The structure of psychopathology in adolescence and its common personality and cognitive correlates

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al., 2014; Tackett et al., 2013). The first objective of this study was to use structural equation modeling to model the structure of psychopathology in an adolescent community-based sample (N = 2,144) including conduct disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), obsessive-compulsive disorder, eating disorders, substance use, anxiety, depression, phobias, and other emotional symptoms, assessed at 16 years. The second objective was to identify common personality and cognitive correlates of psychopathology, assessed at 14 years. Results showed that psychopathology at 16 years fit 2 bifactor models equally well: (a) a bifactor model, reflecting a general psychopathology factor, as well as specific externalizing (representing mainly substance misuse and low ADHD) and internalizing factors; and (b) a bifactor model with a general psychopathology factor and 3 specific externalizing (representing mainly ADHD and ODD), substance use and internalizing factors. The general psychopathology factor was related to high disinhibition/impulsivity, low agreeableness, high neuroticism and hopelessness, high delay-discounting, poor response inhibition and low performance IQ. Substance use was specifically related to high novelty-seeking, sensation-seeking, extraversion, high verbal IQ, and risk-taking. Internalizing psychopathology was specifically related to high neuroticism, hopelessness and anxiety-sensitivity, low novelty-seeking and extraversion, and an attentional bias toward negatively valenced verbal stimuli. Findings reveal several nonspecific or transdiagnostic personality and cognitive factors that may be targeted in new interventions to potentially prevent the development of multiple psychopathologies

Evidence for cognitive vestibular integration impairment in idiopathic scoliosis patients

<p>Abstract</p> <p>Background</p> <p>Adolescent idiopathic scoliosis is characterized by a three-dimensional deviation of the vertebral column and its etiopathogenesis is unknown. Various factors cause idiopathic scoliosis, and among these a prominent role has been attributed to the vestibular system. While the deficits in sensorimotor transformations have been documented in idiopathic scoliosis patients, little attention has been devoted to their capacity to integrate vestibular information for cognitive processing for space perception. Seated idiopathic scoliosis patients and control subjects experienced rotations of different directions and amplitudes in the dark and produced saccades that would reproduce their perceived spatial characteristics of the rotations (vestibular condition). We also controlled for possible alteration of the oculomotor and vestibular systems by measuring the subject's accuracy in producing saccades towards memorized peripheral targets in absence of body rotation and the gain of their vestibulo-ocular reflex.</p> <p>Results</p> <p>Compared to healthy controls, the idiopathic scoliosis patients underestimated the amplitude of their rotations. Moreover, the results revealed that idiopathic scoliosis patients produced accurate saccades to memorized peripheral targets in absence of body rotation and that their vestibulo-ocular reflex gain did not differ from that of control participants.</p> <p>Conclusion</p> <p>Overall, results of the present study demonstrate that idiopathic scoliosis patients have an alteration in cognitive integration of vestibular signals. It is possible that severe spine deformity developed partly due to impaired vestibular information travelling from the cerebellum to the vestibular cortical network or alteration in the cortical mechanisms processing the vestibular signals.</p

Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer

Background Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. Main body The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in cancers that depend on hTERT activation. Knowing that telomeres are crucial for cellular self-renewal, the mechanisms responsible for telomere maintenance have a crucial role in cancer diseases and might be important oncological biomarkers. Thus, rather than quantifying TERT expression and its correlation with telomerase activation, the discovery and the assessment of the mechanisms responsible for TERT upregulation offers important information that may be used for diagnosis, prognosis, and treatment monitoring in oncology. Furthermore, a better understanding of these mechanisms may promote their translation into effective targeted cancer therapies. Conclusion Herein, we reviewed the underlying mechanisms of hTERT regulation, their role in oncogenesis, and the potential clinical applications in telomerase-dependent cancers.info:eu-repo/semantics/publishedVersio

CropPol: a dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved

Time series analysis of the impact of the antimicrobial stewardship program based on the clinical decision support system APSS at the Centre hospitalier universitaire de Sherbrooke

L’utilisation abusive des antimicrobiens est associé à plusieurs conséquences défavorables, dont le développement de la résistance bactérienne. Chaque année, entre 8 000 et 12 000 Canadiens meurent de complications liées aux infections causées par les bactéries multirésistantes. De 2003 à 2005, le Québec a connu une importante éclosion d’infection à Clostridium difficile. Le facteur de risque le plus important pour développer une telle infection est la consommation préalable d’antimicrobiens. L’antibiogouvernance est l’ensemble des stratégies déployées afin de promouvoir et de maximiser le bon usage des antimicrobiens. Ceci inclut la surveillance et les interventions pour optimiser la prescription. Puisqu’une surveillance manuelle de tous les patients et de chacune des doses administrées est impossible au Centre hospitalier universitaire de Sherbrooke (CHUS), une surveillance automatisée prospective des dossiers avec rétroaction aux utilisateurs est initiée par APSS, un système expert en antibiogouvernance qui produit des alertes indiquant que le patient déroge aux lignes directrices. Pour en évaluer l’impact, un devis quasi expérimental rétrospectif, avec une évaluation en séries chronologiques interrompues de 2008 à 2013, a été utilisé. Les données sur tous les adultes hospitalisés du CHUS, un centre académique de 677 lits, ont été extraites de l’entrepôt de données CIRESSS. L’intervention a débuté en août 2010. Les changements des issues d’intérêts avant et après l’intervention ont été évalués en utilisant des analyses de régression segmentée. Pendant les 3 années d’évaluation, plus de 5 665 recommandations ont été acceptées (taux d’approbation de 91%), menant à des modifications ou à des cessations de prescriptions d’antimicrobiens afin de rapprocher la pratique aux lignes directrices. Ces modifications ont été associées à une réduction de la durée moyenne d’hospitalisation des patients avec antimicrobien (2,3 jours), de la consommation (23,8%) et des dépenses en antimicrobiens (33,6%). L’absence de données de microbiologies fiables dans le temps nous a empêché de mesurer l’impact du programme d’antibiogouvernance sur l’évolution de la sensibilité à la ciprofloxacine d’Escherichia coli, du Staphylococcus aureus et de l’Enterococcus sp. L’incidence des infections à C. difficile n’a pas été influencée de façon significative par la mise en place du programme d’antibiogouvernance. En conclusion, le programme d’antibiogouvernance articulé autour du système expert APSS a permis l’atteinte de la majorité des objectifs. Un accès à des données de meilleure qualité sera requis pour pouvoir évaluer les impacts du programme sur les profils de résistance bactérienne.Abstract : Antimicrobial misuse favors the development of adverse effects and antimicrobial resistance. Between 8,000 and 12,000 Canadians die every year from complications related to these multidrug-resistant bacteria infections. From 2003 to 2005, Quebec has experienced significant Clostridium difficile infection outbreaks. The first risk factor for developing a Clostridium difficile infection is exposure to antimicrobials. To address these problems, we have established an antimicrobial stewardship program that promotes optimal use of antimicrobials. Since manual monitoring of all patients and each dose administered is impossible at the University Hospital of Sherbrooke (CHUS), a prospective audit and feedback intervention, led by a pharmacist were triggered by APSS, an expert system for antimicrobial stewardship. Data, from August 2008 to August 2013, on all hospitalized adults receiving antimicrobials were extracted from the data warehouse (CIRESSS) of a 677-bed academic center. The intervention started in August 2010. Changes in outcomes were assessed using segmented regression analyzes. During the 3 years of evaluation, more than 5,665 recommendations were accepted (91% approval rate) leading to modifications or discontinuation of antimicrobial prescriptions to bring the practice closer to the guidelines. The antimicrobial stewardship program has been associated with reductions of the average length of hospitalization in patients with antimicrobials (2.3 days), of antimicrobial consumption (-23.8%), and of antimicrobial cost (-33.6%). The lack of reliable microbiological data over time prevented us from measuring the impact of the antimicrobial stewardship program on the evolution of susceptibility to ciprofloxacin of the Escherichia coli, the Staphylococcus aureus and the Enterococcus. The incidence of Clostridium difficile infections has not been significantly influenced by the implementation of the antimicrobial stewardship program. In conclusion, the antimicrobial stewardship program articulated around the expert system APSS made it possible to reach the majority of the objectives. Access to better quality data will be required to assess the impacts of the program on bacterial resistance

Optimiser la prescription d’antimicrobiens : une solution informatisée

Résumé Objectif : L’objectif de cet article consiste à présenter une intervention d’optimisation de l’usage des antimicrobiens articulée autour de l’utilisation d’un système expert. Mise en contexte : Au Centre hospitalier universitaire de Sherbrooke, une équipe travaille depuis 2005 à la création d’un système d’aide à la décision pour cibler les prescriptions d’antimicrobiens sous-optimales. Résultats : Après 53 semaines d’utilisation, 1344 interventions ont été effectuées, dont 1222 (90,9 %) ont été acceptées par les différentes équipes médicales. Ceci représente une moyenne de 1,7 interventions acceptées/heure de présence de la pharmacienne. Pour la période décrite, la consommation totale en antimicrobiens a diminué de 13,5 %, ce qui représente une économie de 305 000 $(15$/heure de présence de la pharmacienne. Discussion : Les résultats observés s’expliquent par l’évaluation exhaustive de toutes les nouvelles prescriptions et de toutes les modifications subséquentes d’antimicrobiens par le logiciel. De plus, la surveillance hebdomadaire permet également de détecter des pratiques en émergence. Conclusion : La collaboration médicale, pharmaceutique et informatique ont permis de développer un outil adapté à la réalité québécoise afin d’optimiser l’utilisation des antimicrobiens et de diminuer les coûts liés à l’antibiothérapie. Abstract Objective: The purpose of this article is to discuss an intervention optimizing the use of antimicrobials using experts in the field. Context: At the Centre hospitalier universitaire de Sherbrooke, a team has been working since 2005 to create a decisionmaking support system targeting sub-optimal prescriptions for antimicrobials. Results: After 53 weeks of use, 1344 interventions were made of which 1222 (90.0%) were accepted by the different medical teams. This represents, on average, 1.7% of interventions being accepted per hour of pharmacist presence. For this period, total antimicrobial consumption decreased by 13.5%, representing savings of 305 00$(15$ per hour of pharmacist presence. Discussion: The observed results can be explained by the exhaustive review that was done of all new prescriptions and of all subsequent modifications to antimicrobial therapy by the software. In addition, emergent practice habits were detected through weekly surveillance. Conclusion: The collaboration between the medical, pharmacy and information technology fields allowed the development of a tool adapted to the Quebec reality to optimize antimicrobial use and to decrease costs related to antimicrobial therapy. Key words: Antimicrobials, pharmacist, software, surveillance

Cardiorespiratory Alterations in a Newborn Ovine Model of Bacterial Sepsis

International audienceRATIONALE: Neonatal sepsis remains a major problem, partly due to their consequences on cardiorespiratory control. The latter manifest as severe cardiorespiratory events and cause substantial morbidity and mortality, especially in preterm infants. The link between neonatal sepsis, inflammation and altered cardiac and respiratory activity remains poorly understood. Our research program aims to further characterize this link in newborn lambs, who are closer to the human newborn than the murine models previously studied.METHODS: Two six-hour polysomnography recordings were performed on two consecutive days in eight full-term newborn lambs. During the first recording, an IV saline injection (= control) was given, whereas the second recording was performed after an IV injection of 2.5 μg/kg of E. coli LPS 0127:B8. Body temperature, arterial blood gases, states of alertness, locomotor activity, respiratory and heart rates, arterial blood pressure, apneas and cardiac decelerations were measured. RESULTS: LPS injection induced a biphasic increase in body temperature [max To = +1.3oC at 30 and 180 min] and decreased locomotor activity [38.7 (35.4, 54) vs. 93.8 (73, 128.1) m, median (Q1,Q3), p = 0.03] and active wakefulness [21 (17, 23) vs. 28 (19, 31) % p= 0.01] vs. control condition. Meanwhile, quiet wakefulness [51 (47, 53) vs. 42 (37, 47) %, p = 0.03], number of cardiac decelerations [37 (33, 89) vs. 19 (13, 34), p = 0.05], heart rate [245 (229, 261) vs. 180 (172, 183) .min-1, p = 0.005] and respiratory rate [61 (59, 63) vs. 49 (47, 52) .min-1, p = 0.0005] were increased, while total apnea duration [35.7 (18.2, 61.6) vs. 88.5 (42.7, 133.7) s, p = 0.04] was decreased. CONCLUSION: LPS injection mimics a bacterial sepsis in newborn lambs with multiple consequences, including cardiorespiratory alterations. Ongoing studies in the same lambs will provide further results on alterations of heart and respiratory rate variabilities, as well as on brainstem cardiorespiratory center inflammation. The present results will pave the way for similar studies in preterm lambs

Evolution of the global burden of viral infections from unsafe medical injections, 2000-2010.

BACKGROUND: In 2000, the World Health Organization estimated that, in developing and transitional countries, unsafe injections accounted for respectively 5%, 32% and 40% of new infections with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Safe injection campaigns were organized worldwide. The present study sought to measure the progress in reducing the transmission of these viruses through unsafe injections over the subsequent decade. METHODS: A mass action model was updated, to recalculate the number of injection-related HIV, HCV and HBV infections acquired in 2000 and provide estimates for 2010. Data about the annual number of unsafe injections were updated. HIV prevalence in various regions in 2000 and 2010 were calculated from UNAIDS data. The ratio of HIV prevalence in healthcare settings compared to the general population was estimated from a literature review. Improved regional estimates of the prevalence of HCV seropositivity, HBsAg and HBeAg antigenemia were used for 2000 and 2010. For HIV and HCV, revised estimates of the probability of transmission per episode of unsafe injection were used, with low and high values allowing sensitivity analyses. RESULTS: Despite a 13% population growth, there was a reduction of respectively 87% and 83% in the absolute numbers of HIV and HCV infections transmitted through injections. For HBV, the reduction was more marked (91%) due to the additional impact of vaccination. While injections-related cases had accounted for 4.6%-9.1% of newly acquired HIV infections in 2000, this proportion decreased to 0.7%-1.3% in 2010, when unsafe injections caused between 16,939 and 33,877 HIV infections, between 157,592 and 315,120 HCV infections, and 1,679,745 HBV infections. CONCLUSION: From 2000 to 2010, substantial progress was made in reducing the burden of HIV, HCV and HBV infections transmitted through injections. In some regions, their elimination might become a reasonable public health goal