Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain

The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex. Intracerebral hemorrhage triggers astrocyte proliferation and mediates neural stem cell potential via Galectin3 signaling

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Social participation and representations of stroke in stroke patients

L’Accident Vasculaire Cérébral (AVC) est une pathologie fréquente et grave, constituant la première cause de handicap acquis chez l’adulte. Le retentissement de l’AVC sur le quotidien des patients est multiple du fait de la nature polymorphe des séquelles post-AVC et peut engendrer des conséquences dramatiques sur la vie des personnes. Les patients se retrouvent souvent seuls et démunis au moment du retour à domicile et doivent se réadapter à la vie quotidienne en s’ajustant à leur nouvelle condition. Confrontés à l’AVC et ses conséquences, les patients vont développer des représentations de l’AVC influençant les comportements d’autogestion et l’adoption de comportements favorables à la santé. L’objectif de ce travail de thèse était d’identifier à l’aide d’une revue systématique de la littérature et d’une étude quantitative les facteurs contextuels associés à la participation sociale du patient AVC. Les facteurs contextuels sont à la fois relatifs au patient (caractéristiques socio-comportementales, psychosociales, sociodémographiques) et à l’environnement de vie des personnes. De façon complémentaire, une étude qualitative, a été mobilisée dans le but de mieux comprendre l’expérience vécue de l’AVC et notamment d’appréhender les représentations individuelles de l’AVC. La revue de la littérature a montré l’importance des facteurs socio-comportementaux et psychosociaux (estime de soi, motivation, acceptation) ainsi que l’influence des facteurs environnementaux (soutien social, attitudes des autres à l’égard du patient, environnement physique, accès aux soins et services) sur la participation sociale du patient AVC. L’étude quantitative (TYBRA-quanti) a montré de façon additionnelle que le genre, les stratégies d’ajustement à l’AVC et la satisfaction de l’environnement de vie rapportée par le patient représentaient des déterminants indépendants de la participation sociale du patient AVC. Dans un design imbriqué, l’étude qualitative (TYBRA-quali) a permis d’apporter des informations complémentaires quant à l’expérience vécue de l’AVC et notamment concernant les représentations individuelles développées par les patients ne présentant pas de handicap majeur (mRs ≤ 2). Tous rapportaient des problèmes dans la construction d’une identité autour de l’AVC à la fois à la phase aiguë et à la phase chronique. Ils avaient des difficultés à reconnaître que des facteurs de risque liés à des habitudes de vie (tabac, alcool et régime alimentaire) pouvaient avoir un rôle dans la survenue de l’AVC. Le manque d’information ou une information délivrée à un temps inapproprié par les professionnels de santé engendraient une faible connaissance relative aux médicaments de la part des patients et un faible contrôle perçu sur le risque de récidive d’AVC provoquant anxiété et peur. Les patients considérant l’AVC comme une maladie chronique rapportaient plus de difficultés à gérer les conséquences au quotidien. Le soutien de la part des proches mais aussi des professionnels de santé représentait un élément majeur dans le processus de récupération et dans l’adoption de comportements favorables à la santé. Ce travail de recherche avait pour objectif de mieux cerner les répercussions d’un AVC sur la vie quotidienne des patients et la façon dont les personnes y font face. Basée sur trois opérations de recherche aux méthodes variées cette thèse a permis d’apporter des connaissances quant au processus de réadaptation des personnes après un AVC. Cette thèse ouvre la voie à de futures pistes de recherche et cliniques relatives à l’amélioration de l’accompagnement des patients dans la phase de réadaptation. En complément de la prise en charge des déficits fonctionnels et cognitifs des patients, proposer un accompagnement centré sur des processus psychosociaux, socio-comportementaux et écologiques inhérents aux patients permettrait une optimisation du processus de réadaptation (amélioration de la participation sociale et des capacités d’autogestion notamment)Stroke is a frequent and serious disease, constituting the first cause of acquired disability in adults. The impact of stroke on patients’ daily lives is multiple due to the polymorphic nature of post-stroke sequelae, this can have dramatic consequences on people’s lives. Patients often find themselves alone and powerlessness when they return home and have to readapt to daily life by adjusting to their new condition. Faced with stroke and its consequences, patients will develop representations of stroke that influence their self-management behaviours and the adoption of health behaviours favorable to health. The objective of the thesis was to identify, through a systematic literature review and a quantitative study, contextual factors associated with social participation of stroke patients. Contextual factors are both patient-related (socio-behavioural, psychosocial, socio-demographic characteristics) and related to people's living environment. Additionally, we used a qualitative approach to better understand the experience of stroke and in particular to understand individual representations of stroke. The literature review showed the importance of socio-behavioural and psychosocial factors (self-esteem, motivation, acceptance) and also the influence of environmental factors (social support, attitudes of others towards the patient, physical environment, access to care and services) on social participation of stroke patients. The quantitative study (TYBRA-quanti) further showed that gender, coping strategies and patient reported life environment satisfaction were independent determinants of the stroke patient's social participation. In an embedded design, the qualitative study (TYBRA-quali) provided additional information about the experience of stroke, including individual representations developed by patients without major disabilities (mRs ≤ 2). All reported problems in constructing an identity around stroke in both the acute and chronic phases. They had difficulty recognizing that lifestyle risk factors (tobacco, alcohol and diet) could play a role in the occurrence of stroke. Lack of information or information provided at an inappropriate time by health professionals resulted in poor knowledge about medications, and in poor perceived control over the risk of stroke recurrence causing anxiety and fear. Patients who considered stroke as a chronic disease reported more difficulty managing the consequences on daily life. Satisfaction with support from family and health professionals was a major facilitator of the recovery process and of the adoption of health-behaviors favorable to health. The objective of this research work was to better understand the impact of stroke on patients' daily lives and how people cope with it. Based on 3 distinct research methodologies, this thesis led to the production of knowledge on the rehabilitation process of people after stroke. This thesis paves the way for future research and clinical approaches to improving patient support during the rehabilitation phase. In addition to the management of patients' functional and cognitive deficits, providing support focused on psychosocial, socio-behavioural and ecological processes inherent to patients would allow the rehabilitation process to be optimized (in particular by improving social participation and self-management skills

Participation sociale et représentations de l’Accident Vasculaire Cérébral (AVC) chez des patients suite à un AVC

Stroke is a frequent and serious disease, constituting the first cause of acquired disability in adults. The impact of stroke on patients’ daily lives is multiple due to the polymorphic nature of post-stroke sequelae, this can have dramatic consequences on people’s lives. Patients often find themselves alone and powerlessness when they return home and have to readapt to daily life by adjusting to their new condition. Faced with stroke and its consequences, patients will develop representations of stroke that influence their self-management behaviours and the adoption of health behaviours favorable to health. The objective of the thesis was to identify, through a systematic literature review and a quantitative study, contextual factors associated with social participation of stroke patients. Contextual factors are both patient-related (socio-behavioural, psychosocial, socio-demographic characteristics) and related to people's living environment. Additionally, we used a qualitative approach to better understand the experience of stroke and in particular to understand individual representations of stroke. The literature review showed the importance of socio-behavioural and psychosocial factors (self-esteem, motivation, acceptance) and also the influence of environmental factors (social support, attitudes of others towards the patient, physical environment, access to care and services) on social participation of stroke patients. The quantitative study (TYBRA-quanti) further showed that gender, coping strategies and patient reported life environment satisfaction were independent determinants of the stroke patient's social participation. In an embedded design, the qualitative study (TYBRA-quali) provided additional information about the experience of stroke, including individual representations developed by patients without major disabilities (mRs ≤ 2). All reported problems in constructing an identity around stroke in both the acute and chronic phases. They had difficulty recognizing that lifestyle risk factors (tobacco, alcohol and diet) could play a role in the occurrence of stroke. Lack of information or information provided at an inappropriate time by health professionals resulted in poor knowledge about medications, and in poor perceived control over the risk of stroke recurrence causing anxiety and fear. Patients who considered stroke as a chronic disease reported more difficulty managing the consequences on daily life. Satisfaction with support from family and health professionals was a major facilitator of the recovery process and of the adoption of health-behaviors favorable to health. The objective of this research work was to better understand the impact of stroke on patients' daily lives and how people cope with it. Based on 3 distinct research methodologies, this thesis led to the production of knowledge on the rehabilitation process of people after stroke. This thesis paves the way for future research and clinical approaches to improving patient support during the rehabilitation phase. In addition to the management of patients' functional and cognitive deficits, providing support focused on psychosocial, socio-behavioural and ecological processes inherent to patients would allow the rehabilitation process to be optimized (in particular by improving social participation and self-management skills)L’Accident Vasculaire Cérébral (AVC) est une pathologie fréquente et grave, constituant la première cause de handicap acquis chez l’adulte. Le retentissement de l’AVC sur le quotidien des patients est multiple du fait de la nature polymorphe des séquelles post-AVC et peut engendrer des conséquences dramatiques sur la vie des personnes. Les patients se retrouvent souvent seuls et démunis au moment du retour à domicile et doivent se réadapter à la vie quotidienne en s’ajustant à leur nouvelle condition. Confrontés à l’AVC et ses conséquences, les patients vont développer des représentations de l’AVC influençant les comportements d’autogestion et l’adoption de comportements favorables à la santé. L’objectif de ce travail de thèse était d’identifier à l’aide d’une revue systématique de la littérature et d’une étude quantitative les facteurs contextuels associés à la participation sociale du patient AVC. Les facteurs contextuels sont à la fois relatifs au patient (caractéristiques socio-comportementales, psychosociales, sociodémographiques) et à l’environnement de vie des personnes. De façon complémentaire, une étude qualitative, a été mobilisée dans le but de mieux comprendre l’expérience vécue de l’AVC et notamment d’appréhender les représentations individuelles de l’AVC. La revue de la littérature a montré l’importance des facteurs socio-comportementaux et psychosociaux (estime de soi, motivation, acceptation) ainsi que l’influence des facteurs environnementaux (soutien social, attitudes des autres à l’égard du patient, environnement physique, accès aux soins et services) sur la participation sociale du patient AVC. L’étude quantitative (TYBRA-quanti) a montré de façon additionnelle que le genre, les stratégies d’ajustement à l’AVC et la satisfaction de l’environnement de vie rapportée par le patient représentaient des déterminants indépendants de la participation sociale du patient AVC. Dans un design imbriqué, l’étude qualitative (TYBRA-quali) a permis d’apporter des informations complémentaires quant à l’expérience vécue de l’AVC et notamment concernant les représentations individuelles développées par les patients ne présentant pas de handicap majeur (mRs ≤ 2). Tous rapportaient des problèmes dans la construction d’une identité autour de l’AVC à la fois à la phase aiguë et à la phase chronique. Ils avaient des difficultés à reconnaître que des facteurs de risque liés à des habitudes de vie (tabac, alcool et régime alimentaire) pouvaient avoir un rôle dans la survenue de l’AVC. Le manque d’information ou une information délivrée à un temps inapproprié par les professionnels de santé engendraient une faible connaissance relative aux médicaments de la part des patients et un faible contrôle perçu sur le risque de récidive d’AVC provoquant anxiété et peur. Les patients considérant l’AVC comme une maladie chronique rapportaient plus de difficultés à gérer les conséquences au quotidien. Le soutien de la part des proches mais aussi des professionnels de santé représentait un élément majeur dans le processus de récupération et dans l’adoption de comportements favorables à la santé. Ce travail de recherche avait pour objectif de mieux cerner les répercussions d’un AVC sur la vie quotidienne des patients et la façon dont les personnes y font face. Basée sur trois opérations de recherche aux méthodes variées cette thèse a permis d’apporter des connaissances quant au processus de réadaptation des personnes après un AVC. Cette thèse ouvre la voie à de futures pistes de recherche et cliniques relatives à l’amélioration de l’accompagnement des patients dans la phase de réadaptation. En complément de la prise en charge des déficits fonctionnels et cognitifs des patients, proposer un accompagnement centré sur des processus psychosociaux, socio-comportementaux et écologiques inhérents aux patients permettrait une optimisation du processus de réadaptation (amélioration de la participation sociale et des capacités d’autogestion notamment

Illness beliefs and emotional responses in mildly disabled stroke survivors: A qualitative study

International audienceBACKGROUND:As acute stroke services improve, more persons experience mild stroke and need to cope daily with hidden disabilities, which may be influenced by how they perceive stroke, cognitively and emotionally.OBJECTIVE:To investigate cognitive illness beliefs and emotional responses in persons with mild stroke and their possible influences on daily coping.METHODS:Semi-structured interviews were conducted with 24 persons with mild stroke, on average 7.5 months (±0.89) after stroke occurrence. A thematic analysis on verbatim transcripts was guided by the Common-Sense Model of Self-Regulation.RESULTS:All participants experienced difficulties constructing an illness identity at both acute and chronic phase. Behavioral risk factors were less accepted as causes of stroke. Lack (or inappropriate timing) of information from healthcare providers led to limited medication knowledge and low perceived control of stroke recurrence which generated anxiety, fear, and low involvement in coping. Participants who considered stroke a chronic condition experienced more difficulties. Perceived support from relatives and healthcare providers was beneficial for participation in recovery and health behaviour change.CONCLUSION:Despite having mildly disabilities, participants reported difficulties developing illness beliefs conducive to coping, and dealing with their emotional responses. These elements should be considered in tailored programs to improve coping with hidden disabilities post-stroke

Willingness of French General Practitioners to Prescribe mHealth Apps and Devices: Quantitative Study

Background: The field of mobile health (mHealth) is constantly expanding. Integrating mHealth apps and devices in clinical practice is a major and complex challenge. General practitioners (GPs) are an essential link in a patient's care pathway. As they are patients' preferred health care intermediaries, GPs play an important role in supporting patients' transition to mHealth.Objective: This study aims to identify the factors associated with the willingness of French GPs to prescribe mHealth apps and devices to their patients.Methods: This study was part of the ApiAppS project whose overall objective was to help remove barriers GPs face when prescribing mHealth apps and devices by developing a custom-built platform to aid them. The study included GPs recruited from the general practice department of several medical faculties in France (Lyon, Nice, and Rouen) and mailing lists of academic GPs, health care professional associations, and social and professional networks. Participants were asked to complete a web-based questionnaire that collected data on various sociodemographic variables, indicators of their involvement in continued education programs and the amount of time they dedicated to promoting healthy behaviors during patient consultations, and indicators characterizing their patient population. Data on their perceptions of mHealth apps and devices were also collected. Finally, the questionnaire included items to measure GPs' acceptability of prescribing mHealth apps and devices for several health-related dimensions.Results: Of the 174 GPs, 129 (74.1%) declared their willingness to prescribe mHealth apps and devices to their patients. In multivariate analysis, involvement in continued education programs (odds ratio [OR] 6.17, 95% CI 1.52-28.72), a better patient base command of the French language (OR 1.45, 95% CI 1.13-1.88), GP-perceived benefits of mHealth apps and devices for both patients and their medical practice and GP-perceived drivers for mHealth apps and device implementation in their medical practice (OR 1.04, 95% CI 1.01-1.07), and validation of mHealth apps and devices through randomized clinical trials (OR 1.02, 95% CI 1.00-1.04) were all associated with GPs' willingness to prescribe mHealth apps and devices. In contrast, older GPs (OR 0.95, 95% CI 0.91-0.98), female GPs (OR 0.26, 95% CI 0.09-0.69), and those who perceived risks for the patient or their medical practice (OR 0.96, 95% CI 0.94-0.99) were less inclined to prescribe mHealth apps and devices.Conclusions: mHealth apps and devices were generally seen by GPs as useful in general medicine and were, for the most part, favorable to prescribing them. Their full integration in general medicine will be conditioned by the need for conclusive certification, transparency (reliable and precise data concerning mHealth app and device methods of construction and clinical validation), software aids to assist GPs prescribe them, and dedicated training programs

A Qualitative Study of Barriers and Facilitators to Adherence to Secondary Prevention Medications Among French Patients Suffering from Stroke and Transient Ischemic Attack

International audiencePurpose: Secondary prevention medications (SPM) reduce the risk of ischemic stroke (IS) and transient ischemic attack (TIA) recurrence. However, approximately one-third of patients are estimated to be non-adherent. This qualitative study aimed to explore barriers and facilitators to adherence to SPM after IS or TIA. Patients and Methods: Thirty-six face-to-face semi-structured interviews were conducted with 14 TIA patients and 22 IS patients who self-administered their treatment 12 months after IS/TIA. A thematic analysis was performed. Results: Major facilitators to good adherence to SPM were the fear of stroke recurrence and the high level of trust in the prescribing physician. Barriers included a perceived lack and/or inappropriate timing of information about SPM, practical difficulties of taking some SPM (eg, inadequate packaging) and of implementing routines into their daily life. Conclusion: Information on SPM is inadequate in terms of quantity and timing both during the acute IS/TIA period and over the long term. Providing more tailor-made information at an opportune moment, in particular by promoting discussion with their general practitioner (GP) throughout the course of illness and recovery, is essential to ensure that patients are not left alone in the decision-making process regarding adherence to SPM

Contextual determinants of participation after stroke: a systematic review of quantitative and qualitative studies

International audiencePurpose: From a patient’s perspective, participation is a major determinant of quality of life. We aimed to review contextual factors, both personal and environmental, potentially associated with post-stroke participation.Methods: PubMed, PsycINFO, and Web of Science were searched for original quantitative and qualitative studies that investigated contextual factors of post-stroke participation, measured participation as the primary outcome, and met inclusion criteria.Results: Socio-demographic determinants were mostly unrelated with participation or showed discordant and inconclusive results. Although less investigated, psychosocial/psychological factors, particularly self-esteem and acceptance, were associated with participation in most studies. Motivation was found in qualitative studies, but discordant in quantitative ones. Environmental factors were even less investigated and mainly in qualitative studies among patients with communication disabilities. Among these, social support and attitude of others appeared to be major determinants of participation as well as physical environment and societal environment (services and polices).Conclusions: Personal factors, particularly psychological and psychosocial factors, were identified as positively associated with post-stroke participation. Environmental factors such as support, relationships, and positive attitudes towards patients were major facilitators of participation as well as physical environment and accessibility to appropriate services. Most of these factors are modifiable and should be addressed to improve patient participation.Implications for RehabilitationPsychosocial factors (motivational aspects, acceptance of a new condition, self-esteem) and environmental factors (social support, attitudes towards the patient, physical environment, access to health, social services and policies) were identified as determinants of post-stroke participation.A structured evaluation of determinants of participation may be used in clinical practice to propose appropriate support and then improve patients’ recoveryPrograms to improve patients’ psychosocial skills such as self-esteem, acceptance, motivation should be tested and implemented, and policies to develop appropriate services accessibility should be encouraged

Factors associated with post-stroke social participation: A quantitative study based on the ICF framework

International audienceBACKGROUND: Post-stroke social participation is a major determinant of quality of life and life satisfaction. However, few data relating to participation determinants are available, especially the influence of psychological factors and factors related to the living environment. OBJECTIVES: This study investigated determinants of post-stroke social participation within the International Classification of Functioning, Disability and Health framework. METHODS: We contacted people with stroke who had been hospitalized in the Rhône County, included in a previous cohort study, were aged ≥18 years and were not institutionalized. The primary outcome was social participation measured with the Stroke Impact Scale (SIS) 2.0. We performed multiple hierarchical linear regressions to test the following predictors: clinical factors (stroke-related variables, limitations in Activities of Daily Living [ADL]/Instrumental ADL), personal factors (sociodemographic factors, coping strategies) and environmental factors (satisfaction with social relationships and living environment). RESULTS: Among the 352 participants, 63% were men, and mean age was 68.7(SD 14.5) years. In the last multivariate model, variables associated with higher levels of social participation were the use of the positive thinking coping strategy (B (SD)=1.17(0.52), p = 0.03), higher perceived satisfaction with the living environment (B (SD)=0.17(0.07), p = 0.03) and fewer perceived activity limitations (B (SD)=0.55 (0.06), p < 0.001). Conversely, the seeking social support coping style (B (SD)= -1.98 (0.60), p = 0.001), and a higher number of stroke-related sequelae (B (SD)= -1.93(0.53), p = 0.001) were associated with lower social participation. CONCLUSIONS: The identification of potentially modifiable personal and environmental factors that influence social participation provides elements to strengthen existing rehabilitation programs and opens the way for possible psychosocial interventions