Talking bodies: nonverbal behavior in the assessment of depression severity

BACKGROUND: Evaluations of clinical depression are traditionally based on verbal information. Nonverbal expressive behavior, however, being associated with a person's reflexive responses, may reveal negative emotional or social processes that are not under complete control of the patients. However, investigations of nonverbal behavior in the evaluation of depressed patients are still scarce. This study examines the nonverbal behaviors of a group of Brazilian patients, associating their nonverbal behavior with severity of depression. METHODS: Forty depressed patients were evaluated at baseline (T0) and after a two-week transcranial direct current stimulation treatment (T1), according to rating scales and through a 21-category Ethogram for assessment of the frequency of nonverbal behaviors displayed during an interview. RESULTS: Behaviors that were related to negative feelings and social disinterest decreased with corresponding clinical improvement and were associated with increased severity of symptoms at T0 and greater negative affect and dissatisfaction at T1. Pro-social behaviors were associated with milder symptoms at T0 and increased after treatment. Facial, head and hand expressive movements stood out as important indicators because of their associations with severity of depression. LIMITATIONS: Duration of behaviors was not assessed and there was not a healthy control group with which to compare the findings. CONCLUSIONS: These results support the usefulness of nonverbal behavior as an evaluation technique in the assessment of clinical depression.

The ergogenic effect of recombinant human erythropoietin on VO2max depends on the severity of arterial hypoxemia

Treatment with recombinant human erythropoietin (rhEpo) induces a rise in blood oxygen-carrying capacity (CaO(2)) that unequivocally enhances maximal oxygen uptake (VO(2)max) during exercise in normoxia, but not when exercise is carried out in severe acute hypoxia. This implies that there should be a threshold altitude at which VO(2)max is less dependent on CaO(2). To ascertain which are the mechanisms explaining the interactions between hypoxia, CaO(2) and VO(2)max we measured systemic and leg O(2) transport and utilization during incremental exercise to exhaustion in normoxia and with different degrees of acute hypoxia in eight rhEpo-treated subjects. Following prolonged rhEpo treatment, the gain in systemic VO(2)max observed in normoxia (6-7%) persisted during mild hypoxia (8% at inspired O(2) fraction (F(I)O(2)) of 0.173) and was even larger during moderate hypoxia (14-17% at F(I)O(2) = 0.153-0.134). When hypoxia was further augmented to F(I)O(2) = 0.115, there was no rhEpo-induced enhancement of systemic VO(2)max or peak leg VO(2). The mechanism highlighted by our data is that besides its strong influence on CaO(2), rhEpo was found to enhance leg VO(2)max in normoxia through a preferential redistribution of cardiac output toward the exercising legs, whereas this advantageous effect disappeared during severe hypoxia, leaving augmented CaO(2) alone insufficient for improving peak leg O(2) delivery and VO(2). Finally, that VO(2)max was largely dependent on CaO(2) during moderate hypoxia but became abruptly CaO(2)-independent by slightly increasing the severity of hypoxia could be an indirect evidence of the appearance of central fatigue.

Der Einfluss von TGF-beta1 auf regulatorische T-Zellen in einem murinen Modell für Asthma

Ziel der vorliegenden Arbeit war es, den Einfluss von regulatorischen T-Zellen (Treg) auf die Pathogenese des Asthmas in einem murinen Modell zu untersuchen. Es konnte gezeigt werden, dass die Co-Expression von TGF-ß1 und IL-10 auf Treg notwendig ist, um im Tiermodell vor einer Atemwegs-Hyperreagibilität (AHR) zu schützen. Natürliche Treg konnten keinen Schutz vermitteln. Weiterhin wurde gezeigt, dass der Schutz vor AHR durch TGF-ß1 über Empfänger T-Zellen vermittelt wird. Dabei reichte die alleinige Anwesenheit von TGF-ß1 nicht aus, vielmehr musste das Zytokin von Treg exprimiert werden. Ein Einfluss von TGF-ß1 überexprimierenden Treg auf die peribronchiale Entzündung konnte nicht festgestellt werden, wohingegen adoptiver Transfer von natürlichen Treg die Eosinophilen Anzahl in der Bronchiallavage signifikant verringern konnte. Dabei korrelierte die Eosinophilie mit den IL-5 Spiegeln in der Bronchiallavage. In dieser Arbeit konnte also eine Entkopplung der Mechanismen von AHR und Entzündung festgestellt werden. Die weitere Aufklärung der Mechanismen der Suppression der AHR durch TGF-ß1 und IL-10 produzierende Treg könnte daher die Entwicklung neuer therapeutischer Ansätze bei Atemwegserkrankungen ermöglichen.

Die Rolle regulatorischer T-Zellen im experimentellen allergischen Asthma

Im ersten Teil der Dissertation wurde in einem experimentellen Asthmamodell demonstriert, dass die Signaltransduktion über IL-6 das Gleichgewicht zwischen Effektorzellen und regulatorischen T-Zellen durch verschiedene Rezeptorkomponenten kontrolliert. Hierbei zeigte sich, dass speziell das IL-6 Trans-Signaling über den sIL-6R die TH2 Cytokinproduktion steuert. Dagegen führt die Blockade des mIL-6R zur Expansion regulatorischer T-Zellen mit suppressiven Eigenschaften. Diese CD4+CD25+ Tregs induzieren außerdem IFN gamma produzierende CD4+ T-Zellen in der Lunge und verbessern daneben die AHR. Im Überblick konnte in der vorliegenden Dissertation demonstriert werden, dass IL-6 die Balance zwischen der Funktion von Effektorzellen und regulatorischen T-Zellen in der Lunge über unterschiedliche Wege kontrolliert, dem sIL-6R und dem mIL-6R. Im zweiten Teil der Arbeit wurde die lokale Blockade der IL-2R alpha- und IL-2R beta-Kette untersucht. Hier konnte gezeigt werden, dass die Blockade der IL-2R beta-Kette zur Verbesserung der AHR als auch der Rekrutierung eosinophiler Granulozyten in den Atemwegen führt. Beide Blockaden führen zur Reduktion der TH2 Cytokine IL-4 und IL-5, wohingegen IL-13 nur nach Blockade der IL-2R beta-Kette vermindert sezerniert wird. In diesem Zusammenhang wurde auch die Rolle CD4+CD25+ regulatorischer T-Zellen untersucht, wobei eine Induktion dieser Population in den Lymphknoten nach Blockade der IL-2R beta-Kette nachgewiesen werden konnte. Die Blockade der IL-2R beta-Kette wirkt sich positiv auf experimentelle Asthmastudien aus und stellt somit ein mögliches therapeutisches Potential dar, erfordert aber teilweise noch weitere Untersuchungen.

Biomarkers in chronic obstructive pulmonary diseases. Clinical and functional correlations.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct lung diseases with distinctive clinical and inflammatory features. A proportion of asthmatic patients experience a fixed airflow obstruction that persists despite optimal pharmacologic treatment for reasons that are still largely unknown. We found that patients with asthma and COPD sharing a similar fixed airflow obstruction have an increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function is associated with specific features of the underlying inflammation. Airway inflammation increases during asthma exacerbation and disease severity. Less is known about the correlations between symptoms and airway inflammation in COPD patients. We found that there is no correlation between symptoms and lung function in COPD patients. Nevertheless symptoms changes are associated with specific inflammatory changes: cough is associated with an increase of sputum neutrophils in COPD, dyspnoea is associated with an increase of eosinophils. The mechanisms of this correlation remain unknown. Neutrophils inflammation is associated with bacterial colonization in stable COPD. Is not known whether inhaled corticosteroids might facilitate bacterial colonization in COPD patients. We found that the use of inhaled corticosteroids in COPD patients is associated with an increase of airway bacterial load and with an increase of airway pathogen detection. Bacterial and viral infections are the main causes of COPD and asthma exacerbations. Impaired innate immune responses to rhinovirus infections have been described in adult patients with atopic asthma. Whether this impaired immune condition is present early in life and whether is modulated by a concomitant atopic condition is currently unknown. We found that deficient innate immune responses to rhinovirus infection are already present early in life in atopic patients without asthma and in asthmatic subjects. These findings generalize the scenario of increased susceptibility to viral infections to other Th2 oriented conditions.

Die Rolle von Interleukin-22 bei Asthma bronchiale

Interleukin (IL)-22 ist ein Effektorzytokin, das von Zellen des Immunsystems produziert wird und auf Epithelzellen wirkt. Es nimmt eine duale Rolle ein, indem es abhängig vom Gewebe und Zytokinmilieu entweder entzündungsfördernden oder entzündungshemmenden Einfluss ausübt. Über seine Wirkung bei Asthma bronchiale ist bislang noch wenig bekannt. In der vorliegenden Arbeit konnten in einem murinen Modell der allergischen Atemwegsentzündung lymphoide Zellen des angeborenen Immunsystems als Hauptproduzenten für IL-22 detektiert werden, die bislang noch nicht im Zusammenhang mit Asthma bronchiale beschrieben wurden. Es konnte gezeigt werden, dass IL-22- defiziente Mäuse eine verstärkte Atemwegsentzündung entwickelten und sich die IL-22-Defizienz in diesem Modell entzündungsfördernd auf die induzierte Atemwegsentzündung auswirkte. Mit Hilfe einer murinen bronchialen Epithelzelllinie wurden die Mechanismen des IL-22 und die Expression Asthma-relevanter Mediatoren untersucht. Der beobachtete inhibierende IL-22-Effekt ließ sich mit Hilfe seines natürlichen Antagonisten IL-22BP neutralisieren. Diese entzündungshemmende Wirkung des IL-22 konnte ebenfalls in Wildtyp-Mäusen, denen rekombinantes IL-22 intratracheal verabreicht worden war, bestätigt werden.

Klinische, zelluläre und immunologische Charakterisierung des Asthmas im Hinblick auf die Asthma-Kontrolle

Asthma, eine der häufigsten Atemwegserkrankungen, ist ein komplexes Syndrom heterogener Phänotypen. Ihnen allen gemeinsam ist eine Entzündung der Atemwege mit bronchialer Hyperreagibilität und variabler Atemwegsobstruktion.Die Globale Initiative für Asthma (GINA) empfiehlt, eine Therapie am Grad der Asthmakontrolle zu orientieren. Es wird dabei zwischen kontrolliertem, teilweise kontrolliertem und unkontrolliertem Asthma unterschieden. rnDer vorliegenden Dissertation lag die Frage zu Grunde, inwieweit etablierte klinische, funktionelle, zelluläre und Labor-Parameter den Verlauf der Asthmakontrolle wiederspiegeln. Diese Parameter sollten bei klinisch stabiler Kontrolle ebenfalls stabil bleiben, oder eine Änderung gleichgerichtet wiedergeben. Hierzu wurden 120 Patienten im Hinblick auf ihre Asthmakontrolle kategorisiert und im zeitlichen Verlauf an 3 Visiten zum Zeitpunkt 0 (V0), eine Woche (V1) und 6 Monate später (V2) untersucht. Bestimmt wurden klinische Parameter wie Fragebögen zur Asthmakontrolle (ACQ-5 Scores), funktionelle Parameter wie die Lungenfunktion oder die bronchiale Hyperreagibilität zelluläre Parameter wie das Stickoxid im Exhalat (NO) als Korrelat der bronchialen Entzündung, der Anteil eosinophiler Granulozyten im Sputum, die Anzahl eosinophiler und neutrophiler Granulozyten pro nl Blut, die Gesamt-IgE-Spiegel im Serum und zellbiologische Parameter wie die Anteile regulatorischer T-Zellen und die Anteile der T-Zellen, die die Zytokine IFN-ɣ, IL-4, IL-5, IL-10, IL-13 und IL-17 produzieren.rnDie Verbesserung der Asthmakontrolle spiegelte sich in einem Rückgang des NOs um im Median 5,8 ppb (p=0,016) nach 6 Monaten wieder. Sonst ließen sich keine Parameter identifizieren, die die Entwicklung der Asthmakontrolle in positiver oder negativer Richtung abbildeten. Bemerkenswerter Weise bildete selbst der ACQ, der als etabliertes Messinstrument für die Asthmakontrolle gilt, diese Veränderungen nicht ab.rnZellbiologisch unterschieden sich die Patienten mit unterschiedlicher Asthmakontrolle weder in den Anteilen Zytokin-produzierender T-Zellen, noch im Anteil regulatorischer T-Zellen.rnDie Anteile der Zytokin-produzierenden T-Zellen unterlagen im zeitlichen Verlauf zwar deutlicheren Schwankungen als die Anteile regulatorischer T-Zellen, im Median blieben beide jedoch konstant. Die Anteile der Zytokin-produzierenden T-Zellen und regulatorischer Zellen lassen also keine Rückschlüsse auf den Verlauf der Asthmakontrolle zu.rnZusammenfassend ist lediglich das NO geeignet, die Verbesserung der Asthmakontrolle zu beschreiben. Deshalb erscheint es im Angesicht der Ergebnisse dieser Studie nicht sinnvoll, therapeutische Entscheidung lediglich auf Basis eines einzelnen Parameters zu treffen. Hierfür bleibt nach wie vor nur die Zusammenschau verschiedener Untersuchungsergebnisse.rn

Variability of lung function predicts loss of asthma control following withdrawal of inhaled corticosteroid treatment

BACKGROUND One aspect of a multidimensional approach to understanding asthma as a complex dynamic disease is to study how lung function varies with time. Variability measures of lung function have been shown to predict response to beta(2)-agonist treatment. An investigation was conducted to determine whether mean, coefficient of variation (CV) or autocorrelation, a measure of short-term memory, of peak expiratory flow (PEF) could predict loss of asthma control following withdrawal of regular inhaled corticosteroid (ICS) treatment, using data from a previous study. METHODS 87 adult patients with mild to moderate asthma who had been taking ICS at a constant dose for at least 6 months were monitored for 2-4 weeks. ICS was then withdrawn and monitoring continued until loss of control occurred as per predefined criteria. Twice-daily PEF was recorded during monitoring. Associations between loss of control and mean, CV and autocorrelation of morning PEF within 2 weeks pre- and post-ICS withdrawal were assessed using Cox regression analysis. Predictive utility was assessed using receiver operator characteristics. RESULTS 53 out of 87 patients had sufficient PEF data over the required analysis period. The mean (389 vs 370 l/min, p<0.0001) and CV (4.5% vs 5.6%, p=0.007) but not autocorrelation of PEF changed significantly from prewithdrawal to postwithdrawal in subjects who subsequently lost control, and were unaltered in those who did not. These changes were related to time to loss of control. CV was the most consistent predictor, with similar sensitivity and sensitivity to exhaled nitric oxide. CONCLUSION A simple, easy to obtain variability measure of daily lung function such as the CV may predict loss of asthma control within the first 2 weeks of ICS withdrawal.

Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.

Influence of total and specific IgE, serum tryptase, and age on severity of allergic reactions to Hymenoptera stings

The aim of this study was to analyze the influence of total serum IgE and other potential risk factors on severity of systemic allergic Hymenoptera sting reactions.

The inter-rater reliability of the Pulmonary Embolism Severity Index

The Pulmonary Embolism Severity Index (PESI) is a validated clinical prognostic model for patients with acute pulmonary embolism (PE). Our goal was to assess the PESI's inter-rater reliability in patients diagnosed with PE. We prospectively identified consecutive patients diagnosed with PE in the emergency department of a Swiss teaching hospital. For all patients, resident and attending physician raters independently collected the 11 PESI variables. The raters then calculated the PESI total point score and classified patients into one of five PESI risk classes (I-V) and as low (risk classes I/II) versus higher-risk (risk classes III-V). We examined the inter-rater reliability for each of the 11 PESI variables, the PESI total point score, assignment to each of the five PESI risk classes, and classification of patients as low versus higher-risk using kappa ( ) and intra-class correlation coefficients (ICC). Among 48 consecutive patients with an objective diagnosis of PE, reliability coefficients between resident and attending physician raters were > 0.60 for 10 of the 11 variables comprising the PESI. The inter-rater reliability for the PESI total point score (ICC: 0.89, 95% CI: 0.81-0.94), PESI risk class assignment ( : 0.81, 95% CI: 0.66-0.94), and the classification of patients as low versus higher-risk ( : 0.92, 95% CI: 0.72-0.98) was near perfect. Our results demonstrate the high reproducibility of the PESI, supporting the use of the PESI for risk stratification of patients with PE.

Video-based quantification of body movement during social interaction indicates the severity of negative symptoms in patients with schizophrenia

In schizophrenia, nonverbal behavior, including body movement, is of theoretical and clinical importance. Although reduced nonverbal expressiveness is a major component of the negative symptoms encountered in schizophrenia, few studies have objectively assessed body movement during social interaction. In the present study, 378 brief, videotaped role-play scenes involving 27 stabilized outpatients diagnosed with paranoid-type schizophrenia were analyzed using Motion Energy Analysis (MEA). This method enables the objective measuring of body movement in conjunction with ordinary video recordings. Correlations between movement parameters (percentage of time in movement, movement speed) and symptom ratings from independent PANSS interviews were calculated. Movement parameters proved to be highly reliable. In keeping with predictions, reduced movement and movement speed correlated with negative symptoms. Accordingly, in patients who exhibited noticeable movement for less than 20% of the observation time, prominent negative symptoms were highly probable. As a control measure, the percentage of movement exhibited by the patients during role-play scenes was compared to that of their normal interactants. Patients with negative symptoms differed from normal interactants by showing significantly reduced head and body movement. Two specific positive symptoms were possibly related to movement parameters: suspiciousness tended to correlate with reduced head movement, and the expression of unusual thought content tended to relate to increased movement. Overall, a close and theoretically meaningful association between the objective movement parameters and the symptom profiles was found. MEA appears to be an objective, reliable and valid method for quantifying nonverbal behavior, an aspect which may furnish new insights into the processes related to reduced expressiveness in schizophrenia.