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Abstract Background Concentrations of plasma per and poly-fluoroalkyl substances (PFAS) are elevated in the Inuit population of Nunavik and may be causing adverse health effects. Respiratory health outcomes have been associated with PFAS, but have not been explored in Inuit communities. The aim of the study was to examine the association between PFAS and respiratory health outcomes, and the moderating role of nutritional biomarkers. Methods We included up to 1298 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Generalized regression models were used to estimate the associations between six individual PFAS congeners and four self-reported symptoms, four spirometry measures, and physician-diagnosed asthma. Outcomes associated with PFAS from single chemical models were further explored using Bayesian Kernel Machine Regression (BKMR). The modifying effect of n-3 PUFA in red blood cell quartiles and vitamin D deficiency were examined on the associations between PFAS and respiratory outcomes. Results PFNA and PFOS were associated with asthma (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.12, 2.32; OR 1.45 95% CI 1.04, 2.03). PFOA, PFNA, PFDA and PFHxS were associated with a decrease in the ratio between the forced expiratory volume in the first second and forced vital capacity (FEV1/FVC). No associations were observed with self-reported respiratory symptoms. No associations were observed between a PFAS mixture and asthma. Some associations were modified by nutritional factors, namely, stronger associations between PFOA and PFHxS and asthma with lower n-3 PUFA levels and stronger associations between PFDA, PFUnDA and PFOS and FEV1/FVC with vitamin D deficiency. Conclusion These findings add to the growing literature on the impacts of PFAS on respiratory health, and the importance of their global regulation. Associations were modified by nutritional factors pointing to the nutritional value of traditional Inuit foods.

Segmental rectum resections for indications other than endometriosis were reported to result in up to 40% sexual dysfunctions. We, therefore, evaluated sexual function after low bowel resection (n = 33) for deep endometriosis in comparison with conservative excision (n = 23). Sexual function was evaluated with the FSFI-19 (Female Sexuality Functioning Index) and EHP 30 (Endometriosis Health Profile). The pain was evaluated with visual analogue scales. Linear excision and bowel resections improved FSFI, EHP 30, and postoperative pain comparably. By univariate analysis, a decreased sexual function was strongly associated with pain both before (p < 0.0001) and after surgery (p = 0.0012), age (p = 0.05), and duration of surgery (p = 0.023). By multivariate analysis (proc logistic), the FSFI after surgery was predicted only by FSFI before or EHP after surgery. No differences were found between low bowel segmental resection and a more conservative excision. In conclusion, improving pain after surgery can explain the improvement in sexual function. A deleterious effect of a bowel resection on sexual function was not observed for endometriosis. Sexual function in women with endometriosis can be evaluated using a simplified questionnaire such as FSFI-6.

Abstract Background Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally. Methods Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions). Results Of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p

IntroductionPrevious studies have shown benefits of productive art-activity on frail older adults' mental and physical health. In this study, we investigated the effects of art-producing activities in a hybrid format (in-person and online) in a context of lockdown compared with previous studies taking place in museums and their effects on wellbeing, quality of life, physical frailty, and apathy in older adults.MethodsWe conducted a randomized unicentric control trial on a sample of 126 seniors older than 65 years (mean age 71.9 ± 2.3, 81% women) living in Nice (France). Participants were randomized in two parallel groups (intervention group with n = 62 vs. control group with n = 64) conducted during pandemic, between March and May 2021. The intervention group involved participatory art-based activities conducted in a hybrid format, either in-person or online, once a week for 2 h over a 12-week period. No specific intervention was proposed to the control group. The main aim was to evaluate how this hybrid format would impact the wellbeing, quality of life, and physical frailty of participants. The secondary aim was to compare our results with the previous studies conducted by Beauchet et al., and the third aim was to evaluate the impact of the intervention on apathy. Validated scales were implemented in RedCap and administered at baseline (M0) and at the end of the third month (M3).ResultsThe intervention group showed significant improvement in their quality of life (p = 0.017) and their level of apathy (p = 0.016) after intervention. Emotional blunting increased significantly in the control group (p = 0.016) while it remained stable in the intervention group. No significant improvement was observed on the frailty, and wellbeing scores remained constant in both groups.ConclusionThis randomized control trial confirmed emotional effects on seniors practicing an art-based activity in a hybrid format during pandemic on a weekly basis for 3 months.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT04570813.

IntroductionLocal treatments of cancer, including transarterial chemoembolization, could enhance responses to systemic immune checkpoint inhibitors such as anti-PD-1 antibodies. Lipiodol, a radiopaque oil, is widely used for transarterial chemoembolization as a tumor-targeting drug carrier and could be used in emulsion with immunomodulators. This study aimed at evaluating the antitumoral effect of intra-tumoral injection of Lipiodol-immunomodulator emulsions combined with systemic anti-PD-1 therapy in a murine model of colorectal carcinoma. MethodMice (male BALB/c) with anti-PD-1-resistant subcutaneous CT26 tumors were injected with immunomodulators, emulsified or not with Lipiodol (N=10-12/group).ResultsThe TLR-9 agonist CpG displayed antitumor effects, while Poly I:C and QS21 did not. The Lipiodol-CpG emulsion appeared to be stable and maintained CpG within tumors for a longer time. Repeated intra-tumoral injections, combined with anti-PD-1, induced responses towards the tumor as well as to a distant metastatic-like nodule. This treatment was associated with an increase in proliferative CD8+ T cells and of IFN-γ expression, a decrease in proliferative regulatory T cells but also, surprisingly, an increase in myeloid derived suppressor cells.ConclusionsLocal administration of CpG emulsified with Lipiodol led to an effective antitumoral effect when combined to systemic anti-PD-1 therapy. Lipiodol, apart from its radiopaque properties, is an efficient drug-delivery system. The formulated oil-in-water emulsion allows efficient loading and control release of CpG, which induces favorable immune modifications in this murine tumor model.

Introduction: Many developed countries, including Canada, have observed reductions in incidence of diabetes. Given the latest improvements in the case definition of diabetes for the younger population in Quebec, Canada, we sought to examine the evolution of diabetes among adults and children in Quebec, between 2001 and 2019. Methods: Crude and age-standardized incidence and prevalence of diabetes among individuals ≥1 year were calculated using data from the Quebec Integrated Chronic Disease Surveillance System (n≈8,351,500 in 2019), using two case definitions for adults and the youth respectively. Age-standardized all-cause hospitalizations and mortality proportions were calculated among the population ≥20 years. Results: Between 2001 and 2019, age-standardized incidence decreased by 30%, with a crude incidence of 4.6 per 1,000 in 2019. Incidence rates decreased from age group ≥50 years but increased by 25% for the group of 1-19 years. Age-standardized prevalence increased by 42% (crude prevalence in 2019: 8.1%). Males had higher incidence and prevalence of diabetes, with an incremental gap between sexes increasing with age. All-cause hospitalization and mortality proportions among individuals with diabetes declined by 21% and 29% respectively between 2001 and 2019. Age-standardized hospitalizations and mortality ratios for individuals with/without diabetes remained stable and were 2.7 (99% Confidence Intervals [CI]: 2.7-2.8) and 2.2 (99% CI: 2.1-2.3) in 2019, respectively. Conclusion: Despite the reduction of incidence among adults, diabetes incidence increased among the youth and remained high among adults, especially for males. These results highlight the importance of improving earlier preventive care and initiatives for reducing the diabetes burden in Quebec.

Introduction: The use of teleconsultations for mental health has drastically increased since 2020 due to the Covid19 pandemic. In the present paper, we aimed to analyze the advantages and disadvantages of teleconsultations for mental health compared to face-to-face consultations, and to provide recommendations in this domain. Methods: The recommendations were gathered using a Delphi methodology. The expert panel (N = 21) included professionals from the health and ICT domains. They answered questions via two rounds of web surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with non-experts (N = 104). Results: Both the experts and the non-experts with teleconsultation experience reported a general satisfaction concerning teleconsultations. A SWOT analysis revealed several strengths and opportunities of teleconsultations for mental health, but also several weaknesses and threats. The experts provided a set of practical recommendations for the preparation and organization of teleconsultations for mental health. Discussion: Teleconsultations for mental health have the potential to allow access to care for patients in remote and isolated areas. Thus, their use will unlikely be discontinued after the end of the pandemic. In this context, we suggest that the collaboration among clinicians, researchers, and interface designers is crucial to improve usability and user experience for both clinicians and patients. The importance of teaching teleconsultation skills and informing the public on the features of teleconsultations (e.g., data privacy/security) is also highlighted.

ObjectiveApathy is present in many brain disorders, but it is also prevalent to varying degrees in healthy people. While many tools have been developed to assess levels of apathy in pathology, no standardized measure of apathy in healthy people exists.MethodTherefore, this study aimed to validate the French version of the Apathy Motivation Index (f-AMI). The results of 729 participants were analyzed using an exploratory factorial analysis.ResultsPreliminary analyses suggested that the three domains of apathy extracted in the original AMI scale—behavioral activation (BA), social motivation (SM), and emotional sensitivity (ES)—could be found also in the f-AMI. A further exploratory analysis showed that a higher number of factors could be extracted, particularly for women. Specifically, both social and emotional factors could be divided into two sub-factors: (1) social motivation toward strangers or toward an acquaintance and (2) self-directed emotional sensitivity directed toward others. Regarding construct validity, the scores of f-AMI were correlated with the French Dimensional Apathy Scale results. Concerning the divergent validity, emotional sensitivity in apathy is different from depression, anhedonia, and fatigue levels.ConclusionThese results suggest that the f-AMI can be used to assess levels of apathy in healthy adults.

IntroductionThe risk of developing Alzheimer's disease (AD) in older adults increasingly is being discussed in the literature on Post-Acute COVID-19 Syndrome (PACS). Remote digital Assessments for Preclinical AD (RAPAs) are becoming more important in screening for early AD, and should always be available for PACS patients, especially for patients at risk of AD. This systematic review examines the potential for using RAPA to identify impairments in PACS patients, scrutinizes the supporting evidence, and describes the recommendations of experts regarding their use.MethodsWe conducted a thorough search using the PubMed and Embase databases. Systematic reviews (with or without meta-analysis), narrative reviews, and observational studies that assessed patients with PACS on specific RAPAs were included. The RAPAs that were identified looked for impairments in olfactory, eye-tracking, graphical, speech and language, central auditory, or spatial navigation abilities. The recommendations' final grades were determined by evaluating the strength of the evidence and by having a consensus discussion about the results of the Delphi rounds among an international Delphi consensus panel called IMPACT, sponsored by the French National Research Agency. The consensus panel included 11 international experts from France, Switzerland, and Canada.ResultsBased on the available evidence, olfaction is the most long-lasting impairment found in PACS patients. However, while olfaction is the most prevalent impairment, expert consensus statements recommend that AD olfactory screening should not be used on patients with a history of PACS at this point in time. Experts recommend that olfactory screenings can only be recommended once those under study have reported full recovery. This is particularly important for the deployment of the olfactory identification subdimension. The expert assessment that more long-term studies are needed after a period of full recovery, suggests that this consensus statement requires an update in a few years.ConclusionBased on available evidence, olfaction could be long-lasting in PACS patients. However, according to expert consensus statements, AD olfactory screening is not recommended for patients with a history of PACS until complete recovery has been confirmed in the literature, particularly for the identification sub-dimension. This consensus statement may require an update in a few years.

Introduction Post-traumatic stress disorder (PTSD) symptoms in youth are influenced by parental anxiety and stress. When parents have high levels of stress or have developed PTSD themselves, children tend to show more anxiety symptoms. Parental stress can affect the severity of children’s PTSD and lower the success of recovery. However, the influence of parental stress on the effectiveness of trauma-focused therapies (eye movement desensitisation and reprocessing and cognitive behavioural therapy) has not yet been investigated to our knowledge. Hence, we will measure parental stress (using both validated scales and vocal acoustic markers) and investigate how it influences children’s PTSD recovery.Method and analysis Sixty children between the ages of 7 and 15 years who experienced type 1 trauma will be recruited at the Nice Pediatric Psychotrauma Center in France. We plan to measure stress using two different approaches. We will ask parents to answer validated scales of stress and mood in general. Stress will also be measured using vocal acoustic markers. Parents will be recorded while narrating their child’s trauma and during the narrative of a positive and neutral recall of events. Child participants will have to complete anxiety, PTSD and depression scales before the beginning of the trauma-focused therapy and after 3 months of treatment.Linear mixed effects models and differential statistics, such as significance testing corrected for multiple testing, will be used to determine the validity of speech features for the proposed hypotheses. Repeated measures analysis of variance will be performed on the clinical scales scores according to parental stress. Correlations will be performed between clinical scales of parents and children according to time of assessment.Ethics and dissemination This study was approved by the Committee for the Protection of Individuals of the University of Nice Sophia Antipolis (CERNI) on 21 February 2022, under the number CER2022-015.All participants will be informed that this is an observational study and their consent taken prior to the experiment. Participants will be informed that they can withdraw from the study at any time and that it would not affect the care provided.Trial registration number CER AVIS n° 2022-015.

Diminished interest is a core feature of apathy that shows high prevalence in people with Mild and Major Neurocognitive disorders (NCD). In the clinical setting, apathy is mainly assessed using clinical scales and questionnaires, but new technologies are starting to be employed to complement classical instruments. Here, we explored the performance of the “Interest game,” a ludic application that assesses personal interests, in discriminating between persons with and without diminished interest based on the Apathy Diagnostic Criteria. Two hundred and twenty-seven elderly participants (56 healthy controls, 118 persons with mild-NCD, and 53 with major-NCD) completed the Interest game and were assessed by clinicians concerning the presence and the severity of apathy. Results showed that the application scores varied with the presence of apathy, the type of disorder, and the education level. Cutoff scores calculated for persons with Mild-NCD resulted in a sensitivity of 0.68 and a specificity of 0.65 for the main score index, suggesting the interest of employing this application in the clinical setting to complement the classical assessment.

Abstract Apathy and fatigue have a high prevalence in many pathological populations, but they are also present in healthy adults. The relationship between apathy and fatigue, which are both multidimensional, is still poorly understood. This study aims to describe the associations between the subdimensions of both apathy and fatigue and to investigate their overlaps and dissociations in healthy people. 729 participants (mean age = 30.8 ± 10.7 years) completed online self-assessment questionnaires. The Apathy Motivation Index and Dimensional Apathy Scale were used to assess apathy. The Multidimensional Fatigue Inventory was used to assess fatigue. The executive dimension of apathy showed the strongest correlations with mental fatigue and the two appeared to be underpinned by the same latent factor, according to exploratory factor analysis (EFA). The factor structure of EFA showed overlaps between behavioral apathy and both reduced motivation and activity in fatigue. Emotional and social dimensions of apathy were separately underpinned by a latent factor that comprised no items of fatigue. Apathy and fatigue have reduced activity and mental difficulties in common, whereas emotional and social disorders distinguish apathy from fatigue. This has important implications for assessing apathy and fatigue in the general population, and may be relevant for clinical practice.

The court trial of the 14th of July 2016 terrorist attack in Nice (France) opened in September 2022 and ended in December 2022. Engaging in court proceedings, whether as a victim or a witness, can lead to a significant risk of traumatic reactivation (i.e., the re-emergence of post-traumatic stress symptoms). The present protocol aimed to improve knowledge of the pathophysiology of traumatic reactivation due to the media coverage of the trial by assessing sleep disturbances and somatic symptoms that could reappear if there is a traumatic reactivation. Method and Analysis: This is a monocentric longitudinal study, with recruitment solely planned at the Nice Pediatric Psychotrauma Center (NPPC). We intended to include 100 adolescents aged 12 to 17 years who were directly or indirectly exposed to the attack and included in the “14-7” program). Assessments began one month before the trial, in August 2022, and were scheduled once a month until the end of the trial. A smartwatch recorded sleep activity. Somatic and PTSD symptoms and sleep were assessed through validated questionnaires. The main analyses comprised the variance and regression analyses of predictors of clinical evolution over time. Ethics and Dissemination: The National Ethics Committee “NORD OUEST III” approved the “14-7” program protocol (number 2017-A02212-51). The specific amendment for this research was approved in April 2022 by the same national ethical committee. Inclusions started in August 2022.

BackgroundMajor depressive episode (MDE) is a common clinical syndrome. It can be found in different pathologies such as major depressive disorder (MDD), bipolar disorder (BD), posttraumatic stress disorder (PTSD), or even occur in the context of psychological trauma. However, only 1 syndrome is described in international classifications (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5]/International Classification of Diseases 11th Revision [ICD-11]), which do not take into account the underlying pathology at the origin of the MDE. Clinical interviews are currently the best source of information to obtain the etiological diagnosis of MDE. Nevertheless, it does not allow an early diagnosis and there are no objective measures of extracted clinical information. To remedy this, the use of digital tools and their correlation with clinical symptomatology could be useful. ObjectiveWe aimed to review the current application of digital tools for MDE diagnosis while highlighting shortcomings for further research. In addition, our work was focused on digital devices easy to use during clinical interview and mental health issues where depression is common. MethodsWe conducted a narrative review of the use of digital tools during clinical interviews for MDE by searching papers published in PubMed/MEDLINE, Web of Science, and Google Scholar databases since February 2010. The search was conducted from June to September 2021. Potentially relevant papers were then compared against a checklist for relevance and reviewed independently for inclusion, with focus on 4 allocated topics of (1) automated voice analysis, behavior analysis by (2) video and physiological measures, (3) heart rate variability (HRV), and (4) electrodermal activity (EDA). For this purpose, we were interested in 4 frequently found clinical conditions in which MDE can occur: (1) MDD, (2) BD, (3) PTSD, and (4) psychological trauma. ResultsA total of 74 relevant papers on the subject were qualitatively analyzed and the information was synthesized. Thus, a digital phenotype of MDE seems to emerge consisting of modifications in speech features (namely, temporal, prosodic, spectral, source, and formants) and in speech content, modifications in nonverbal behavior (head, hand, body and eyes movement, facial expressivity, and gaze), and a decrease in physiological measurements (HRV and EDA). We not only found similarities but also differences when MDE occurs in MDD, BD, PTSD, or psychological trauma. However, comparative studies were rare in BD or PTSD conditions, which does not allow us to identify clear and distinct digital phenotypes. ConclusionsOur search identified markers from several modalities that hold promise for helping with a more objective diagnosis of MDE. To validate their potential, further longitudinal and prospective studies are needed.

IntroductionThe impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).MethodsTo determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.ResultsNo global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.DiscussionThese results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is characterized by a severe ADAMTS13 deficiency due to the presence of anti-ADAMTS13 auto-antibodies, with subsequent accumulation of circulating ultra-large von Willebrand factor (VWF) multimers. The role of endothelial cell activation as a trigger of the disease has been suggested in animal models but remains to be demonstrated in humans. We prospectively obtained plasma from the first plasma exchange of 25 patients during iTTP acute phase. iTTP but not control plasma, induced a rapid VWF release and P-selectin exposure on the surface of dermal human micro-vascular endothelial cell (HMVEC-d), associated with angiopoietin-2 and endothelin-1 secretion, consistent with Weibel-Palade bodies exocytosis. Calcium (Ca2+) blockade significantly decreased VWF release, whereas iTTP plasma induced a rapid and sustained Ca2+ flux in HMVEC-d which correlated in retrospect, with disease severity and survival in 62 iTTP patients. F(ab)’2 fragments purified from the immunoglobulin G fraction of iTTP plasma mainly induced endothelial cell activation with additional minor roles for circulating free heme and nucleosomes, but not for complement. Furthermore, two anti-ADAMTS13 monoclonal antibodies purified from iTTP patients’ B cells, but not serum from hereditary TTP, induced endothelial Ca2+ flux associated with Weibel-Palade bodies exocytosis in vitro, whereas inhibition of endothelial ADAMTS13 expression using small intering RNA, significantly decreased the stimulating effects of iTTP immunoglobulin G. In conclusion, Ca2+-mediated endothelial cell activation constitutes a “second hit” of iTTP, is correlated with the severity of the disease and may constitute a possible therapeutic target.

Abstract Background Appropriate training of health professionals has been recommended to increase organ donation rates. Some studies have shown insufficient knowledge among medical students. This survey aims to describe their knowledge and attitude toward organ donation (OD). Method We designed, pre-tested and conducted an online survey of all undergraduate medical students from Montreal, Laval and Sherbrooke universities in 2016–2017. Multivariate linear regression identified factors associated with a better knowledge score. Results Twenty-two percent (750/3344) of students completed the survey. Ninety-one percent of students adequately knew that neurological death is irreversible; 76% acknowledged that someone could be neurologically deceased while his heart is still beating; 69% were not aware of circulatory determination of death. For only one knowledge item, senior students had a better answer than junior students. Total knowledge score was associated with exposure to OD during medical studies and comfort in answering patients’ questions about OD (p

Abstract Background The progressive ageing of the population is leading to an increasing number of people affected by cognitive decline, including disorders in executive functions (EFs), such as action planning. Current procedures to evaluate cognitive decline are based on neuropsychological tests, but novel methods and approaches start to be investigated. Reach-to-grasp (RG) protocols have shown that intentions can influence the EFs of action planning. In this work, we proposed a novel ring-shaped wearable inertial device, SensRing, to measure kinematic parameters during RG and after-grasp (AG) tasks with different end-goals. The aim is to evaluate whether SensRing can characterize the motor performances of people affected by Mild Neurocognitive Disorder (MND) with impairment in EFs. Methods Eight Individuals with dysexecutive MND, named d-MND, were compared to ten older healthy subjects (HC). They were asked to reach and grasp a can with three different intentions: to drink (DRINK), to place it on a target (PLACE), or to pass it to a partner (PASS). Twenty-one kinematic parameters were extracted from SensRing inertial data. Results Seven parameters resulted able to differentiate between HC and d-MND in the RG phase, and 8 features resulted significant in the AG phase. d-MND, indeed, had longer reaction times (in RG PLACE), slower peak velocities (in RG PLACE and PASS, in AG DRINK and PLACE), longer deceleration phases (in all RG and AG DRINK), and higher variability (in RG PLACE, in AG DRINK and PASS). Furthermore, d-MND showed no significant differences among conditions, suggesting that impairments in EFs influence their capabilities in modulating the action planning based on the end-goal. Conclusions Based on this explorative study, the system might have the potential for objectifying the clinical assessment of people affected by d-MND by administering an easy motor test. Although these preliminary results have to be investigated in-depth in a larger sample, the portability, wearability, accuracy, and ease-of use of the system make the SensRing potentially appliable for remote applications at home, including analysis of protocols for neuromotor rehabilitation in patients affected by MND.

Abstract Detailed whole-cell modeling requires an integration of heterogeneous cell processes having different modeling formalisms, for which whole-cell simulation could remain tractable. Here, we introduce BiPSim, an open-source stochastic simulator of template-based polymerization processes, such as replication, transcription and translation. BiPSim combines an efficient abstract representation of reactions and a constant-time implementation of the Gillespie’s Stochastic Simulation Algorithm (SSA) with respect to reactions, which makes it highly efficient to simulate large-scale polymerization processes stochastically. Moreover, multi-level descriptions of polymerization processes can be handled simultaneously, allowing the user to tune a trade-off between simulation speed and model granularity. We evaluated the performance of BiPSim by simulating genome-wide gene expression in bacteria for multiple levels of granularity. Finally, since no cell-type specific information is hard-coded in the simulator, models can easily be adapted to other organismal species. We expect that BiPSim should open new perspectives for the genome-wide simulation of stochastic phenomena in biology.

The acute response after a terror attack may have a crucial impact on the physical and psychological wellbeing of the victims. Preparedness of the professionals involved in the acute response is a key element to ensure effective interventions, and can be improved through trainings. Today in Europe there is a recognized lack of inter-professional and international trainings, which are important, among others, to respond to the needs and the rights of victims affected by a terrorist attack in another country than their home country. In this paper we report the perspectives of an expert panel composed by different categories of professionals on the possible role of interprofessional trainings provided remotely. The experts discussed the pertinence of remote trainings for professionals involved in the acute response of a terror attack, and highlighted their Strengths, Weaknesses, Opportunities and Threats (SWOT analysis). We concluded that, while remote trainings cannot replace in-person trainings, they may be useful to share knowledge about the role and the organization of the different categories of professionals, thus potentially improving response coordination, and to easily share good practices across professionals and countries.

Abstract Motor and Cognitive Dual-Task (MCDT) represents an innovative chance to assess Mild Cognitive Impairment (MCI). We compare two novel MCDTs, fore-finger tapping (FTAP), toe-tapping (TTHP), to gold standards for cognitive screening (Mini-Mental State Examination—MMSE), and to a well-established MCDT (GAIT). We administered the aforementioned MCDTs to 44 subjects (MCIs and controls). Motor parameters were extracted, and correlations with MMSE investigated. Logistic regression models were built, and AUC areas computed. Spearman’s correlation demonstrated that FTAP and TTHP significantly correlate with MMSE, at each cognitive load. AUC areas computed report similar (FTAP, 0.87), and even higher (TTHP, 0.97) capability to identify MCIs, if compared to GAIT (0.92). We investigated the use of novel MCDT approaches to assess MCI, aiming to enrich the clinical repertoire with objective and non-invasive tools. Our protocol shows good correlations with MMSE, and reaches high performances in identifying MCI, adopting simpler exercises.

ObjectiveA defect of the waking systems could constitute a factor of vulnerability for sudden infant death syndrome (SIDS). A decrease in orexin levels, which promotes wakefulness and activates histaminergic neurons (another hypothalamic wake-promoting system) has already been demonstrated between 2 and 6 months. This work aims to study the levels of histamine (HA), tele-methylhistamine (t-MeHA), its direct metabolite, and t-MeHA/HA ratio in the cerebrospinal fluid (CSF) of healthy children, to evaluate the maturation of the histaminergic system and its possible involvement in SIDS.MethodsSeventy Eight French children between 0 and 20 years (48.7% boys) were included, all of whom had a clinical indication for lumbar puncture, but subsequently found to be normal. Measurements of HA and t-MeHA in CSF were performed by reverse phase liquid chromatography coupled to mass spectrometry detection. Statistical analyses were performed using Spearman correlations and Non-parametric pairwise ranking tests.ResultsA negative correlation was found between age and CSF HA (r = −0.44, p < 10−4) and t-MeHA (r = −0.70, p < 10−4) levels. In pairwise comparisons, no difference in CSF HA and t-MeHA levels was observed between youngest age groups (i.e., 0–2 mo vs. 3–6 mo), but CSF HA and t-MeHA levels were significantly lower in older children (i.e., >6 mo vs. 0–6 mo). The CSF HA decrease with age was only observed in boys, who also presented global lower CSF HA levels than girls.ConclusionCSF HA and t-MeHA levels decrease with age in boys, and global levels are lower in boys than in girls. These results reveal changes in histaminergic transmission and metabolism during maturation. Whether lower CSF histamine values in boys compared to girls could contribute to their higher risk of SIDS warrants further research.

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders.

Olfactory identification disorder is regarded as an early marker of Alzheimer's disease (AD) and of similar diagnostic significance of biological or cognitive markers. Premature damage of the entorhinal olfactory cortex, the hippocampus and the orbitofrontal cortex characterize AD and suggest a specific impairment of olfactory identification. The use of psychophysical olfactory identification tests in clinical diagnostic practice is therefore strongly recommended, but not required. As these widespread tests are rarely used, an innovative test, adapted to this target group has been developed. It has been used and validated in a routine care protocol at different Memory Centers in France and in Quebec, Canada. A total of 157 participants were recruited: including 63 Alzheimer's patients and 94 healthy controls. The test was composed of 14 odorants diluted into 4 different concentrations. A computer interface generated randomization of 6 odors per participant and the automatic calculation of identification scores, of perceptual thresholds and of composite scores. All participants underwent a Mini Mental Scale Examination within the previous three months or on the same day of the olfactory test. The Alzheimer's patients had a score between 20 and 30 and healthy controls participants had a score above 28 without any loss of points on recalled items. The results show that our olfactory identification test is able to significantly differentiate Alzheimer's patients from healthy controls (p < 0.001), and to distinguish the French population tested from the Quebec population (p < 0.001). This study highlights an olfactory identification disorder as a target for early diagnosis of AD. Its cultural qualities make it a potential candidate for differentiated calibration between France and Quebec.

Abstract Several therapeutic options are currently available to treat excessive daytime sleepiness (EDS) in patients suffering from narcolepsy or obstructive sleep apnea. However, there are no comparisons between the various wake‐promoting agents in terms of mechanism of action, efficacy, or safety. The goal of this study was to compare amphetamine, modafinil, solriamfetol, and pitolisant at their known primary pharmacological targets, histamine H3 receptors (H3R), dopamine, norepinephrine, and serotonin transporters, and in various in vivo preclinical models in relation to neurochemistry, locomotion, behavioral sensitization, and food intake. Results confirmed that the primary pharmacological effect of amphetamine, modafinil, and solriamfetol was to increase central dopamine neurotransmission, in part by inhibiting its transporter. Furthermore, solriamfetol increased levels of extracellular dopamine in the nucleus accumbens, and decreased the 3,4‐dihydroxyphenyl acetic acid (DOPAC)/DA ratio in the striatum, as reported for modafinil and amphetamine. All these compounds produced hyperlocomotion, behavioral sensitization, and hypophagia, which are common features of psychostimulants and of compounds with abuse potential. In contrast, pitolisant, a selective and potent H3R antagonist/inverse agonist that promotes wakefulness, had no effect on striatal dopamine, locomotion, or food intake. In addition, pitolisant, devoid of behavioral sensitization by itself, attenuated the hyperlocomotion induced by either modafinil or solriamfetol. Therefore, pitolisant presents biochemical, neurochemical, and behavioral profiles different from those of amphetamine and other psychostimulants such as modafinil or solriamfetol. In conclusion, pitolisant is a differentiated therapeutic option, when compared with psychostimulants, for the treatment of EDS, as this agent does not show any amphetamine‐like properties within in vivo preclinical models.

Introduction Early detection of cognitive impairments is crucial for the successful implementation of preventive strategies. However, in rural isolated areas or so-called ‘medical deserts’, access to diagnosis and care is very limited. With the current pandemic crisis, now even more than ever, remote solutions such as telemedicine platforms represent great potential and can help to overcome this barrier. Moreover, current advances made in voice and image analysis can help overcome the barrier of physical distance by providing additional information on a patients’ emotional and cognitive state. Therefore, the aim of this study is to evaluate the feasibility and reliability of a videoconference system for remote cognitive testing empowered by automatic speech and video analysis.Methods and analysis 60 participants (aged 55 and older) with and without cognitive impairment will be recruited. A complete neuropsychological assessment including a short clinical interview will be administered in two conditions, once by telemedicine and once by face-to-face. The order of administration procedure will be counterbalanced so half of the sample starts with the videoconference condition and the other half with the face-to-face condition. Acceptability and user experience will be assessed among participants and clinicians in a qualitative and quantitative manner. Speech and video features will be extracted and analysed to obtain additional information on mood and engagement levels. In a subgroup, measurements of stress indicators such as heart rate and skin conductance will be compared.Ethics and dissemination The procedures are not invasive and there are no expected risks or burdens to participants. All participants will be informed that this is an observational study and their consent taken prior to the experiment. Demonstration of the effectiveness of such technology makes it possible to diffuse its use across all rural areas (‘medical deserts’) and thus, to improve the early diagnosis of neurodegenerative pathologies, while providing data crucial for basic research. Results from this study will be published in peer-reviewed journals.

The logopenic variant of Primary Progressive Aphasia (lvPPA), a syndromic disorder centered on language impairment, often presents variable underlying neurodegenerative pathologies such as Alzheimer Disease (AD). Actual language assessment tests and lumbar puncture, focused on AD diagnosis, cannot precisely distinguish the symptoms, or predict their progression at onset time. We analyzed acoustic markers, aiming to discriminate lvPPA and AD as well as the influence of AD biomarkers on acoustic profiles at the beginning of the disease. We recruited people with AD (n = 8) and with lvPPA (n = 8), with cerebrospinal fluid biomarker profiles determined by lumbar puncture. The participants performed a sentence repetition task that allows assessing potential lvPPA phonological loop deficits. We found that temporal and prosodic markers significantly differentiate the lvPPA and AD group at an early stage of the disease. Biomarker and acoustic profile comparisons discriminated the two lvPPA subgroups according to their biomarkers. For lvPPA with AD biomarkers, acoustic profile equivalent to an atypical AD form with a specific alteration of the phonological loop is shown. However, lvPPA without AD biomarkers has an acoustic profile approximating the one for DLFT. Therefore, these results allow us to classify lvPPA differentially from AD based on acoustic markers from a sentence repetition task. Furthermore, our results suggest that acoustic analysis would constitute a clinically efficient alternative to refused lumbar punctures. It offers the possibility to facilitate early, specific, and accessible neurodegenerative diagnosis and may ease early care with speech therapy, preventing the progression of symptoms.

Immune cells have the ubiquitous capability to migrate disregarding the adhesion properties of the environment, which requires a versatile adaptation of their adhesiveness mediated by integrins, a family of specialized adhesion proteins. Each subtype of integrins has several ligands and several affinity states controlled by internal and external stimuli. However, probing cell adhesion properties on live cells without perturbing cell motility is highly challenging, especially in vivo. Here, we developed a novel in vitro method using micron-size beads pulled by flow to functionally probe the local surface adhesiveness of live and motile cells. This method allowed a functional mapping of the adhesiveness mediated by VLA-4 and LFA-1 integrins on the trailing and leading edges of live human T lymphocytes. We show that cell polarization processes enhance integrin-mediated adhesiveness toward cell rear for VLA-4 and cell front for LFA-1. Furthermore, an inhibiting crosstalk of LFA-1 toward VLA-4 and an activating crosstalk of VLA-4 toward LFA-1 were found to modulate cell adhesiveness with a long-distance effect across the cell. These combined signaling processes directly support the bistable model that explains the emergence of the versatile guidance of lymphocyte under flow. Molecularly, Sharpin, an LFA-1 inhibitor in lymphocyte uropod, was found involved in the LFA-1 deadhesion of lymphocytes; however, both Sharpin and Myosin inhibition had a rather modest impact on adhesiveness. Quantitative 3D immunostaining identified high-affinity LFA-1 and VLA-4 densities at around 50 and 100 molecules/μm2 in basal adherent zones, respectively. Interestingly, a latent adhesiveness of dorsal zones was not grasped by immunostaining but assessed by direct functional assays with beads. The combination of live functional assays, molecular imaging, and genome editing is instrumental to characterizing the spatiotemporal regulation of integrin-mediated adhesiveness at molecular and cell scales, which opens a new perspective to decipher sophisticated phenotypes of motility and guidance.

Abstract Background Certain neuropsychiatric symptoms (NPS), namely apathy, depression, and anxiety demonstrated great value in predicting dementia progression, representing eventually an opportunity window for timely diagnosis and treatment. However, sensitive and objective markers of these symptoms are still missing. Therefore, the present study aims to investigate the association between automatically extracted speech features and NPS in patients with mild neurocognitive disorders. Methods Speech of 141 patients aged 65 or older with neurocognitive disorder was recorded while performing two short narrative speech tasks. NPS were assessed by the neuropsychiatric inventory. Paralinguistic markers relating to prosodic, formant, source, and temporal qualities of speech were automatically extracted, correlated with NPS. Machine learning experiments were carried out to validate the diagnostic power of extracted markers. Results Different speech variables are associated with specific NPS; apathy correlates with temporal aspects, and anxiety with voice quality—and this was mostly consistent between male and female after correction for cognitive impairment. Machine learning regressors are able to extract information from speech features and perform above baseline in predicting anxiety, apathy, and depression scores. Conclusions Different NPS seem to be characterized by distinct speech features, which are easily extractable automatically from short vocal tasks. These findings support the use of speech analysis for detecting subtypes of NPS in patients with cognitive impairment. This could have great implications for the design of future clinical trials as this cost-effective method could allow more continuous and even remote monitoring of symptoms.

Background: White matter hyperintensities (WMH) contribute to cognitive decline and increase risk for dementia. Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by the emergence and persistence of neuropsychiatric symptoms (NPS) in later life as an at-risk state for incident cognitive decline and dementia. Both WMH and MBI are common in patients with mild cognitive impairment (MCI), but few studies have established the link between these two risk markers in this population. Methods: Participants were memory clinic patients with MCI from the French MEMENTO study. WMH volume was quantified using brain magnetic resonance imaging. Participants were categorized into MBI+ and MBI- status based on NPS persistence, and the association between MBI status and domains with WMH volume was assessed with linear regression. Results: A total of 768 participants [mean age 72.8 (SD=8.00); 57% female] were included. MBI (i.e., persistent NPS) was present in 229 participants (29.8%). MBI+ status was significantly associated with lower MMSE score and male sex. Compared to MBI-, MBI+ status was associated with 9.4% higher WMH volume [p = 0.01 (95% CI 2.0% to 16.7%)]. In this model, MMSE score was not associated with WMH volume. None of the MBI domains individually predicted greater WMH volume, although emotional dysregulation, impulse dyscontrol, and apathy trended towards significance. Conclusions: In a memory clinic sample of older adults with MCI, MBI was associated with higher WMH volume. Global MBI status outperformed MMSE and individual MBI domains, supporting the utility of MBI, a multi-NPS-domain composite assessment, for predicting WMH volume.

Abstract Introduction The aim of this study was to evaluate the efficacy of a serious exergame in improving the neuropsychiatric symptoms of patients with neurocognitive disorders. Methods X‐Torp is a serious exergame combining motor and cognitive activities. Ninety‐one subjects (mean age = 81.7 years, mean Mini‐Mental State Examination = 18.3) were recruited in 16 centers. Centers were randomized into intervention and control centers. Subjects underwent assessment for cognitive and behavioral symptoms at baseline (BL), the end of the intervention (W12), and 12 weeks after the end of the intervention (W24). Results The comparison of neuropsychiatric symptoms between BL and W12 and W24 showed that subjects of the intervention group improved in apathy between BL and W12. Mixed analysis (time BL, W12, W24 x group) indicated a significant increase in apathy and neuropsychiatric symptoms in the control subjects. Discussion The use of X‐Torp improved neuropsychiatric symptoms, particularly apathy. Future studies should more consistently use behavioral and neuropsychiatric symptoms as outcome measures.

Background: One of the main symptoms of COVID-19 is hyposmia or even anosmia. Olfactory identification is most often affected. In addition, some cognitive disorders tend to appear following the infection, particularly regarding executive functions, attention, and memory. Olfaction, and especially olfactory identification, is related to semantic memory which manages general knowledge about the world. The main objective of this study was to determine whether semantic memory is impaired in case of persistent post COVID-19 olfactory disorders. Methods: 84 patients (average age of 42.8 ± 13.6 years) with post COVID-19 olfactory loss were included after consulting to the ENT department. The clinical evaluation was carried out with the Pyramid and Palm Tree Test, the word-retrieval task from the Grémots, the Sniffin’ Sticks Test and the Computerised Olfactory Test for the Diagnosis of Alzheimer’s Disease. Results: Semantic memory was impaired in 20% (n = 17) of patients, especially in the 19–39 age-group. The olfactory threshold was only significantly correlated with the semantic memory scores. Conclusions: Similar to all cognitive disorders, semantic disorders can have a negative impact on quality of life if left untreated. It is essential to carry out specific assessments of post COVID-19 patients to accurately determine their disorders and to put in place the best possible rehabilitation, such as speech and language therapy, to avoid quality-of-life impairment.

Today, in rural isolated areas or so-called ‘medical deserts’, access to diagnosis and care is very limited. With the current pandemic crisis, now even more than ever, telemedicine platforms are gradually more employed for remote medical assessment. Only a few are tailored to comprehensive teleneuropsychological assessment of older adults. Hence, our study focuses on evaluating the feasibility of performing a remote neuropsychological assessment of older adults suffering from a cognitive complaint. 50 participants (aged 55 and older) were recruited at the local hospital of Digne-les-Bains, France. A brief neuropsychological assessment including a short clinical interview and several validated neuropsychological tests was administered in two conditions, once by Teleneuropsychology (TNP) and once by Face-to-Face (FTF) in a crossover design. Acceptability and user experience was assessed through questionnaires. Results show high agreement in most tests between the FTF and TNP conditions. The TNP was overall well accepted by the participants. However, differences in test performances were observed, which urges the need to validate TNP tests with broader samples with normative data.

In this article, we quantitatively study, through stochastic models, the effects of several intracellular phenomena, such as cell volume growth, cell division, gene replication as well as fluctuations of available RNA polymerases and ribosomes. These phenomena are indeed rarely considered in classic models of protein production and no relative quantitative comparison among them has been performed. The parameters for a large and representative class of proteins are determined using experimental measures. The main important and surprising conclusion of our study is to show that despite the significant fluctuations of free RNA polymerases and free ribosomes, they bring little variability to protein production contrary to what has been previously proposed in the literature. After verifying the robustness of this quite counter-intuitive result, we discuss its possible origin from a theoretical view, and interpret it as the result of a mean-field effect.

We introduce a probabilistic generative model for disentangling spatio-temporal disease trajectories from collections of high-dimensional brain images. The model is based on spatio-temporal matrix factorization, where inference on the sources is constrained by anatomically plausible statistical priors. To model realistic trajectories, the temporal sources are defined as monotonic and time-reparameterized Gaussian Processes. To account for the non-stationarity of brain images, we model the spatial sources as sparse codes convolved at multiple scales. The method was tested on synthetic data favourably comparing with standard blind source separation approaches. The application on large-scale imaging data from a clinical study allows to disentangle differential temporal progression patterns mapping brain regions key to neurodegeneration, while revealing a disease-specific time scale associated to the clinical diagnosis.

Primary progressive aphasia (PPA) brings together neurodegenerative pathologies whose main characteristic is to start with a progressive language disorder. PPA diagnosis is often delayed in non-specialised clinical settings. With the technologies’ development, new writing parameters can be extracted, such as the writing pressure on a touch pad. Despite some studies having highlighted differences between patients with typical Alzheimer’s disease (AD) and healthy controls, writing parameters in PPAs are understudied. The objective was to verify if the writing pressure in different linguistic and non-linguistic tasks can differentiate patients with PPA from patients with AD and healthy subjects. Patients with PPA (n = 32), patients with AD (n = 22) and healthy controls (n = 26) were included in this study. They performed a set of handwriting tasks on an iPad® digital tablet, including linguistic, cognitive non-linguistic, and non-cognitive non-linguistic tasks. Average and maximum writing pressures were extracted for each task. We found significant differences in writing pressure, between healthy controls and patients with PPA, and between patients with PPA and AD. However, the classification of performances was dependent on the nature of the tasks. These results suggest that measuring writing pressure in graphical tasks may improve the early diagnosis of PPA, and the differential diagnosis between PPA and AD.

Abstract Background Safety warnings from health authorities are currently intended to limit the use of antipsychotics (APs) in dementia-related conditions to treat neuropsychiatric symptoms, such as disturbing and/or delusional behaviors. The aim of this study is to investigate prevalence, correlates and trends of AP prescribing among people with dementia between 2010 and 2014 in the French population. Methods AP prescribing and associated factors among individuals with AD, mixed dementia and vascular dementia in the French National Alzheimer Database between 2010 and 2014 were analyzed using multivariate generalized estimating equations models (n = 199,549). Results In 2014, 7.7% of people with dementia were prescribed an AP. Compared with 2010 there was a 16% increase in AP use. Multivariate analysis showed a linear increase risk of prescription with an adjusted odds ratio (95% confidence interval) of 1.23 (1.17–1.30) in 2014 compared with 2010. Factors associated with AP prescribing were male gender, more severe cognitive decline and living in long-term care facilities. Older age and higher education were protective toward AP prescribing. The type of dementia did not have any influence on AP prescribing. Conclusion An increase in AP prescribing among individuals with dementia in French specialized settings over the last 5 years occurred despite safety warnings. This phenomenon suggests that alternative solutions for the management of behavioral and psychiatric symptoms in these populations are still urgently needed.

BackgroundReliable epidemiological data on Alzheimer's disease are scarce. However, these are necessary to adapt healthcare policy in terms of prevention, care and social needs related to this condition. To estimate the prevalence rate in the Alpes-Maritimes on the French Riviera, with a population of one million, we present a capture-recapture procedure applied to cases of Alzheimer's disease, based on two epidemiological surveillance systems.MethodsTo estimate the total number of patients affected by Alzheimer's disease, a capture-recapture study included a cohort of patients with Alzheimer's disease or receiving medications only eligible for use for this condition, recorded by a specific health insurance information system (Health Insurance Cohort, HIC), and those registered in the French National Alzheimer's Data Bank ("Banque Nationale Alzheimer", BNA) in 2010 and 2011. We applied Bayesian estimation of the Mt ecological model, taking into account age and gender as covariates, i.e. factors of inhomogeneous catchability.ResultsOverall, 5,562 patients with Alzheimer's disease were recorded, of whom only 856 were common to both information systems. Mean age and F/M sex ratio differed between BNA and HIC surveillance systems, 81 vs 84 years and 2.7 vs 3.2, respectively. A Bayesian estimation, with age and gender as covariates, yields an estimate of 15,060 cases of Alzheimer's disease [95%HPDI: 14,490-15,630] in the Alpes-Maritimes. The completeness of the HIC and BNA databases were respectively of 25.4% and 17.2%. The estimated prevalence rate among the population over 65 years old was 6.3% in 2010-2011.ConclusionsThis study demonstrates that it is possible to determine the number of subjects affected by Alzheimer's disease in a geographical unit, using available data from two existing surveillance systems in France, i.e. 15,060 cases in the Alpes-Maritimes. This is the first stage of a population-based approach in view of adapting available resources to the population's needs.

Acibenzolar-S-methyl (ASM) is a chemical compound, which is able to induce resistance in several model and non-model plants, but the end-players of this induced defense remain ill-defined. Here, we test the hypothesis that treatment with ASM can protect apple (Malus × domestica) against the rosy apple aphid (Dysaphis plantaginea) and investigate the defense molecules potentially involved in resistance. We measured aphid life traits and performed behavioral assays to study the effect of ASM on plant resistance against the aphid, and then combined transcriptomic, bioinformatics, metabolic and biochemical analyses to identify the plant compounds involved in resistance. Plants treated with ASM negatively affected several life traits of the aphid and modified its feeding and host seeking behaviors. ASM treatment elicited up-regulation of terpene synthase genes in apple and led to the emission of (E,E)-α-farnesene, a sesquiterpene that was repellent to the aphid. Several genes encoding amaranthin-like lectins were also strongly up-regulated upon treatment and the corresponding proteins accumulated in leaves, petioles and stems. Our results link the production of specific apple proteins and metabolites to the antibiosis and antixenosis effects observed against Dysaphis plantaginea, providing insight into the mechanisms underlying ASM-induced herbivore resistance.

The scanning of surrounding tissues by T lymphocytes to detect cognate antigens requires high speed, sensitivity and specificity. T-cell receptor (TCR) co-receptors such as CD8 increase detection performance, but the exact mechanism remains incompletely understood. Here, we used a laminar flow chamber to measure at the single molecule level the kinetics of bond formation and rupture between TCR- transfected CD8+ and CD8− Jurkat cells and surfaces coated with five peptide-exposing major histocompatibility antigens (pMHCs) of varying activating power. We also used interference reflection microscopy to image the spreading of these cells dropped on pMHC-exposing surfaces. CD8 did not influence the TCR–pMHC interaction during the first few seconds following cell surface encounter, but it promoted the subsequent spreading responses, suggesting that CD8 was involved in early activation rather than binding. Further, the rate and extent of spreading, but not the lag between contact and spreading initiation, depended on the pMHC. Elucidating T-lymphocyte detection strategy may help unravel underlying signaling networks.

Background: At present, the assessment of autonomy in daily living activities, one of the key symptoms in Alzheimer’s disease (AD), involves clinical rating scales. Methods: In total, 109 participants were included. In particular, 11 participants during a pre-test in Nice, France, and 98 participants (27 AD, 38 mild cognitive impairment—MCI—and 33 healthy controls—HC) in Thessaloniki, Greece, carried out a standardized scenario consisting of several instrumental activities of daily living (IADLs), such as making a phone call or preparing a pillbox while being recorded. Data were processed by a platform of video signal analysis in order to extract kinematic parameters, detecting activities undertaken by the participant. Results: The video analysis data can be used to assess IADL task quality and provide clinicians with objective measurements of the patients’ performance. Furthermore, it reveals that the HC statistically significantly outperformed the MCI, which had better performance compared to the AD participants. Conclusions: Accurate activity recognition data for the analyses of the performance on IADL activities were obtained.

The use of Serious Games (SG) in the health domain is expanding. In the field of Neurodegenerative Diseases (ND) such as Alzheimer’s Disease, SG are currently employed to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. The design of SG for people with ND implies collaborations between professionals in ND and professionals in SG design. As the field is quite young, professionals specialized in both ND and SG are still rare, and recommendations for the design of SG for people with ND are still missing. This perspective paper aims to provide recommendations in terms of ergonomic choices for the design of SG aiming at stimulating people with ND, starting from the existing SG already tested in this population: “MINWii”, “Kitchen and Cooking”, and “X-Torp”. We propose to rely on nine ergonomic criteria: eight ergonomic criteria inspired by works in the domain of office automation: Compatibility, Guidance, Workload, Adaptability, Consistency, Significance of codes, Explicit control and Error management; and one ergonomic criterion related to videogame: the game rules. Perspectives derived from this proposal are also discussed.

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.

Objective: Affective disorders are frequently encountered among elderly populations, and the use of Information and Communication Technologies (ICT) could provide an added value for their recognition and assessment in addition to current clinical methods. The diversity and lack of consensus in the emerging field of ICTs is however a strong limitation for their global use in daily practice. The aim of the present article is to provide recommendations for the use of ICTs for the assessment and management of affective disorders among elderly populations with or without dementia.Methods: A Delphi panel was organized to gather recommendations from experts in the domain. A set of initial general questions for the use of ICT in affective disorders was used to guide the discussion of the expert panel and to analyze the Strengths, Weaknesses, Opportunities, and Threats (SWOT) of employing ICT in elderly populations with affective disorders. Based on the results collected from this first round, a web survey was sent to local general practitioners (GPs) and to all interns in psychiatry in France. Results: The results of the first round revealed that ICT may offer very useful tools for practitioners involved in the diagnosis and management of affective disorders. However, the results of the web survey showed the interest to better explain to current and coming practitioners the utility of ICT especially for AD patients.

BACKGROUND:Many studies have highlighted the high prevalence of executive disorders in stroke. However, major uncertainties remain due to use of variable and non-validated methods. The objectives of this study were: 1) to characterize the executive disorder profile in stroke using a standardized battery, validated diagnosis criteria of executive disorders and validated framework for the interpretation of neuropsychological data and 2) examine the sensitivity of the harmonization standards protocol proposed by the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) for the diagnosis of Vascular Cognitive Impairment. METHODS:237 patients (infarct: 57; cerebral hemorrhage: 54; ruptured aneurysm of the anterior communicating artery (ACoA): 80; cerebral venous thrombosis (CVT): 46) were examined by using the GREFEX battery. The patients' test results were interpreted with a validated framework derived from normative data from 780 controls. RESULTS:Dysexecutive syndrome was observed in 88 (55.7%; 95%CI: 48-63.4) out of the 156 patients with full cognitive and behavioral data: 40 (45.5%) had combined behavioral and cognitive syndromes, 29 (33%) had a behavioral disorder alone and 19 (21.6%) had a cognitive syndrome alone. The dysexecutive profile was characterized by prominent impairments of initiation and generation in the cognitive domain and by hypoactivity with disinterest and anticipation loss in the behavioral domain. Cognitive impairment was more frequent (p = 0.014) in hemorrhage and behavioral disorders were more frequent (p = 0.004) in infarct and hemorrhage. The harmonization standards protocol underestimated (p = 0.007) executive disorders in CVT or ACoA. CONCLUSIONS:This profile of executive disorders implies that the assessment should include both cognitive tests and a validated inventory for behavioral dysexecutive syndrome. Initial assessment may be performed with a short cognitive battery, such as the harmonization standards protocol. However, administration of a full cognitive battery is required in selected patients.

Virtual Reality (VR) has emerged as a promising tool in many domains of therapy and rehabilitation, and has recently attracted the attention of researchers and clinicians working with elderly people with MCI, Alzheimer's disease and related disorders. Here we present a study testing the feasibility of using highly realistic image-based rendered VR with patients with MCI and dementia. We designed an attentional task to train selective and sustained attention, and we tested a VR and a paper version of this task in a single-session within-subjects design. Results showed that participants with MCI and dementia reported to be highly satisfied and interested in the task, and they reported high feelings of security, low discomfort, anxiety and fatigue. In addition, participants reported a preference for the VR condition compared to the paper condition, even if the task was more difficult. Interestingly, apathetic participants showed a preference for the VR condition stronger than that of non-apathetic participants. These findings suggest that VR-based training can be considered as an interesting tool to improve adherence to cognitive training in elderly people with cognitive impairment.

Narcolepsy is characterized by excessive daytime sleepiness (EDS), cataplexy, direct onsets of rapid eye movement (REM) sleep from wakefulness (DREMs) and deficiency of orexins, neuropeptides that promote wakefulness largely via activation of histamine (HA) pathways. The hypothesis that the orexin defect can be circumvented by enhancing HA release was explored in narcoleptic mice and patients using tiprolisant, an inverse H3-receptor agonist. In narcoleptic orexin−/− mice, tiprolisant enhanced HA and noradrenaline neuronal activity, promoted wakefulness and decreased abnormal DREMs, all effects being amplified by co-administration of modafinil, a currently-prescribed wake-promoting drug. In a pilot single-blind trial on 22 patients receiving a placebo followed by tiprolisant, both for 1 week, the Epworth Sleepiness Scale (ESS) score was reduced from a baseline value of 17.6 by 1.0 with the placebo (p>0.05) and 5.9 with tiprolisant (p

This paper aimed to look for the existence of a common core when envisaging intra-familial interactions as perceived by adolescents, which could be shared by sociology, psychoanalysis and child and adolescent psychiatry. An empirical study based on a mixed-method design collected the responses of 194 adolescents to the instruction "In the next half hour, would you please write as freely as you wish about your relationships in your family, explaining how things are". All answers were then analyzed and 18 dimensions related to 3 different theoretical frameworks were rated blind using numerical scores by two independent raters from each discipline. Inter-rater reliability was good. A parallel analysis evidenced a strong underlying factor explaining a large amount of variance (>50%). This factor is bipolar, it reflects the level of positivity/negativity in the adolescent's point of view concerning his/her intra-familial relationships. A second factor can marginally be considered (10% of the variance). The 2-factor analysis found one factor related to positive feelings and the other to negative feelings. This finding of unidimensionality supports family study as an intervention science.

THE AIM OF THIS STUDY: was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer's disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer's disease diagnosis. DESIGN: we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451). RESULTS: The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels. CONCLUSIONS: Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer's disease and related disorders.