Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. METHODS: A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP) monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS) co-administered with SP (AS + SP), was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. FINDINGS: Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from <1% to 2% between the two sites and across the five survey years. A multivariable logistic regression model was fitted to adjust for age, socioeconomic status, bed net use and rainfall. In the presence of consistently high coverage and efficacy of SP monotherapy and AS + SP in the comparison and intervention areas, the introduction of ACT in the intervention site was associated with a modest reduction in the adjusted asexual parasitaemia prevalence of 5 percentage-points or 23% (p < 0.0001) relative to the comparison site. Gametocytaemia prevalence did not differ significantly (p = 0.30). INTERPRETATION: The introduction of ACT at fixed health facilities only modestly reduced asexual parasitaemia prevalence. ACT is effective for treatment of uncomplicated malaria and should have substantial public health impact on morbidity and mortality, but is unlikely to reduce malaria transmission substantially in much of sub-Saharan Africa where individuals are rapidly re-infected.

Perceived discrimination against diabetics in the workplace and in work-related insurances in Switzerland.

To investigate the prevalence and risk factors of perceived diabetes-related discrimination in the workplace and in work-related insurances in persons with diabetes mellitus in Switzerland. 509 insulin-treated diabetic subjects representative of the northwestern Swiss population responded to a self-report questionnaire on perceived diabetes-related discrimination in the workplace and in work-related insurances (salary loss insurance, supplementary occupational plan). Discrimination was defined as being treated differently at least once in relation to diabetes. The reported rates of different aspects of discrimination in the workplace and in work-related insurances ranged between 5-11% and 4-15% respectively. Risk factors that independently increased the risk of not being hired due to diabetes were the presence of at least two severe hypoglycaemic events/year and relevant diabetic complications (OR 5.6 and OR 2.6 respectively; both<0.05). The presence of at least two severe hypoglycaemic events/year was also associated with an increased risk of losing one's job (OR 6.5, <0.01). Overweight or obesity were related to increased discrimination in work-related insurances (OR for denial 2.1-2.4; OR for reserve 3.9-4.4; all<0.05). Perceived diabetes-related discrimination in the workplace and by work-related insurances is a common problem. In the light of our findings the introduction of effective non-discrimination legislation for patients with chronic illnesses appears to be desirable.

Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCζ in the Goto Kakizaki rat model.

Diabetic retinopathy is associated with ocular inflammation, leading to retinal barrier breakdown, macular edema, and visual cell loss. We investigated the molecular mechanisms involved in microglia/macrophages trafficking in the retina and the role of protein kinase Cζ (PKCζ) in this process. Goto Kakizaki (GK) rats, a model for spontaneous type 2 diabetes were studied until 12 months of hyperglycemia. Up to 5 months, sparse microglia/macrophages were detected in the subretinal space, together with numerous pores in retinal pigment epithelial (RPE) cells, allowing inflammatory cell traffic between the retina and choroid. Intercellular adhesion molecule-1 (ICAM-1), caveolin-1 (CAV-1), and PKCζ were identified at the pore border. At 12 months of hyperglycemia, the significant reduction of pores density in RPE cell layer was associated with microglia/macrophages accumulation in the subretinal space together with vacuolization of RPE cells and disorganization of photoreceptors outer segments. The intraocular injection of a PKCζ inhibitor at 12 months reduced iNOS expression in microglia/macrophages and inhibited their migration through the retina, preventing their subretinal accumulation. We show here that a physiological transcellular pathway takes place through RPE cells and contributes to microglia/macrophages retinal trafficking. Chronic hyperglycemia causes alteration of this pathway and subsequent subretinal accumulation of activated microglia/macrophages.

Tumor-host interactions Part 1: Stromal signatures of breast and prostate cancer Part 2: GLG1 and the control of the secretory pathway in tumor cells

Tumor-host interaction is a key determinant during cancer progression, from primary tumor growth to metastatic dissemination. At each step, tumor cells have to adapt to and subvert different types of microenvironment, leading to major phenotypic and genotypic alterations that affect both tumor and surrounding stromal compartments. Understanding the molecular mechanisms that govern tumor-host interplay may be essential for better comprehension of tumorigenesis in an effort to improve current anti-cancer therapies. The present work is composed of two projects that address tumor-host interactions from two different perspectives, the first focusing on the characterization of tumor-associated stroma and the second on membrane trafficking in tumor cells. Part 1. To selectively address stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to analyze the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Comparison showed that invasive breast and prostate cancer elicit distinct, tumor-specific stromal responses, with a limited panel of shared induced and/or repressed genes. Both breast and prostate tumor-specific deregulated stromal gene sets displayed statistically significant survival-predictive ability for their respective tumor type. By contrast, a stromal gene signature common to both tumor types did not display prognostic value, although expression of two individual genes within this common signature was found to be associated with patient survival. Part 2. GLG1 is known as an E-selectin ligand and an intracellular FGF receptor, depending on cell type and context. Immunohistochemical and immunofluorescence analyses showed that GLG1 is primarily localized in the Golgi of human tumor cells, a central location in the biosynthetic/secretory pathways. GLG1 has been shown to interact with and to recruit the ARF GEF BIGI to the Golgi membrane. Depletion of GLG1 or BIGI markedly reduced ARF3 membrane localization and activation, and altered the Golgi structure. Interestingly, these perturbations did not impair constitutive secretion in general, but rather seemed to impair secretion of a specific subset of proteins that includes MMP-9. Thus, GLG1 coordinates ARF3 activation by recruiting BIGI to the Golgi membrane, thereby affecting secretion of specific molecules. - Les interactions tumeur-hôte constituent un élément essentiel à la progression tumorale, de la croissance de la tumeur primaire à la dissémination des métastases. A chaque étape, les cellules tumorales doivent s'adapter à différents types de microenvironnement et les détourner à leur propre avantage, donnant lieu à des altérations phénotypiques et génotypiques majeures qui affectent aussi bien la tumeur elle-même que le compartiment stromal environnant. L'étude des mécanismes moléculaires qui régissent les interactions tumeur-hôte constitue une étape essentielle pour une meilleure compréhension du processus de tumorigenèse dans le but d'améliorer les thérapies anti cancer existantes. Le travail présenté ici est composé de deux projets qui abordent la problématique des interactions tumeur-hôte selon différentes perspectives, le premier se concentrant sur la caractérisation du stroma tumoral et le second sur le trafic intracellulaire des cellules tumorales. Partie 1. Pour examiner les changements d'expression des gènes dans le stroma en réponse à la progression du cancer, des puces à ADN Affymetrix ont été utilisées afin d'analyser les transcriptomes des cellules stromales issues de carcinomes invasifs du sein et de la prostate et collectées par microdissection au laser. L'analyse comparative a montré que les cancers invasifs du sein et de la prostate provoquent des réponses stromales spécifiques à chaque type de tumeur, et présentent peu de gènes induits ou réprimés de façon similaire. L'ensemble des gènes dérégulés dans le stroma associé au cancer du sein, ou à celui de la prostate, présente une valeur pronostique pour les patients atteints d'un cancer du sein, respectivement de la prostate. En revanche, la signature stromale commune aux deux types de cancer n'a aucune valeur prédictive, malgré le fait que l'expression de deux gènes présents dans cette liste soit liée à la survie des patients. Partie 2. GLG1 est connu comme un ligand des sélectines E ainsi que comme récepteur intracellulaire pour des facteurs de croissances FGFs selon le type de cellule dans lequel il est exprimé. Des analyses immunohistochimiques et d'immunofluorescence ont montré que dans les cellules tumorales, GLG1 est principalement localisé au niveau de l'appareil de Golgi, une place centrale dans la voie biosynthétique et sécrétoire. Nous avons montré que GLG1 interagit avec la protéine BIGI et participe à son recrutement à la membrane du Golgi. L'absence de GLG1 ou de BIGI réduit drastiquement le pool d'ARF3 associé aux membranes ainsi que la quantité d'ARF3 activés, et modifie la structure de l'appareil de Golgi. Il est particulièrement intéressant de constater que ces perturbations n'ont pas d'effet sur la sécrétion constitutive en général, mais semblent plutôt affecter la sécrétion spécifique d'un sous-groupe défini de protéines comprenant MMP-9. GLG1 coordonne donc l'activation de ARF3 en recrutant BIGI à la membrane du Golgi, agissant par ce moyen sur la sécrétion de molécules spécifiques.

Lipid rafts act as specialised domains for tetanus toxin binding and internalisation in neurons

Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity is well established, the mechanism by which this neurotoxin interacts with the neuronal surface is not known. In this study, we characterize p15s, the first plasma membrane TeNT binding proteins and we show that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells. Fluorescence lifetime imaging microscopy measurements confirm the close association of the binding domain of TeNT and Thy-1 at the plasma membrane. We find that TeNT is recruited to detergent-insoluble lipid microdomains on the surface of neuronal cells. Finally, we show that cholesterol depletion affects a raft subpool and blocks the internalization and intracellular activity of the toxin. Our results indicate that TeNT interacts with target cells by binding to lipid rafts and that cholesterol is required for TeNT internalization and/or trafficking in neurons.

Elevated hypertension risk for African-origin populations in biracial societies : Modeling the Epidemiologic Transition Study.

OBJECTIVES: Blood pressures in persons of African descent exceed those of other racial/ethnic groups in the United States. Whether this trait is attributable to the genetic factors in African-origin populations, or a result of inadequately measured environmental exposures, such as racial discrimination, is not known. To study this question, we conducted a multisite comparative study of communities in the African diaspora, drawn from metropolitan Chicago, Kingston, Jamaica, rural Ghana, Cape Town, South Africa, and the Seychelles. METHODS: At each site, 500 participants between the age of 25 and 49 years, with approximately equal sex balance, were enrolled for a longitudinal study of energy expenditure and weight gain. In this study, we describe the patterns of blood pressure and hypertension observed at baseline among the sites. RESULTS: Mean SBP and DBP were very similar in the United States and South Africa in both men and women, although among women, the prevalence of hypertension was higher in the United States (24 vs. 17%, respectively). After adjustment for multiple covariates, relative to participants in the United States, SBP was significantly higher among the South Africans by 9.7 mmHg (P < 0.05) and significantly lower for each of the other sites: for example, Jamaica: -7.9 mmHg (P = 0.06), Ghana: -12.8 mmHg (P < 0.01) and Seychelles: -11.1 mmHg (P = 0.01). CONCLUSION: These data are consistent with prior findings of a blood pressure gradient in societies of the African diaspora and confirm that African-origin populations with lower social status in multiracial societies, such as the United States and South Africa, experience more hypertension than anticipated based on anthropometric and measurable socioeconomic risk factors.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies. J. Med. Virol. 88:94-99, 2016. © 2015 Wiley Periodicals, Inc.

Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action

Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk−/−) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk−/− mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk−/− mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.

Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action

Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk−/−) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk−/− mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk−/− mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.

Investigating the effects of arousal state on cognitive performance in individuals with and without mild head injury

We examined the cognitive and emotional sequelae following mild head injury (MHI; e.g., concussion) in high-functioning individuals and whether persons with MHI pre~ent, both physiologically and via self-report, in a manner different from (i.e., underaroused) that of persons who have no history of head injury. We also investigated the effect arousal state ~as on the cognitive performance of this population. Using a quasiexperimental research design (N = 91), we examined changes in attention, working memory, and cognitive flexibility (subtests ofthe WAIS-III, 1997,WMS-III, 1997, & DKEFS, 2002) as a function of manipulated arousal (i.e., induced psychosocial stress/activation; reduced activation/relaxation). In addition to self-reported arousal and state anxiety (State-Trait Anxiety Inventory; Speilberger, 1983a) measures, physiological indices of arousal state (i.e., electrodermal responsivity, heart rate, and respiration activity) were recorded (via Polygraph Professional Suite, 2008) across a 2.5 hour interval while completing various cognitive tasks. Students also completed the Post-concussive Symptom Checklist (Gouvier et aI., 1992). The results demonstrate that university students who report a history ofMHI (i.e., "altered state of consciousness") experience significantly lower levels of anxiety, were physiologically underaroused, and were less responsive to stressors in their environment, compared to their non-~HI cohorts. As expected, cognitive flexibility (but not other neuropsychological measures of cognition) was advantaged with increased stress, and disadvantaged with reduced stress, in persons with reported MHI, but not for those without reported MHI which provided limited support for our hypothesis. Further, university students who had no complaints related to their previous MHI endorsed a greater number of traditional post-concussive symptoms in terms of intensity, duration and frequency as compared to students who did not report a MHI. The underarousal in traumatic brain injury has been associated with (ventromedial prefrontal cortex) VMPFC disruption and may be implicated in MHI generally. Students who report sustaining a previous MHI may be less able to physiologically respond and/or cognitively appraise, stressful experiences as compared to their no-MHI cohort and experience persistent, long-lasting consequences despite the subtle nature of a history of head injury.

Sleep and information processing in individuals who have sustained a traumatic brain injury

Individuals who have sustained a traumatic brain injury (TBI) often complain of t roubl e sleeping and daytime fatigue but little is known about the neurophysiological underpinnings of the s e sleep difficulties. The fragile sleep of thos e with a TBI was predicted to be characterized by impairments in gating, hyperarousal and a breakdown in sleep homeostatic mechanisms. To test these hypotheses, 20 individuals with a TBI (18- 64 years old, 10 men) and 20 age-matched controls (18-61 years old, 9 men) took part in a comprehensive investigation of their sleep. While TBI participants were not recruited based on sleep complaint, the fmal sample was comprised of individuals with a variety of sleep complaints, across a range of injury severities. Rigorous screening procedures were used to reduce potential confounds (e.g., medication). Sleep and waking data were recorded with a 20-channel montage on three consecutive nights. Results showed dysregulation in sleep/wake mechanisms. The sleep of individuals with a TBI was less efficient than that of controls, as measured by sleep architecture variables. There was a clear breakdown in both spontaneous and evoked K-complexes in those with a TBI. Greater injury severities were associated with reductions in spindle density, though sleep spindles in slow wave sleep were longer for individuals with TBI than controls. Quantitative EEG revealed an impairment in sleep homeostatic mechanisms during sleep in the TBI group. As well, results showed the presence of hyper arousal based on quantitative EEG during sleep. In wakefulness, quantitative EEG showed a clear dissociation in arousal level between TBls with complaints of insomnia and TBls with daytime fatigue. In addition, ERPs indicated that the experience of hyper arousal in persons with a TBI was supported by neural evidence, particularly in wakefulness and Stage 2 sleep, and especially for those with insomnia symptoms. ERPs during sleep suggested that individuals with a TBI experienced impairments in information processing and sensory gating. Whereas neuropsychological testing and subjective data confirmed predicted deficits in the waking function of those with a TBI, particularly for those with more severe injuries, there were few group differences on laboratory computer-based tasks. Finally, the use of correlation analyses confirmed distinct sleep-wake relationships for each group. In sum, the mechanisms contributing to sleep disruption in TBI are particular to this condition, and unique neurobiological mechanisms predict the experience of insomnia versus daytime fatigue following a TBI. An understanding of how sleep becomes disrupted after a TBI is important to directing future research and neurorehabilitation.

Empathy and Emotion Processing in Mild Head Injury and Sub-clinical Psychopathy

The current study sought to investigate the nature of empathic responding and emotion processing in persons who have experienced Mild Head Injury (MHI) and how this relationship between empathetic responding and head injury status may differ in those with higher psychopathic characteristics (i.e., subclinical psychopathy). One-hundred university students (36% reporting having a previous MHI) completed an Emotional Processing Task (EPT) using images of neutral and negative valence (IAPS, 2008) designed to evoke empathy; physiological responses were recorded. Additionally, participants completed measures of cognitive competence and various individual differences (empathy - QCAE; Reniers, 2011; Psychopathy - SRP-III, Williams, Paulhus & Hare, 2007) and demographics questionnaires. MHI was found to be associated with lower affective empathy and physiological reactivity (pulse rate) while viewing images irrespective of valence, reflecting a pattern of generalized underarousal. The empathic deficits observed correlated with the individual’s severity of injury such that the greater number of injury characteristics and symptoms endorsed by a subject, the more dampened the affective and cognitive empathy reactions to stimuli and the lower his/her physiological reactivity. Importantly, psychopathy interacted with head injury status such that the effects of psychopathy were significant only for individuals indicating a MHI. This group, i.e., MHI subjects who scored higher on psychopathy, displayed the greatest compromise in empathic responding. Interestingly, the Callous Affect component of psychopathy was found to account for the empathic and emotion processing deficits observed for individuals who report a MHI; in contrast, the Interpersonal Manipulation component emerged as a better predictor of empathic and emotion deficits observed in the No MHI group. These different patterns may indicate the involvement of different underlying processes in the manifestation of empathic deficits associated with head injury or subclinical psychopathy. It also highlights the importance of assessing for prior head injury in populations with higher psychopathic characteristics due to the possible combined/enhanced influences. The results of this study have important social implications for persons who have experienced a concussion or limited neural trauma since even subtle injury to the head may be sufficient to produce dampened emotion processing, thereby impacting one’s social interactions and engagement (i.e., at risk for social isolation or altered interpersonal success). Individuals who experience MHI in conjunction with certain personality profiles (e.g., higher psychopathic characteristics) may be particularly at risk for being less capable of empathic compassion and socially-acceptable pragmatics and, as a result, may not be responsive to another person’s emotional well-being.

Working memory in Alzheimer’s disease and mild cognitive impairment (MCI) : assessment and intervention

L’objectif principal de cette thèse est d’examiner et d’intervenir auprès des déficits de la mémoire de travail (MdeT) à l’intérieur de deux populations cliniques : la maladie d’Alzheimer (MA) et le trouble cognitif léger (TCL). La thèse se compose de trois articles empiriques. Le but de la première expérimentation était d’examiner les déficits de MdeT dans le vieillissement normal, le TCL et la MA à l’aide de deux versions de l’empan complexe : l’empan de phrases et l’empan arithmétique. De plus, l’effet de «l’oubli» (forgetting) a été mesuré en manipulant la longueur de l’intervalle de rétention. Les résultats aux tâches d’empan complexe indiquent que la MdeT est déficitaire chez les individus atteints de TCL et encore plus chez les gens ayant la MA. Les données recueillies supportent également le rôle de l’oubli à l’intérieur de la MdeT. L’augmentation de l’intervalle de rétention exacerbait le déficit dans la MA et permettait de prédire un pronostic négatif dans le TCL. L’objectif de la deuxième étude était d’examiner la faisabilité d’un programme d’entraînement cognitif à l’ordinateur pour la composante de contrôle attentionnel à l’intérieur de la MdeT. Cette étude a été réalisée auprès de personnes âgées saines et de personnes âgées avec TCL. Les données de cette expérimentation ont révélé des effets positifs de l’entraînement pour les deux groupes de personnes. Toutefois, l’absence d’un groupe contrôle a limité l’interprétation des résultats. Sur la base de ces données, la troisième expérimentation visait à implémenter une étude randomisée à double-insu avec groupe contrôle d’un entraînement du contrôle attentionnel chez des personnes TCL avec atteinte exécutive. Ce protocole impliquait un paradigme de double-tâche composé d’une tâche de détection visuelle et d’une tâche de jugement alpha-arithmétique. Alors que le groupe contrôle pratiquait simplement la double-tâche sur six périodes d’une heure chacune, le groupe expérimental recevait un entraînement de type priorité variable dans lequel les participants devaient gérer leur contrôle attentionnel en variant la proportion de ressources attentionnelles allouée à chaque tâche. Les résultats montrent un effet significatif de l’intervention sur une des deux tâches impliquées (précision à la tâche de détection visuelle) ainsi qu’une tendance au transfert à une autre tâche d’attention divisée, mais peu d’effets de généralisation à d’autres tâches d’attention. En résumé, les données originales rapportées dans la présente thèse démontrent un déficit de la MdeT dans les maladies neurodégénératives liées à l’âge, avec un gradient entre le TCL et la MA. Elles suggèrent également une préservation de la plasticité des capacités attentionnelles chez les personnes à risque de développer une démence.

Objective neuropsychological deficits in post-traumatic stress disorder and mild traumatic brain injury: what remains beyond symptom similarity?

This exploratory study intends to characterize the neuropsychological profile in persons with post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) using objective measures of cognitive performance. A neuropsychological battery of tests for attention, memory and executive functions was administered to four groups: PTSD (n = 25), mTBI (n = 19), subjects with two formal diagnoses: Post-traumatic Stress Disorder and Mild Traumatic Brain Injury (mTBI/PTSD) (n = 6) and controls (n = 25). Confounding variables, such as medical, developmental or neurological antecedents, were controlled and measures of co-morbid conditions, such as depression and anxiety, were considered. The PTSD and mTBI/PTSD groups reported more anxiety and depressive symptoms. They also presented more cognitive deficits than the mTBI group. Since the two PTSD groups differ in severity of PTSD symptoms but not in severity of depression and anxiety symptoms, the PTSD condition could not be considered as the unique factor affecting the results. The findings underline the importance of controlling for confounding medical and psychological co-morbidities in the evaluation and treatment of PTSD populations, especially when a concomitant mTBI is also suspected.

Reliability of a quantitative clinical posture assessment tool among persons with idiopathic scoliosis

Objective To determine overall, test–retest and inter-rater reliability of posture indices among persons with idiopathic scoliosis. Design A reliability study using two raters and two test sessions. Setting Tertiary care paediatric centre. Participants Seventy participants aged between 10 and 20 years with different types of idiopathic scoliosis (Cobb angle 15 to 60°) were recruited from the scoliosis clinic. Main outcome measures Based on the XY co-ordinates of natural reference points (e.g. eyes) as well as markers placed on several anatomical landmarks, 32 angular and linear posture indices taken from digital photographs in the standing position were calculated from a specially developed software program. Generalisability theory served to estimate the reliability and standard error of measurement (SEM) for the overall, test–retest and inter-rater designs. Bland and Altman's method was also used to document agreement between sessions and raters. Results In the random design, dependability coefficients demonstrated a moderate level of reliability for six posture indices (ϕ = 0.51 to 0.72) and a good level of reliability for 26 posture indices out of 32 (ϕ ≥ 0.79). Error attributable to marker placement was negligible for most indices. Limits of agreement and SEM values were larger for shoulder protraction, trunk list, Q angle, cervical lordosis and scoliosis angles. The most reproducible indices were waist angles and knee valgus and varus. Conclusions Posture can be assessed in a global fashion from photographs in persons with idiopathic scoliosis. Despite the good reliability of marker placement, other studies are needed to minimise measurement errors in order to provide a suitable tool for monitoring change in posture over time.