighborhoods where risks tend to accumulate, have diverse needs for support. Throughout Europe different models of service-coordination and integration exist, but a systematic overview of experiences and evidence on effectiveness is not available. The aim of this initial review is to: - identify facilitators and challenges at the interpersonal and at the structural-organizational level that are relevant to successful coordination, collaboration and integration of multiple services for young children (e.g. communication, case management, financial resources, policy measures); - identify models of working and domains for the development of a common framework; - summarize the potential impact of inter-agency working upon children, families and communities

Concepts émergents dans le référentiel de compétences CanMEDS pour les médecins

Background: The CanMEDS physician competency framework will be updated in 2025. The revision occurs during a time of disruption and transformation to society, healthcare, and medical education caused by the COVID-19 pandemic and growing acknowledgement of the impacts of colonialism, systemic discrimination, climate change, and emerging technologies on healthcare and training. To inform this revision, we sought to identify emerging concepts in the literature related to physician competencies. Methods: Emerging concepts were defined as ideas discussed in the literature related to the roles and competencies of physicians that are absent or underrepresented in the 2015 CanMEDS framework. We conducted a literature scan, title and abstract review, and thematic analysis to identify emerging concepts. Metadata for all articles published in five medical education journals between October 1, 2018 and October 1, 2021 were extracted. Fifteen authors performed a title and abstract review to identify and label underrepresented concepts. Two authors thematically analyzed the results to identify emerging concepts. A member check was conducted. Results: 1017 of 4973 (20.5%) of the included articles discussed an emerging concept. The thematic analysis identified ten themes: Equity, Diversity, Inclusion, and Social Justice; Anti-racism; Physician Humanism; Data-Informed Medicine; Complex Adaptive Systems; Clinical Learning Environment; Virtual Care; Clinical Reasoning; Adaptive Expertise; and Planetary Health. All themes were endorsed by the authorship team as emerging concepts. Conclusion: This literature scan identified ten emerging concepts to inform the 2025 revision of the CanMEDS physician competency framework. Open publication of this work will promote greater transparency in the revision process and support an ongoing dialogue on physician competence. Writing groups have been recruited to elaborate on each of the emerging concepts and how they could be further incorporated into CanMEDS 2025.Contexte : Le référentiel de compétences CanMEDS pour les médecins sera mis à jour en 2025. Cette révision intervient à un moment où la société, les soins de santé et l’enseignement médical sont bouleversés et en pleine mutation à cause de la pandémie de la COVID-19; on est aussi à l’heure où l’on reconnaît de plus en plus les effets du colonialisme, de la discrimination systémique, des changements climatiques et des nouvelles technologies sur les soins de santé et la formation des médecins. Pour éclairer cette révision, nous avons tenté d’extraire de la littérature scientifique les concepts émergents se rapportant aux compétences des médecins. Méthodes : Les concepts émergents ont été définis comme des idées ayant trait aux rôles et aux compétences des médecins qui sont débattues dans la littérature, mais qui sont absentes ou sous-représentées dans le cadre CanMEDS 2015. Nous avons réalisé une recherche documentaire, un examen des titres et des résumés, et une analyse thématique pour repérer les concepts émergents. Les métadonnées de tous les articles publiés dans cinq revues d’éducation médicale entre le 1er octobre 2018 et le 1er octobre 2021 ont été extraites. Quinze auteurs ont effectué un examen des titres et des résumés pour relever et étiqueter les concepts sous-représentés. Deux auteurs ont procédé à une analyse thématique des résultats pour dégager les concepts émergents. Une vérification a été faite par les membres de l’équipe. Résultats : Parmi les 4973 articles dépouillés, 1017 (20,5 %) abordaient un concept émergent. Les dix thèmes suivants sont ressortis de l’analyse thématique : l’équité, la diversité, l’inclusion et la justice sociale; l’antiracisme; humanisme des médecin; la médecine fondée sur les données; les systèmes adaptatifs complexes; l’environnement de l’apprentissage clinique; les soins virtuels; le raisonnement clinique; l’expertise adaptative; et la santé planétaire. L’ensemble de ces thèmes ont été approuvés comme concepts émergents par l’équipe de rédaction. Conclusion : Cet examen de la littérature a permis de relever dix concepts émergents qui peuvent servir à éclairer la révision du référentiel de compétences CanMEDS pour les médecins qui aura lieu en 2025. La publication en libre accès de ce travail favorisera la transparence du processus de révision et le dialogue continu sur les compétences des médecins. Des groupes de rédaction ont été recrutés pour développer chacun des concepts émergents et pour examiner la façon dont ils pourraient être intégrés dans la version du référentiel CanMEDS de 2025

Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies

To study how virus evolution affects neutralization sensitivity and to determine changes that occur in and around epitopes, we tested the ability of 13 anti-HIV-1 gp120 (anti-V2, anti-V3, anti-CD4bd and anti-carbohydrate) human monoclonal antibodies (mAbs) to neutralize sequential viruses obtained from five HIV-1 chronically infected drug naïve individuals. Overall, primary viruses collected from patients at first visit were resistant to neutralization by all anti-HIV-1 mAbs with the exception of one virus sensitive to IgG1b12. Four of the five patients' viruses evolved increased sensitivity to neutralization by anti-V3 mAbs. Virus collected from a patient obtained 31 months later, evolved increased sensitivity to anti-V2, anti-V3, and anti-CD4bd mAbs. Furthermore, the anti-V2 and anti-CD4bd mAbs also exhibited increased neutralization capacities against virus collected from a patient 29 months later. Of the seven anti-V3 mAbs, five showed increased potency to neutralize the evolved virus from a patient collected after 11 months, and three exhibited increased potency against viruses from two patients collected 29 and 36 months later. Anti-V3 mAbs exhibited the most breadth and potency in neutralizing the evolving viruses. Sequence analysis of the envelope regions revealed amino acid conservation within the V3 loop, while most of the changes identified occurred outside the core epitopes and in particular within the C3 region; these may account for increased neutralization sensitivity. These studies demonstrate that in vivo, HIV-1 can evolve increased neutralization sensitivity to mAbs and that the spectrum of neutralization capacities by mAbs can be broader when studied in longitudinal analysis

Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort

<p>Abstract</p> <p>Background</p> <p>Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system.</p> <p>Methods</p> <p>Exposure to background particulate matter less than 10 μm in diameter (PM₁₀) and nitrogen dioxide (NO₂) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets.</p> <p>Results</p> <p>Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 μg/m³increase in PM₁₀levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO₂exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO₂exposure and an increased percentage of CD8+ T-cells.</p> <p>Conclusions</p> <p>These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.</p