Cognitive Flexibility and Clinical Severity in Eating Disorders

OBJECTIVES: The aim of this study was to explore cognitive flexibility in a large dataset of people with Eating Disorders and Healthy Controls (HC) and to see how patient characteristics (body mass index [BMI] and length of illness) are related to this thinking style. METHODS: A dataset was constructed from our previous studies using a conceptual shift test--the Brixton Spatial Anticipation Test. 601 participants were included, 215 patients with Anorexia Nervosa (AN) (96 inpatients; 119 outpatients), 69 patients with Bulimia Nervosa (BN), 29 Eating Disorder Not Otherwise Specified (EDNOS), 72 in long-term recovery from AN (Rec AN) and a comparison group of 216 HC. RESULTS: The AN and EDNOS groups had significantly more errors than the other groups on the Brixton Test. In comparison to the HC group, the effect size decrement was large for AN patients receiving inpatient treatment and moderate for AN outpatients. CONCLUSIONS: These findings confirm that patients with AN have poor cognitive flexibility. Severity of illness measured by length of illness does not fully explain the lack of flexibility and supports the trait nature of inflexibility in people with AN

Acute Cerebrovascular Disease in the Young The Stroke in Young Fabry Patients Study

Background and Purpose-Strokes have especially devastating implications if they occur early in life; however, only limited information exists on the characteristics of acute cerebrovascular disease in young adults. Although risk factors and manifestation of atherosclerosis are commonly associated with stroke in the elderly, recent data suggests different causes for stroke in the young. We initiated the prospective, multinational European study Stroke in Young Fabry Patients (sifap) to characterize a cohort of young stroke patients. Methods-Overall, 5023 patients aged 18 to 55 years with the diagnosis of ischemic stroke (3396), hemorrhagic stroke (271), transient ischemic attack (1071) were enrolled in 15 European countries and 47 centers between April 2007 and January 2010 undergoing a detailed, standardized, clinical, laboratory, and radiological protocol. Results-Median age in the overall cohort was 46 years. Definite Fabry disease was diagnosed in 0.5% (95% confidence interval, 0.4%-0.8%; n=27) of all patients; and probable Fabry disease in additional 18 patients. Males dominated the study population (2962/59%) whereas females outnumbered men (65.3%) among the youngest patients (18-24 years). About 80.5% of the patients had a first stroke. Silent infarcts on magnetic resonance imaging were seen in 20% of patients with a first-ever stroke, and in 11.4% of patients with transient ischemic attack and no history of a previous cerebrovascular event. The most common causes of ischemic stroke were large artery atherosclerosis (18.6%) and dissection (9.9%). Conclusions-Definite Fabry disease occurs in 0.5% and probable Fabry disease in further 0.4% of young stroke patients. Silent infarcts, white matter intensities, and classical risk factors were highly prevalent, emphasizing the need for new early preventive strategies

Mental health of returnees: refugees in Germany prior to their state-sponsored repatriation

von Lersner U, Wiens U, Elbert T, Neuner F. Mental health of returnees: refugees in Germany prior to their state-sponsored repatriation. BMC International Health and Human Rights. 2008;8(1): 8

Mental health of refugees following state-sponsored repatriation from Germany

von Lersner U, Elbert T, Neuner F. Mental health of refugees following state-sponsored repatriation from Germany. BMC Psychiatry. 2008;8(1): 88.BACKGROUND: In recent years, Voluntary Assisted Return Programmes (VARPs) have received increasing funding as a potential way of reducing the number of refugees in EU member states. A number of factors may affect the mental well-being of returnees. These include adjustment to the home country following return, difficult living conditions, and long-term effects resulting from the severe traumatic stress that had originally driven the affected out of their homes. Little is known about the extent to which these and other factors may promote or inhibit the willingness of refugees to return to their country of origin. The present pilot study investigated refugees who returned to their country of origin after having lived in exile in Germany for some 13 years. METHODS: Forty-seven VARP participants were interviewed concerning their present living conditions, their views of their native country, and their attitudes towards a potential return prior to actually returning. 33 participants were interviewed nine months after returning to their country of origin. Mental health and well-being were assessed using the questionnaires Posttraumatic Stress Diagnostic Scale (PDS) and EUROHIS and the structured Mini International Neuropsychiatric Interview (M.I.N.I.).Our objectives were to examine the mental health status of refugees returning to their home country following an extended period of exile. We also aimed to assess the circumstances under which people decided to return, the current living conditions in their home country, and retrospective returnee evaluations of their decision to accept assisted return. RESULTS: Prior to returning to their home country, participants showed a prevalence rate of 53% for psychiatric disorders. After returning, this rate increased to a sizeable 88%. Substantial correlations were found between the living situation in Germany, the disposition to return, and mental health. For two thirds of the participants, the decision to return was not voluntary. CONCLUSION: Psychological strain among study participants was of a considerable magnitude. As a result of traumatic stress experienced during war and refuge, victims were vulnerable and not well equipped to cope with either post-migration stressors in exile or with a return to their country of origin. It is noteworthy that the majority returned under pressure from immigration authorities. Living conditions after return (such as housing, work, and health care) were poor and unstable. Participants also had great difficulty readapting to the cultural environment after having lived abroad for an average of 13 years. Current VARPs do not take these factors into account and are therefore not able to assist in a humanitarian reintegration of voluntary returnees

Building ProteomeTools based on a complete synthetic human proteome.

We describe ProteomeTools, a project building molecular and digital tools from the human proteome to facilitate biomedical research. Here we report the generation and multimodal liquid chromatography-tandem mass spectrometry analysis of \u3e330,000 synthetic tryptic peptides representing essentially all canonical human gene products, and we exemplify the utility of these data in several applications. The resource (available at http://www.proteometools.org) will be extended to \u3e1 million peptides, and all data will be shared with the community via ProteomicsDB and ProteomeXchange

Impairment of Immunoproteasome Function by β5i/LMP7 Subunit Deficiency Results in Severe Enterovirus Myocarditis

Proteasomes recognize and degrade poly-ubiquitinylated proteins. In infectious disease, cells activated by interferons (IFNs) express three unique catalytic subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 forming an alternative proteasome isoform, the immunoproteasome (IP). The in vivo function of IPs in pathogen-induced inflammation is still a matter of controversy. IPs were mainly associated with MHC class I antigen processing. However, recent findings pointed to a more general function of IPs in response to cytokine stress. Here, we report on the role of IPs in acute coxsackievirus B3 (CVB3) myocarditis reflecting one of the most common viral disease entities among young people. Despite identical viral load in both control and IP-deficient mice, IP-deficiency was associated with severe acute heart muscle injury reflected by large foci of inflammatory lesions and severe myocardial tissue damage. Exacerbation of acute heart muscle injury in this host was ascribed to disequilibrium in protein homeostasis in viral heart disease as indicated by the detection of increased proteotoxic stress in cytokine-challenged cardiomyocytes and inflammatory cells from IP-deficient mice. In fact, due to IP-dependent removal of poly-ubiquitinylated protein aggregates in the injured myocardium IPs protected CVB3-challenged mice from oxidant-protein damage. Impaired NFκB activation in IP-deficient cardiomyocytes and inflammatory cells and proteotoxic stress in combination with severe inflammation in CVB3-challenged hearts from IP-deficient mice potentiated apoptotic cell death in this host, thus exacerbating acute tissue damage. Adoptive T cell transfer studies in IP-deficient mice are in agreement with data pointing towards an effective CD8 T cell immune. This study therefore demonstrates that IP formation primarily protects the target organ of CVB3 infection from excessive inflammatory tissue damage in a virus-induced proinflammatory cytokine milieu