Premières initiatives d’intégration sociale des malades mentaux dans une phase de pré-désinstitutionnalisation. L’exemple de Saint-Jean-de-Dieu, 1910–1950

Cet article sur les premières initiatives d’intégration sociale des malades mentaux, dans l’exemple de l’Hôpital Saint-Jean-de-Dieu, présente la mise en place d’une phase de désinstitutionnalisation au cours des premières décennies du XXe siècle. Notre étude s’inscrit dans le courant historiographique récent qui propose une relecture de la période pré-Révolution tranquille au Québec. Nous entendons y contribuer en démontrant que les politiques, les stratégies et les pratiques des Soeurs de la Providence et des psychiatres ont mis en place un système de désinstitutionnalisation et de réintégration des patients dans leur famille dès les années 1910, soit un demi-siècle avant que ne s’amorce la première vague de désinstitutionnalisation des années 1960 orchestrée par les auteurs du rapport Bédard. This article on the first initiatives of social integration of the mentally ill, using the example of the Hôpital St-Jean-de-Dieu, explores the implementation of a period of deinstitutionalization in the early decades of the 20th century. Our study is situated in the recent historiography that offers a rereading of the period just prior to the Quiet Revolution in Quebec. We intend to contribute by demonstrating that the policies, strategies and practices of the Sisters of Providence and the psychiatrists of St-Jean-de-Dieu developed a system of deinstitutionalization that reintegrated patients into their family as early as the 1910s, half a century before the first wave of deinstitutionalization of the 1960s was orchestrated by the authors of the Bédard report

The MHC class I peptide repertoire is molded by the transcriptome

Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells

Silencing of Amyloid Precursor Protein Expression Using a New Engineered Delta Ribozyme

Alzheimer's disease (AD) etiological studies suggest that an elevation in amyloid-β peptides (Aβ) level contributes to aggregations of the peptide and subsequent development of the disease. The major constituent of these amyloid peptides is the 1 to 40–42 residue peptide (Aβ40−42) derived from amyloid protein precursor (APP). Most likely, reducing Aβ levels in the brain may block both its aggregation and neurotoxicity and would be beneficial for patients with AD. Among the several possible ways to lower Aβ accumulation in the cells, we have selectively chosen to target the primary step in the Aβ cascade, namely, to reduce APP gene expression. Toward this end, we engineered specific SOFA-HDV ribozymes, a new generation of catalytic RNA tools, to decrease APP mRNA levels. Additionally, we demonstrated that APP-ribozymes are effective at decreasing APP mRNA and protein levels as well as Aβ levels in neuronal cells. Our results could lay the groundwork for a new protective treatment for AD

The Role of Expectations in Treatment Outcome and Symptom Development in Anxiety Disorders

For more than 60 years, researchers have been interested in determining the impact of expectations on treatment outcome. Earlier studies mostly focused on two types of expectations: prognostic and process expectations. Aims: To review how four different types of expectations (prognostic, process, anxiety expectancy and anxiety sensitivity) contribute to psychotherapy outcome, and to the development of clinical disorders, especially anxiety. Conclusions: First, the role of process and prognostic expectancies in clinical disorders and psychotherapy outcome should be clarified by addressing the methodological flaws of the earlier expectancy studies. Second, studies, especially those on anxiety disorders, may benefit from evaluating the four different types of expectations to determine their relative impact on outcome, and on the development and maintenance of these disorders. Third, possible links with other clinical disorders should be further explored. Finally, expectancies should be assessed prior to treatment and after several sessions to determine the extent to which the treatment\u27s failure in modifying initial low expectancies contribute to a poor outcome

ER stress affects processing of MHC class I-associated peptides

<p>Abstract</p> <p>Background</p> <p>Viral infection and neoplastic transformation trigger endoplasmic reticulum (ER) stress. Thus, a large proportion of the cells that must be recognized by the immune system are stressed cells. Cells respond to ER stress by launching the unfolded protein response (UPR). The UPR regulates the two key processes that control major histocompatibility complex class I (MHC I)-peptide presentation: protein synthesis and degradation. We therefore asked whether and how the UPR impinges on MHC I-peptide presentation.</p> <p>Results</p> <p>We evaluated the impact of the UPR on global MHC I expression and on presentation of the H2K^b-associated SIINFEKL peptide. EL4 cells stably transfected with vectors coding hen egg lysozyme (HEL)-SIINFEKL protein variants were stressed with palmitate or exposed to glucose deprivation. UPR decreased surface expression of MHC I but did not affect MHC I mRNA level nor the total amount of intracellular MHC I proteins. Impaired MHC I-peptide presentation was due mainly to reduced supply of peptides owing to an inhibition of overall protein synthesis. Consequently, generation of H2K^b-SIINFEKL complexes was curtailed during ER stress, illustrating how generation of MHC I peptide ligands is tightly coupled to ongoing protein synthesis. Notably, the UPR-induced decline of MHC I-peptide presentation was more severe when the protein source of peptides was localized in the cytosol than in the ER. This difference was not due to changes in the translation rates of the precursor proteins but to increased stability of the cytosolic protein during ER stress.</p> <p>Conclusion</p> <p>Our results demonstrate that ER stress impairs MHC I-peptide presentation, and that it differentially regulates expression of ER- vs. cytosol-derived peptides. Furthermore, this work illustrates how ER stress, a typical feature of infected and malignant cells, can impinge on cues for adaptive immune recognition.</p

Priority interventions to improve the management of chronic non-cancer pain in primary care: a participatory research of the ACCORD program

Purpose: There is evidence that the management of chronic non-cancer pain (CNCP) in primary care is far from being optimal. A 1-day workshop was held to explore the perceptions of key actors regarding the challenges and priority interventions to improve CNCP management in primary care. Methods: Using the Chronic Care Model as a conceptual framework, physicians (n=6), pharmacists (n=6), nurses (n=6), physiotherapists (n=6), psychologists (n=6), pain specialists (n=6), patients (n=3), family members (n=3), decision makers and managers (n=4), and pain researchers (n=7) took part in seven focus groups and five nominal groups. Results: Challenges identified in focus group discussions were related to five dimensions: knowledge gap, “work in silos”, lack of awareness that CNCP represents an important clinical problem, difficulties in access to health professionals and services, and patient empowerment needs. Based on the nominal group discussions, the following priority interventions were identified: interdisciplinary continuing education, interdisciplinary treatment approach, regional expert leadership, creation and definition of care paths, and patient education programs. Conclusion: Barriers to optimal management of CNCP in primary care are numerous. Improving its management cannot be envisioned without considering multifaceted interventions targeting several dimensions of the Chronic Care Model and focusing on both clinicians and patients

Using multisensory virtual reality nature immersion as a therapeutic modality for improving HRV and cognitive functions in post-traumatic stress disorder: a pilot-study

Introduction: Immersive virtual reality (VR) applications are burgeoning within healthcare as they promote high levels of engagement. Notwithstanding, existing solutions only stimulate two of our five senses (audio and visual), thus may not be optimal in the sense of promoting immersion and of “being present”. In this paper, we explore the benefits of an immersive multisensory experience as a therapeutic modality for participants suffering from post-traumatic stress disorder (PTSD).Methods: In addition to 360-degree videos and corresponding natural sounds, nature smells are also presented by means of a portable ION 2 scent diffusion device attached to an Oculus Quest 2 VR head-mounted display. A 3-week 12-sessions protocol was applied to a sample of 20 participants diagnosed with PTSD.Results and discussion: We report the outcomes seen from a battery of qualitative metrics, including cognitive functioning tests, psychological symptoms, severity of PTSD, and several self-reported questionnaires and heart rate variability (HRV) metrics. Results are compared not only between pre-and post intervention, but also after a 3-month follow-up period. Results suggest a decrease in the severity of PTSD, as well as improvements in processing speed and sustained attention post-intervention, but also sustained decrease in the severity of PTSD and in dissociative tendencies at the 3-month follow-up. Overall, participants rated the experience as highly immersive and produced very mild to no symptoms of cybersickness, thus corroborating the feasibility and usefulness of the proposed multisensory immersive VR tool for reducing PTSD symptoms

Pharmacogenomics of the efficacy and safety of Colchicine in COLCOT

© 2021 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes.Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.info:eu-repo/semantics/publishedVersio