Disease-stabilizing treatment with all-trans retinoic acid and valproic acid in acute myeloid leukemia: serum hsp70 and hsp90 levels and serum cytokine profiles are determined by the disease, patient age, and anti-leukemic treatment

Heat shock protein (HSP) 70 and HSP90 are released by primary human acute myeloid leukemia (AML) cells during stress-induced spontaneous in vitro apoptosis. The AML cells also show constitutive release of several cytokines and the systemic serum levels of several soluble mediators are altered in patients with untreated AML. In the present study, we have investigated serum levels of HSP70/HSP90 and the serum cytokine profiles of patients with untreated AML and patients receiving AML-stabilizing palliative treatment based on all-trans retinoic acid (ATRA) plus valproic acid. Patients with untreated AML showed increased HSP90 levels and a distinct serum cytokine profile when compared with healthy controls, and low pre-therapy HSP90 levels were associated with a prolonged survival during treatment with ATRA + valproic acid + theophyllin. Hierarchical cluster analysis showed a close association between HSP70, HSP90, IL-1 receptor antagonist (IL-1ra), and hepatocyte growth factor (HGF) levels. Furthermore, disease-stabilizing therapy altered the serum-cytokine profile, but the correlations between HSP70/HSP90/IL-1ra/HGF were maintained only when ATRA + valproic acid were combined with theophyllin but not when combined with cytarabine. We conclude that both HSP levels and serum cytokine profiles are altered and may represent possible therapeutic targets or prognostic markers in human AML.     

Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala

Major depression has been repeatedly associated with amygdala hyper‐responsiveness to negative (but not positive) facial expressions at early, automatic stages of emotion processing using subliminally presented stimuli. However, it is not clear whether this “limbic bias” is a correlate of depression or represents a vulnerability marker preceding the onset of the disease. Because childhood maltreatment is a potent risk factor for the development of major depression in later life, we explored whether childhood maltreatment is associated with amygdalar emotion processing bias in maltreated but healthy subjects. Amygdala responsiveness to subliminally presented sad and happy faces was measured by means of fMRI at 3 T in N = 150 healthy subjects carefully screened for psychiatric disorders. Childhood maltreatment was assessed by the 25‐item childhood trauma questionnaire (CTQ). A strong association of CTQ‐scores with amygdala responsiveness to sad, but not happy facial expressions emerged. This result was further qualified by an interaction of emotional valence and CTQ‐scores and was not confounded by trait anxiety, current depression level, age, gender, intelligence, education level, and more recent stressful life‐events. Childhood maltreatment is apparently associated with detectable changes in amygdala function during early stages of emotion processing which resemble findings described in major depression. Limbic hyper‐responsiveness to negative facial cues could be a consequence of the experience of maltreatment during childhood increasing the risk of depression in later life. Limitation: the present association of limbic bias and maltreatment was demonstrated in the absence of psychopathological abnormalities, thereby limiting strong conclusions. Hum Brain Mapp 34:2899–2909, 2013. © 2012 Wiley Periodicals, Inc.     

Exposure to estrogen and women's risk for Parkinson's disease: A prospective cohort study in Denmark

BackgroundStudies have suggested that estrogen is protective against Parkinson's disease; however, the results have been inconsistent.MethodsOur cohort comprised 27,466 women from the prospective Diet, Cancer and Health study. At inclusion, all the cohort members filled in questionnaires on diet and lifestyle, including reproductive factors, use of hormone products, and smoking habits. The cohort was followed up for Parkinson's disease in the Danish Hospital Register, and risks associated with indicators of exposure to estrogen were estimated in a Cox proportional hazards model.ResultsNo significant association was found between reproductive factors and risk for Parkinson's disease. Use of oral contraceptives was associated with a nonsignificantly increased risk (hazard ratio, 1.30; 95% confidence interval, 0.81–2.09), as was use of hormone replacement therapy (1.41; 0.90–2.21).ConclusionsOur data do not support the hypothesis of a protective effect of estrogen on the risk for Parkinson's disease in women.     

Dichotic listening performance predicts language comprehension

Dichotic listening performance is considered a reliable and valid procedure for the assessment of language lateralisation in the brain. However, the documentation of a relationship between language functions and dichotic listening performance is sparse, although it is accepted that dichotic listening measures language perception. In particular, language comprehension should show close correspondence to perception of language stimuli. In the present study, we tested samples of reading-impaired and normally achieving children between 10 and 13 years of age with tests of reading skills, language comprehension, and dichotic listening to consonant-vowel (CV) syllables. A high correlation between the language scores and the dichotic listening performance was expected. However, since the left ear score is believed to be an error when assessing language laterality, covariation was expected for the right ear scores only. In addition, directing attention to one ear input was believed to reduce the influence of random factors, and thus show a more concise estimate of left hemisphere language capacity. Thus, a stronger correlation between language comprehension skills and the dichotic listening performance when attending to the right ear was expected. The analyses yielded a positive correlation between the right ear score in DL and language comprehension, an effect that was stronger when attending to the right ear. The present results confirm the assumption that dichotic listening with CV syllables measures an aspect of language perception and language skills that is related to general language comprehension.     

Measuring target detection performance in paradigms with high event rates

ObjectivesCombining behavioral and neurophysiological measurements inevitably implies mutual constraints, such as when the neurophysiological measurement requires fast-paced stimulus presentation and hence the attribution of a behavioral response to a particular preceding stimulus becomes ambiguous. We develop and test a method for validly assessing behavioral detection performance in spite of this ambiguity.MethodsWe examine four approaches taken in the literature to treat such situations. We analytically derive a new variant of computing the classical parameters of signal detection theory, hit and false alarm rates, adapted to fast-paced paradigms.ResultsEach of the previous approaches shows specific shortcomings (susceptibility towards response window choice, biased estimates of behavioral detection performance). Superior performance of our new approach is demonstrated for both simulated and empirical behavioral data. Further evidence is provided by reliable correspondence between behavioral performance and the N2b component as an electrophysiological indicator of target detection.ConclusionsThe appropriateness of our approach is substantiated by both theoretical and empirical arguments.SignificanceWe demonstrate an easy-to-implement solution for measuring target detection performance independent of the rate of event presentation. Thus overcoming the measurement bias of previous approaches, our method will help to clarify the behavioral relevance of different measures of cortical activation.     

Mental health as perceived by persons with mental disorders – an interpretative phenomenological analysis study

In this interpretative phenomenological analysis study, we explored how persons with mental disorders perceive mental health. Adapting a salutogenic theoretical framework, 12 former inpatients were interviewed. The analysis revealed experiences of mental health as a movement, like walking up and down a staircase. Perceived mental health is expressed both verbally in an everyday language and through body language. Mental health is an aspect of being that is always present and which is nourished by four domains of life: the emotional; physical; social and spiritual domains. Mental health is experienced in everyday life as a sense of energy, and as more or less wellbeing. Exploring persons' meanings of mental health from a subjective perspective can extend the knowledge base that can be used in mental health promotion strategies.     

Visuoconstructional Abilities in Cognitively Healthy Illiterate Turkish Immigrants: A Quantitative and Qualitative Investigation

Assessment of visuospatial function is an integral part of most neuropsychological assessments and is frequently assessed by visuoconstructional tests. A significant impact of limited schooling and illiteracy has been found on numerous neuropsychological tests and it can be difficult to interpret test results from illiterate individuals. In this study, quantitative and qualitative aspects of performance of elderly cognitively healthy illiterate and literate Turkish immigrants were compared on five commonly used visuoconstructional tests. Significantly poorer performances of illiterate compared to literate subjects were found in copying of two- and three-dimensional geometric designs, and in Clock Drawing Test performance. A systematic qualitative analysis found lacking three-dimensionality, “curved angles”, omissions, distorted relation between elements, and spatial disorganization to be common error types in illiterate subjects. Performances were not found to be influenced by duration of residence in Denmark or level of acculturation. The results warrant caution in the interpretation of visuoconstructional test performances in illiterate subjects, as they can easily be misinterpreted as signs of cognitive dysfunction.     

Ethnic differences in stress among residents in a deprived neighbourhood in Denmark

The present research aimed to explore how stress varies by socio-demographic characteristics among immigrants compared to the host population in a deprived neighbourhood. Data used in the analyses were collected through questionnaires from 1160 inhabitants in Esbjerg, Denmark. Logistic regression analyses were conducted separately for ethnic Danes and immigrants to examine the stress' association with gender, age, education, marital status, economic situation, social deprivation, unemployment, sick leave and loneliness. Although stress frequency was higher among immigrants than ethnic Danes, stress was significantly associated only with gender among immigrants and with all variables but gender and marital status among ethnic Danes. The association of stress with socio-demographic characteristics shows a different pattern between immigrants and the host population residents in a deprived neighbourhood. Socio-demographic characteristics by themselves cannot explain significant differences in stress levels between people. Specific circumstances in people's life may change the experience's meaning and eventually health outcomes.