Rastreamento da infecção latente por tuberculose em pacientes com artrite idiopática juvenil previamente à terapia anti‐TNF em um país de alto risco para tuberculose

ResumoObjetivoAvaliar, em um país endêmico, a eficácia em longo prazo do rastreamento à procura de infecção latente por tuberculose (ILTB) e profilaxia primária em pacientes com AIJ em uso de bloqueadores do TNF.MétodosTrata‐se de uma coorte retrospectiva que incluiu pacientes com AIJ elegíveis para a terapia anti‐TNF. Os pacientes foram rastreados à procura de ILTB previamente ao uso de anti‐TNF por meio do teste tuberculínico (TT), radiografia de tórax e história de exposição à TB. Os indivíduos foram acompanhados regularmente em intervalos de dois meses.ResultadosIncluíram‐se 69 pacientes com AIJ com idade atual de 17,4±5,8 anos, com média de duração da doença de 5±4,9 anos; 47 pacientes receberam um único anti‐TNF, enquanto 22 foram transferidos para outro anti‐TNF uma ou duas vezes: 57 foram tratados com etanercepte, 33 com adalimumabe e três com infliximabe. O rastreamento à procura de ILTB foi positivo em três pacientes: um era TT positivo e tinha história de exposição à TB e dois apenas eram TT positivo. Não foi diagnosticado caso de TB ativa durante o período de estudo (mediana de seguimento de 3,8 anos).ConclusãoA avaliação em longo prazo revelou que o rastreamento à procura de ILTB e a profilaxia primária antes do tratamento com anti‐TNF foram eficazes em um país de alto risco para TB e o TT foi o parâmetro mais sensível para identificar esses pacientes.AbstractObjectivesTo evaluate, in an endemic country, the long‐term efficacy of latent tuberculosis infection (LTBI) screening and primary prophylaxis in patients with JIA receiving TNF blockers.MethodsThis was a retrospective cohort that included JIA patients eligible to anti‐TNF therapy. Patients were screened for LTBI prior to anti‐TNF using tuberculin skin test (TST), chest X‐ray and history of exposure to TB. Subjects were regularly followed at 2‐month intervals.ResultsSixty‐nine JIA patients with current age of 17.4±5.8 years, mean disease duration of 5.0±4.9 years were included. Forty‐seven patients received a single anti‐TNF, while 22 patients switched to another anti‐TNF once or twice: 57 were treated with etanercepte, 33 patients with adalimumab and 3 infliximab. LTBI screening was positive in three patients: one had TST‐positive and history of TB exposure and two had solely TST‐positive. No active TB was diagnosed during the study period (median of follow‐up was 3.8 years).ConclusionLong‐term evaluation revealed that LTBI screening and primary prophylaxis before anti‐TNF treatment was effective in a high‐risk country and TST was the most sensitive parameter to identify these patients

Quantifying Individual Variation in the Propensity to Attribute Incentive Salience to Reward Cues

If reward-associated cues acquire the properties of incentive stimuli they can come to powerfully control behavior, and potentially promote maladaptive behavior. Pavlovian incentive stimuli are defined as stimuli that have three fundamental properties: they are attractive, they are themselves desired, and they can spur instrumental actions. We have found, however, that there is considerable individual variation in the extent to which animals attribute Pavlovian incentive motivational properties (“incentive salience”) to reward cues. The purpose of this paper was to develop criteria for identifying and classifying individuals based on their propensity to attribute incentive salience to reward cues. To do this, we conducted a meta-analysis of a large sample of rats (N = 1,878) subjected to a classic Pavlovian conditioning procedure. We then used the propensity of animals to approach a cue predictive of reward (one index of the extent to which the cue was attributed with incentive salience), to characterize two behavioral phenotypes in this population: animals that approached the cue (“sign-trackers”) vs. others that approached the location of reward delivery (“goal-trackers”). This variation in Pavlovian approach behavior predicted other behavioral indices of the propensity to attribute incentive salience to reward cues. Thus, the procedures reported here should be useful for making comparisons across studies and for assessing individual variation in incentive salience attribution in small samples of the population, or even for classifying single animals

Three-Dimensional X-ray Observation of Atmospheric Biological Samples by Linear-Array Scanning-Electron Generation X-ray Microscope System

Recently, we developed a soft X-ray microscope called the scanning-electron generation X-ray microscope (SGXM), which consists of a simple X-ray detection system that detects X-rays emitted from the interaction between a scanning electron beam (EB) and the thin film of the sample mount. We present herein a three-dimensional (3D) X-ray detection system that is based on the SGXM technology and designed for studying atmospheric biological samples. This 3D X-ray detection system contains a linear X-ray photodiode (PD) array. The specimens are placed under a CuZn-coated Si3N4 thin film, which is attached to an atmospheric sample holder. Multiple tilt X-ray images of the samples are detected simultaneously by the linear array of X-ray PDs, and the 3D structure is calculated by a new 3D reconstruction method that uses a simulated-annealing algorithm. The resulting 3D models clearly reveal the inner structure of the bacterium. In addition, the proposed method can easily be used for diverse samples in a broad range of scientific fields

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formación (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.This work was funded by an INSERM AVENIR and Agence Nationale de la Recherche (ANR) ANR12 SAMA00201 grant to DB, the région Poitou-Charentes, an AXA research fund fellowship to ABR, and a Ministère de la Recherche et de la Technologie grant to NV. AM was supported by the Behavioural and Clinical Neuroscience Institute of Cambridge.This is the accepted manuscript of a paper published in Neuropsychopharmacology (2015) 40, 577–589; doi:10.1038/npp.2014.204; published online 17 September 2014