Do Swiss adolescents perceive the negative effects of their illegal substance use?

This study explores adolescents' perceptions of adverse consequences linked to their illegal psychoactive substance (IPS) use, as they are often thought to minimise them. From a Swiss nationally representative sample of 8740 adolescents aged 16 to 20 pursuing post-mandatory education, 2515 participants reported IPS use in the past month on a self-administered anonymous questionnaire. The percentages of participants reporting problems in four areas (individual, school, relationships and sexual) were assessed, depending on the type of IPS consumption over the last 30 days: occasional cannabis users: ≤2 times; regular cannabis users: ≥3 times; and poly-consumers: cannabis plus at least one other substance used. The percentages varied significantly across these three groups with 26.9% of occasional users, 53.8% of regular users, and 73.3% of poly-consumers reporting at least one problem. Compared to occasional cannabis users, poly-consumers were more likely to report problems in all four categories [relative risk ratio (RRR): 3.38 to 5.44], while regular cannabis users often reported only school and relationship problems [RRR: 2.43 to 3.23]. Thus, many adolescents seem to perceive the negative effects of their IPS use, with heavier consumption being associated with increasing problems. Physicians should feel confident questioning adolescents on the adverse consequences of their IPS consumption, as they are likely to be responsive on this issue.

EMT and EGFR in CTCs cytokeratin negative non-metastatic breast cancer.

Circulating tumor cells (CTCs) are frequently associated with epithelial-mesenchymal transition (EMT).The objective of this study was to detect EMT phenotype through Vimentin (VIM) and Slug expression in cytokeratin (CK)-negative CTCs in non-metastatic breast cancer patients and to determine the importance of EGFR in the EMT phenomenon. In CK-negative CTCs samples, both VIM and Slug markers were co-expressed in the most of patients. Among patients EGFR+, half of them were positive for these EMT markers. Furthermore, after a systemic treatment 68% of patients switched from CK- to CK+ CTCs. In our experimental model we found that activation of EGFR signaling by its ligand on MCF-7 cells is sufficient to increase EMT phenotypes, to inhibit apoptotic events and to induce the loss of CK expression. The simultaneous detection of both EGFR and EMT markers in CTCs may improve prognostic or predictive information in patients with operable breast cancer.

Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFa blockers

Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)a blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNFa blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNFa therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNFa blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI.

Predicting response and survival in chemotherapy-treated triple-negative breast cancer.

BACKGROUND In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). METHODS Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. RESULTS Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. CONCLUSIONS The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

The hairy and enhancer of split 1 is a negative regulator of the repressor element silencer transcription factor.

Silencing of the transcriptional repressor REST is required for terminal differentiation of neuronal and beta-cells. In this study, we hypothesized that REST expression is controlled by hairy and enhancer of split 1 (HES-1), a transcriptional repressor that plays an important role in brain and pancreas development. We identified several N elements (CTNGTG) within the promoter of REST and confirmed that HES-1 associates with the endogenous promoter of REST. Moreover, using a cells model that overexpress HES-1 and a combination of experimental approaches, we demonstrated that HES-1 reduces endogenous REST expression. Taken together, these results indicate that HES-1 is an upstream negative regulator of REST expression.

Positive and negative regulation of cellular immune responses in physiologic conditions and diseases.

The immune system has evolved to allow robust responses against pathogens while avoiding autoimmunity. This is notably enabled by stimulatory and inhibitory signals which contribute to the regulation of immune responses. In the presence of a pathogen, a specific and effective immune response must be induced and this leads to antigen-specific T-cell proliferation, cytokines production, and induction of T-cell differentiation toward an effector phenotype. After clearance or control of the pathogen, the effector immune response must be terminated in order to avoid tissue damage and chronic inflammation and this process involves coinhibitory molecules. When the immune system fails to eliminate or control the pathogen, continuous stimulation of T cells prevents the full contraction and leads to the functional exhaustion of effector T cells. Several evidences both in vitro and in vivo suggest that this anergic state can be reverted by blocking the interactions between coinhibitory molecules and their ligands. The potential to revert exhausted or inactivated T-cell responses following selective blocking of their function made these markers interesting targets for therapeutic interventions in patients with persistent viral infections or cancer.

A-8a 2003 Summary of Food Stamp Errors - Active and Negative Cases, April 2003 - September 2003

Summary of food stamp errors.

Caractéristiques cliniques des leucémies lymphoblastiques aiguës de type T immature (E-rosette négatif) détecté par l'anticorps monoclonal LAU-A1 [Clinical characteristics of immature T-type (negative E-rosette) acute lymphoblastic leukemia detected by LAU-A1 monoclonal antibody]

Immature T-ALL is a newly defined subgroup of ALL in which the blasts lack the receptor for sheep erythrocytes (ER) and the usual T-cell markers, but express the 40 kDa pan-T surface antigen recognized by our monoclonal antibody LAU-A1. Patients with immature T-ALL represent 10% of all cases of adult ALL. Leukocyte counts are lower and spleen, liver and lymph node enlargement is less prominent, but mediastinal enlargement is more frequent than in mature (ER-positive) T-ALL. 7 patients with immature T-ALL (median age 42 years, range 13-73) were treated with intensified chemotherapy regimens, and only one 47-year-old female entered a short-lived complete remission. The overall survival of our patients was poor (median 7.5 months, with only one patient surviving at 15 months) and seemed not to be influenced by age. Our study indicates that immature T-ALL can only be accurately identified by the use of monoclonal antibodies recognizing the 40 kDa pan-T antigen, and that immature T-ALL is a separate disease entity typified by a poor prognosis.

Negative Fukui functions: new insights based on electronegativity equalization

The occurrence of negative values for Fukui functions was studied through the electronegativity equalization method. Using algebraic relations between Fukui functions and different other conceptual DFT quantities on the one hand and the hardness matrix on the other hand, expressions were obtained for Fukui functions for several archetypical small molecules. Based on EEM calculations for large molecular sets, no negative Fukui functions were found

A8a Summary of Food Stamp Errors-Active and Negative cases, July 2004

A-8A summary of food stamp errors active and negative cases

A-8a 2003 Summary of Food Stamp Errors - Active and Negative Cases, April 2001 - September 2001

Summary of food stamp errors.

The human Ia-associated invariant chain is synthesized in Ia-negative B cell variants and is not expressed on the cell surface of both Ia-negative and Ia-positive parental cells.

The expression of Ia-associated human Invariant (In) chain glycoproteins was studied in the Raji B cells as well as in their RJ 2.2.5 Ia-negative derived variant cells by using a specific rabbit anti-human In chain antiserum. Two-dimensional gel electrophoresis of immunoprecipitates from either biosynthetically labeled or surface labeled cells were analyzed. In addition, flow microfluorometric analysis of stained cells was performed. The results indicate that the In chain is constitutively produced in the Ia-negative B cell variant. Moreover, it appears that several forms of In chain-related molecules, with different charges and distinct m.w. are equally expressed in Ia-positive and Ia-negative B cells. Finally, no evidence could be obtained that the In molecular family was expressed on the cell surface of Ia-positive Raji and Ia-negative RJ 2.2.5 cells.

Emotional attention as a modulatory system of perception

Report for the scientific sojourn carried out at the University Medical Center, Swiss, from 2010 to 2012. Abundant evidence suggests that negative emotional stimuli are prioritized in the perceptual systems, eliciting enhanced neural responses in early sensory regions as compared with neutral information. This facilitated detection is generally paralleled by larger neural responses in early sensory areas, relative to the processing of neutral information. In this sense, the amygdala and other limbic regions, such as the orbitofrontal cortex, may play a critical role by sending modulatory projections onto the sensory cortices via direct or indirect feedback.The present project aimed at investigating two important issues regarding these mechanisms of emotional attention, by means of functional magnetic resonance imaging. In Study I, we examined the modulatory effects of visual emotion signals on the processing of task-irrelevant visual, auditory, and somatosensory input, that is, the intramodal and crossmodal effects of emotional attention. We observed that brain responses to auditory and tactile stimulation were enhanced during the processing of visual emotional stimuli, as compared to neutral, in bilateral primary auditory and somatosensory cortices, respectively. However, brain responses to visual task-irrelevant stimulation were diminished in left primary and secondary visual cortices in the same conditions. The results also suggested the existence of a multimodal network associated with emotional attention, presumably involving mediofrontal, temporal and orbitofrontal regions Finally, Study II examined the different brain responses along the low-level visual pathways and limbic regions, as a function of the number of retinal spikes during visual emotional processing. The experiment used stimuli resulting from an algorithm that simulates how the visual system perceives a visual input after a given number of retinal spikes. The results validated the visual model in human subjects and suggested differential emotional responses in the amygdala and visual regions as a function of spike-levels. A list of publications resulting from work in the host laboratory is included in the report.

Emotional attention as a modulatory system of perception

Report for the scientific sojourn carried out at the University Medical Center, Swiss, from 2010 to 2012. Abundant evidence suggests that negative emotional stimuli are prioritized in the perceptual systems, eliciting enhanced neural responses in early sensory regions as compared with neutral information. This facilitated detection is generally paralleled by larger neural responses in early sensory areas, relative to the processing of neutral information. In this sense, the amygdala and other limbic regions, such as the orbitofrontal cortex, may play a critical role by sending modulatory projections onto the sensory cortices via direct or indirect feedback.The present project aimed at investigating two important issues regarding these mechanisms of emotional attention, by means of functional magnetic resonance imaging. In Study I, we examined the modulatory effects of visual emotion signals on the processing of task-irrelevant visual, auditory, and somatosensory input, that is, the intramodal and crossmodal effects of emotional attention. We observed that brain responses to auditory and tactile stimulation were enhanced during the processing of visual emotional stimuli, as compared to neutral, in bilateral primary auditory and somatosensory cortices, respectively. However, brain responses to visual task-irrelevant stimulation were diminished in left primary and secondary visual cortices in the same conditions. The results also suggested the existence of a multimodal network associated with emotional attention, presumably involving mediofrontal, temporal and orbitofrontal regions Finally, Study II examined the different brain responses along the low-level visual pathways and limbic regions, as a function of the number of retinal spikes during visual emotional processing. The experiment used stimuli resulting from an algorithm that simulates how the visual system perceives a visual input after a given number of retinal spikes. The results validated the visual model in human subjects and suggested differential emotional responses in the amygdala and visual regions as a function of spike-levels. A list of publications resulting from work in the host laboratory is included in the report.