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Context: To tackle the systemic injustices experienced by people in vulnerable situations, occupational therapists' agency, i.e. their power to act, is necessary. However, occupational therapists feel ill-equipped to exercise this power, and would like to develop their skills. The general aim of this research was therefore to document occupational therapists' perception of their skills before and after agency training., Methods: We used a mixed sequential explanatory design, comprising a quantitative component consisting of a pre- and post-training self-administered questionnaire and a descriptive qualitative component with group interviews., Results: A total of 103 occupational therapists completed the training between January 19 and October 19, 2019. Their sense of competence improved, especially for those with no prior training in agency. The skills perceived as having developed the most corresponded to the skills deemed a priority for development, namely effective communication, intentional collaboration, and observation and analysis. On the other hand, occupational therapists emphasized that they had not mastered the exercise of these skills in a real-life context., Conclusion: Although continuing education is one way of improving the skills needed to exercise agency, questions remain as to the optimal modalities for ensuring their full and lasting development., Competing Interests: Aucun conflit à rapporter., (© 2024 Carrier, Éthier, Beaudoin, Hudon, Bédard, Jasmin, Lavoie-Trudeau, Verville; licence Synergies Partners.)

Avatar therapy (AT) is a novel virtual reality-based psychotherapy that has been developed to treat auditory verbal hallucinations (AVH) in treatment-resistant schizophrenia. Various psychotherapeutic components, such as emotions and sense of presence, could contribute to clinical outcomes. However, the interplay between sense of presence, emotions, and clinical response has seldom been investigated. This study aimed to explore the relations between sense of presence, emotions, and clinical outcomes in AT. To conduct this investigation, data from previous and ongoing AT trials were used. Sense of presence and emotions were assessed using standardized questionnaires. AVH were evaluated using the Psychotic Symptom Rating Scales. While sense of presence was positively associated with positive emotions such as control and serenity, no significant associations were found for negative emotions. Moreover, a higher level of sense of presence was associated with a bigger decrease in AVH. Overall, positive emotions seem to be associated with sense of presence in AT. Sense of presence also seems to be involved in the therapeutic outcome, thereby suggesting that this could be an important component related to clinical response. More studies are needed to confirm these trends, which could be generalized to other virtual reality-based psychotherapies.

Heterozygous activin receptor-like kinase 1 (ALK1) mutations are associated with two vascular diseases: hereditary hemorrhagic telangiectasia (HHT) and more rarely pulmonary arterial hypertension (PAH). Here, we aimed to understand the impact of ALK1 mutations on BMP9 and BMP10 transcriptomic responses in endothelial cells. Endothelial colony-forming cells (ECFCs) and microvascular endothelial cells (HMVECs) carrying loss of function ALK1 mutations were isolated from newborn HHT and adult PAH donors, respectively. RNA-sequencing was performed on each type of cells compared to controls following an 18 h stimulation with BMP9 or BMP10. In control ECFCs, BMP9 and BMP10 stimulations induced similar transcriptomic responses with around 800 differentially expressed genes (DEGs). ALK1-mutated ECFCs unexpectedly revealed highly similar transcriptomic profiles to controls, both at the baseline and upon stimulation, and normal activation of Smad1/5 that could not be explained by a compensation in cell-surface ALK1 level. Conversely, PAH HMVECs revealed strong transcriptional dysregulations compared to controls with > 1200 DEGs at the baseline. Consequently, because our study involved two variables, ALK1 genotype and BMP stimulation, we performed two-factor differential expression analysis and identified 44 BMP9-dysregulated genes in mutated HMVECs, but none in ECFCs. Yet, the impaired regulation of at least one hit, namely lunatic fringe (LFNG), was validated by RT-qPCR in three different ALK1-mutated endothelial models. In conclusion, ALK1 heterozygosity only modified the BMP9/BMP10 regulation of few genes, including LFNG involved in NOTCH signaling. Future studies will uncover whether dysregulations in such hits are enough to promote HHT/PAH pathogenesis, making them potential therapeutic targets, or if second hits are necessary., (© 2024. The Author(s).)

The interest in new 5-HT₆ agents stems from their ability to modulate cognition processing, food motivation and anxiety-like behaviors. While these findings come primarily from rodent studies, no studies on primates have been published. Furthermore, our understanding of where and how they act in the brain remains limited. Although the striatum is involved in all of these processes and expresses the highest levels of 5-HT₆ receptors, few studies have focused on it. We thus hypothesized that 5-HT 6 receptor blockade would influence food motivation and modulate behavioral expression in non-human primates through striatal 5-HT 6 receptors. This study thus aimed to determine the effects of acute administration of the SB-258585 selective 5-HT 6 receptor antagonist on the feeding motivation and behaviors of six male macaques. Additionally, we investigated potential 5-HT 6 targets using PET imaging to measure 5-HT 6 receptor occupancy throughout the brain and striatal subregions. We used a food-choice task paired with spontaneous behavioral observations, checking 5-HT 6 receptor occupancy with the specific PET imaging [ 18 F]2FNQ1P radioligand. We demonstrated, for the first time in non-human primates, that modulation of 5-HT 6 transmission, most likely through the striatum (the putamen and caudate nucleus), significantly reduces food motivation while exhibiting variable, weaker effects on behavior. While these results are consistent with the literature showing a decrease in food intake in rodents and proposing that 5-HT 6 receptor antagonists can be used in obesity treatment, they question the antagonists' anxiolytic potential., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To review current and future treatment options for IgE-mediated food allergy., Recent Findings: Recent years have seen major developments in both allergen-specific and allergen-non-specific treatment options, with the first FDA-approved peanut oral immunotherapy (OIT) product becoming available in 2020. In addition to OIT, other immunotherapy modalities, biologics, adjunct therapies, and novel therapeutics are under investigation. Food allergy is a potentially life-threatening condition associated with a significant psychosocial impact. Numerous products and protocols are under investigation, with most studies focusing on OIT. A high rate of adverse events, need for frequent office visits, and cost remain challenges with OIT. Further work is needed to unify outcome measures, develop treatment protocols that minimize adverse events, establish demographic and clinical factors that influence candidate selection, and identify patient priorities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Central pontine myelinolysis (CPM) is a rare demyelinating disease that affects the pons and which can cause extreme disabilities such as locked-in syndrome (LIS) in the initial phase. The aim of the study was to describe the evolution over a 12-month period of two patients with CPM causing an initial LIS., Method: We retrospectively report the unexpected clinical outcome of these two patients in relation with the anatomical damages documented by brain MRI, associated with diffusion tensor imaging and reconstruction of corticospinal tracts in tractography. The following clinical parameters systematically assessed at 3, 6, 9, and 12 months: muscle testing on 12 key muscles (Medical Research Council), prehension metrics (box and block test and purdue pegboard), and independence for acts of daily living (functional independence measure)., Results: Both patients showed a progressive recovery beginning between 2 and 3 months after the onset of symptoms, leading to almost complete autonomy at 12 months (FIM > 110), with motor strength greater than 4/5 in all joint segments (MRC > 50/60). On brain MRI with tractography, CST appeared partially preserved at pons level., Interpretation: The possibility of a near-complete functional recovery at 12 months is important to consider given the ethical issues at stake and the discussions about limiting care that may take place initially. It seems to be the consequence of reversible myelin damage combined with partially preserved neurons. Development of collateral pathways or resolution of conduction block may explain this recovery. MRI comprising DTI and tractography could play a key role in the prognosis of motor recovery., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Among older adults with disabilities, maintaining active aging can often be compromised. However, the literature highlights a positive link between mental health and autonomy on one hand, and self-determined motivation on the other. Therefore, self-determined motivation may be improved by promoting mental health and, in the end, older adults autonomy. In this context, the « pôle bien-être autonomie », a mental health promotion program, has been set up to offer activities adapted to the disabilities and needs of the elderly, hence fostering active aging. The purpose of this longitudinal study is to test the hypothesis that promoting the mental health of disabled older adults would preserve their autonomy through the development of self-determined motivation. The theoretical model was tested using structural equation modelling on data of 170 participants. A RCT was conducted between 2019 and 2021 with the same cohort. Results of the structural equation modelling support the importance of promoting mental health in maintaining active aging. Evaluation of the promotion program indicates a decrease in levels of depression, an increase in the frequency of self-determined activities and in the autonomy of beneficiaries after three months of operation. The discussion focuses on the relevance of a processual analysis of the promotion program and on new directions to maintain autonomy for seniors with disabilities.

Background: Pain management and early mobilization strategies are recommended in clinical practice guidelines for the prevention of delirium in older adults. However, available data on the implementation of these strategies in trauma are limited., Aims: To describe the use of pain management and early mobilization strategies in older adults at a level I trauma center, as well as the facilitators and barriers to their implementation., Methods: A convergent mixed methods study was used. Quantitative data were collected from sixty medical records. Qualitative data was collected through a focus group with healthcare providers to explore their perspectives regarding the use of the target practices and on barriers and facilitators to their implementation. Descriptive statistics were calculated, and a thematic analysis using an inductive and deductive interpretative descriptive approach was undertaken., Results: A question on the presence/absence of pain was the most frequently documented pain assessment method. Pain assessment was poorly documented. Frequencies of non-opioid and opioid administrations were similar, but non-pharmacological strategies were not widely used. The first mobilization was performed quickly and was most commonly to a chair. The focus group discussion confirmed many of the data collected in the medical records. Barriers to implementing the targeted strategies were primarily related to organizational context and facilitation processes., Conclusions: Areas for improvement were identified including pain assessment, the use of non-pharmacological pain management strategies and ambulation as a mobilization strategy. Our findings will serve as a starting point for optimizing and adapting practices for geriatric trauma patients and evaluating their impact., Competing Interests: Declaration of competing interest The authors declare that they have no known competing personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Recent longitudinal studies point toward the existence of a positive relationship between cannabis use and violence in people with severe mental disorders (SMD). However, the existence of a dose-response relationship between the frequency/severity of cannabis use and violence has seldom been investigated. Therefore, this study aims to determine if such a relationship exists in a psychiatric population. Methods: To do so, a total of 98 outpatients (81 males and 17 females, all over 18 years of age) with SMD were recruited at the Institut universitaire de santé mentale de Montréal (Montréal, Canada) and included in the analyses. Clinical evaluations were conducted every 3 months for a year. Substance use, violent behaviors, and potential covariables were assessed through self-reported assessments, urinary testing, as well as clinical, criminal, and police records. Using generalized estimating equations, the association between cannabis use frequency (nonusers, occasional, regular, and frequent users) and violence was investigated, as well as the association between the severity of cannabis use and violent behaviors. Results: It was found that cannabis use frequency and severity were significant predictors of violent behaviors. After adjustment for time, age, sex, ethnicity, diagnoses, impulsivity, and use of alcohol and stimulants, odds ratios were of 1.91 ( p <0.001) between each frequency profile and 1.040 ( p <0.001) for each increase of one point of the severity of cannabis use score (ranging from 0 to 79). Conclusions: Despite the high attrition rate, these findings may have important implications for clinicians as cannabis use may have serious consequences in psychiatric populations. Nevertheless, the mechanisms underlying this association remain unclear.

Background: Bevacizumab-a humanized monoclonal antibody-has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted., Methods: This study is a double-blind multicenter randomized phase 2 trial with a 1:1 active-treatment-to-placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3-month period before and after treatment., Results: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention-to-treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty-nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm., Conclusion: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

(1) Background: Approximately 30% of schizophrenia patients are known to be treatment-resistant. For these cases, more personalized approaches must be developed. Virtual reality therapeutic approaches such as avatar therapy (AT) are currently undergoing investigations to address these patients' needs. To further tailor the therapeutic trajectory of patients presenting with this complex presentation of schizophrenia, quantitative insight about the therapeutic process is warranted. The aim of the study is to combine a classification model with a regression model with the aim of predicting the therapeutic outcomes of patients based on the interactions taking place during their first immersive session of virtual reality therapy. (2) Methods: A combination of a Linear Support Vector Classifier and logistic regression was conducted over a dataset comprising 162 verbatims of the immersive sessions of 18 patients who previously underwent AT. As a testing dataset, 17 participants, unknown to the dataset, had their first immersive session presented to the combinatory model to predict their clinical outcome. (3) Results: The model accurately predicted the clinical outcome for 15 out of the 17 participants. Classification of the therapeutic interactions achieved an accuracy of 63%. (4) Conclusion: To our knowledge, this is the first attempt to predict the outcome of psychotherapy patients based on the content of their interactions with their therapist. These results are important as they open the door to personalization of psychotherapy based on quantitative information about the interactions taking place during AT.

Purpose: Few studies have demonstrated that peer-led manual wheelchair (MWC) skills training can increase MWC skills, MWC use self-efficacy and satisfaction with participation of MWC users. Limited information is available on MWC skills training in the community. The primary objective was to measure the influence of Roulez avec confiance (RAC, which translated to "Wheeling with confidence"), a peer-led community-based wheelchair skills training program, on satisfaction with participation. The secondary objectives were to explore the: (1) influence of RAC on MWC use self-efficacy, MWC skills, and quality of life; (2) experiences of the participants who completed RAC and (3) three-month retention of outcomes., Methods: A parallel mixed design was used with validated questionnaires on satisfaction with participation (WhOM), MWC use self-efficacy (WheelCon-M), MWC skills (WST-Q), quality of life (SWLS) and a semi-structured interview on participants' experiences. Non-parametric longitudinal analyses of the questionnaires and thematic content analysis of the interviews were completed., Results: Nineteen community-dwelling MWC users participated. There was a statistically significant increase ( p  < 0.0001) in all outcomes except quality of life ( p  = 0.16). Improvements were retained after three months. Participants mentioned their background influenced their experiences in RAC. Positive elements about RAC and areas for improvement were discussed. Participants reported overall positive social experiences and stated that the physical environment influenced RAC. Finally, participants spoke about what they learned and emotions they felt during RAC., Conclusions: Peer-led community-based MWC training influenced satisfaction with participation, MWC skills, and MWC use self-efficacy. This study was a first step in demonstrating the efficiency of RAC.IMPLICATIONS FOR REHABILITATIONLimited information is available on manual wheelchair skills training in the community.Peer-led community-based manual wheelchair training influenced satisfaction with participation, manual wheelchair skills and use self-efficacy.This study was a first step in demonstrating the efficiency of Roulez Avec Confiance .

Background:  Since they are key witnesses to the systemic difficulties and social inequities experienced by vulnerable patients, health and social service (HSS) professionals and clinical managers must act as change agents. Using their expertise to achieve greater social justice, change agents employ a wide range of actions that span a continuum from the clinical (microsystem) to the societal (macrosystem) sphere and involve actors inside and outside the HSS system. Typically, however, clinical professionals and managers act in a circumscribed manner, that is, within the clinical sphere and with patients and colleagues. Among the hypotheses explaining this reduced scope of action is the fear of reprisal. Little is known about the prevalence of this fear and its complex dynamics., Objective:  The overall aim is to gain a better understanding of the complex dynamic process leading to clinical professionals' and managers' fear of reprisal in their change agent actions and senior administrators' and managers' determination of wrongdoing. The objectives are (1) to estimate the prevalence of fear of reprisal among clinical professionals and managers; (2) to identify the factors involved in (a) the emergence of this fear among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; (3) to describe the process of emergence of (a) the fear of reprisal among clinical professionals and managers, and (b) the determination of wrongdoing by senior administrators and managers; and (4) to document the legal and ethical issues associated with the factors identified (objective 2) and the processes described (objective 3)., Methods:  Based on the Exit, Voice, Loyalty, Neglect model, a 3-part sequential mixed methods design will include (1) a web-based survey (objective 1), (2) a qualitative grounded theory design (objectives 2 and 3), and (3) legal and ethical analysis (objective 4). Survey: 77,794 clinical professionals or clinical managers working in the Québec public HSS system will be contacted via email. Data will be analyzed using descriptive statistics. Grounded theory design: for each of the 3 types of participants (clinical professionals, clinical managers, and senior administrators and managers), a theoretical sample of 15 to 30 people will be selected via various strategies. Data will be independently analyzed using constant comparison process. Legal and ethical analysis: situations described by participants will be analyzed using, respectively, applicable legislation and jurisprudence and 2 ethical models., Results:  This ongoing study began in June 2022 and is scheduled for completion by March 2027., Conclusions:  Instead of acting, fear of reprisal could induce clinical professionals to tolerate situations that run counter to their social justice values. To ensure they use their capacities for serving a population that is or could become vulnerable, it is important to know the prevalence of the fear of reprisal and gain a better understanding of its complex dynamics., International Registered Report Identifier (irrid): PRR1-10.2196/48400., (©Annie Carrier, François Bolduc, Nathalie Delli-Colli, Finn Makela, Anne Hudon, Marie-Eve Caty, Arnaud Duhoux, Michaël Beaudoin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 21.09.2023.)

Low self-esteem is a vulnerability factor for depressive disorders, and the prevention of psychological disorders is essential in cancer patients. The enhancement of self-esteem in breast cancer patients may therefore be an appropriate clinical target. Previous studies have shown the efficacy of the Lexical Association Technique to enhance self-esteem in healthy subjects. This study aims to test the clinical efficacy and acceptability of the Lexical Association Technique on the self-esteem of cancer patients. A double-blind randomized controlled trial was conducted on 63 breast cancer patients during their radiotherapy treatment. Global self-esteem measures were taken using the Rosenberg Self-Esteem Scale before and after the Lexical Association Technique and 1 month after its end. The results showed a significant improvement in global self-esteem in patients immediately after performing the Lexical Association Technique compared to an active control group. However, the positive effects did not last 1 month. These results confirm the efficacy and suitability of the Lexical Association Technique for cancer patients. Avenues of research are proposed to extend the effects of the technique and increase its transdiagnostic applicability., (© 2022 The Authors. Applied Psychology: Health and Well-Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

Background: Several methods have been proposed to foster recovery of consciousness in patients with disorders of consciousness (DoC)., Objective: Critically assess pharmacological and non-pharmacological treatments for patients with chronic DoC., Methods: A narrative mini-review, and critical analysis of the scientific literature on the various proposed therapeutic approaches, with particular attention to level of evidence, risk-benefit ratio, and feasibility., Results and Discussion: Personalised sensory stimulation, median nerve stimulation, transcranial direct current stimulation (tDCS), amantadine and zolpidem all have favourable risk-benefit ratios and are easy to implement in clinical practice. These treatments should be proposed to every patient with chronic DoC. Comprehensive patient management should also include regular lifting, pain assessment and treatment, attempts to restore sleep and circadian rhythms, implementation of rest periods, comfort and nursing care, and a rehabilitation program with a multi-disciplinary team with expertise in this field. More invasive treatments may cause adverse effects and require further investigation to confirm preliminary, encouraging results and to better define responders' intervention parameters. Scientific studies are essential and given the severity of the disability and handicap that results from DoC, research in this area should aim to develop new therapeutic approaches., Competing Interests: Disclosure of interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Preferences of informal caregivers of people with neurocognitive disorders for technological solutions are important in user- centered design approaches. It is crucial to take into consideration the needs and preferences of users when developing new technology to facilitate their uptake., Objectives: The objective of this study was to determine caregiver preferences for potential technological solutions to help address their needs and compare technology preferences of caregivers who provide care to those with and without neurocognitive disorders (NCD)., Methods: This was a quantitative descriptive study. We surveyed informal caregivers of older adults with disability in Canada. Participants were asked to answer questions about their preferences for 10 potential technological solutions that could be developed to make caregiving easier., Results: Data from 125 respondents (72 caregivers of people with NCD and 53 caregivers of people with non-NCD-related disabilities) were analyzed. Generally, caregivers preferred web-based solutions as these were among the first five choices for both groups combined. However, there were some differences in the order of preference of potential solutions in both groups., Conclusion: Informal caregivers of people with NCD preferred web-based solutions to help address their needs., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Francois Routhier and Claudine Auger had salary support from Fonds de recherche du Québec– Santé (FRSQ) Research Scholar program., (© The Author(s) 2023.)

(1) Background: The therapeutic mechanisms underlying psychotherapeutic interventions for individuals with treatment-resistant schizophrenia are mostly unknown. One of these treatment techniques is avatar therapy (AT), in which the patient engages in immersive sessions while interacting with an avatar representing their primary persistent auditory verbal hallucination. The aim of this study was to conduct an unsupervised machine-learning analysis of verbatims of treatment-resistant schizophrenia patients that have followed AT. The second aim of the study was to compare the data clusters obtained from the unsupervised machine-learning analysis with previously conducted qualitative analysis. (2) Methods: A k-means algorithm was performed over the immersive-session verbatims of 18 patients suffering from treatment-resistant schizophrenia who followed AT to cluster interactions of the avatar and the patient. Data were pre-processed using vectorization and data reduction. (3): Results: Three clusters of interactions were identified for the avatar's interactions whereas four clusters were identified for the patient's interactions. (4) Conclusion: This study was the first attempt to conduct unsupervised machine learning on AT and provided a quantitative insight into the inner interactions that take place during immersive sessions. The use of unsupervised machine learning could yield a better understanding of the type of interactions that take place in AT and their clinical implications.

Cannabis use disorder (CUD) is a complex issue, even more so when it is comorbid with a severe mental disorder (SMD). Available interventions are at best slightly effective, and their effects are not maintained over time. Therefore, the integration of virtual reality (VR) may increase efficacy; however, it has not yet been investigated in the treatment of CUD. A novel approach, avatar intervention for CUD, uses existing therapeutic techniques from other recommended therapies (e.g., cognitive behavioral methods, motivational interviewing) and allows participants to practice them in real-time. During immersive sessions, participants are invited to interact with an avatar representing a significant person related to their drug use. This pilot clinical trial aimed to evaluate the short-term efficacity of avatar intervention for CUD on 19 participants with a dual diagnosis of SMD and CUD. Results showed a significant moderate reduction in the quantity of cannabis use (Cohen's d = 0.611, p = 0.004), which was confirmed via urinary quantification of cannabis use. Overall, this unique intervention shows promising results. Longer-term results, as well as comparison with classical interventions in a larger sample, are warranted through a future single-blind randomized controlled trial.

Introduction: Behavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness., Methods: Hence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject's own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN ('SON effect', primary endpoint assessed by temporal clustering permutation tests)., Results: Patients were either coma ( n  = 38), unresponsive wakefulness syndrome (UWS, n  = 30) or minimally conscious state (MCS, n  = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a 'SON effect'. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients ( p  = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients ( p  = 0.013 for comparison between groups). Among the 72 survivors' patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome., Discussion: About 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferré, Heine, Naboulsi, Gobert, Beaudoin-Gobert, Dailler, Buffières, Corneyllie, Sarton, Riu, Luauté, Silva and Perrin.)

Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [ 11 C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [ 11 C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [ 11 C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [ 15 O 2 ]H 2 OPET imaging. [ 11 C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation., (© 2023. The Author(s).)

Genome-wide association studies have identified >250 genetic variants associated with coronary artery disease (CAD), but the causal variants, genes and molecular mechanisms remain unknown at most loci. We performed pooled CRISPR screens to test the impact of sequences at or near CAD-associated genetic variants on vascular endothelial cell functions. Using CRISPR knockout, inhibition and activation, we targeted 1998 variants at 83 CAD loci to assess their effect on three adhesion proteins (E-selectin, ICAM1, VCAM1) and three key endothelial functions (nitric oxide and reactive oxygen species production, calcium signalling). At a false discovery rate ≤10%, we identified significant CRISPR perturbations near 42 variants located within 26 CAD loci. We used base editing to validate a putative causal variant in the promoter of the FES gene. Although a few of the loci include genes previously characterized in endothelial cells (e.g. AIDA, ARHGEF26, ADAMTS7), most are implicated in endothelial dysfunction for the first time. Detailed characterization of one of these new loci implicated the RNA helicase DHX38 in vascular endothelial cell senescence. While promising, our results also highlighted several limitations in using CRISPR perturbations to functionally dissect GWAS loci, including an unknown false negative rate and potential off-target effects., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: BPK is an inventor on patents and/or patent applications filed by Mass General Brigham that describe genome engineering technologies, is a consultant for EcoR1 capital and ElevateBio, and is an advisor to Acrigen Biosciences, Life Edit Therapeutics, and Prime Medicine. The remaining authors declare that they have no competing interests., (Copyright: © 2023 Wünnemann 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.)

(1) Background: Very little is known about the inner therapeutic processes of psychotherapy interventions for patients suffering from treatment-resistant schizophrenia. Avatar therapy (AT) is one such modalities in which the patient is undergoing immersive sessions in which they interact with an Avatar representing their main persistent auditory verbal hallucination. The aim of this study is to identify the most prevalent dyadic interactions between the patient and the Avatar in AT for patient's suffering from TRS. (2) Methods: A content analysis of 256 verbatims originating from 32 patients who completed AT between 2017 and 2022 at the Institut universitaire en santé mentale de Montréal was conducted to identify dyadic interactions between the patients and their Avatar. (3) Results: Five key dyads were identified to occur on average more than 10 times for each participant during the immersive sessions across their AT: (Avatar: Reinforcement, Patient: Self-affirmation), (Avatar: Provocation, Patient: Self-affirmation), (Avatar: Coping mechanisms, Patient: Prevention), (Patient: Self-affirmation, Avatar: Reinforcement), and (Patient: Self-appraisal, Avatar: Reinforcement). (4) Conclusion: These dyads offer a first qualitative insight to the interpersonal dynamics and patient-avatar relationships taking place during AT. Future studies on the implication of such dyadic interactions with the therapeutic outcome of AT should be conducted considering the importance of dyadic relationships in psychotherapy.

Avatar Therapy has a significant impact on symptoms, beliefs, and quality of life of patients with treatment-resistant schizophrenia. However, little is known about how these changes are implemented into their lives and to which aspects of their lives these improvements relate. Ten consecutive patients enrolled in an ongoing clinical trial were assessed using semi-guided interviews before as well as three months after Avatar Therapy. These encounters have been recorded and transcribed so that the discourse could be thoroughly analyzed, leading to the generation of an extensive theme grid. As the cases were analyzed, the grid was adapted in a back-and-forth manner until data saturation occurred. The content analysis allowed the identification of nine main themes representing different aspects of the patients' lives, each of which was subdivided into more specific codes. By analyzing the evolution of their frequency, it was observed that, following therapy, patients presented with fewer psychotic symptoms, better self-esteem, more hobbies and projects, and an overall improved lifestyle and mood. Finally, investigating the impact of Avatar Therapy on quality of life allows for a deeper understanding of how people with treatment-resistant schizophrenia can achieve meaningful changes and move towards a certain recovery process.

Virtual reality immersion enables a person to embody avatars that strongly deviate from his/her biological body. Interestingly, the person's expectations about the embodied avatar lead to congruous behavior, phenomenon referred to as the Proteus effect. The objective of the present study was to investigate, in virtual reality, the relationship between body-shape representation and expected physical abilities in a locomotor imagery task, in the context of overweight avatar embodiment. Given the negative stereotypes concerning overweight people's physical abilities, we expected overweight avatar embodiment to have a negative impact on performance in the locomotor imagery task. Thirty-five healthy-weight participants, with a body mass index between 16.5 and 30 at the time of the experiment or in the past, embodied both a healthy-weight avatar and an overweight avatar on two different experimental sessions while performing the imagery task (walking four different distances on two different slopes). In accordance with our hypothesis, participants took longer to perform the locomotor imagery task when embodying an overweight avatar than when embodying a healthy-weight one (the "avatar effect")-especially so when the distance to be covered was long. We conclude that, as has already been reported for people with anorexia nervosa, considering one's own body to be fatter than it really is leads to congruent weight-related behavior., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Promoting the mental health of vulnerable elderly patients is a public health priority., Context: In many cases, mental health interventions for elderly people are not appropriate for those with multiple physical disabilities., Objectives: This article aims to provide gerontology professionals with an overview of the types of interventions available based on their practice setting (home or long-term care facility) and the characteristics of the people who use them (over 75 years old with physical disabilities)., Method: A systematic literature review was conducted using the PsycInfo, PubMed, and Cochrane databases, using data ranging from 2001-2022. All interventions aimed at addressing mental health issues were included, regardless of their research methodology., Results: A total of 18 studies were included in this systematic review. The methodological limitations of these studies had a negative impact on our ability to draw conclusions and generalizations about the results of this review. However, the social and psychological support interventions studied seem to hold much promise., Discussion: The provision of personalized support seems to be an important factor in determining the success of an intervention, whether at home or in a long-stay facility., Conclusion: Further studies are needed to provide evidence of the effectiveness of these interventions.

Avatar Therapy (AT) is a modern therapeutic alternative for patients with schizophrenia suffering from persistent auditory verbal hallucinations. Its intrinsic therapeutical process is currently qualitatively analyzed via human coders that annotate session transcripts. This process is time and resource demanding. This creates a need to find potential algorithms that can operate on small datasets and perform such annotations. The first objective of this study is to conduct the automated text classification of interactions in AT and the second objective is to assess if this classification is comparable to the classification done by human coders. A Linear Support Vector Classifier was implemented to perform automated theme classifications on Avatar Therapy session transcripts with the use of a limited dataset with an accuracy of 66.02% and substantial classification agreement of 0.647. These results open the door to additional research such as predicting the outcome of a therapy.

While research focus remains mainly on psychotic symptoms, it is questionable whether we are placing enough emphasis on improving the quality of life (QoL) of schizophrenia patients. To date, the predictive power of QoL remained limited. Therefore, this study aimed to accurately predict the QoL within schizophrenia using supervised learning methods. The authors report findings from participants of a large randomized, double-blind clinical trial for schizophrenia treatment. Potential predictors of QoL included all available and non-redundant variables from the dataset. By optimizing parameters, three linear LASSO regressions were calculated (N = 697, 692, and 786), including 44, 47, and 41 variables, with adjusted R-squares ranging from 0.31 to 0.36. Best predictors included social and emotion-related symptoms, neurocognition (processing speed), education, female gender, treatment attitudes, and mental, emotional, and physical health. These results demonstrate that machine learning is an excellent predictive tool to process clinical data. It appears that the patient's perception of their treatment has an important impact on patients' QoL and that interventions should consider this aspect.Trial registration: ClinicalTrials.gov Identifier: NCT00014001., (© 2022. The Author(s).)

Purpose: Training is recommended to improve safe and effective use of mobility aids. The internet offers a large amount of information and it can be difficult to identify resources with good quality. This project aimed to create a catalogue of online educational resources for mobility device training. The objective of this study was to identify and assess the quality of existing online educational resources for mobility device training for individuals with physical disabilities and caregivers., Methods: A Google search was conducted in October 2016 and replicated in January 2018. Resources were included if they were educational, were available in English or French, provided instruction or training in mobility aid use, were free of charge, and were targeted towards mobility device users or their caregivers. Resources were assessed using a modified version of the Journal of the American Medical Association (JAMA) benchmarks for the evaluation of technical quality., Results: Two hundred and seventy-one resources were included in the final analysis. Two resources were added by the research team for a total of 273 resources. The average JAMA quality score per mobility device varied between 3 (for crutches) and 5 (for knee scooters) out of 6, and weighted average was 3.6. The two resources added by the research team obtained a JAMA quality score of 6. 58 resources were retained for the catalogue., Conclusions: The results suggest that the technical quality of online educational resources for mobility device training could be improved. A need for higher quality resources for device users and caregivers was identified.Implications for rehabilitationThe overall technical quality of online educational resources for mobility device training for users and caregivers is low.A Mobility Device Training Catalogue is freely available and summarizes the highest quality online resources found on mobility device training.The Mobility Device Training Catalogue is intended for use by users and caregivers, but it may also provide clinicians with a tool that may be shared with their clients.

Numerous studies showed that cancer significantly increases the risk of developing depressive and anxious symptoms. It has been shown that self-esteem is an important psychological resource and is associated with many health behaviors. Furthermore, the vulnerability model of low self-esteem, which has received strong empirical support, highlights that low self-esteem is a real risk factor in the development of depressive disorders. This article aims at providing an overview of the involvement of self-esteem in the psychological adjustment to cancer. After briefly reviewing the literature, we suggest that its implication in the development of depressive disorders and its association with coping strategies and social support in cancer patients justify the consideration of self-esteem in oncology psychological care, especially in young adult patients and those with significant physical impairment following treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Niveau, New and Beaudoin.)

Background: A growing body of literature has detailed the use of qualitative analyses to measure the therapeutic processes and intrinsic effectiveness of psychotherapies, which yield small databases. Nonetheless, these approaches have several limitations and machine learning algorithms are needed., Objective: The objective of this study is to conduct a systematic review of the use of machine learning for automated text classification for small data sets in the fields of psychiatry, psychology, and social sciences. This review will identify available algorithms and assess if automated classification of textual entities is comparable to the classification done by human evaluators., Methods: A systematic search was performed in the electronic databases of Medline, Web of Science, PsycNet (PsycINFO), and Google Scholar from their inception dates to 2021. The fields of psychiatry, psychology, and social sciences were selected as they include a vast array of textual entities in the domain of mental health that can be reviewed. Additional records identified through cross-referencing were used to find other studies., Results: This literature search identified 5442 articles that were eligible for our study after the removal of duplicates. Following abstract screening, 114 full articles were assessed in their entirety, of which 107 were excluded. The remaining 7 studies were analyzed. Classification algorithms such as naive Bayes, decision tree, and support vector machine classifiers were identified. Support vector machine is the most used algorithm and best performing as per the identified articles. Prediction classification scores for the identified algorithms ranged from 53%-91% for the classification of textual entities in 4-7 categories. In addition, 3 of the 7 studies reported an interjudge agreement statistic; these were consistent with agreement statistics for text classification done by human evaluators., Conclusions: A systematic review of available machine learning algorithms for automated text classification for small data sets in several fields (psychiatry, psychology, and social sciences) was conducted. We compared automated classification with classification done by human evaluators. Our results show that it is possible to automatically classify textual entities of a transcript based solely on small databases. Future studies are nevertheless needed to assess whether such algorithms can be implemented in the context of psychotherapies., (©Alexandre Hudon, Mélissa Beaudoin, Kingsada Phraxayavong, Laura Dellazizzo, Stéphane Potvin, Alexandre Dumais. Originally published in JMIR Mental Health (https://mental.jmir.org), 22.10.2021.)

Background.: When acting effectively in their social change agent (SCA) role, occupational therapists can impact population health and occupational justice. However, empirical evidence of the influence of personal and environmental factors on their ability to act as SCAs is scarce., Purpose.: To explore personal and environmental factors that influence the ability of occupational therapists to act as effective SCAs., Method.: We conducted a descriptive interpretive qualitative study with 18 Québec occupational therapists recognized as successful SCAs. We collected data through semi-structured interviews with three focus groups and analyzed them thematically using a lexicon., Findings.: We identified nine cross-cutting personal factors, including discovery, effective communication, and planning, that enable occupational therapists to act as successful SCAs. Six thematic groups of environmental factors facilitated or hindered their actions., Implications.: To act effectively as SCAs, occupational therapists need to consider personal and environmental factors involved in their change project.

Background: Outcomes associated with physician responses to recommendations from an antimicrobial stewardship program (ASP) at an individual patient level have not yet been assessed. We aimed to compare clinical characteristics and mortality risk among patients for whom recommendations from an ASP were accepted or refused., Methods: A prospective cohort study was performed with hospitalized adults who received intravenous or oral antimicrobials at a 677-bed academic centre in Canada in 2014-2017. We included patients with an alert produced by a clinical decision support system (CDSS) for whom a recommendation was made by the pharmacist to the attending physician. The outcome was 90-day in-hospital all-cause mortality., Results: We identified 3,197 recommendations throughout the study period, of which 2,885 (90.2%) were accepted. The median length of antimicrobial treatment was significantly shorter when a recommendation was accepted (0.26 versus 1.78 d; p < 0.001). Refusal of a recommendation was not associated with mortality (odds ratio 1.32; 95% confidence interval, 0.93 to 1.89; p = 0.12). The independent risk factors associated with in-hospital mortality were age, Charlson Comorbidity Index score, admission to a critical care unit, duration between admission and recommendation, and issuance of a recommendation on a carbapenem., Conclusions: The duration of antimicrobial treatment was significantly shorter when a recommendation originating from a CDSS-assisted ASP program was accepted. Future prospective studies including potential residual confounding variables, such as the source of infection or physiological derangement, might help in understanding whether CDSS-assisted ASP will have a direct impact on patient mortality., Competing Interests: JP, LV, MB, and VN are shareholders of Lumed, the company commercializing APSS., (Copyright © 2021, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

In the context of demographic aging, preventing autonomy loss is a major issue. Adapting care systems to help keep seniors at home is a daily challenge. "La Mutualité Française", a national mutual insurance company, has implemented in one of its healthcare services an innovative program to strengthen well-being: "The Well-Being Autonomy Pole." This program comprises five Prevention and Support Care components and hypothesizes that strengthening the well-being of elderly people already suffering from physical limitations would prevent their autonomy decline. The originality of this program is its focus on elderly people who have rarely been studied in terms of preventing autonomy loss, given their existing functional limitations. A first evaluation was carried out over three months to verify the methodological feasibility of an impact assessment and to provide preliminary results on the effectiveness of the program. Key findings suggest improved levels of self-esteem, physical well-being, psychological autonomy and decreased anxiety. Methodological limitations of this first feasibility assessment and perspectives for future research are discussed.

Background.: Change agents' actions have been studied mainly from a theoretical perspective., Purpose.: This study aimed to empirically identify occupational therapists' actual change agent actions., Method.: As part of a research partnership with the Canadian Association of Occupational Therapists-Québec chapter, we conducted this cross-sectional pilot study using an online survey., Findings.: The change agent practices of our 103 participants involve many types of actions but show underinvestment in mass communication. Mass communication actions are more frequent when participants have greater experience, additional academic degrees, and training in change agency. Also, occupational therapists with additional academic degrees and change agency training tend to use a wider variety of actions. Finally, our participants' actions principally target actors in the clinical context, rarely political actors., Implications.: Our results suggest that occupational therapists can and will invest in the full range of change agent actions provided they can acquire the necessary knowledge and skills.

Objective: Because the therapeutic processes of Avatar Therapy remain equivocal, the current study aims to further extend our previous findings by analysing the evolution of the avatars' and patients' speech and changes in patient responses as sessions progressed., Design: Eighteen patients with treatment-resistant schizophrenia were selected from two clinical trials on Avatar Therapy. Three coders analysed both the avatars' and patients' discourse during immersive therapy sessions using content analysis methods., Results: Our analyses enabled the categorization of the avatar discourse into confrontational techniques (e.g., provocation) and positive techniques (e.g., reinforcement). Patients responded to these utterances using coping mechanism or by expressing emotions, beliefs, self-perceptions or aspirations. Through identification of mutual changes in the interaction between the patient and their avatar, a shift was observed over the sessions from confrontation to a constructive dialogue. Assertiveness, emotional responses and prevention strategies seemed to be central to the therapeutic process, and these usually occur in response to positive techniques., Conclusion: Investigating AT's therapeutic process may help to identify components to achieve positive outcomes and can enable the development of more effective treatments. Further studies should explore the association between these themes and therapeutic response to help predict which patients will better respond to Avatar Therapy., (© 2021 John Wiley & Sons, Ltd.)

SAR efforts directed at identifying RORγt inverse agonists structurally different from our clinical compound 1 (BMS-986251) led to tricyclic-carbocyclic analogues represented by 3 - 7 and culminated in the identification of 3d (BMS-986313), with structural differences distinct from 1 . The X-ray co-crystal structure of 3d with the ligand binding domain of RORγt revealed several key interactions, which are different from 1 . The in vitro and in vivo PK profiles of 3d are described. In addition, we demonstrate robust efficacy of 3d in two preclinical models of psoriasis-the IMQ-induced skin lesion model and the IL-23-induced acanthosis model. The efficacy seen with 3d in these models is comparable to the results observed with 1 .

Background: Quality of life (QoL) is an important parameter to monitor during rehabilitation; however, accurate assessment is challenging. Among individuals with spinal cord injury (SCI), assessing QoL is further challenged due to complex sequelae, such as secondary health conditions and factors related to community integration. A Participation and Quality of Life (PAR-QoL) toolkit was created to aid clinicians and researchers in the selection of QoL outcomes tools specific to SCI. Objectives: The aim of this study was to evaluate the use and usability of the PAR-QoL toolkit. Methods: A cross-sectional study was conducted using an online survey from December 2013 to November 2016. Google Analytics were collected from April 2012 to April 2018. Survey sections addressed "use" (behavioral practices and actual use) and "usability" (perceived ease of use and perceived usefulness). Any person who visited the PAR-QoL website was invited to complete the survey. Summary statistics and percent concordances were calculated to describe results from the survey and Google Analytics. Results: The PAR-QoL website had 188,577 users. The five most visited webpages were outcome tools, with bounce rates ranging from 77% to 90%. Of the 46 survey respondents, 67% were not current users of the PAR-QoL website, and 87% intended to use the resources in the future. Conclusion: Uptake of the PAR-QoL website is currently limited. Usability of the PAR-QoL website may be improved by modifying navigation, removing the "less useful" components, ensuring regular updates of content and resources, and promoting the website., (© 2020 Thomas Land Publishers, Inc.)

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10 -9 , including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies., Competing Interests: Declaration of Interests Competing financial interests are declared in Table S1F., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The aim of this meta-analysis was to investigate the extent to which cannabis use among youths is associated with the risk of perpetrating physical violence., Methods: Searches were conducted in PubMed, PsycINFO, Web of Science, and Google Scholar for articles published from the inception of each database to July 2019. All studies that examined both cannabis use and the perpetration of physical violence in a sample of youths and young adults <30 years old were included. The meta-analysis was performed with a random-effects model. Risk of publication bias was assessed with Egger's test. Guidelines from the Meta-Analysis of Observational Studies in Epidemiology were followed., Results: After screening 11,348 potential studies, 30 study arms were included, yielding a total of 296,815 adolescents and young adults. The odds ratio for the pooled studies was 2.11 (95% CI=1.64, 2.72). The pooled odds ratios were 2.15 (95% CI=1.58, 2.94) and 2.02 (95% CI=1.26, 3.23) for the cross-sectional and longitudinal studies, respectively. Preliminary evidence suggests that the risk of violence was higher for persistent heavy users (odds ratio=2.81, 95% CI=1.68, 4.74) compared with past-year users (odds ratio=2.05, 95% CI=1.5, 2.8) and lifetime users (odds ratio=1.94, 95% CI=1.29, 2.93). The odds ratio for unadjusted studies was 2.62 (95% CI=1.89, 3.62), and for studies using odds ratios adjusted for potential confounding factors, 2.01 (95% CI=1.57, 2.56)., Conclusions: These results demonstrate a moderate association between cannabis use and physical violence, which remained significant regardless of study design and adjustment for confounding factors (i.e., socioeconomic factors, other substance use). Cannabis use in this population is a risk factor for violence.

Objectives: Interindividual differences in cognitive aging may be explained by differences in cognitive reserve (CR) that are built up across the life span. A plausible but underresearched mechanism for these differences is that CR helps compensating cognitive decline by enhancing motivation to cope with challenging cognitive situations. Theories of motivation on cognition suggest that perceived capacity and intrinsic motivation may be key mediators in this respect., Method: In 506 older adults, we assessed CR proxies (education, occupation, leisure activities), motivation (perceived capacity, intrinsic motivation), and a global measure of cognitive functioning., Results: Perceived capacity, but not intrinsic motivation, significantly mediated the relation between CR and cognitive performance., Discussion: Complementary with neurobiological and cognitive processes, our results suggest a more comprehensive view of the role of motivational aspects built up across the life span in determining differences in cognitive performance in old age., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The prevalence of mobility disability reaches up to 20.5% among older adults. Mobility is a key factor of participation, thus rehabilitation interventions often aim to improve mobility and participation. Peer-based approaches to intervention delivery have become increasingly common. This study aims to identify peer-based rehabilitation interventions and summarize their influence on mobility and participation among individuals with mobility disabilities. Method: A systematic review was conducted using CINALH, EMBASE, MEDLINE, and PsycINFO. Articles that evaluated peer-based rehabilitation interventions for individuals with a mobility disability and assessed mobility or participation, as defined in the International Classification of Functioning, Disability and Health framework, were included. Study quality was assessed using the Physical Therapy Evidence Database and the Quality Assessment Tool for Before-After Studies With No Control Group. Results: Thirteen peer-based studies were identified. Six peer-led studies evaluated participation and two evaluated mobility. Seven professional-led studies evaluated participation and six evaluated mobility. Randomized controlled trials had fair to high quality. The quality of pre-post studies ranged from poor to good. Conclusion: Peer-based interventions should not be overlooked as a potential intervention strategy, but further research is needed to establish their influence on mobility and participation.Implications for rehabilitationPeers offer a unique model of intervention that could support clinicians in their effort to improve mobility and participation outcomes for individuals with disabilities.There are currently two main models of peer-based interventions in rehabilitation: professional-led (peers assist professionals to facilitate the intervention) and peer-led interventions (peers facilitate the intervention).Both professional-led and peer-led models of intervention could be helpful in facilitating participation and in increasing mobility.

When an individual embodies an avatar, the latter's characteristics or stereotype can change the individual's behavior and attitudes; this is known as the Proteus effect. Here, we looked at whether the embodiment of an avatar resembling an elderly adult (seen from a first-person perspective and facing a virtual mirror) changed mentally represented physical activity in a motor imagery task performed by young adult participants (N = 52). To ensure that the impact of embodiment of an elderly avatar on the motor imagery task was not influenced by a potentially confounded stereotype assimilation effect (due to the mere presence of an avatar), a "young" avatar and an "elderly" avatar were always present together in the virtual environment-even though only one (the self-avatar) was embodied at a given time. We found that it took longer for the participants to perform the motor imagery task with the elderly self-avatar than with the young self-avatar. The more negative the participant's beliefs about motor activity in the elderly, the greater the observed effect of the avatar on motor imagery performance. We conclude that knowledge about the characteristics of an embodied avatar can modify the subject's level of mentally represented physical activity.

Although recent studies have shown a moderately strong association between cannabis use and violence among people with severe mental disorders, the direction of this association has not been investigated prospectively in a population with schizophrenia. Therefore, this study aims to determine, using cross-lag models, whether a temporal relationship between cumulative cannabis use and violence exists in a population with schizophrenia. The authors reported findings covering an 18-month period from a randomized, double-blind clinical trial of antipsychotic medications for schizophrenia treatment. Among the 1460 patients enrolled in the trial, 965 were followed longitudinally. Although persistent cannabis use predicted subsequent violence, violence did not predict cannabis use. The relationship was therefore unidirectional and persisted when controlling for stimulants and alcohol use. Finally, a significant body of evidence suggests a link between persistent cannabis use and violence among people with mental illnesses. Studies to further investigate the mechanisms underlying this association should be conducted.

Hereditary hemorrhagic telangiectasia is a rare but ubiquitous genetic disease. Epistaxis is the most frequent and life-threatening manifestation and tacrolimus, an immunosuppressive agent, appears to be an interesting new treatment option because of its anti-angiogenic properties. Our objective was to evaluate, six weeks after the end of the treatment, the efficacy on the duration of nosebleeds of tacrolimus nasal ointment, administered for six weeks to patients with hereditary hemorrhagic telangiectasia complicated by nosebleeds, and we performed a prospective, multicenter, randomized, placebo-controlled, double-blinded, ratio 1:1 phase II study. Patients were recruited from three French Hereditary Hemorrhagic Telangiectasia (HHT) centers between May 2017 and August 2018, with a six-week follow-up, and we included people aged over 18 years, diagnosed with hereditary hemorrhagic telangiectasia and epistaxis (total duration > 30 min/6 weeks prior to inclusion). Tacrolimus ointment 0.1% was self-administered by the patients twice daily. About 0.1 g of product was to be administered in each nostril with a cotton swab. A total of 50 patients was randomized and treated. Mean epistaxis duration before and after treatment in the tacrolimus group were 324.64 and 249.14 min, respectively, and in the placebo group 224.69 and 188.14 min, respectively. Epistaxis duration improved in both groups, with no significant difference in our main objective comparing epistaxis before and after treatment ( p = 0.77); however, there was a significant difference in evolution when comparing epistaxis before and during treatment ( p = 0.04). Toxicity was low and no severe adverse events were reported. In conclusion, tacrolimus nasal ointment, administered for six weeks, did not improve epistaxis in HHT patients after the end of the treatment. However, the good tolerance, associated with a significant improvement in epistaxis duration during treatment, encouraged us to perform a phase 3 trial on a larger patient population with a main outcome of epistaxis duration during treatment and a longer treatment time.

Objective: The adverse effects of anxiety on cognition are widely recognized. According to Attentional Control Theory, worry (i.e. facet of cognitive anxiety) is the component that is responsible for these effects, and working memory capacity (WMC) plays an important role in regulating them. Despite the increasing importance of this problem with aging, little is known about how these mechanisms interact in old age. In this study, we explored the distinct contributions of the somatic and cognitive components of anxiety to neuropsychological performance, and the potential moderating role of WMC. Method: We administered cognitive tasks testing processing speed, cognitive flexibility and working memory to 605 older adults, who also underwent depression and test anxiety assessments (data from VLV study). Results: Multiple regression analyses showed that cognitive (but not somatic) aspects of anxiety affected cognitive flexibility. The effect of cognitive anxiety on processing speed was moderated by WMC: the anxiety-performance association was lower for participants with greater WMC. Conclusion: Results confirmed the specific role of worry in the anxiety-performance relationship in old age and supported the hypothesis that working memory resources regulates its deleterious effect on cognition. The absence of a moderation effect in the more costly switching task may reflect a limitation of resources with aging.

The aim of this study was to investigate the causal role of an early serotonin injury on parkinsonian-like motor symptomatology. Monkeys were pretreated with 3,4-methylenedioxy-N-methamphetamine (MDMA, or "ecstasy"), known to lesion serotonergic fibers, before being administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We combined behavioural assessment, PET imaging, and immunohistochemistry. Strikingly, prior MDMA administration aggravated MPTP-induced Parkinsonism and associated dopaminergic injury. Monkeys with early MDMA lesions developed parkinsonian deficits more rapidly and more severely. Interestingly, not all symptoms were impacted. Bradykinesia, rigidity and freezing were not affected by early MDMA lesions, whereas spontaneous activities, tremor and abnormal posture were significantly aggravated. Finally, as expected, MDMA induced a decrease of the serotonergic transporter availability. More surprisingly, we found that MDMA evoked also a decreased availability of the dopaminergic transporter to a lesser extent. Altogether, these results show that MDMA administration in non-human primates not only damage serotonergic terminals, but also injure dopaminergic neurons and enhance MPTP neurotoxic action, a completely new result in primates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

RORγt is an important nuclear receptor that regulates the production of several pro-inflammatory cytokines such as IL-17 and IL-22. As a result, RORγt has been identified as a potential target for the treatment of various immunological disorders such as psoriasis, psoriatic arthritis, and inflammatory bowel diseases. Structure and computer-assisted drug design led to the identification of a novel series of tricyclic RORγt inverse agonists with significantly improved in vitro activity in the reporter (Gal4) and human whole blood assays compared to our previous chemotype. Through careful structure activity relationship, several potent and selective RORγt inverse agonists have been identified. Pharmacokinetic studies allowed the identification of the lead molecule 32 with a low peak-to-trough ratio. This molecule showed excellent activity in an IL-2/IL-23-induced mouse pharmacodynamic study and demonstrated biologic-like efficacy in an IL-23-induced preclinical model of psoriasis.