The attentional boost effect in young and adult euthymic bipolar patients and healthy controls

In the Attentional Boost Effect (ABE), stimuli encoded with to-be-responded targets are later recognized more accurately than stimuli encoded with to-be-ignored distractors. While this effect is robust in young adults, evidence regarding healthy older adults and clinical populations is sparse. The present study investigated whether a significant ABE is present in bipolar patients (BP), who, even in the euthymic phase, suffer from attentional deficits, and whether the effect is modulated by age. Young and adult euthymic BP and healthy controls (HC) presented with a sequence of pictures paired with target or distractor squares were asked to pay attention to the pictures and press the spacebar when a target square appeared. After a 15-min interval, their memory of the pictures was tested in a recognition task. The performance in the detection task was lower in BP than in HC, in both age groups. More importantly, neither young nor adult BP exhibited a significant ABE; for HC, a robust ABE was only found in young participants. The results suggest that the increase in the attentional demands of the detection task in BP and in adult HC draws resources away from the encoding of target-associated stimuli, resulting in elimination of the ABE. Clinical implications are discussed

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

Forgetting unwanted memories: active forgetting and implications for the development of psychological disorders

Intrusive memories are a common feature of many psychopathologies, and suppressioninduced forgetting of unwanted memories appears as a critical ability to preserve mental health. In recent years, biological and cognitive studies converged in revealing that forgetting is due to active processes. Recent neurobiological studies provide evidence on the active role of main neurotransmitter systems in forgetting, suggesting that the brain actively works to suppress retrieval of unwanted memories. On the cognitive side, there is evidence that voluntary and involuntary processes (here termed “intentional” and “incidental” forgetting, respectively) contribute to active forgetting. In intentional forgetting, an inhibitory control mechanism suppresses awareness of unwanted memories at encoding or retrieval. In incidental forgetting, retrieval practice of some memories involuntarily suppresses the retrieval of other related memories. In this review we describe recent findings on deficits in active forgetting observed in psychopathologies, like post-traumatic stress disorder, depression, schizophrenia, and obsessive-compulsive disorder. Moreover, we report studies in which the role of neurotransmitter systems, known to be involved in the pathogenesis of mental disorders, has been investigated in active forgetting paradigms. The possibility that biological and cognitive mechanisms of active forgetting could be considered as hallmarks of the early onset of psychopathologies is also discussed

The role of baseline HIV-1 RNA, drug resistance, and regimen type as determinants of response to first-line antiretroviral therapy

The factors influencing virological response to first-line combined antiretroviral therapy (cART) in an Italian cohort of HIV-1-infected patients were examined. Eligible patients were those enrolled in a national prospective observational cohort (Antiretroviral Resistance Cohort Analysis), starting first-line cART between 2001 and 2011 and who had at least one follow-up of HIV-1 RNA. The primary endpoint was virological success, defined as the first viral load &lt;50 copies/ml. Time to events were analyzed by Kaplan-Meier analysis and Cox proportional hazard model. One thousand three hundred five patients met the study inclusion criteria. In a multivariable model adjusting for transmission mode, presence of transmitted drug resistance, baseline CD4+ cell count, viral subtype, and type of NRTI backbone employed, independent predictors of virological success were higher baseline viral load ( 65500,000 vs. &lt;100,000 HR 0.52; P&lt;0.001), a weighted genotypic susceptibility score (wGSS) &lt;3 (HR 0.58; P=0.003), male sex (HR 0.76 P=0.001), and type of initial third drug employed (integrase inhibitor vs. boosted protease inhibitors HR 3.23; P&lt;0.001). In the subset with HIV-1 RNA &gt;100,000 copies/ml, virologic success was only associated with the use of integrase inhibitors in the first cART regimen. Independent predictors of immunological success were baseline CD4+ cell count and wGSS &lt;3. High baseline HIV-1 RNA, predicted activity of the first-line regimen based on genotypic resistance testing, gender, and use of new agents were found to predict time to achieve virological success. The type of initial nucleoside analog backbone was not found to predict virological response

Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice.

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1-log(10) increase, P=0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice