Negative induced mood influences word production: An event-related potentials study with a covert picture naming task.

The present event-related potentials (ERPs) study investigated the effects of mood on phonological encoding processes involved in word generation. For this purpose, negative, positive and neutral affective states were induced in participants during three different recording sessions using short film clips. After the mood induction procedure, participants performed a covert picture naming task in which they searched letters. The negative compared to the neutral mood condition elicited more negative amplitudes in a component peaking around 290ms. Furthermore, results from source localization analyses suggested that this activity was potentially generated in the left prefrontal cortex. In contrast, no differences were found in the comparison between positive and neutral moods. Overall, current data suggest that processes involved in the retrieval of phonological information during speech generation are impaired when participants are in a negative mood. The mechanisms underlying these effects were discussed in relation to linguistic and attentional processes, as well as in terms of the use of heuristics.

Affective norms of 875 Spanish words for five discrete emotional categories and two emotional dimensions.

In the present study, we introduce affective norms for a new set of Spanish words, the Madrid Affective Database for Spanish (MADS), that were scored on two emotional dimensions (valence and arousal) and on five discrete emotional categories (happiness, anger, sadness, fear, and disgust), as well as on concreteness, by 660 Spanish native speakers. Measures of several objective psycholinguistic variables--grammatical class, word frequency, number of letters, and number of syllables--for the words are also included. We observed high split-half reliabilities for every emotional variable and a strong quadratic relationship between valence and arousal. Additional analyses revealed several associations between the affective dimensions and discrete emotions, as well as with some psycholinguistic variables. This new corpus complements and extends prior databases in Spanish and allows for designing new experiments investigating the influence of affective content in language processing under both dimensional and discrete theoretical conceptions of emotion. These norms can be downloaded as supplemental materials for this article from www.dropbox.com/s/o6dpw3irk6utfhy/Hinojosa%20et%20al_Supplementary%20materials.xlsx?dl=0 .

Caveolin-1 is required for TGF-ß-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17.

Transforming growth factor-beta (TGF-ß) plays a dual role in hepatocytes, inducing both pro- and anti-apoptotic responses, whose balance decides cell fate. Survival signals are mediated by the epidermal growth factor receptor (EGFR) pathway, which is activated by TGF-ß in these cells. Caveolin-1 (Cav1) is a structural protein of caveolae linked to TGF-ß receptors trafficking and signaling. Previous results have indicated that in hepatocytes, Cav1 is required for TGF-ß-induced anti-apoptotic signals, but the molecular mechanism is not fully understood yet. In this work, we show that immortalized Cav1(-/-) hepatocytes were more sensitive to the pro-apoptotic effects induced by TGF-ß, showing a higher activation of caspase-3, higher decrease in cell viability and prolonged increase through time of intracellular reactive oxygen species (ROS). These results were coincident with attenuation of TGF-ß-induced survival signals in Cav1(-/-) hepatocytes, such as AKT and ERK1/2 phosphorylation and NFκ-B activation. Transactivation of the EGFR pathway by TGF-ß was impaired in Cav1(-/-) hepatocytes, which correlated with lack of activation of TACE/ADAM17, the metalloprotease responsible for the shedding of EGFR ligands. Reconstitution of Cav1 in Cav1(-/-) hepatocytes rescued wild-type phenotype features, both in terms of EGFR transactivation and TACE/ADAM17 activation. TACE/ADAM17 was localized in detergent-resistant membrane (DRM) fractions in Cav1(+/+) cells, which was not the case in Cav1(-/-) cells. Disorganization of lipid rafts after treatment with cholesterol-binding agents caused loss of TACE/ADAM17 activation after TGF-ß treatment. In conclusion, in hepatocytes, Cav1 is required for TGF-ß-mediated activation of the metalloprotease TACE/ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGF-ß pro-apoptotic effects. Therefore, Cav1 contributes to the pro-tumorigenic effects of TGF-ß in liver cancer cells.

Neuroprotective Properties of Standardized Extracts of Hypericum perforatum on Rotenone Model of Parkinson's Disease.

Hipericum perforatum is a well-known herbal for its antidepressant property. Recently, it has been shown to have nootropic effects against neurodegenerative disorders. The aim of the present study was to evaluate the protective role of chronic administration of two standardized extract of Hypericum perforatum SHP1 rich in hyperforin (6%) and SHP2 extract poor in hyperforin (0.2%) on the neurodegeneration induced by chronic administration of rotenone in rats. Quercetin in liposomes, one active constituent, was tested in the same experimental conditions. The animals received pretreatments with SHP1 (4 mg/Kg, ip), SHP2 (4 mg/Kg, ip) or quercetin liposomes (25 and 100 mg/kg, ip) 60 min before of rotenone injection (2.5 mg/kg) for 45 days. Pretreatment of the animals with SHP1 and SHP2 efficiently halted deleterious toxic effects of rotenone, revealing normalization of catalepsy in addition to amelioration of neurochemical parameters. Also, SHP1 reduced neuronal damage, diminishing substantia nigra dopaminergic cell death caused by the pesticide, indicating benefit of neuroprotective therapy. In general, the SHP1 was more active than SHP2. In addition, SHP1 inhibited the apoptotic cascade by decreasing Bax levels. The results presented here indicate that mainly hyperforin and quercetin, may be involved in the neuroprotective action of Hypericum standardized extracts. Combination of dietary antioxidants could provide better therapeutic advantage for the management of Parkinson, and possibly other neurodegenerative disorders. Therefore H. perforatum standardized extract enriched in hyperforin, could be a better alternative for depressed elderly patients with degenerative disorders exhibiting elevated oxidative stress status.

Non-FDG PET in oncology.

Although FDG PET and PET/CT have a well established role in the management of most cancer patients, they also have some limitations. For the last 15-20 years a growing number of non-FDG PET tracers have been used in research. Many of these new PET tracers are being investigated for the non-invasive assessment of different biologic functions in cancer cells. This unique information should contribute to making personalized cancer therapy a reality. This paper reviews the non-FDG PET tracers that are most likely to find clinical application, some of them in the near future.

Longitudinal studies of ischemic penumbra by using 18F-FDG PET and MRI techniques in permanent and transient focal cerebral ischemia in rats.

At present, the goal of stroke research is the identification of a potential recoverable tissue surrounding the ischemic core, suggested as ischemic penumbra, with the aim of applying a treatment that attenuates the growth of this area. Our purpose was to determine whether a combination of imaging techniques, including (18)F-FDG PET and MRI could identify the penumbra area. Longitudinal studies of (18)F-FDG PET and MRI were performed in rats 3 h, 24 h and 48 h after the onset of ischemia. A transient and a permanent model of focal cerebral ischemia were performed. Regions of interest were located, covering the ischemic core, the border that progresses to infarction (recruited tissue), and the border that recovers (recoverable tissue) with early reperfusion. Analyses show that permanent ischemia produces severe damage, whereas the transient ischemia model does not produce clear damage in ADC maps at the earliest time studied. The only significant differences between values for recoverable tissue, (18)F-FDG (84±2%), ADC (108±5%) and PWI (70±8%), and recruited tissue, (18)F-FDG (77±3%), ADC (109±4%) and PWI (77±4%), are shown in (18)F-FDG ratios. We also show that recoverable tissue values are different from those in non-infarcted tissue. The combination of (18)F-FDG PET, ADC and PWI MRI is useful for identification of ischemic penumbra, with (18)F-FDG PET being the most sensitive approach to its study at early times after stroke, when a clear DWI deficit is not observed.

Event-related potential correlates of visual identity negative priming unbiased by trial-by-trial effects.

Negative priming (NP) refers to slowed reaction times and/or less accurate responses in people responding to a target that was ignored on a previous trial. Although extensive research with behavioral measures has been conducted, little is known about the electrophysiological mechanisms underlying this effect. The few previous studies carried out have led to contradictory results, supporting either episodic-retrieval or inhibition-based theoretical perspectives. In this study, we analyzed the ERP correlates of negative priming by using an experimental global context which, similar to the NP standard context, included Attended repetition trials. In addition, we presented relevant stimuli in separate blocks instead of the more usual randomized design. The NP effect can be biased by strategies adopted by participants when attended and ignored repetition trials are presented randomly. Specifically, we observed an enhanced N2 when a distractor from the previous trial became the target in the next trial. It is supposed that this finding reflects the involvement of additional attentional resources in the selection of a previously inhibited distractor as the new target stimuli.

Patients' perception and effectiveness of a treatment containing enfuvirtide when used in HIV-infected patients without very advanced disease.

PURPOSE: To evaluate the satisfaction with self-injected enfuvirtide (ENF) and the clinical outcome of HIV-infected patients without very advanced disease. METHOD: ESPPE is a multicenter observational study that included 103 evaluated patients showing baseline characteristics predictive of positive outcome: CD4 >100 cells/mm3, viral load (VL) <100,000 copies/mL, previous treatment with a maximum of 10 antiretroviral drugs, and concomitant use of 2 active drugs. By using validated surveys, patients were questioned 6 months after the prescription of ENF about their quality of life (QoL) and acceptance of self-injections and adherence to the treatment. RESULTS: At 6 months, the mean CD4 increase was 121 cells/mm3 (p < .05) and 65% (intent-to-treat, ENF stopped=failure) had VL <50 copies/mL (p < .001). Fourteen patients discontinued the treatment, mostly due to intolerance (6). The majority (>89%) assessed all items relating QoL as "excellent," "very good," or "good." The treatment satisfaction index on a visual analog scale scored a median of 8.1 out of 10; when participants were asked about the interference of injections on their daily activities, 87% answered "never" or "only sometimes." CONCLUSION: Effectiveness and patients' perception about ENF remain good when ENF was used in patients without very advanced disease. QoL was not impaired after ENF use.

Evaluation of the effect of training using auditory stimulation on rhythmic movement in Parkinsonian patients--a combined motor and [18F]-FDG PET study.

INTRODUCTION: A programme of rehabilitation using auditory cues has previously been shown to decrease movement variability in the gait of Parkinsonian patients. OBJECTIVE AND METHODS: We studied the temporal variability of finger-tapping and gait in 9 patients with Parkinson's disease (PD) before and after they undertook a physical rehabilitation programme. Positron Emission Tomography (PET) using 2-deoxy-2[(18)F]fluoro-D-glucose (FDG) was performed in these subjects to look for changes in metabolic brain activity after completion of the rehabilitation program. RESULTS: The reduction of variability was seen not only in gait but also other repetitive movements such as finger tapping. Furthermore, here we show differences in resting regional cerebral glucose utilisation in these patients compared to healthy controls (significant hypometabolism-p < 0.001-for the PD group in the right parietal and temporal lobes, left temporal and frontal lobes and a hypermetabolism in the left cerebellum) and specific changes following the improvements in repetitive movement abilities (significant metabolic increment-p < 0.001-in the PD group in the right cerebellum and in the right parietal and temporal lobes). CONCLUSIONS: Although our study does not allow us to draw firm conclusions, it provides new information on the neural basis of auditory stimulation in PD. Our results extend those from previous studies to show improvement in the temporal variability of two types of rhythmic movements after participation by PD patients in a physical rehabilitation programme, along with changes in glucose uptake in several brain areas involved in sensorimotor processing.

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Integrin regulation of membrane domain trafficking and Rac targeting.

Integrins are crucial regulators of essential cellular processes such as gene expression, cell proliferation and migration. Alteration of these processes is central to tumourigenesis. Integrin signals mediate anchorage dependence of cell growth, while growth of cancer cells is anchorage-independent. Integrins critically regulate Rho family GTPases, that are also involved in cell-cycle progression and oncogenesis. In addition to their effect on GTP loading, integrins independently control the translocation of GTP-bound Rac to the plasma membrane. This step is essential for Rac binding to effectors. Integrins increase membrane affinity for Rac, leading to RhoGDI dissociation and effector coupling locally, in the vicinity of activated/bound integrins. Integrin-regulated Rac binding sites are within CEMMs (cholesterol-enriched membrane microdomains). Integrins control Rac signalling by preventing the internalization of its binding sites in CEMMs. Integrin regulation of signalling pathways initiated in CEMMs may be important for the spatial control of cell migration and anchorage dependence of cell growth.

Distinct functions of Vav1 in JNK1 activation in Jurkat T cells versus non-haematopoietic cells.

Vav1, the 95-kDa protein encoded by the vav1 proto-oncogene, is expressed exclusively in haematopoietic cells, where it becomes phosphorylated on tyrosine residues in response to antigen receptor ligation. Vav1 was found to act as a Rac1-specific guanine nucleotide exchange factor and to activate c-Jun N-terminal kinase (JNK1) in vitro and in ectopic expression systems using non-haematopoietic cells. Here, we studied the role of Vav1 in JNK1 activation in T cells versus non-haematopoietic cells. Vav1 overexpression activated JNK1 in COS7 and 293T cells but not in Jurkat T lymphocytes. In contrast, constitutively activated Rac1 efficiently stimulated JNK1 in both cell types under the same conditions. Vav1 did function in T cells because it clearly stimulated the activity of a nuclear factor of activated T-cell reporter plasmid in the same cells. Moreover, Vav1 induction of JNK1 in T cells required coexpression with calcineurin. This cooperation was cell type specific because it was not observed in COS7 or 293T cells. In contrast, Vav1 did not cooperate with calcineurin to activate either extracellular signal-regulated kinase 2 or p38. These findings demonstrate that Vav1 alone is a poor activator of the JNK1 pathway in T cells and emphasize the importance of studying the physiological functions of Vav1 in haematopoietic cells.

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro.

We combined whole-cell recordings with Neurobiotin labeling to examine the electrophysiological and morphological properties of neurons from the ventral subicular complex in vitro (including the subicular, presubicular, and parasubicular areas). No a priori morphological sampling criteria were used to select cells. Cells were classified as bursting (IB), regular-spiking (RS), and fast-spiking (FS) according to their firing patterns in response to depolarizing current pulses. A number of cells remained unclassified. We found 54% RS, 26% IB, 11% FS, and 9% unclassified cells out of a total of 131 neurons examined. We also found cells showing intrinsic membrane potential oscillations (MPO) (6%), which represented a subgroup of the unclassified cells. We analyzed several electrophysiological parameters and found that RS and IB cells can be subclassified into two separate subgroups. RS cells were subclassified as tonic and adapting, according to the degree of firing adaptation. Both responded with single spikes to orthodromic stimulation. IB cells were subclassified in two subgroups according to their capacity to fire more than one burst, and showed different responses to orthodromic stimulation. We observed that bursting in these two subgroups appeared to involve both Ca2+ and persistent Na+ components. Both IB and RS cells, as well as MPO neurons, were projecting cells. FS cells were morphologically identified as local circuit interneurons. We also analyzed the spatial distribution of these cell types from the vicinity of CA1 to the parasubicular areas. We conclude that, in contrast to the commonly accepted idea of the subicular complex as a bursting structure, there is a wide electrophysiological variability even within a given cellular group.

[Pressure support ventilation]. / Modalidades de soporte.

Assisted mechanical ventilation is highly useful in clinical practice and allows good interaction between the patient and ventilator. The major uses of this mode are to reduce the work of breathing in patients with intact spontaneous breathing and to provide additional support during weaning from mechanical ventilation, especially when this has been prolonged.