Neural reward processing in individuals remitted from major depression.

BACKGROUND: Dysfunctional behavioural and neural processing of reward has been found in currently depressed individuals. However, little is known about altered reward processing in remitted depressed individuals. METHOD: A total of 23 medication-free individuals with remitted major depressive disorder (rMDD) and 23 matched healthy controls (HCs) performed a reward task during functional magnetic resonance imaging. We also investigated reward dependence, novelty seeking and harm avoidance using the Tridimensional Personality Questionnaire and their association with neural responses of reward processing. RESULTS: Compared to HCs, individuals with rMDD exhibited enhanced responses to reward-predicting cues in the hippocampus, amygdala and superior frontal gyrus. When reward was delivered, rMDD subjects did not significantly differ from HCs. In both groups neural activity during reward anticipation was negatively correlated with harm avoidance. CONCLUSIONS: Our results show that rMDD is characterized by hyperactivation in fronto-limbic regions during reward anticipation. Alterations in neural activation during reward processing might reflect an increased effort in remitted depressed individuals to allocate neural activity for executive and evaluative processes during anticipatory reward processing.

Rationale and design of INTERSTROKE: a global case-control study of risk factors for stroke.

UNLABELLED: Stroke is a major global health problem. It is the third leading cause of death and the leading cause of adult disability. INTERHEART, a global case-control study of acute myocardial infarction in 52 countries (29,972 participants), identified nine modifiable risk factors that accounted for >90% of population-attributable risk. However, traditional risk factors (e.g. hypertension, cholesterol) appear to exert contrasting risks for stroke compared with coronary heart disease, and the etiology of stroke is far more heterogeneous. In addition, our knowledge of risk factors for stroke in low-income countries is inadequate, where a very large burden of stroke occurs. Accordingly, a similar epidemiological study is required for stroke, to inform effective population-based strategies to reduce the risk of stroke. METHODS: INTERSTROKE is an international, multicenter case-control study. Cases are patients with a first stroke within 72 h of hospital presentation in whom CT or MRI is performed. Proxy respondents are used for cases unable to communicate. Etiological and topographical stroke subtype is documented for all cases. Controls are hospital- and community-based, matched for gender, ethnicity and age (+/-5 years). A questionnaire (cases and controls) is used to acquire information on known and proposed risk factors for stroke. Cardiovascular (e.g. blood pressure) and anthropometric (e.g. waist-to-hip ratio) measurements are obtained at the time of interview. Nonfasting blood samples and random urine samples are obtained from cases and controls. Study Significance: An effective global strategy to reduce the risk of stroke mandates systematic measurement of the contribution of the major vascular risk factors within defined ethnic groups and geographical locations.

Comparison of adverse events of biologicals for treatment of juvenile idiopathic arthritis: a systematic review.

Objectives: Treatment of juvenile idiopathic arthritis has changed rapidly since the introduction of various biologics almost twenty years ago. Many clinical trials have been performed to monitor efficacy and safety of new agents. The aim of this review is to summarize safety concerns, which were observed during prospective clinical trials. Methods: Since etanercept was the first biologic approved and remains the most frequently used, as first biologic in polyarticular JIA patients, the authors calculated the relative risk of the adverse events for all examined biologicals and compared the values with the value of etanercept. Results: Relative rates for all adverse events showed similar rates for etanercept, infliximab, golimumab, and tocilizumab, whereas adalimumab showed higher rates and abatacept lower rates. Comparison of rates for serious adverse events demonstrated, that rates seemed comparable for etanercept, adalimumab, infliximab, and tocilizumab. Again, abatacept showed a lower rate, whereas golimumab seems to have a higher relative risk for serious adverse events. Rate of infection was lowest in patients treated with abatacept or tocilizumab, patients treated with etanercept, adalimumab and Infliximab again had similar rates. Conclusion: The safety profiles of actually approved biologics are highly acceptable. However, further observation, especially long-term observation through registry studies, is required.

Experimental cranial pain elicited by capsaicin: a PET study.

Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.

cDNA cloning of a novel secreted isoform of the human receptor for advanced glycation end products and characterization of cells co-expressing cell-surface scavenger receptors and Swedish mutant amyloid precursor protein.

The receptor for advanced glycation end products (RAGE) has been proposed as a cell surface receptor that binds amyloid-beta protein (Abeta), thereby triggering its cytotoxic effects [S.D. Yan, X. Chen, J. Fu, M. Chen, H. Zhu, A. Roher, T. Slattery, L. Zhao, M. Nagashima, J. Morser, A. Migheli, P. Nawroth, D. Stern, A.M. Schmidt, RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease, Nature 382 (1996) 685-691.]. A cDNA library of human lung was screened for RAGE with an appropriate hybridization probe. In addition to cell surface RAGE, one clone was found which encodes a new version of RAGE, termed hRAGEsec, which lacks the 19 amino acids of the membrane-spanning region and is therefore secreted. Comparison with the genomic sequence revealed that the synthesis of the secreted isoform requires alternative splicing. The deduced protein sequence of the mature hRAGEsec consists of 321 amino acids with a predicted molecular mass of 35.66 kDa. The pattern of expression of hRAGEsec in human brain was analyzed by in situ hybridization histochemistry. The most intense expression of the gene in contrast to cell surface RAGE was detected in hippocampal CA3 pyramidal cells, dentate gyrus granule cells, cortical neurons as well as glial cells in white matter. To investigate the interaction between Abeta and RAGE and another scavenger receptor, SRA, under physiological conditions, they were co-expressed with human betaAPP(695)-SFAD in a human cell and the level of Abeta in the condition medium was assessed by immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) analysis. A nearly 100% reduction of Abeta from the conditioned medium of hRAGE cells and approximately 40% reduction from the SRA-cells implied that hRAGE could be a prominent cell surface receptor interacting with Abeta.

An analysis of learned helplessness: II. The processing of success.

Helpless children attribute their failures to lack of ability and view them as insurmountable. Mastery-oriented children, in contrast, tend to emphasize motivational factors and to view failure as surmountable. Although the performance of the two groups is usually identical during success of prior to failure, past research suggests that these groups may well differ in the degree to which they perceive that their successes are replicable and hence that their failures are avoidable. The present study was concerned with the nature of such differences. Children performed a task on which they encountered success and then failure. Half were asked a series of questions about their performance after success and half after failure. Striking differences emerged: Compared to mastery-oriented children, helpless children underestimated the number of success (and overestimated the number of failures), did not view successes as indicative of ability, and did not expect the successes to continue. subsequent failure led them to devalue ;their performance but left the mastery-oriented children undaunted. Thus, for helpless children, successes are less salient, less predictive, and less enduring--less successful.

Factors predicting the subjective well-being of nations.

Subjective well-being (SWB) in 55 nations, reported in probability surveys and a large college student sample, was correlated with social, economic, and cultural characteristics of the nations. The SWB surveys, representing nations that include three fourths of the earth's population, showed strong convergence. Separate measures of the predictor variables also converged and formed scales with high reliability, with the exception of the comparison variables. High income, individualism, human rights, and societal equality correlated strongly with each other, and with SWB across surveys. Income correlated with SWB even after basic need fulfillment was controlled. Only individualism persistently correlated with SWB when other predictors were controlled. Cultural homogeneity, income growth, and income comparison showed either low or inconsistent relations with SWB.

Development of alcohol-associated cues and cue-induced brain activation in alcoholics.

The objective of this study was to develop new standardized alcohol-associated cues and assess their effects on brain activation with functional magnetic resonance imaging (fMRI). Pictures of alcoholic and neutral beverages and affectively neutral pictures were presented to 44 abstinent alcoholics and 37 age-matched healthy control subjects. We assessed the skin conductance response, and the elicited arousal and valence. Alcoholics and control subjects did not differ in arousal, valence or skin conductance response evoked by alcohol-associated and affectively neutral stimuli, while nonalcoholic beverages were rated as more unpleasant and arousing by alcoholics compared with control subjects. In the fMRI pilot study, alcohol and abstract pictures were presented to six abstinent alcoholics and induced a significant activation of brain areas associated with visual emotional processes such as the fusiform gyrus, parts of the brain reward system (basal ganglia and orbitofrontal gyrus) and further brain regions in the frontal and parietal cortices associated with the attention network. These observations suggest that standardized pictures of alcoholic beverages can be used to assess brain circuits involved in the processing and evaluation of alcohol cues.

Attributional style and learned helplessness: relationship to the use of causal schemata and depressive symptoms in children.

The attributional style associated with learned helplessness in children is examined in terms of its stability over a six-month period; impact on causal schemata used by children; and association with depressive symptoms. Seventy-three fifth grade children provided attributions for success and failure and were divided into learned helpless and mastery-oriented groups on the basis of the attributions typically associated with these response patterns. The attributional styles were relatively stable, influenced responses to stimuli used to investigate the use of causal schemata and were related to depressive symptoms. These results are discussed in terms of research on learned helplessness in children and several research questions are identified.

Effects of stressor controllability on psychophysiological, cognitive and behavioural responses in patients with major depression and dysthymia.

BACKGROUND: The experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed. METHOD: A total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1-S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram. RESULTS: Depressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample. CONCLUSIONS: These findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.

Cross-reactions among grass pollen allergens.

We studied cross-reactions of pollen extracts from the grasses Phleum pratense, Lolium perenne, Poa pratensis and Festuca pratensis. We used immunoelectrophoretic techniques (Tandem-CIE, absorption in situ) and RAST inhibition, which allowed us to detect the high antigenic and allergenic relationships of the single grass pollens. Phleum pratense, however, revealed antigenic and allergenic differences as compared to the other 3 grasses.

Further observations on the course and prognosis of chronic obstructive lung disease.

Long-term survival data are presented for 200 patients with chronic airway obstruction of uncertain etiology who were enrolled in a prospective study approximately 14 years ago. Early death rates were closely related to the initial level of ventilatory impairment. Subjects with relatively mild impairment on entry to the study had a favorable prognosis for the first 5 to 7 years of follow-up but then began to show a higher death rate; there are few long-term survivors in the total series.

[Identification of allergens in 5 grasses using crossed radioimmunoelectrophoresis (CRIE)]. / Allergenidentifizierung bei 5 Gräsern mit Hilfe der gekreuzten Radioimmunelektrophorese (CRIE).

Using crossed radioimmunoelectrophoresis ( CRIE ) aqueous extracts from pollen of Phleum pratense , Lolium perenne, Poa pratensis , Festuca pratensis and Alopecurus pratensis were investigated for allergen composition. We detected between 24 and 32 antigens. Employing sera from 11 patients with well established hay fever, IgE binding could be demonstrated in 15 out of 28 antigens in Phleum pratense , 13 out of 32 in Lolium perenne, 14 out of 26 in Poa pratensis , 12 out of 24 Festuca pratensis and 12 out of 24 antigens in Alopecurus pratensis . The 11 patients showed an individual pattern of sensitization against the various pollen allergens.

[Pollinosis in chrysanthemum growers]. / Pollinosis bei Chrysanthemenzüchtern.

Pollinosis, first of all mugwort pollinosis, due to pollens of wind pollinated Asteraceae is not seldom. On the other hand allergic reactions to pollens of insect pollinated members of this plant family are a rarity. 8 cases of pollinosis to Chrysanthemums in a floriculture farm are offered, caused by the work specific conditions of exposure in artificial pollination. The analysis of allergens and RAST inhibition tests showed us a close relationship of allergens of Chrysanthemum pollens and pollens of mugwort. It was possible to continue cultivating work in all cases because of several protective measures and hyposensitization.

Increased shortening reaction in Parkinson's disease reflects a difficulty in modulating long loop reflexes.

Short and medium latency electromyographic (EMG) responses to stretch of the triceps surae muscle and long latency EMG responses (LL) in the anterior tibial muscle (TA) were evoked by toe-up tilt of a movable platform while standing or sitting, in normal subjects and patients with Parkinson's disease. With the stimulus parameters used (amplitude 4 degrees, velocity 50 degrees/s), LL in TA were absent in normals while sitting, but were present in 11 of the 12 patients with Parkinson's disease. In patients, LL latencies were identical in both positions. The results indicate that patients with Parkinson's disease have difficulty modulating long latency responses according to functional demands. Long latency responses in TA in the sitting position may correspond to the shortening reaction observed by others when much stronger stimuli were used.

Antigens of Timothy and other grass pollen extracts identified by monoclonal antibodies.

Using a series of monoclonal antibodies raised against pollen extract of timothy grass pollen (Phleum pratense) we identified individual (species-specific) and cross-reactive epitopes shared by different grass and tree pollens in EIA experiments. These epitopes are heterogenously distributed as detected by means of immunoblotting. Crossed radioimmunoelectrophoresis experiments revealed binding of monoclonal antibodies to major allergens of timothy grass pollen extract.

The relationship between frequency of ventilator circuit changes and infectious hazard.

The relationship between frequency of ventilator circuit changes and risk of ventilator-associated pneumonia was studied using 2 independent approaches. The first was an in-use aerosol contamination study with patients on 8-hour, 16-hour, or 24-hour ventilator changing schedules. The second approach was a study comparing the incidence of pneumonia in patients on ventilators for 2 one-year periods when the ventilator circuit changing time differed. In-use aerosol sampling of 513 ventilator treatment periods showed bacterial contamination greater than 100 organisms per aerosol in 1.8 per cent of 8-hour cycles, in 2.5 per cent of 16-hour cycles, and in 5.4 per cent of 24-hour cycles. These differences were not significant. The incidence of ventilator-associated pneumonia was the same for one-year periods when ventilator circuits were changed either every 8 or every 24 hours. It was concluded that changing ventilator circuits every 24 hours provides adequate protection from ventilator-associated pneumonia.