Épidémiologie des réactions d'allure allergique au vaccin contre la grippe pandémique A(H1N1)pdm09

À l’automne 2010, le Québec a réalisé une campagne de vaccination de masse contre la grippe pandémique A(H1N1) en utilisant presque exclusivement un nouveau vaccin adjuvanté à l’AS03 (Arepanrix, GlaxoSmithKline). Les données de surveillance recueillies durant la campagne de vaccination ont montré que le taux de déclaration d’anaphylaxie, une réaction systémique sévère souvent attribuable à l’allergie, s’est avéré être supérieur à celui historiquement observé avec les vaccins contre la grippe saisonnière (8 contre < 1 cas par million de doses, respectivement). De plus, l’évaluation systématique des déclarations de manifestations cliniques inhabituelles (MCI) d’allure allergique a démontré que l’anaphylaxie avait été sous-diagnostiquée parmi les cas déclarés. Plus du deux tiers des MCI d’allure allergique observées durant la campagne de vaccination contre la grippe pandémique sont survenues chez des femmes. En tenant compte du nombre de doses administrées, les femmes avaient un risque deux fois plus élevé que les hommes. De plus, ce risque était plus important durant les années de vie reproductive, soit entre l’âge de 20 et 49 ans. Notre étude cas-témoin appariée a identifié certains facteurs de risque dont l’histoire personnelle et familiale d’allergie, la présence d’une infection respiratoire et la prise de médicaments pour l’asthme dans les jours précédant la vaccination, le statut de travailleur de la santé, et une vaccination dans les 4 premières semaines de campagne. Toutefois, aucun de ces facteurs n’expliquait une grande partie des anaphylaxies ou des MCI d’allure allergique. La présence d’une allergie aux œufs ou au poisson, deux composantes potentiellement allergènes du vaccin, ne s’est pas avéré être un facteur de risque significatif de MCI d’allure allergique. Nous avons aussi réalisé une étude clinique en allergie auprès d’une centaine de cas déclarés durant la campagne de vaccination contre la grippe pandémique qui a montré que peu de ces événements pouvaient être attribuables à une allergie IgE-dépendante au vaccin ou à ses composantes. Cette recherche a mis en évidence le risque plus élevé d’anaphylaxie et de MCI d’allure allergique chez les femmes en âge reproducteur mais n’a pas réussi à identifier d’autres facteurs de risque majeurs. Elle a toutefois démontré que le mécanisme habituellement évoqué pour les expliquer soit la présence d’IgE ciblant une des composantes du vaccin semble jouer un rôle très mineur

Memory for public events in mild cognitive impairment and Alzheimer’s disease : the importance of rehearsal

Ribot’s law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer’s disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960–1975; 1976–1990; 1991–2005; 2006–2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models

Vulnerability to semantic and phonological interference in normal aging and amnestic Mild Cognitive Impairment (aMCI)

Objective: To determine whether the increased vulnerability to semantic interference previously observed in amnestic mild cognitive impairment (aMCI) is specifically associated with semantic material or if it also affects other types of material, suggesting generalized executive and inhibitory impairment. Method: Seventy-two participants divided into two groups (33 aMCI, 39 normal control [NC]) matched for age and education were included. They completed a comprehensive neuropsychological examination, the French version of the Loewenstein Acevedo Scale for Semantic Interference and Learning (LASSI-L; semantic interference test), and a homologous experimental phonological test, the phonological interference and learning test. Independent sample t tests, mixed analysis of variance (ANOVA), and analysis of covariance (ANCOVA) on memory and interference scores were conducted to compare memory and interference in both conditions for both groups. Results: For memory scores, results revealed significant main effects of group (NC > aMCI) and condition (semantic > phonological) and significant interactions (poorer performance in the semantic condition for aMCI). aMCI committed more phonological false recognition errors, were disproportionately more vulnerable to retroactive semantic interference, and showed a higher percentage of intrusion errors associated with proactive semantic interference than NC. Conclusions: To our knowledge, this is the first study to compare vulnerability to interference in aMCI and normal aging with two similarly designed semantic and phonological word list learning tasks. Taken together, our results suggest that aMCI present with broad difficulties in source memory and inhibition, but that impaired deep semantic processing results in additional semantic intrusion errors during proactive interference and impacts their ability to show good recall after an interference list (greater semantic retroactive interference). Results are discussed according to the level-of-processing and activation/monitoring theories

From VIH-TAVIE™ to TAVIE-WOMAN™: Development of a Web-Based Virtual Nursing Intervention to Meet the Specific Needs of Women Living With HIV

The web-based virtual nursing intervention VIH-TAVIE™ was designed to help people living with HIV (PLWH) adhere to their antiretroviral treatment (ART). The content of the intervention is generic and gender neutral. However, it is recognised that women living with HIV (WLWH) experience their condition in a unique way and face gender-specific challenges regarding ART intake. Consequently, it seemed appropriate to adapt VIH-TAVIE™ specifically for women. The purpose of this paper is to present the qualitative results of an evaluative study of VIH-TAVIE™ that describe the experience of six WLWH who received the web-based computer-delivered intervention and to present the content and specificities of an offshoot intervention under development, TAVIE-Woman™. The following themes emerged from the content analysis of interviews with the WLWH about : 1) presence of actual nurse on site to facilitate transition to virtual mode; 2) virtual nurse humanises experience of computer-delivered intervention; 3) learners’ appreciation of medium and content; and 4) perceived benefits following participation in the intervention. To adapt VIH-TAVIETM for women, discussions were also held with a healthcare team in a mother-child university hospital centre. The gender-specific content added to TAVIE-WomanTM included digital storytelling of HIV-positive women, various topics about changing ARV medication during pregnancy, neonatal ART prophylaxis, disclosure  to children,  adapting to life with HIV, selecting a birth-control method, and social support. Ultimately, the purpose of TAVIE-WomanTM is to support WLWH by offering them 24/7 access to tailored education and reliable quality information

The impact of time and repeated exposure on famous person knowledge in amnestic Mild cognitive impairment and Alzheimer’s disease

Objective: Famous people knowledge has been shown to be impaired early in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI). However, the question of whether recently acquired knowledge is more impaired than remotely acquired knowledge remains a matter of debate. The aim of this study was to investigate the patterns of semantic memory impairment in aMCI and AD by investigating two factors that may influence the retrieval of such knowledge, namely remoteness and frequency of repetition of information over time. Method: Three groups (19 controls, 20 aMCI and 20 AD patients) were compared on a test assessing general and specific biographical knowledge about famous people, where the period of acquired fame (remote vs recent) and the type of fame (enduring vs transient) were controlled for. Results: Global performance of aMCI and AD patients was significantly poorer than that of controls. However, different patterns of recall were observed as a function of time and type of fame. A temporal gradient was found in both patient groups for enduring names but not for transient ones, whereby knowledge about remote enduring famous persons was better recalled. Patients were more impaired at questions assessing specific biographical knowledge (unique to an individual) than more general knowledge. Conclusions: Tests of famous people knowledge offer a unique opportunity to investigate semantic deficits in aMCI and AD, because they make it possible to estimate the time at which memories were acquired, as well as the type of fame. Results are discussed in light of memory consolidation models. Keywords

PD1/PD-L1 dependent immunosuppression by huiPS-derived cell population

Poster presentationInternational audienc

Differential involvement of the anterior temporal lobes in famous people semantics

The ability to recognize a famous person occurs through semantic memory. Previous neuroimaging studies have shown that the anterior temporal lobes (ATLs) are involved in the recognition of famous people. However, it is still a matter of debate whether the semantic processing of names or pictures of famous people has an impact on the activation of ATLs. The aim of this study was to explore the pattern of activation associated with a semantic processing of famous people based on face and written name stimuli. Fifteen healthy young individuals participated in our fMRI study, in which they were asked to perform a semantic categorization judgment task, based on profession, of visually presented pictures, and names of famous people. Neuroimaging findings showed a common pattern of activation for faces and names mainly involving the inferior frontal regions, the posterior temporal lobe, the visual cortex, and the ATLs. We found that the comparison names vs. pictures lead to significant activation in the anterior superior temporal gyrus. On the other hand, faces vs. names seemed associated with increased activation in the medial ATL. Moreover, our results demonstrated that the functional connectivity network anchored to the medial ATL, compared to the anterior STG, is more connected to the bilateral occipital lobe and fusiform gyrus that are regions implicated in the visual system and visual processing of faces. This study provides critical evidence of the differential involvement of ATL regions in semantics of famous people

Quantitative profiling of the UGT transcriptome in human drug metabolizing tissues

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5’ and/or 3’ termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodelling in favour of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome

Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing

A comprehensive view of the human UDP-glucuronosyltransferase (UGT) transcriptome is a prerequisite to the establishment of an individual’s UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the ten human UGT loci genes in normal and tumoral metabolic tissues by targeted RNA next generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon-exon junctions. We recover all previously known UGT1 and UGT2 enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGT variants. We further expose a revised genomic structure of UGT loci and provide a comprehensive repertoire of transcripts for each UGT gene. Data also uncover a remodelling of the UGT transcriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGT expression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases. Keywords: Alternative splicing, transcriptome, glucuronidation, RNA sequencing, drug metabolism, glucuronosyltransferase (UGT

An examination of semantic impairment in amnestic MCI and AD : What can we learn from verbal fluency?

Introduction The Verbal Fluency Test (VF) is commonly used in neuropsychology. Some studies have demonstrated a marked impairment of semantic VF compared to phonemic VF in Alzheimer’s disease (AD). Since amnestic Mild Cognitive Impairment (aMCI) is associated with increased risk of conversion to incident AD, it is relevant to examine whether a similar impairment is observed in this population. The objective of the present empirical study is to compare VF performance of aMCI patients to those of AD and elderly controls matched one-to-one for age and education. Method Ninety-six participants divided into three equal groups (N = 32: AD, aMCI and Controls) were included in this study. Participants in each group were, on average, 76 years of age and had 13 years of education. A repeated measures ANOVA with the Group (AD, aMCI, NC) as between-subject factor and the Fluency condition (“P” and “animals”) as within-subject factor was performed. T-tests and simple ANOVAs were also conducted to examine the interaction. Results There was a significant interaction between the groups and the verbal fluency condition. In AD, significantly fewer words were produced in both conditions. In contrast, participants with aMCI demonstrated a pattern similar to controls in the phonemic condition, but generated significantly fewer words in the semantic condition. Conclusion These results indicate a semantic memory impairment in aMCI revealed by a simple, commonly-used neuropsychological test. Future studies are needed to investigate if semantic fluency deficits can help predict future conversion to AD