Emotional modulation of the ability to inhibit a prepotent response during childhood.

The present study examined the bottom-up influence of emotional context on response inhibition, an issue that remains largely unstudied in children. Thus, 62 participants, aged from 6 to 13 years old, were assessed with three stop signal tasks: one with circles, one with neutral faces, and one with emotional faces (happy and sad). Results showed that emotional context altered response inhibition ability in childhood. However, no interaction between age and emotional influence on response inhibition was found. Positive emotions were recognized faster than negative emotions, but the valence did not have a significant influence on response inhibition abilities.

Pain intensity among institutionalized elderly: a comparison between numerical scales and verbal descriptors

AbstractOBJECTIVECorrelating two unidimensional scales for measurement of self-reported pain intensity for elderly and identifying a preference for one of the scales.METHODA study conducted with 101 elderly people living in Nursing Home who reported any pain and reached ( 13 the scores on the Mini-Mental State Examination. A Numeric Rating Scale - (NRS) of 11 points and a Verbal Descriptor Scale (VDS) of five points were compared in three evaluations: overall, at rest and during movement.RESULTSWomen were more representative (61.4%) and the average age was 77.0±9.1 years. NRS was completed by 94.8% of the elderly while VDS by 100%. The association between the mean scores of NRS with the categories of VDS was significant, indicating convergent validity and a similar metric between the scales.CONCLUSIONPain measurements among institutionalized elderly can be made by NRS and VDS; however, the preferred scale for the elderly was the VDS, regardless of gender.

Modulation of inflammatory pathways by the HIV protease inhibitors

Les inhibiteurs de la protéase du VIH (IP) constituent une des classes de traitements antirétroviraux parmi les plus utilisés au cours de l'infection par le VIH. Leur utilisation est associée à divers effets secondaires, notamment la dyslipidémie, la résistance à l'insuline, la lipodystrophie et certaines complications cardio-vasculaires. Ces molécules ont également des propriétés anti-tumorales, décrites chez des patients non infectés par le VIH. Pourtant, les mécanismes moléculaires à l'origine de ces effets annexes restent méconnus. Dans ce travail, nous démontrons que les IP, comme le Nelfinavir, le Ritonavir, le Lopinavir, le Saquinavir et l'Atazanavir, entrainent la production d'interleukine-lß (IL-lß), une puissante cytokine pro-inflammatoire, connue pour son rôle central dans les maladies inflammatoires. La sécrétion d'IL-lß requiert la formation de l'inflammasome, un complexe protéique intracellulaire servant de plateforme d'activation de la caspase-1 et, par la suite, à la maturation protéolytique de certaines cytokines, dont l'IL-lß. Dans les macrophages murins en culture primaire, ainsi que dans une lignée de monocytes humains, nous démontrons que les IP augmentent la maturation et la sécrétion de l'IL-lß via l'induction d'un inflammasome dépendant de ASC. De plus, nous établissons que les IP induisent spécifiquement l'activation de AIM2, un inflammasome détectant la présence intracytosolique d'ADN viral ou bactérien. Nos résultats démontrent l'existence d'une nouvelle voie d'activation de l'inflammasome AIM2 par un signal endogène dont la nature reste à définir. Ces données suggèrent que AIM2 pourrait jouer un rôle important dans la promotion de l'activité anti-tumorale ainsi que dans les autres effets annexes observés chez les patients traités par IP. -- HIV protease inhibitors (Pis) are among the most often used classes of antiretroviral drugs for HIV infection. Treatment of patients with HIV-PIs is associated with the development of metabolic side effects including dyslipidemia, insulin resistance, lipodystrophy and cardiovascular complications. In addition, these drugs have been reported to have anti¬tumoral properties in non-infected patients, however the molecular mechanisms causing these off-target effects are still unclear. Here we show that the HIV-PIs, such as Nelfinavir, Ritonavir, Lopinavir, Saquinavir and Atazanavir, activate the production of interleukin-lß (IL-lß), a potent pro-inflammatory cytokine that plays a central role in the pathogenesis of inflammatory diseases. The release of IL-lß depends on the activation of the inflammasome, a multiprotein complex that serves as a platform for caspase-1 activation and subsequent proteolytic maturation of cytokines including IL-lß. We found that in mouse primary macrophages as well as in a human monocytic cell line, the HIV-PIs augment the maturation and secretion of IL-lß by triggering an ASC-dependent inflammasome activation. Moreover, we show that the HIV-PIs specifically engage AIM2, a recently characterized inflammasome -forming protein that was described to detect the cytosolic release of bacterial and viral DNA. Our findings demonstrate a new pathway of activation of the AIM2 inflammasome by a yet to be defined endogenous signal and may suggest a possible role for AIM2 in promoting anti¬tumoral activity and off-target effects observed in HIV-PIs treated patients.

L'orientation du patient souffrant d'un syndrome douloureux abdominal aigu a domicile [Hospitalisation criteria for the acute abdominal pain patient seen at home or in an ambulatory setting].

Dealing at patient's home with an acute abdominal pain may be particularly challenging for the primary care physician. In such a clinical situation, the part of laboratory and radiological investigations is increasing in the diagnostic process. The decision to keep the patient at home based on a clinical evaluation alone may represent a great medical responsibility for the physician. Emergency departments (ED) are of course in charge of investigating such patients with a wide panel of investigation techniques. But these structures are chronically overcrowded resulting frequently in long and difficult periods of waiting. Based on a literature review, a description of useful clinical symptoms and signs is summarized and should help the decision process for the orientation of the patient.

What kind of relationships between the evolution of pain, beliefs and bio-psycho-social complexity after a locomotor traumatism?

Introduction: Pain and beliefs have an influence on the patient's course in rehabilitation, pain causes fears and fears influence pain perception. The aim of this study is to understand pain and beliefs evolutions during rehabilitation taking into account of bio-psycho-social complexity.Patients and methods: 631 consecutive patients admitted in rehabilitation after a musculoskeletal traumatism were included and assessed at admission and at discharge. Pain was measured by VAS (Visual Analogical Scale), bio-psycho-social complexity by Intermed scale, and beliefs by judgement on Lickert scales. Four kinds of beliefs were evaluated: fear of a severe origin of pain, fear of movement, fear of pain and feeling of distress (loss of control). The association between the changes in pain and beliefs during the hospitalization was assessed by linear regressions.Results: After adjustment for gender, age, education and native language, patients with a decrease in pain during rehabilitation have higher probability of decreasing their fears. For the distress feeling, this relationship is weaker among bio-psycho-socially complex patients (odds-ratio 1.22 for each decreasing of 10mm/100 VAS) than among non-complex patients (OR 1.47). Patients with a pain decrease of 30% or more during hospitalization have higher probability of seeing their fears decrease, this relationship being stronger in complex patient for fear of a severe origin of pain.Discussion: The relationships between evolution of pain and beliefs move in the same direction. The higher a patient feels pain, the less they could be able to modify their dysfunctional beliefs. When the pain diminishes of 30% or more, the probability to challenge the beliefs is increased. The prognostic with regard to feeling of distress and fear of a severe origin of pain, is worse among bio-psycho-socially complex patients.

Behavioural alteration in chronic pain: are brain glia involved?

Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive chronic pain-associated impairments. Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or schizophrenia) glial changes in brain regions involved in mood control (prefrontal and cingulate cortices, amygdala and the hippocampus) have been recurrently described. Besides, glial cells have been undoubtedly identified as key actors in the sensory component of chronic pain, owing to the profound phenotypical changes they undergo throughout the sensory pathway. Hence, the possibility arises that brain astrocytes and microglia react in upper brain structures as well, mediating the related mood and cognitive dysfunctions in chronic pain. So far, only very few studies have provided results in this prospect, mainly indirectly in pain-independent researches. Nevertheless, the first scant available data seem to merge in a unified description of a brain glial reaction occurring after chronic peripheral lesion. The present article uses this scarce literature to formulate the provocative theory of a glia-driven mood and cognitive dysfunction in chronic pain, expounding upon its validity and putative therapeutical impact as well as its current limitations and expected future developments.

Implementation study of a clinical prediction score to rule out cardiogenic chest pain in community: Cluster randomized trial

1.1 Fundamentals Chest pain is a common complaint in primary care patients (1 to 3% of all consultations) (1) and its aetiology can be miscellaneous, from harmless to potentially life threatening conditions. In primary care practice, the most prevalent aetiologies are: chest wall syndrome (43%), coronary heart disease (12%) and anxiety (7%) (2). In up to 20% of cases, potentially serious conditions as cardiac, respiratory or neoplasic diseases underlie chest pain. In this context, a large number of laboratory tests are run (42%) and over 16% of patients are referred to a specialist or hospitalized (2).¦A cardiovascular origin to chest pain can threaten patient's life and investigations run to exclude a serious condition can be expensive and involve a large number of exams or referral to specialist -­‐ often without real clinical need. In emergency settings, up to 80% of chest pains in patients are due to cardiovascular events (3) and scoring methods have been developed to identify conditions such as coronary heart disease (HD) quickly and efficiently (4-­‐6). In primary care, a cardiovascular origin is present in only about 12% of patients with chest pain (2) and general practitioners (GPs) need to exclude as safely as possible a potential serious condition underlying chest pain. A simple clinical prediction rule (CPR) like those available in emergency settings may therefore help GPs and spare time and extra investigations in ruling out CHD in primary care patients. Such a tool may also help GPs reassure patients with more common origin to chest pain.

Exercise and nonspecific low back pain: a literature review.

We reviewed the literature to clarify the effects of exercise in preventing and treating nonspecific low back pain. We evaluated several characteristics of exercise programs including specificity, individual tailoring, supervision, motivation enhancement, volume, and intensity. The results show that exercise is effective in the primary and secondary prevention of low back pain. When used for curative treatment, exercise diminishes disability and pain severity while improving fitness and occupational status in patients who have subacute, recurrent, or chronic low back pain. Patients with acute low back pain are usually advised to continue their everyday activities to the greatest extent possible rather than to start an exercise program. Supervision is crucial to the efficacy of exercise programs. Whether general or specific exercises are preferable is unclear, and neither is there clear evidence that one-on-one sessions are superior to group sessions. Further studies are needed to determine which patient subsets respond to specific characteristics of exercise programs and which exercise volumes and intensities are optimal.

Modulation of cdk2, cyclin D1, p16INK4a, p21WAF and p27Kip1 expression in endothelial cells by TNF/IFN gamma.

BACKGROUND: Regional administration of high doses of tumor necrosis factor (TNF) and interferon gamma (IFN gamma) to metastatic melanoma patients causes selective disruption of the tumor vasculature. This effect is paralleled by decreased endothelial cell proliferation and suppressed integrin alpha V beta 3-mediated adhesion in vitro. Overexpression of the cyclin-dependent kinase (cdk) inhibitory protein p16INK4a was reported to interfere with integrin alpha V beta 3-dependent melanoma cell adhesion. MATERIALS AND METHODS: TNF- and IFN gamma-treated HUVEC were analyzed for cell cycle progression and for protein expression by flow cytometry and Western blotting, respectively. p16INK4a was overexpressed by transient transfection, and HUVEC adhesion was tested in short-term adhesion assays. RESULTS: TNF and IFN gamma synergistically induced a G1 arrest associated with reduced levels of cyclin D1 and cdk2, and increased expression of the cdk inhibitors p16INK4a, p21WAF and p27Kip1. p16INK4a overexpression, however, had no effect on alpha V beta 3-mediated adhesion. CONCLUSION: These results implicate the down-regulation of cyclin D1 and cdk-2, and up-regulation of p16INK4a, p21WAF and p27Kip1 in the suppression of endothelial cell proliferation induced by TNF/IFN gamma and demonstrate that increased p16INK4a levels are not sufficient to suppress alpha V beta 3-mediated endothelial cell adhesion.

Der akute anale Schmerz [Acute anal pain].

Acute anal pain is a common proctological problem. A detailed history together with the clinical examination are crucial for the diagnosis. An acute perianal vein thrombosis can be successfully excised within the first 72 hours. Acute anal fissures are best treated conservatively using stool regulation and topical medications reducing the sphincter spasm. A chronic anal fissure needs surgery. Perianal abscesses can very often be incised and drained in local anesthesia. Proctalgia fugax and the levator ani syndrome are exclusion diagnoses and are treated symptomatically.

Hommes et femmes: sommes-nous tous égaux face à la douleur [Are there differences between men and women with pain?].

An increasing number of articles are published on the differences about pain in men and women. These differences seem to be due to the sex, the biological dimension of the person, and to the gender, which is the role given to that person in a given social and culture environment. The pain prevalence is higher in women, its threshold and tolerance are lower. The pain interpretation, its perception and the coping is also different in men and women. Finally doctors translate and treat pain differently. This article proposes some explanations on these differences which should help us to treat this frequent and noxious symptom for the quality of life in a better way.

Influence of CYP2D6 activity on pre-emptive analgesia by the N-methyl-D-aspartate antagonist dextromethorphan in a randomized controlled trial of acute pain.

BACKGROUND: There is some evidence that dextromethorphan (DM) is effective as a pre-emptive analgesic agent.  DM is mainly metabolized to dextrorphan (DOR) by CYP2D6 whose activity can be inhibited by pharmacologic intervention. OBJECTIVES: To investigate the efficacy of DM as a pre-emptive analgesic agent and describe the population pharmacokinetics in the presence of normal and poor CYP2D6 metabolism in acute post-operative pain. STUDY DESIGN: Double blind, randomized, placebo-controlled trial SETTING: Post-surgical analgesic consumption after knee ligament surgery, a setting of acute pain. METHODS: Forty patients were randomized to a single oral dose of 50 mg quinidine or placebo, administered 12 hours before 50 mg DM. Patients were genotyped for the major CYP2D6 and ABCB1 variants and phenotyped for CYP2D6 using urine DM/DOR metabolic ratios and blood samples for population pharmacokinetic modeling. RESULTS: Quinidine was effective in inhibiting CYP2D6 activity, with 2-fold reduction of DM to DOR biotransformation clearance, prolonged DM half-life, and increased DM systemic availability. Patients in the quinidine group required significantly less often NSAIDs than patients in the placebo group (35.3% vs. 75.0%, P = 0.022). The odds ratio for NSAID consumption in the placebo vs. quinidine group was 5.5 (95% confidence interval (CI) 1.3 - 22.7) at 48 hours after surgery. LIMITATIONS: While this study shows an impact of DM on pre-emptive analgesia and is mechanistically interesting, the findings need to be confirmed in larger trials. CONCLUSION: CYP2D6 inhibition by quinidine influenced the pre-emptive analgesic effectiveness of DM confirming that CYP2D6 phenotypic switch increases the neuromodulatory effect of oral dextromethorphan.