Disease profiles of detainees in the Canton of Vaud in Switzerland: gender and age differences in substance abuse, mental health and chronic health conditions.

BACKGROUND: Literature on the disease profile of prisoners that differentiates by age and gender remains sparse. This study aimed to describe the health of correctional inmates in terms of substance abuse problems and mental and somatic health conditions, and compare it by gender and age. METHODS: This study examined cross-sectional data from the Canton of Vaud in Switzerland on the health conditions of detainees who were in prison on January 1, 2011 or entered prison in 2011. Health conditions validated by physician examination were reported using the International Classification of Diseases (ICD) version 10. The analyses were descriptive by groups of prisoners: the entire sample (All), Men, Older adults and Women. RESULTS: A total of 1,664 individuals were included in the analysis. Men comprised 91.5 % of the sample and had a mean age of 33 years. The other 8.5 % were women and had an average age of 39. Older adults (i.e., age 50 and older) represented 7 % of the total sample. Overall, 80 % of inmates were non-Swiss citizens, but the proportion of Swiss prisoners was higher among the older adults (51 %) and women (29 %). Overall, 41 % of inmates self-reported substance abuse problems. Of those, 27 % were being treated by psychiatrists for behavioral disorders related to substance abuse. Chronic infectious diseases were found in 9 % of the prison population. In addition, 27 % of detainees suffered from serious mental health conditions. Gender and age had an influence on the disease profile of this sample: compared to the entire prison population, the older inmates were less likely to misuse illegal drugs and to suffer from communicable infections but exhibited more problems with alcohol and a higher burden of chronic health conditions. Female prisoners were more disposed to mental health problems (including drug abuse) and infectious diseases. In terms of chronic diseases, women suffered from the same conditions as men, but the diseases were more prevalent in women. CONCLUSION: It is important to understand the different disease profiles of prisoners by gender and age, as it helps identify the needs of different groups and tailor age-and gender-specific interventions.

Development of the ability to inhibit a prepotent response: influence of working memory and processing speed.

This study aimed to examine developmental trends in response inhibition during childhood and to control for possible developmental influence of other basic cognitive processes (such as working memory and processing speed). In addition, we explored the relationships between response inhibition, working memory, and processing speed, as they are thought to be integral to cognitive control. Therefore, we assessed these three cognitive abilities in 159 children aged from 5 to 12. Results showed an improvement in response inhibition ability from 5 to 10 years of age. This improvement remained significant after controlling for the influence of working memory and processing speed. Furthermore, the developmental relationships showed an early differentiation between response inhibition, working memory, and processing speed. Thus, these processes were independent and need to be treated as such in further studies.

Posttraumatic stress avoidance symptoms as mediators in the development of alcohol use disorders after exposure to childhood sexual abuse in a Swiss community sample.

This study examined the role of posttraumatic stress disorder (PTSD) symptoms of re-experience, avoidance, and hyperarousal in the relationship between different types of trauma and alcohol use disorders (AUD). We used data from 731 trauma-exposed individuals who participated in the first wave of the PsyCoLaus-study. Trauma characteristics were assessed relatively to the occurrence of lifetime PTSD symptoms and AUD. The results suggest that lifetime and childhood sexual abuse as well as overall childhood trauma were directly linked to AUD and PTSD symptoms, in particular to avoidance symptoms. From single symptom clusters PTSD avoidance was found to specifically mediate the trauma-AUD pathway. Both childhood and sexual trauma strongly contribute to the comorbidity of PTSD and AUD and avoidance-type symptoms appear to play a central role in maintaining this association. Hence, the alleviation of avoidance symptoms might be an important target for therapeutic intervention among victims of sexual abuse before specific addiction treatment is initiated.

Association of car ownership and physical activity across the spectrum of human development : Modeling the Epidemiologic Transition Study (METS).

BACKGROUND: Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana. METHODS: Twenty-five hundred adults, ages 25-45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures (reported as average daily duration of moderate to vigorous PA, MVPA) and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods. RESULTS: Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA). CONCLUSIONS: PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important.

La collaboration interprofessionnelle à l'interface des institutions socio-éducative et psychiatrique. Jeux et enjeux de l'intervention auprès de personnes en situation de handicap mental et de troubles psychiques

La prise en charge et le suivi de personnes en situation de handicap mental souffrant de troubles psychiques et se trouvant donc à l'interface des domaines socio:éducatif et psychiatrique, constituent des défis complexes en matière de collaboration interprofessionnelle. Dans le canton de Vaud, les acteurs concernés par ce problème s'efforcent depuis de nombreuses années de créer des réseaux pluridisciplinaires visant un meilleur échange entre professionnels et le développement de compétences et de connaissances permettant d'améliorer le bien:être des bénéficiaires. Ce travail se propose ainsi d'étudier et de questionner ces modalités de travail dans une perspective socioculturelle (Vygotski, 1934/1997), afin d'en comprendre le fonctionnement, d'en éclairer les mécanismes et de fournir des pistes de réflexion aux professionnels. Il repose sur un travail de terrain mené auprès des membres du Dispositif de Collaboration Psychiatrie Handicap Mental (DCPHM) du Département de psychiatrie du CHUV, dont la mission principale est de faciliter la collaboration entre les institutions socio:éducatives et psychiatriques spécialisées dans le suivi des personnes en situation de handicap mental et souffrant de troubles psychiques. Le travail empirique est basé sur une approche qualitative et compréhensive des interactions sociales, et procède par une étude de terrain approfondie. Les données recueillies sont variées : notes de terrain et récolte de documentation, enregistrement de réunions d'équipe au sein du DCPHM et de réunions de réseau, et entretiens de différents types. L'analyse montre que le travail de collaboration qui incombe à l'équipe est constitué d'obstacles qui sont autant d'occasions de développement professionnel et de construction identitaire. Les résultats mettent en lumière des mécanismes discursifs de catégorisation concourant à la fois à la construction des patients comme objets d'activité, et à la construction d'une place qui légitime les interventions de l'équipe dans le paysage socio:éducatif et psychiatrique vaudois et la met au centre de l'arène professionnelle. -- Care and follow:up for people with mental disabilities suffering from psychological disorders : therefore at the interface between the socio:educational and psychiatric fields : represent complex challenges in terms of interprofessional collaboration. In the canton of Vaud, the caregivers involved in this issue have been trying for years to build multidisciplinary networks in order to better exchange between professionals and develop skills and knowledge to improve the recipients' well:being. This work thus proposes to study and question these working methods in a sociocultural perspective (Vygotski, 1934/1997) so as to understand how they operate, highlight inherent mechanisms and provide actionable insights to the professionals. It is based on fieldwork conducted among members of the Dispositif de Collaboration Psychiatrie Handicap Mental (DCPHM), of the Psychiatry Department at the CHUV University Hospital in Lausanne, whose main mission is to facilitate collaboration between the socio:educational and psychiatric institutions specialising in monitoring people presenting with both mental handicap and psychiatric disorder. The empirical work is based on a qualitative and comprehensive approach to social interactions, and conducted based on an in:depth field study. The data collected are varied - field notes and documentation collection, recordings of team meetings within the DCPHM and network meetings, and various types of interviews. The analysis shows that the collaborative work that befalls the team consists of obstacles, all of which provide opportunities for professional development and identity construction. The results highlight discursive strategies of categorisation which contribute both to the construction of the patients as objects of activity and to building a position that legitimates the team's interventions in the socio: educational and psychiatric landscape of canton Vaud and puts it in the centre of the professional arena.

Creatine deficiency syndomes : a new model of partial GAMT deficiency affecting brain cell development

Les syndromes de déficiences cérébrales en créatine (CCDS) sont dus à des mutations dans les gènes GATM et G AMT (codant pour les enzymes AGAT et G AMT de la voie de synthèse de créatine) ainsi que SLC6A8 (transporteur de créatine), et génèrent une absence ou une très forte baisse de créatine (Cr) dans le cerveau, mesurée par spectroscopic de résonance magnétique. Les patients CCDS développent des handicaps neurologiques sévères. Les patients AGAT et GAMT peuvent être traités avec des doses importantes de Cr, mais gardent dans la plupart des cas des séquelles neurologiques irréversibles. Aucun traitement efficace n'existe à ce jour pour la déficience en SLC6A8. Bien que de nombreux modèles aient été développés pour comprendre la Cr cérébrale en conditions physiologiques, les pathomécanismes des CCDS ne sont pas encore compris. Des souris transgéniques pour les gènes Gatm, Gamt et Slc6a8 ont été générées, mais elles ne miment que partiellement la pathologie humaine. Parmi les CCDS, la déficience en GAMT est la plus sévère, en raison de l'accumulation cérébrale de l'intermédiaire guanidinoacétate (GAA). Alors que la toxicité cérébrale du GAA a été étudiée par exposition directe au GAA d'animaux adultes sains, les mécanismes de la toxicité du GAA en condition de déficience en GAMT dans le cerveau en développement sont encore inconnus. Le but de ce projet était donc de développer un modèle de déficience en GAMT dans des cultures 3D primaires de cellules nerveuses de rat en agrégats par knock-down du gène GAMT, en utilisant un virus adéno-associé (AAV) induisant le mécanisme d'interférence à l'ARN (RNAi). Le virus scAAV2, à la multiplicité d'infection de 1000, s'est révélé le plus efficace pour transduire tous les types de cellules nerveuses des cultures (neurones, astrocytes, oligodendrocytes), et générer un knock-down maximal de la protéine GAMT de 85% (jour in vitro 18). Cette déficience partielle en GAMT s'est révélée insuffisante pour générer une déficience en Cr, mais a causé l'accumulation attendue de GAA, à des doses comparables aux niveaux observés dans le LCR des patients GAMT. Le GAA a induit une croissance axonale anarchique accompagnée d'une baisse de l'apoptose naturelle, suivis par une induction tardive de mort cellulaire non-apoptotique. Le co-traitement par la Cr a prévenu tous les effets toxiques du GAA. Ce travail montre que l'accumulation de GAA en absence de déficience en Cr est suffisante pour affecter le développement du tissu nerveux, et suggère que des formes de déficiences en GAMT supplémentaires, ne présentant pas de déficiences en Cr, pourraient être découvertes par mesure du GAA, en particulier à travers les programmes récemment proposés de dépistage néonatal de la déficience en GAMT. -- Cerebral creatine deficiency syndromes (CCDS) are caused by mutations in the genes GATM and GAMT (respectively coding for the two enzymes of the creatine synthetic pathway, AGAT and GAMT) as well as SLC6A8 (creatine transporter), and lead to the absence or very strong decrease of creatine (Cr) in the brain when measured by magnetic resonance spectroscopy. Affected patients show severe neurological impairments. While AGAT and GAMT deficient patients can be treated with high dosages of Cr, most remain with irreversible brain sequelae. No treatment has been successful so far for SLC6A8 deficiency. While many models have helped understanding the cerebral Cr pathways in physiological conditions, the pathomechanisms underlying CCDS are yet to be elucidated. Transgenic mice carrying mutations in the Gatm, Gamt and Slc6a8 genes have been developed, but only partially mimic the human pathology. Among CCDS, GAMT deficiency is the most severe, due to the CNS accumulation of the guanidinoacetate (GAA) intermediate. While brain toxicity of GAA has been explored through direct GAA exposure of adult healthy animals, the mechanisms underlying GAA toxicity in GAMT deficiency conditions on the developing CNS are yet unknown. The aim of this project was thus to develop and characterize a GAMT deficiency model in developing brain cells by gene knockdown, by adeno-associated virus (AAV)-driven RNA interference (RNAi) in rat 3D organotypic primary brain cell cultures in aggregates. scAAV2 with a multiplicity of infection of 1000 was shown as the most efficient serotype, was able to transduce all brain cell types (neurons, astrocytes, oligodendrocytes) and to induce a maximal GAMT protein knockdown of 85% (day in vitro 18). Metabolite analysis showed that partial GAMT knockdown was insufficient to induce Cr deficiency but generated the awaited GAA accumulation at concentrations comparable to the levels observed in cerebrospinal fluid of GAMT-deficient patients. Accumulated GAA induced axonal hypersprouting paralleled with inhibition of natural apoptosis, followed by a later induction in non-apoptotic cell death. Cr supplementation led to the prevention of all GAA-induced toxic effects. This work shows that GAA accumulation without Cr deficiency is sufficient to affect CNS development, and suggests that additional partial GAMT deficiencies, which may not show the classical brain Cr deficiency, may be discovered through GAA measurement including by recently proposed neonatal screening programs for GAMT deficiency.

Evaluation of molecular, cellular and behavioral consequences of serotonin 1A receptor deletion

In 1998, three different research groups simultaneously reported increased anxiety-related behavior in tests of conflict in their serotonin 1a (5-HT1a) receptor knockout (KO) line with male mice being more severely affected by 5-HT1a receptor deletion than female KO. Similarly, in the hippocampus, we observed increased dendritic complexity in the stratum radiatum of CA1 pyramidal neurons in male but not in female 5-HT1a receptor KO mice. These observations prompted us to investigate gender- dependent differences of 5-HT1a receptor deletion in hippocampal-related behavioral tasks. Testing our mice in anxiety-related paradigms, we reproduced the original studies showing increased anxiety- related behavior in male 5-HT1a receptor KO mice when compared to male WT mice, but no difference between female 5-HT1a receptor KO and WT mice. Similarly, male 5-HT1a receptor KO mice were impaired in association of aversive stimuli fear conditioning paradigms. We argue that increased dendritic complexity and increased synaptic strength of CA3-CA1 synapses in the stratum radiatum impaired proper signal propagation attributed to overactivation of CA1 pyramidal neurons leading to impaired fear memory of male 5-HT1a receptor KO mice. Similar mechanisms in the ventral hippocampus are likely to have contributed to gender-dependent differences in anxiety-related behavior in our and the original studies from 1998. In this study, we started to shed light on the 5-HT1a receptor downstream signaling pathways involved in dendritogenesis of pyramidal neurons during early postnatal development. We could show that NR2B-containing NMDA receptor during development acts downstream of 5-HT1a receptor and is responsible for increased amount of branching in male 5-HT1a receptor KO mice. Conversely, protein and NR2B mRNA expression was increased in 5-HT1a receptor KO mice at P15. Although the exact signaling cascade of 5-HT1a receptor regulating NR2B-containing NMDA receptor has not been determined, CaMKII is a potential downstream effector to influence transportation and removal of NR2B-containing NMDA receptors to and from the synapse. In contrast, Erk1/2 likely acts downstream of NR2B-containing NMDA receptors and was shown to be sufficient to regulate dendritic branching. Moreover, increased NR2B-containing NMDA receptor mediated cell death via excitotoxicity during development and is likely to be involved in reduced survival of adult born neurons in the hippocampus of 5-HT1a receptor KO male. The convergence of 5-HT1a receptor signaling onto NR2B-containing NMDA receptor signaling enables estrogen to interfere with its downstream pathway via G-protein coupled estrogen receptor 1 activation resulting in normalization of branching and behavior in female 5-HT1a receptor mice. In conclusion, our data strongly suggests a hormone- regulated mechanism that by converging on NR2B-containing NMDA receptor signaling is able to normalize morphology of pyramidal neurons and behavior of female 5-HT1a receptor KO mice. Our findings provide a possible explanation for gender-dependent differences in the occurrence of mental disorders with 5-HT1a receptor abnormalities as a strong predisposing factor. -- En 1998, trois équipes de recherche ont décrit un comportement de type anxieux dans des tests de conflit pour leur souris transgéniques avec une délétion du gène pour le récepteur 5-HT1a de la sérotonine. De plus, les trois groupes rapportent un phénotype plus sévère pour le comportement anxieux chez les souris transgéniques mâles que femelles. Dans l'hippocampe, la région avec la densité de récepteur 5-HT1a la plus élevée dans le télencéphale, nous avons observé dans le stratum radiatum une complexité accrue des arborisations dendritiques des neurones pyramidaux du secteur CA1 chez les souris transgénique mâles mais pas chez les femelles. Cette observation nous a encouragés à initier cette étude sur les différences en fonction du genre utilisant les tests comportementaux en rapport avec les fonctions de l'hippocampe chez les souris déficientes pour le récepteur 5-HT1a.Testant nos souris avec des paradigmes associés à l'anxiété, nous avons reproduit les données originales montrant que les souris transgéniques mâles ont un phénotype plus sévère que les souris mâles sauvages, mais qu'aucune différence n'est observée entre les femelles sauvages et transgéniques. De même, les souris mâles déficientes pour le récepteur 5-HT1a sont handicapées dans les tests de conditionnement au stress avec des stimuli aversifs. Nous faisons l'hypothèse que l'augmentation de la complexité de l'arborisation dendritique et l'augmentation de la force du signal synaptique entres les régions CA3 et CA1 de l'hippocampe dans le stratum radiatum perturbe la propagation du signal nerveux qui conduit à l'hyperactivation des neurones du secteur CA1. Ceci conduit à une mémoire de stress altérée chez les souris mâles déficientes pour le récepteur 5-HT1a. Un mécanisme similaire dans l'hippocampe ventral contribue probablement aux différences en fonction du genre dans les tests pour le comportement de type anxieux qui ont été rapportés dans les études originales de 1998. Les mesures de protéine et de mRNA ont mis en évidence une augmentation de l'expression du récepteur NMDA contenant la sous- unité NR2B dans les souris déficientes pour le récepteur 5-HT1a à P15. Dans les cultures organotypiques d'hippocampe, nous avons commencé à disséquer les messagers secondaires à l'activation du récepteur 5-HT1a qui sont impliqués dans la régulation de la croissance dendritique des neurones pyramidaux pendant la période postnatale précoce. Nous avons démontré que les récepteurs NR2B sont en aval de l'activation du récepteur 5-HT1a et qu'ils sont impliqués dans l'accroissement du nombre de dendrites chez la souris mâle déficiente pour le récepteur 5-HT1a. Bien que la cascade de signalisation du récepteur 5-HT1a pour réguler les récepteurs NMDA contenant le NR2B ne soit pas établie, CaMKII est identifié comme un effecteur potentiel pour altérer le transport du récepteur NMDA à la synapse. D'autre part, Erk1/2 est probablement un messager en aval du NR2B du récepteur NMDA, et a été documenté comme suffisant pour réguler l'arborisation dendritique. L'augmentation de NR2B à la synapse des souris déficientes pour le récepteur 5-HT1a peut conduire à une augmentation de l'excitotoxicité dans les cellules. Nous avons observé une augmentation chez la souris déficiente pour le récepteur 5-HT1a de la mort cellulaire dans des tranches d'hippocampe stimulées, ce qui peut être en relation avec la réduction de la survie des neurones générés dans l'hippocampe de la souris mâle transgénique adulte par rapport à la souris mâle sauvage. De plus, la convergence de la signalisation du récepteur 5-HT1a sur la signalisation de la sous-unité NR2B du récepteur NMDA permet à l'oestrogène d'interférer avec sa voie de signalisation du récepteur de l'oestrogène couplé à une protéine G (GPER-1), ceci permettant à l'oestrogène de réduire la taille de l'arborisation des neurones pyramidaux de CA1 chez la femelle de la souris déficiente pour le récepteur 5-HT1a. En conclusion, nos observations suggèrent fortement qu'un mécanisme hormonal convergeant sur la voie de signalisation de la sous-unité NR2B du récepteur NMDA permet la normalisation de l'exubérance des dendrites des neurones CA1 de l'hippocampe et du comportement des souris femelles déficientes pour le récepteur 5-HT1a. Ceci donne une explication possible pour la différence en fonction du genre dans l'apparition de troubles mentaux avec les variations du récepteur 5-HT1a comme facteur de prédisposition important.

Screening of mental health and substance users in frequent users of a general Swiss emergency department.

BACKGROUND: The objectives of this study were to determine the proportions of psychiatric and substance use disorders suffered by emergency departments' (EDs') frequent users compared to the mainstream ED population, to evaluate how effectively these disorders were diagnosed in both groups of patients by ED physicians, and to determine if these disorders were predictive of a frequent use of ED services. METHODS: This study is a cross-sectional study with concurrent and retrospective data collection. Between November 2009 and June 2010, patients' mental health and substance use disorders were identified prospectively in face-to-face research interviews using a screening questionnaire (i.e. researcher screening). These data were compared to the data obtained from a retrospective medical chart review performed in August 2011, searching for mental health and substance use disorders diagnosed by ED physicians and recorded in the patients' ED medical files (i.e. ED physician diagnosis). The sample consisted of 399 eligible adult patients (≥18 years old) admitted to the urban, general ED of a University Hospital. Among them, 389 patients completed the researcher screening. Two hundred and twenty frequent users defined by >4 ED visits in the previous twelve months were included and compared to 169 patients with ≤4 ED visits in the same period (control group). RESULTS: Researcher screening showed that ED frequent users were more likely than members of the control group to have an anxiety, depressive disorder, post-traumatic stress disorder (PTSD), or suffer from alcohol, illicit drug abuse/addiction. Reviewing the ED physician diagnosis, we found that the proportions of mental health and substance use disorders diagnosed by ED physicians were low both among ED frequent users and in the control group. Using multiple logistic regression analyses to predict frequent ED use, we found that ED patients who screened positive for psychiatric disorders only and those who screened positive for both psychiatric and substance use disorders were more likely to be ED frequent users compared to ED patients with no disorder. CONCLUSIONS: This study found high proportions of screened mental health and/or substance use disorders in ED frequent users, but it showed low rates of detection of such disorders in day-to-day ED activities which can be a cause for concern. Active screening for these disorders in this population, followed by an intervention and/or a referral for treatment by a case-management team may constitute a relevant intervention for integration into a general ED setting.

Association between frailty and delirium in older adult patients discharged from hospital.

BACKGROUND: Delirium and frailty - both potentially reversible geriatric syndromes - are seldom studied together, although they often occur jointly in older patients discharged from hospitals. This study aimed to explore the relationship between delirium and frailty in older adults discharged from hospitals. METHODS: Of the 221 patients aged >65 years, who were invited to participate, only 114 gave their consent to participate in this study. Delirium was assessed using the confusion assessment method, in which patients were classified dichotomously as delirious or nondelirious according to its algorithm. Frailty was assessed using the Edmonton Frailty Scale, which classifies patients dichotomously as frail or nonfrail. In addition to the sociodemographic characteristics, covariates such as scores from the Mini-Mental State Examination, Instrumental Activities of Daily Living scale, and Cumulative Illness Rating Scale for Geriatrics and details regarding polymedication were collected. A multidimensional linear regression model was used for analysis. RESULTS: Almost 20% of participants had delirium (n=22), and 76.3% were classified as frail (n=87); 31.5% of the variance in the delirium score was explained by frailty (R (2)=0.315). Age; polymedication; scores of the Confusion Assessment Method (CAM), instrumental activities of daily living, and Cumulative Illness Rating Scale for Geriatrics; and frailty increased the predictability of the variance of delirium by 32% to 64% (R (2)=0.64). CONCLUSION: Frailty is strongly related to delirium in older patients after discharge from the hospital.

Pre-existing astrocytes form functional perisynaptic processes on neurons generated in the adult hippocampus.

The adult dentate gyrus produces new neurons that morphologically and functionally integrate into the hippocampal network. In the adult brain, most excitatory synapses are ensheathed by astrocytic perisynaptic processes that regulate synaptic structure and function. However, these processes are formed during embryonic or early postnatal development and it is unknown whether astrocytes can also ensheathe synapses of neurons born during adulthood and, if so, whether they play a role in their synaptic transmission. Here, we used a combination of serial-section immuno-electron microscopy, confocal microscopy, and electrophysiology to examine the formation of perisynaptic processes on adult-born neurons. We found that the afferent and efferent synapses of newborn neurons are ensheathed by astrocytic processes, irrespective of the age of the neurons or the size of their synapses. The quantification of gliogenesis and the distribution of astrocytic processes on synapses formed by adult-born neurons suggest that the majority of these processes are recruited from pre-existing astrocytes. Furthermore, the inhibition of astrocytic glutamate re-uptake significantly reduced postsynaptic currents and increased paired-pulse facilitation in adult-born neurons, suggesting that perisynaptic processes modulate synaptic transmission on these cells. Finally, some processes were found intercalated between newly formed dendritic spines and potential presynaptic partners, suggesting that they may also play a structural role in the connectivity of new spines. Together, these results indicate that pre-existing astrocytes remodel their processes to ensheathe synapses of adult-born neurons and participate to the functional and structural integration of these cells into the hippocampal network.

Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons.

Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment. Furthermore, DRP1 loss affects synaptic transmission and memory function. Although these changes culminate in hippocampal atrophy, they are not sufficient to cause neuronal cell death within 10 weeks of genetic Drp1 ablation. Collectively, our in vivo observations clarify the role of mitochondrial fission in neurons, demonstrating that Drp1 ablation in adult forebrain neurons compromises critical neuronal functions without causing overt neurodegeneration.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. AIM: The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. DESIGN: Case control study. POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. RESULTS: None of the variable considered showed statistically significant changes after BoNT-A injection. CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. CLINICAL REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

Quality assessment of primary care for common mental disorders in isolated communities: Taking advantage of health records.

INTRODUCTION: This article is part of a research study on the organization of primary health care (PHC) for mental health in two of Quebec's remote regions. It introduces a methodological approach based on information found in health records, for assessing the quality of PHC offered to people suffering from depression or anxiety disorders. METHODS: Quality indicators were identified from evidence and case studies were reconstructed using data collected in health records over a 2-year observation period. Data collection was developed using a three-step iterative process: (1) feasibility analysis, (2) development of a data collection tool, and (3) application of the data collection method. The adaptation of quality-of-care indicators to remote regions was appraised according to their relevance, measurability and construct validity in this context. RESULTS: As a result of this process, 18 quality indicators were shown to be relevant, measurable and valid for establishing a critical quality appraisal of four recommended dimensions of PHC clinical processes: recognition, assessment, treatment and follow-up. CONCLUSIONS: There is not only an interest in the use of health records to assess the quality of PHC for mental health in remote regions but also a scientific value for the rigorous and meticulous methodological approach developed in this study. From the perspective of stakeholders in the PHC system of care in remote areas, quality indicators are credible and provide potential for transferability to other contexts. This study brings information that has the potential to identify gaps in and implement solutions adapted to the context.

Maturation and Functional Integration of New Granule Cells into the Adult Hippocampus.

The adult hippocampus generates functional dentate granule cells (GCs) that release glutamate onto target cells in the hilus and cornus ammonis (CA)3 region, and receive glutamatergic and γ-aminobutyric acid (GABA)ergic inputs that tightly control their spiking activity. The slow and sequential development of their excitatory and inhibitory inputs makes them particularly relevant for information processing. Although they are still immature, new neurons are recruited by afferent activity and display increased excitability, enhanced activity-dependent plasticity of their input and output connections, and a high rate of synaptogenesis. Once fully mature, new GCs show all the hallmarks of neurons generated during development. In this review, we focus on how developing neurons remodel the adult dentate gyrus and discuss key aspects that illustrate the potential of neurogenesis as a mechanism for circuit plasticity and function.

Continuum of care for persons with common mental health disorders in Nunavik: a descriptive study.

BACKGROUND: Changing Directions, Changing Lives, the Mental Health Strategy for Canada, prioritizes the development of coordinated continuums of care in mental health that will bridge the gap in services for Inuit populations. OBJECTIVE: In order to target ways of improving the services provided in these contexts to individuals in Nunavik with depression or anxiety disorders, this research examines delays and disruptions in the continuum of care and clinical, individual and organizational characteristics possibly associated with their occurrences. DESIGN: A total of 155 episodes of care involving a common mental disorder (CMD), incident or recurring, were documented using the clinical records of 79 frontline health and social services (FHSSs) users, aged 14 years and older, living in a community in Nunavik. Each episode of care was divided into 7 stages: (a) detection; (b) assessment; (c) intervention; (d) planning the first follow-up visit; (e) implementation of the first follow-up visit; (f) planning a second follow-up visit; (g) implementation of the second follow-up visit. Sequential analysis of these stages established delays for each one and helped identify when breaks occurred in the continuum of care. Logistic and linear regression analysis determined whether clinical, individual or organizational characteristics influenced the breaks and delays. RESULTS: More than half (62%) the episodes of care were interrupted before the second follow-up. These breaks mostly occurred when planning and completing the first follow-up visit. Episodes of care were more likely to end early when they involved anxiety disorders or symptoms, limited FHSS teams and individuals over 21 years of age. The median delay for the first follow-up visit (30 days) exceeded guideline recommendations significantly (1-2 weeks). CONCLUSION: Clinical primary care approaches for CMDs in Nunavik are currently more reactive than preventive. This suggests that recovery services for those affected are suboptimal.