Search

Aurore Margat,1 Benoit Pétré,2 Soizic David,1 Daniela Toro Arrocet,1 Vincent de Andrade,1 Cyril Crozet,1 Delphine Kirkove,2 Rémi Gagnayre1 1Education and Health Promotion Laboratory (LEPS), (UR 3412), UFR SMBH, Sorbonne Paris-Nord University, Bobigny, France; 2Department of Public Health, University of Liege, Liège, BelgiumCorrespondence: Aurore Margat, Email aurore.margat@univ-paris13.frIntroduction: The management of a pandemic, such as COVID-19, requires the full participation of citizens. This recent situation has revealed the undermining of user participation in the decision-making process. Thus, this study aims to assess the involvement of users in the design and administration of surveys for health crisis monitoring and to stimulate reflection on information processes shared upstream during the decision-making process.Methods: A literature search was conducted on population monitoring surveys published during the first containment period in Belgium and France between April and May 2020. The selected studies were first analyzed according to a reading grid based on the criteria proposed by the World Health Organization (WHO) for monitoring populations and supplemented by data from a descriptive analysis of the selected studies. Second, with the objective of specifically evaluating the involvement of users in monitoring surveys, this study evaluated the surveys according to the following parameters: content of a study based on themes presented in surveys; inclusion of health literacy (HL); and factors of commitment of the respondents to the survey.Results: A total of 45 studies were selected for final analysis. The majority of the surveys focused on the effect of COVID-19 on well-being. Furthermore, analysis indicated that, in summary, the HL of people concerned as well as the involvement of respondents is poorly considered, which remains limited in terms of the design and administration of the surveys.Discussion: Although the principles of health democracy seemed to have been established, the exceptional regime induced by the epidemic overlooked the observance of such principles. This result indicates the need to reconsider the participation of citizens as real partners in care, including health crisis management.Keywords: COVID-19, health democracy, survey, citizen engagement, health literacy

Benoit Pétré,1 Delphine Kirkove,1 Vincent de Andrade,2 Cyril Crozet,2 Daniela Toro-Arrocet,2 Aurore Margat,2 Rémi Gagnayre2 1Department of Public Health, University of Liege, Liège, Belgium; 2Education and Health Practices Laboratory, UR 3412, UFR Santé Médecine Biologie Humaine, Sorbonne Paris-Nord University, Bobigny, FranceCorrespondence: Benoit PétréDepartment of Public Health, University of Liège, Quartier Hôpital, Avenue Hippocrate 13 (B23), Liège, 4000, BelgiumTel +32 4 366 2505Email benoit.petre@uliege.beAbstract: The COVID-19 pandemic has compelled public authorities to establish preventive measures involving individual behaviour modification strategies (mask-wearing, social distancing, etc.) with a view to community protection. In this context, documenting people’s behaviour changes, the impact of public health measures, and individuals’ knowledge, motivations, and beliefs – even their perception of how the crisis is being managed – is essential for understanding the experience of the population and adapting the management approach accordingly. This article presents findings and lessons on how to monitor a population’s behaviour during a crisis, obtained by reviewing forty-five surveys conducted in Belgium and France during the first Covid-19 stay-at-home order, from April to May 2020. The central message is to argue that the citizens’ role in this type of survey – and in managing the crisis, more generally – should be reconsidered by thinking of them as true health partners and members of a community that could be mobilised to help.Keywords: pandemic, covid 19, community monitoring, preventive health behavior

The enhancement of efficiency in power generation gas turbine requires the development of new superalloys capable of withstanding higher temperatures. The development of AD730TM superalloy was achieved to provide to this new cast & wrought (C&W) superalloy a higher combination between mechanical properties, microstructural stability and cost than that of other C&W superalloys with a temperature capability up to 750 ∘C. Supersolvus heat-treatment of AD730TM was studied to improve the creep properties of fine grain AD730TM superalloy which were not high enough to reach the foreseen conditions of future power generation gas turbine disks. Firstly, the grain growth was studied to select the supersolvus temperature 1120 ∘C and to obtain a homogeneous coarse grain microstructure. Then, various supersolvus heat-treatments with different cycles were tested and applied on a forged pancake with a section representative of power generation gas turbine disk. The average grain size was evaluated to be close to 200 μm for all heat-treatments. Tensile, creep, fatigue and fatigue crack growth tests were performed to compare the various heat-treatments. FEG-SEM examinations were also realized to discuss the relationships between heat-treatment, intragranular gamma prime precipitation and mechanical properties. Finally, a comparison made with other supersolvus heat treated C&W superalloys shows that AD730TM properties obtained with coarse grain microstructure are at the expected level and enable applications for power generation gas turbine discs.

With the appearance of variant Creutzfeldt-Jakob disease (CJD) and the detection of infectious prions in the peripheral organs of persons with sporadic CJD, the development of decontamination methods that are compatible with medical equipment has become a major issue. Here, we show that a formulation of copper metal ions in combination with hydrogen peroxide dramatically reduces the level of prion protein (PrP)(Sc) (the scrapie isoform of PrP) present in homogenates of samples from prion-infected brains, including brain samples from humans with CJD. An animal bioassay confirmed the reduction in prion infectivity, indicating that this novel Cu(2+)-H(2)O(2) formulation has great potential for prion decontamination. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to point out the recent characteristics and developments of therapeutic patient education (TPE) in rheumatoid arthritis through an analysis of the international articles published from 2003 to 2008.Method: Studies were selected from major databases, using the following keywords: rheumatoid arthritis, patient education, self-management, programs. Three authors independently reviewed each study and selected the data using the patient education research categories (PERC). Articles consistently related to patient education in rheumatoid arthritis (37 among 109) were included.Results: The selected articles have been published in 23 scientific journals. The majority of them concern TPE for adult patients with rheumatoid arthritis. TPE is delivered in several structures and group education represents the most widespread educational strategy mainly provided by a multiprofessional team. There are two types of programs: educational, aiming to make the patient competent in the daily management of his disease and psycho-educational ones, aiming to improve coping and to decrease stress, anxiety and depression. Twenty-eight studies show the effectiveness of TPE on the basis of bio-clinical, educational, psychosocial, economical criteria, but the majority of these positive results are observed in short-term. Barriers to TPE are linked to cultural and socio-economic factors.Conclusion: A large number of studies still assess the positive effects of TPE. Nowadays, the problems of short-term efficacy of TPE and the cultural and social barriers to this practice have become a major issue for research. [ABSTRACT FROM AUTHOR]

Proteolytic cell surface release ('shedding') of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, for the human body neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated thus far. In this study, cleavage site prediction and generation (plus detailed characterization) of sPrP-specific antibodies enabled us to identify PrP cleaved at tyrosin 226 as the physiological and apparently strictly ADAM10-dependent shed form in humans. Using cell lines, neural stem cells and brain organoids, we show that shedding of human PrP can be stimulated by PrP-binding ligands without targeting the protease, which may open novel therapeutic perspectives. Site-specific antibodies directed against human sPrP also detect the shed form in brains of cattle, sheep and deer, hence in all most relevant species naturally affected by fatal and transmissible prion diseases. In human and animal prion diseases, but also in patients with Alzheimer`s disease, sPrP relocalizes from a physiological diffuse tissue pattern to intimately associate with extracellular aggregated deposits of misfolded proteins characteristic for the respective pathological condition. Findings and research tools presented here will accelerate novel insight into the roles of PrP shedding (as a process) and sPrP (as a released factor) in neurodegeneration and beyond., (© 2024. The Author(s).)

Introduction: The accessibility of Therapeutic Patient Education (TPE) is essential to reduce social inequalities and to meet the challenges posed by the increase in chronic diseases. In France, the distribution of TPE throughout the territory is heterogeneous and patients still lack sufficient access. With these perspectives in mind, a municipal health center has developed an innovative TPE device by involving concerned patients from the outset., Objectives: The objectives of this article are to present the methodology implemented to co-construct a TPE program for patients with one or more prevalent diseases in the territory, as well as the results of the co-construction., Methods: Creation of a project team with various actors: patients, health professionals, administrators, researchers. Organization of synchronous and asynchronous times., Results: Four meetings and numerous exchanges made it possible to: define the common values and operating rules of the project team, reflect on the coordination of the care pathway, identify the specific and shared needs of patients affected by type 2 diabetes, arterial hypertension and/or obesity, agree on the principles of the device., Conclusion: The advantages of this device were discussed: flexible organization with numerous links with local actors, development of partnerships, expansion of the population concerned. Questions and difficulties were encountered, such as the coordination of actors and the representation of partner patients for the targeted diseases. This device will be tested and evaluated, mainly with an objective of improving it.

Although diabetes is common among people living with HIV/AIDS (PLWHA), few data exists on how migrants from Sub-Saharan Africa (SSA) experience living with these two coexisting conditions in France. The objective of this study was to analyze perception of polypathology among PLWHA from SSA with type 2 diabetes and identify barriers and facilitators to their self-management. A qualitative study was conducted using semi-structured interviews from November 2019 to April 2020 with participants selected from a cohort of PLWHA and diabetes at Avicenne University Hospital. A total of 12 semi-structured interviews were conducted and analyzed using thematic analysis with inductive approach. Stigma remained a major issue in self-managing HIV, and some participants did not consider themselves as having a polypathology, as HIV has always been considered as a distinct condition. In general, emotion-based resources (e.g spirituality, trust in the medical discourse) and social support were mobilized more than problem-solving resources (e.g perception of medication as life-saving). Participants used the same main resource in self-management of HIV and diabetes, and resources used differed from participant to participant. This study highlighted challenges in self-management of diabetes and HIV in this population and complexity related to the socioeconomic and cultural specificities. Self-management could be more successful if patients and carers move in the same direction, having identified the individual coping resources to reach objectives., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 de Monteynard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Mesenchymal stem/stromal cells (MSCs) are multipotent cells with strong tissue repair and immunomodulatory properties. Due to their ability to repress pathogenic immune responses, and in particular T cell responses, they show therapeutic potential for the treatment of autoimmune diseases, organ rejection and graft versus host disease. MSCs have the remarkable ability to export their own mitochondria to neighboring cells in response to injury and inflammation. However, whether mitochondrial transfer occurs and has any role in the repression of CD4 + Th1 responses is unknown., Methods and Results: In this report we have utilized CD4 + T cells from HNT TCR transgenic mice that develop Th1-like responses upon antigenic stimulation in vitro and in vivo. Allogeneic bone marrow-derived MSCs reduced the diabetogenic potential of HNT CD4 + T cells in vivo in a transgenic mouse model of disease. In co-culture experiments, we have shown that MSCs were able to reduce HNT CD4 + T cell expansion, expression of key effector markers and production of the effector cytokine IFNγ after activation. This was associated with the ability of CD4 + T cells to acquire mitochondria from MSCs as evidenced by FACS and confocal microscopy. Remarkably, transfer of isolated MSC mitochondria to CD4 + T cells resulted in decreased T cell proliferation and IFNγ production. These effects were additive with those of prostaglandin E2 secreted by MSCs. Finally, we demonstrated that both co-culture with MSCs and transfer of isolated MSC mitochondria prevent the upregulation of T-bet, the master Th1 transcription factor, on activated CD4 + T cells., Conclusion: The present study demonstrates that transfer of MSC mitochondria to activated CD4 + T cells results in the suppression of Th1 responses in part by downregulating T-bet expression. Furthermore, our studies suggest that MSC mitochondrial transfer might represent a general mechanism of MSC-dependent immunosuppression., (© 2023. The Author(s).)

Introduction: To cope with the increased number of patients with chronic diseases, the ASALEE scheme promotes cooperation between doctors and patient education (PE) nurses in a health center in Lorraine. They observe behaviors of absence, cancellation, and postponement of the first consultation among referred patients., Objective: Our study explores the medical orientation practices for patients during their first PE consultation., Method: Observation of these practices was combined with semi-structured interviews., Results: Four doctors and 17 patients were observed and interviewed, following referral to the PE nurse for six of them and to a specialist doctor for the remaining 11. 27 criteria and 72 indicators were involved, concerning PE orientation practices. 15 of these also appeared in the 22 criteria for the medical specialist. These criteria open up new prospects for improving PE, such as "Quality of the doctor-patient relationship" and "Lack of knowledge and skills in PE"., Discussion and Conclusion: The improvement of medical orientation practices in PE is enabled by professional practice analysis groups and by the social acceptability of patient empowerment and engagement.

Corruption of cellular prion protein (PrPC) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrPC, however, remain poorly elucidated. With the perspective to grasp the molecular pathways of neurodegeneration occurring in prion diseases, and to identify therapeutic targets, achieving a better understanding of PrPC roles is a priority. Based on global approaches that compare the proteome and metabolome of the PrPC expressing 1C11 neuronal stem cell line to those of PrPnull-1C11 cells stably repressed for PrPC expression, we here unravel that PrPC contributes to the regulation of the energetic metabolism by orienting cells towards mitochondrial oxidative degradation of glucose. Through its coupling to cAMP/protein kinase A signaling, PrPC tones down the expression of the pyruvate dehydrogenase kinase 4 (PDK4). Such an event favors the transfer of pyruvate into mitochondria and its conversion into acetyl-CoA by the pyruvate dehydrogenase complex and, thereby, limits fatty acids β-oxidation and subsequent onset of oxidative stress conditions. The corruption of PrPC metabolic role by pathogenic prions PrPSc causes in the mouse hippocampus an imbalance between glucose oxidative degradation and fatty acids β-oxidation in a PDK4-dependent manner. The inhibition of PDK4 extends the survival of prion-infected mice, supporting that PrPSc-induced deregulation of PDK4 activity and subsequent metabolic derangements contribute to prion diseases. Our study posits PDK4 as a potential therapeutic target to fight against prion diseases., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: J.M.L has non-financial competing interests with Hoffmann La Roche Ltd laboratories. He acts as an expert witness for Hoffmann La Roche Ltd laboratories.

Neurogenesis plays a crucial role during neurodevelopment and its dysfunction can lead to neurodevelopmental disorders. A recent hypothesis stipulates that exogenous factors could corrupt this process and predispose to neurodegenerative disorders later in life. The presence of pesticide residues in the diet represents a threat of which we have recently become aware of. Indeed, they could corrupt neurogenesis, especially during gestation, potentially leading to impaired neuronal and synaptic functions. Since the effects of this low-noise contamination have not yet been evaluated on the neurodevelopment, we investigated the impact of fungicide residues on WT mice exposed throughout gestation. Thus, mice were exposed to fungicides, cyprodinil, mepanipyrim and pyrimethanil, alone at 0.1 μg/L during gestation until P3. Besides, another group was exposed to a cocktail of these three fungicides (0.1 μg/L each) for the same time. Exposure was performed through drinking water at the regulatory limit dose of the European countries (0.1 μg/L). No general toxicity was observed in neonates on body and brain weight upon fungicide exposure. However, results showed that gestational exposure to fungicide residues substantially promoted an increase of neural precursor cells at P3. This corrupted neurogenesis was linked to increased levels of β-catenin, likely through the crosstalk of the PI3K/Akt and Wnt/β-catenin pathways, both involved in cell proliferation. Fungicide exposure also altered protein expression of PSD95 and NMDA receptors in P3 neonates, two targets of the β-catenin signaling pathway. Adult neural stem cell extractions from mice treated with the fungicide cocktail, showed an increase proliferation and differentiation combined with a reduction of their migration properties. In addition, in vitro studies on hippocampal primary cell cultures treated with various concentrations of fungicides showed neurotoxic effects. To conclude, corruption of neurogenesis by this chemical assault could be a fertile ground for the development of neurological diseases later in life., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In the brain of patients with Alzheimer's disease (AD), the number and length of microtubules (MTs) are significantly and selectively reduced. MTs are involved in a wide range of cellular functions, and defects of the microtubular system have emerged as a unifying hypothesis for the heterogeneous and variable clinical presentations of AD. MTs orchestrate their numerous functions through the spatiotemporal regulation of the binding of specialised microtubule-associated proteins (MAPs) and molecular motors. Covalent posttranslational modifications (PTMs) on the tubulin C-termini that protrude at the surface of MTs regulate the binding of these effectors. In neurons, MAP tau is highly abundant and its abnormal dissociation from MTs in the axon, cellular mislocalization and hyperphosphorylation, are primary events leading to neuronal death. Consequently, compounds targeting tau phosphorylation or aggregation are currently evaluated but their clinical significance has not been demonstrated yet. In this review, we discuss the emerging link between tubulin PTMs and tau dysfunction. In neurons, high levels of glutamylation and detyrosination profoundly impact the physicochemical properties at the surface of MTs. Moreover, in patients with early-onset progressive neurodegeneration, deleterious mutations in enzymes involved in modifying MTs at the surface have recently been identified, underscoring the importance of this enzymatic machinery in neurology. We postulate that pharmacologically targeting the tubulin-modifying enzymes holds promise as therapeutic approach for the treatment of neurodegenerative diseases., Competing Interests: Declaration of Competing Interest A patent entitled “Methods for purifying proteins having a tubulin carboxypeptidase activity and peptidic based inhibitors thereof” has been filed by CNRS. KR, KH and SvdL are shareholders of MT-act, a preclinical stage spin-off company of the Institute of Human Genetics, Montpellier, France., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Health professionals working with older persons are not sufficiently aware of the sensory and functional difficulties experienced by older patients. Innovative educational activities, such as the aging-simulation experience, can facilitate this awareness. This study describes the effects of an aging-simulation experience on health professionals' representations towards age-related limitations., Methods: 306 health professionals, enrolled in university training in geriatrics/gerontology in the 2015-2016 and 2016-2017 academic years, experienced an aging-simulation session wearing a special suit according to a predefined scenario. Before and after the aging-simulation experience, participants completed free association tests, with the inductive words vision, hearing, movement, fine dexterity and balance. Semantic categories were created from participants' free evocations using a correspondence table manually produced in Excel 2013 for Windows (Microsoft Corporation, Redmond, Washington). Moreover, participants' opinions on difficulties experienced by older people in relation to age-related limitations were studied using Likert scale questions., Results: In total, 3060 free evocations were collected, and ten semantic categories were created. These categories were composed of participants' geriatric knowledge, about age-related limitations, and participants' feelings, about the experience of these limitations. These two aspects were impacted by the aging-simulation experience. Moreover, changes observed resulted in a better consideration of difficulties associated with age-related limitations., Conclusions: The aging-simulation experience is an effective educational tool to raise awareness among health professionals of age-related difficulties. This sensory activity allows health professionals to put themselves in the shoes of older patients and to feel age-related difficulties.

Background: Comprehensive transcriptomic analyses have shown that colorectal cancer (CRC) is heterogeneous and have led to the definition of molecular subtypes among which the stem-cell, mesenchymal-like group is associated with poor prognosis. The molecular pathways orchestrating the emergence of this subtype are incompletely understood. In line with the contribution of the cellular prion protein PrP C to stemness, we hypothesize that deregulation of this protein could lead to a stem-cell, mesenchymal-like phenotype in CRC., Methods: We assessed the distribution of the PrP C -encoding PRNP mRNA in two large CRC cohorts according to molecular classification and its association with patient survival. We developed cell-based assays to explore the impact of gain and loss of PrP C function on markers of the mesenchymal subtype and to delineate the signalling pathways recruited by PrP C . We measured soluble PrP C in the plasmas of 325 patients with metastatic CRC and probed associations with disease outcome., Findings: We found that PRNP gene expression is enriched in tumours of the mesenchymal subtype and is associated with poor survival. Our in vitro analyses revealed that PrP C controls the expression of genes that specify the mesenchymal subtype through the recruitment of the Hippo pathway effectors YAP and TAZ and the TGFß pathway. We showed that plasma levels of PrP C are elevated in metastatic CRC and are associated with poor disease control., Interpretation: Our findings define PrP C as a candidate driver of the poor-prognosis mesenchymal subtype of CRC. They suggest that PrP C may serve as a potential biomarker for patient stratification in CRC., Funding: Grant support was provided by the following: Cancéropôle Ile de France (grant number 2016-1-EMERG-36-UP 5-1), Association pour la Recherche sur le Cancer (grant number PJA 20171206220), SATT Ile de France Innov (grant number 415) as well as INSERM., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite multiple efforts to find treatments, prion diseases are still incurable. The currently available therapeutic strategies are mostly based on compounds to inhibit pathological PrP (PrPSc) accumulation, and cellular PrP (PrP C ) conversion into PrP Sc . However, they cannot reverse the pathological changes already present in the brain. Cell-based therapeutic strategies could promote the repair of the pre-existing brain damage. The few available data come mostly from preclinical studies using neural stem cells, bone marrow-derived microglia and mesenchymal stem cells, as cell sources. Moreover, the benefits of cell-based therapeutic strategies could be linked not only to the replacement of damaged cells, but also to the secretion of trophic factors by the grafted cells that might modulate inflammation, cell death, or endogenous neurogenesis., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: This study aimed to understand the influence of local media, religion and cultural beliefs on the therapeutic compliance of patients living with HIV., Methods: This study was conducted in two rural hospitals in the Central Kongo province of the Democratic Republic of Congo. Semi-directional interviews were conducted with patients on antiretroviral therapy using a phenomenological qualitative method., Results: Our results indicated that patients living with HIV in the rural region of the Democratic Republic of Congo are in a constant state of tension between the messages for compliance to antiretroviral treatment advocated by caregivers, and those broadcasted by audiovisual media, religious leaders and local beliefs. This dissonance constitutes a real barrier to therapeutic compliance., Conclusion: Collaborative strategies between healthcare providers, patients, as well as religious, media and traditional organizations are urgently needed., Competing Interests: The authors declare no competing interests.

Introduction: Many educational institutions offer professionals continuing education in therapeutic patient education (TPE). Some also provide it for students in initial training., Objectives: 1) Describe the methods of implementing the training in two nurse training institutes (IFSI); 2) Determine the conditions conducive to the development of competencies for students in initial training., Method: Nineteen semi-structured interviews were conducted with trainers, external speakers, students in training, and registered nurses. A questionnaire sent to trainers and external speakers was used to supplement the information gathered., Results: All stakeholders had different levels of training and had experience in TPE. Multiprofessionality in teaching was favored. Several pedagogical activities were proposed to make up for the lack of experience of the students and the shortage of internships, among them role-playing, exchanges of practices, and creation of tools. The training was evaluated in terms of satisfaction and acquisition., Discussion: The training courses implemented largely follow the quality criteria described in the literature., Conclusion: This type of training could be replicated with other students in initial training, or even interprofessional training. The effects of this training should be assessed.