Landschaftsverband Westfalen-Lippe

Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.

The geographic and temporal origins of the domestic dog remain controversial, as genetic data suggest a domestication process in East Asia beginning 15,000 years ago, whereas the oldest doglike fossils are found in Europe and Siberia and date to >30,000 years ago. We analyzed the mitochondrial genomes of 18 prehistoric canids from Eurasia and the New World, along with a comprehensive panel of modern dogs and wolves. The mitochondrial genomes of all modern dogs are phylogenetically most closely related to either ancient or modern canids of Europe. Molecular dating suggests an onset of domestication there 18,800 to 32,100 years ago. These findings imply that domestic dogs are the culmination of a process that initiated with European hunter-gatherers and the canids with whom they interacted.

BACKGROUND: For many years, low back pain has been both the leading cause of days lost from work and the leading indication for medical rehabilitation. The goal of the German Disease Management Guideline (NDMG) on nonspecific low back pain is to improve the treatment of patients with this condition. METHODS: The current update of the NDMG on non-specific low back pain is based on articles retrieved by a systematic search of the literature for systematic reviews. Its recommendations for diagnosis and treatment were developed by a collaborative effort of 29 scientific medical societies and organizations and approved in a formal consensus process. RESULTS: If the history and physical examination do not arouse any suspicion of a dangerous underlying cause, no further diagnostic evaluation is indicated for the time being. Passive, reactive measures should be taken only in combination with activating measures, or not at all. When drugs are used for symptomatic treatment, patients should be treated with the most suitable drug in the lowest possible dose and for as short a time as possible. CONCLUSION: A physician should be in charge of the overall care process. The patient should be kept well informed over the entire course of his or her illness and should be encouraged to adopt a healthful lifestyle, including regular physical exercise.

Sixty patients with a first acute myocardial infarction and no current treatment with cardioactive drugs were included in a prospective study of the relationship between serum potassium concentration and the early occurrence of ventricular tachycardia and premature ventricular contractions (PVCs). Serum potassium level (range 2.5 to 5 mmol/liter) was estimated 3.8 +/- 2.5 hr (mean +/- SD) after the onset of the infarction, and Holter monitoring was performed during the subsequent 12 hr. In multivariate analysis, serum potassium level was negatively and age positively related to ventricular tachycardia. Among the subclasses of PVCs (frequent unifocal, multifocal, couplets, bigeminy), serum potassium concentration was negatively related to the frequent unifocal subclass; hypertension was related to couplets and to the presence of any of the subclasses, and serum aspartate aminotransferase concentration was related to multifocal PVCs. Heart failure leading to death was related to all subclasses of PVC. Serum potassium concentration is an independent inverse predictor of the occurrence of ventricular tachycardia and frequent unifocal PVCs early in acute myocardial infarction.

Type 1 (non-neuronopathic) Gaucher disease was the first lysosomal storage disorder for which an effective enzyme replacement therapy was developed and it has become a prototype for treatments for related orphan diseases. There are currently four treatment options available to patients with Gaucher disease, nevertheless, almost 25% of Type 1 Gaucher patients do not gain timely access to therapy because of delays in diagnosis after the onset of symptoms. Diagnosis of Gaucher disease by enzyme testing is unequivocal, but the rarity of the disease and nonspecific and heterogeneous nature of Gaucher disease symptoms may impede consideration of this disease in the differential diagnosis. To help promote timely diagnosis and optimal management of the protean presentations of Gaucher disease, a consensus meeting was convened to develop algorithms for diagnosis and disease management for Gaucher disease. The defect in Gaucher disease is an inherited deficiency of the lysosomal enzyme acid β-glucosidase (glucocerebrosidase, GBA1), which results in the accumulation of glucocerebroside within lysosomes of macrophages. Systemic accumulation of these glycolipid-lipid engorged cells (eponymously known as Gaucher cells, Fig. 1) results in variable combinations of splenomegaly with associated abdominal discomfort; anemia associated with chronic fatigue; bleeding due to thrombocytopenia and/or Gaucher disease-related coagulopathy; hepatomegaly, abnormal tests of liver function; and a diverse pattern of bone disease [1]. Increased susceptibility to infections may result from impaired neutrophil function and neutropenia [2]. Rarely, the lungs, lymphatic system, skin, eyes, kidneys, and the heart are involved and, in the rare neuronopathic forms, neurodegenerative disease results [1]. Gaucher disease is traditionally classified into three broad phenotypic categories: Type 1 (non-neuronopathic disease); Type 2, fulminant neuronopathic disease that is fatal during infancy; and Type 3, chronic neuronopathic disease, that usually results in death in childhood or early adult life [1]. Further distinct phenotypic categories may be recognized within these broad groups. Bone marrow smear and biopsy from a patient with N370S homozygous Gaucher disease showing classical striated macrophages and marrow replacement. Smear: Gaucher cells (×100). Core: bone marrow replacement by Gaucher cells (×20). Type 1 (non-neuronopathic) Gaucher disease accounts for more than 90% all Gaucher disease patients. Its prevalence world wide is 1 in 50,000 to 100,000 but it is as high as ∼1 in 850 in individuals of Ashkenazi heritage [3-6]. The broadest phenotypic spectrum in Gaucher disease with respect to age of onset, rate of progression, and organs affected occurs in Type 1 Gaucher disease [7]. Homozygosity for the N370S mutation is the most common genotype in the Ashkenazim in whom it accounts for ∼70% of all disease alleles. It is associated with atypical presentation in adults or the older patient and is notable for significant skeletal disease despite inconspicuous classical manifestations (splenomegaly, hepatomegaly, anemia, and thrombocytopenia). However, severe disease with classic manifestations presenting in childhood may occur in a minority of N370S homozygous patients [8, 9]. The most common disease allele of GBA1 world wide is L444P mutation, which occurs in the sequence of the closely linked pseudogene; it is believed that gene conversion events lead to L444P mutation in the active gene. It seems likely that the most frequent genotype of Type 1 Gaucher disease in populations of European descent in the world is N370S/L444P. Generally this genotype leads to more severe disease compared with N370S homozygosity [1, 10, 11] (Figs. 2 and 3). Relationship between age of presentation at extent of splenomegaly (determined by volumetric MRI with normal spleen volume at 0.2% body weight; extent of splenomegaly is indicated by multiple of normal, i.e. ×N). Three most common genotypes in North American Gaucher disease patient populations are depicted: N370S/N370S, N370S/L444P, and N370S/84G ins G). The results show that the majority of older N370S homozygous patients harbor no, or minimal, splenomegaly). (a and b). Comparison of severity of hepatomegaly and bone disease (Herman score [9]) in patients with intact spleen and those with prior splenectomy stratified for GBA1 gene genotype. The numbers of patients are depicted at the bottom of the bars. Treatment with macrophage-targeted mannose-terminated glucocerebrosidase enzyme replacement therapy (imiglucerase, Cerezyme®, Genzyme Corporation, Cambridge, MA) is the standard of care for Type 1 Gaucher disease and of non-neuronopathic manifestations of Type 3 Gaucher disease. Evidence from the ICGG Gaucher Registry, indicates that enzyme replacement with imiglucerase and its predecessor alglucerase reverses hematological and visceral manifestations of the disease [12] and reduces the bone marrow burden of Gaucher cells resulting in amelioration of osteopenia, bone pain, risk of bone crises and overall improvement in quality of life [13-16]. Several aspects of bone disease, such as osteonecrosis, osteofibrosis, and lytic lesions cannot be reversed but timely initiation of enzyme therapy reduces the risk of these irreversible complications [8, 17]. Other variants of macrophage-targeted enzyme replacement therapies are undergoing clinical trials: velaglucerase, a human fibroblast-derived enzyme, was recently approved for treatment of Type 1 Gaucher disease [18] and taliglucerase, a plant derived enzyme is in clinical trials [19]. Substrate reduction therapy (Zavesca® miglustat, Actelion Pharmaceuticals, Allschwil, Switzerland) is approved for patients with mild Gaucher disease who are unable to receive enzyme replacement therapy [20, 21]. A more specific and potent inhibitor of glucosylceramide synthesis, eliglustat tartrate is currently in Phase 3 trials having shown impressive efficacy and safety in Phase 2 trials [22, 23]. Prompt diagnosis before the occurrence of irreversible complications underpins the Gaucher disease management model [24]. The early symptoms of Type 1 Gaucher disease tend to reflect the hematological aspects of the disease (splenomegaly, anemia, thrombocytopenia, and bleeding tendency) [25]. Patients with Gaucher disease, therefore, are most likely to be referred to hematologists for diagnosis and management. However, only ∼20% of hematologists/oncologists in one study considered Gaucher disease in differential diagnoses even in the presence of all classical symptoms [8]. Diagnosis may be achieved in high-risk groups, such as individuals of Ashkenazi Jewish ancestry, by opportunistic screening (i.e., those with any of the manifestations of Gaucher disease or those with surrogate indicators of disease, i.e, severe osteoporosis, hyperferritinemia, gallstones, and low HDL cholesterol) and family screening after diagnosis in a family member [26]. The aim of the consensus meeting was to develop algorithms for diagnosis and management based on current understanding of the full clinical spectrum of presentations of Gaucher disease. The authors' combined experience of 362 patients with Gaucher disease revealed a consistent pattern of previous misdiagnoses that included leukemia, immune thrombocytopenia purpura, autoimmune disease, hepatic cirrhosis, idiopathic avascular necrosis, viral disease, idiopathic splenomegaly, and anemia of chronic disease. Misdiagnosis led to complications such as avascular necrosis, osteopenia, liver disease, and bleeding complications and inappropriate procedures such as splenectomy, liver biopsy, and empirical corticosteroid therapy (see Appendix). Malignancy is commonly the first diagnosis entertained in patients who are eventually diagnosed with Gaucher disease [8, 27]. Interestingly, the first patient ever described with Gaucher disease by Dr Philippe Gaucher in 1882 was believed to harbor malignancy affecting the spleen. In one study, the diagnosis most frequently considered was hematologic malignancy (leukemia 65%, lymphoma 36%, multiple myeloma 22%, chronic granulocytic leukemia 14%) [8]. It should be noted that the risk of hematological malignancies in Gaucher disease is increased, especially of multiple myeloma [9, 28-31]. The life-time risk of multiple myeloma in Gaucher disease is higher than 25-fold compared with the general population [9, 29-32]. In patients of Ashkenazi ancestry, the frequency of Gaucher disease is ∼1 in 800 while hematologic malignancies are much less frequent at ∼1 in 2,500 [33]. Therefore, in this ethnic group, it is prudent to test for Gaucher disease as a first-line investigation, in any patient presenting with splenomegaly and cytopenia. It is important to keep in mind that the most common genotype in this ethnic group, homozygosity for N370S mutation is often characterized by mild cytopenia and splenomegaly that escape initial detection. Therefore, presence of conditions associated with Gaucher disease should alert the clinician, i.e., hyperferritinemia, low HDL cholesterol, premature gallstones or osteoporosis, and gammopathy. In the non-Ashkenazi populations Gaucher disease is markedly less frequent (∼1 in 40,000) compared with hematologic malignancies. In this setting, it would be appropriate to consider Gaucher disease in the differential diagnosis after malignancies have been ruled out. In this setting, bone marrow biopsy is usually performed; it should become routine to search for Gaucher cells as well as for evidence of hematological malignancies. The above considerations form the rationale for the diagnostic algorithm stratified by ethnicity (Figs. 4 and 5). Portal hypertension due to advanced liver disease from well-known etiologies must be ruled out before application of the algorithm. Diagnosis algorithm for individuals of Ashkenazi origin. Diagnosis of Gaucher disease should be considered in any individual of Ashkenazi Jewish ancestry presenting with mild, moderate or severe splenomegaly. When splenomegaly is absent, Gaucher disease should be considered in the presence of thrombocytopenia (even if mild), bleeding tendency, unexplained stable hyperferritinemia with normal transferrin saturation, or increased inflammatory markers. *In patients with bleeding diatheses, coagulopathies such as factor XI deficiency common in Askenazim [34] should be excluded. Diagnostic algorithm for individuals of non-Ashkenazi Jewish origin. Compared with Gaucher disease, malignancy is likely to be the more frequent cause of splenomegaly in this population. In this setting it is reasonable to perform bone marrow biopsy in initial investigations. The finding of Gaucher cells in bone marrow aspirate will suggest Gaucher disease although Gaucher disease and malignancy are not mutually exclusive. Pseudo-Gaucher cells have also been observed in malignant conditions in the absence of Gaucher disease [35]. In developing these diagnostic algorithms, the authors focused on splenomegaly, as a key presenting sign since it is present in the vast majority of Gaucher patients [10]. In the ICGG Registry 87% of patients have splenomegaly in excess of five times normal (median spleen volume = 15.2 × normal) [6]. However, Gaucher disease may occur without splenomegaly and the absence of splenomegaly does not exclude Gaucher disease (Fig. 2). This is often the case in older adults homozygous for the N370S mutation in whom splenomegaly is mild and may not be present [9]. Splenomegaly is defined precisely by volumetric measurement of the spleen by MRI, CT or ultrasound scanning followed by conversion to weight (1 mL equals 1 gm) as multiple of the normal spleen size, i.e., 0.2% body weight [36]. Splenectomy in patients with Gaucher disease is associated with aggressive disease in the liver, skeleton, and the lungs [37] (Fig. 3). Therefore, it should become mandatory to test for Gaucher disease in any patient being considered for splenectomy when the cause of splenomegaly has not been established. Assessment of splenomegaly in Gaucher disease should be combined with an examination of spleen parenchyma. There is almost 20% incidence of focal splenic defects in Gaucher disease and its incidence increases with increasing spleen size [38]. These lesions may represent focal collections of Gaucher cells or areas of infarction and have been a source of misdiagnosis as splenic neoplasms. The diagnostic test for Gaucher disease is the demonstration of low acid β-glucosidase activity in peripheral blood leukocytes (normal range 2.1–5.3 μmol/l/hr) [39]. The assay is performed in blood leukocytes using a fluorescent substrate, 4-methyumbelliferone β-glucoside. The test requires 10 mL EDTA blood sample shipped at ambient temperature by overnight delivery to the lab. Molecular analysis of GBA1 gene is complicated by presence of highly homologous pseudogene that harbors several mutations, which if present in the active gene leads to Gaucher disease. A number of techniques have been developed to circumvent potential problems arising from this situation in order to analyze only the active gene sequences uncontaminated by pseudogene sequences [40]. A negative screen for common GBA1 mutations does not exclude Gaucher disease (see Discussion). Therefore, undertaking sequencing of the entire coding region of GBA1 gene is recommended in patients strongly suspected of harboring Gaucher disease when a screen for common mutations is negative [40]. Mutation analysis of the GBA1 gene may provide some prognostic information although there is considerable variation of disease severity among patients harboring an identical GBA1 genotype [7] (Fig. 2). Knowledge of the GBA1 mutation in a proband also facilitates family screening for genetic counseling purposes since heterozygote carriers cannot be reliably identified by enzyme assays. Routine bone marrow examination is not necessary for diagnosis. It has been discouraged in the diagnosis of Gaucher disease, due to availability of less invasive and robust enzymatic test and the fact that it may cause bleeding complications due to thrombocytopenia and coagulopathy. Many patients report having had this procedure usually before Gaucher disease had been considered. Care should be exercised in the interpretation of bone marrow samples as false-negative results are common especially upon examination of bone marrow aspirate as opposed to bone marrow biopsy. Conversely, the presence of pseudo-Gaucher cells may lead to erroneous diagnosis [35]. Pseudo-Gaucher cells have been found in diverse conditions such as multiple myeloma [41], myelodysplasia and myelodysplastic syndromes [42], chronic myeloid leukemia [43], pulmonary tuberculosis [44], mycobacterioses [45], and sickle cell disease [46]. Occasionally bone marrow biopsy may be indicated in a patient with Gaucher disease suspected of a superimposed hematologic disorder, i.e., myelofibrosis, multiple myeloma, or other hematologic malignancy. Several serum proteins are consistently elevated in Gaucher disease, with some being used as biomarkers for routine monitoring, i.e., angiotensin-converting enzyme (ACE), tartrate-resistant acid phosphatase (TRAP), chitotriosidase, and a chemokine, CCL18 [47, 48]. The finding of elevated levels of one or more of these markers is never sufficient to diagnose Gaucher disease since these markers may be elevated in other Other are common in Gaucher disease, such as low low serum and and elevated [9, a diagnosis of Gaucher disease is the should be on of all disease (Fig. to disease to for enzyme replacement and to develop and of life and a severity score using one of the that are in the are of in treatment skeletal is especially important since it is the of most irreversible which occur without of neuronopathic Gaucher disease has been described In non-neuronopathic disease examination should also a search for symptoms and of and peripheral (see Discussion). A in the management and of Gaucher disease is that it is a chronic disease that is at variable and leads to [9, treatment and to the manifestations of Gaucher disease are based on the experience with alglucerase and imiglucerase enzyme replacement therapy which is a for all other treatment Assessment of to treatment is derived from a body of evidence The heterogeneous and chronic nature of Type 1 Gaucher disease requires an disease management model with respect to enzyme and in disease be achieved by therapy before irreversible complications occur compared with a It is that there is a for imiglucerase therapy Therefore, for patients in whom disease is a i.e., moderate to severe disease those with complications such as and pulmonary the initial of imiglucerase is usually body weight in a Patients may to after initial disease (Fig. In patients with such as pulmonary enzyme therapy followed by other appropriate therapy should be adult patients with less severe disease, initial of body is a prudent patients may not treatment because have mild or even disease such patients are usually of N370S homozygous genotype. These patients should be to of disease that treatment be before symptoms or irreversible occurs (Fig. It is important to that patients may be harbor significant disease manifestations such as splenomegaly, and These patients should receive treatment to disease and algorithm. of patients therapy imiglucerase as have been a may be with to that disease does not Treatment must be one treatment will all patients. The diagnosis and management algorithms are likely to be to the majority of patients with Gaucher disease despite there being more than mutations in the GBA1 gene that to vast phenotypic mutations ins 2 and for of disease in patients of Ashkenazi Jewish ancestry and in patients of non-Ashkenazi descent [1]. In the most disease genotype is the homozygous being associated with severe childhood onset and a high risk of [1, 10, There is phenotypic among patients with GBA1 genotype as well as among affected (Fig. 2). is only in by GBA1 gene mutations and the important of has been but Gaucher disease may be associated with manifestations that escape an with the enzymatic defect and lysosomal storage of The understanding of the of GBA1 mutations and of glucosylceramide accumulation in macrophages and its on other cell severe has been described in some patients with Type 1 Gaucher disease, and this has its non-neuronopathic in Type 1 is believed to from within by gain of function mutations in GBA1 that lead to N370S is such a or accumulation of rare but fatal of Type 1 is pulmonary hypertension that occurs in and may of cells in the disease Other of complications peripheral and hematologic malignancies [9, The increased risk of multiple myeloma and in Type 1 Gaucher disease has been to chronic immune macrophages Type 3 Gaucher disease a distinct is associated with homozygosity for mutation that disease, and and [40]. is the most severe of Type 2 disease, a that is in GBA1 these have the of Gaucher disease. into the of Gaucher disease have revealed important of cell other than in of Gaucher disease the the management of Gaucher disease and the for affected patients has a and it an of to the in the of phenotypic of Gaucher disease, the and understanding of the of enzyme replacement therapy with imiglucerase into algorithms for management. Further is with in gene therapy and therapy for mutations that result in defects A is therapy that to to therapy for with [22, this is likely to represent a significant to current therapy and to some of the in of diagnosis using blood will access to testing and timely diagnosis. The to develop diagnostic and disease management algorithms was in of the for and early diagnosis of Gaucher disease among hematologists [8]. Genzyme an to the consensus of in and the management of Gaucher disease convened in to and clinical with the of developing diagnosis and management algorithms for Gaucher disease. out of by or of by on such as to individual to also by to from the Gaucher Registry of patients world The 10 experience of Gaucher disease presentations and in of the world in an to of the a of the of misdiagnosis from case are included in Appendix). the first meeting of of misdiagnoses in Gaucher disease, presenting sign and symptoms in Gaucher patients from clinical and those described in the on these key diagnostic These the for the of diagnostic The algorithms for diagnosis and management of Gaucher disease developed and and between The authors are to for with of the or in this are those of the from and had to a body for several Further not performed at this the age of was diagnosed with Gaucher disease for N370S family screening a diagnosis of Gaucher disease in The patient had mild splenomegaly, and was not the patient was that had mild Type 1 Gaucher disease and not the patient had an onset of severe bone in the (Fig. of liver volume × and spleen volume × avascular and of the of childhood MRI revealed avascular the and The patient had score of (normal range to the age of enzyme the age of replacement. (a and b). MRI showing avascular in the in a homozygous for N370S mutation with and cytopenia There is infarction in the that eventually replacement. There is of marrow in the due to marrow normal marrow MRI is depicted in that in childhood due to avascular was not When the patient was diagnosed with Gaucher disease as an adult family severe bone disease was not identified due to on and hematologic which indicated only mild disease. A was for chronic liver disease due to the finding of and elevated liver negative and The patient had chronic bone in diagnosed as the age of was diagnosed with of severe anemia and due to thrombocytopenia Bone marrow examination revealed almost replacement by Gaucher A diagnosis of Type 1 Gaucher disease was glucocerebrosidase revealed chronic liver disease and bone marrow The patient for with bone disease, liver disease, and eventually bone marrow a routine a Ashkenazi was found to have and hyperferritinemia was blood and was for an with early onset disease. A liver biopsy revealed Gaucher cells (Fig. The diagnosis of Type 1 Gaucher disease was by low acid β-glucosidase activity in blood leukocytes and homozygosity for the N370S Further revealed splenomegaly and biopsy showing accumulation of of cells Gaucher in the to normal A was diagnosed with Gaucher disease on liver biopsy performed for of and are common in Gaucher disease. A was followed for for severe thrombocytopenia, diagnosed as immune thrombocytopenia was with without The patient had a previous and developed pain, which was to be to the was to because of Further revealed splenomegaly, advanced avascular of the and Bone marrow biopsy revealed Gaucher Misdiagnosis as led to chronic corticosteroid therapy and eventually to avascular and A patient a with symptoms due to However, there was and bone marrow revealed Gaucher The diagnosis was by low acid β-glucosidase activity in blood Further splenomegaly, elevated chitotriosidase, normal and Gaucher disease may be associated with symptoms. In this with A and abdominal examination and appropriate have the of Gaucher disease liver and bone marrow biopsy. procedures a high risk of bleeding in this

Rats were given Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum to evaluate blood glucose and plasma insulin levels in rats under various conditions. The cassia extract was superior to the zeylanicum extract. The cassia extract was slightly more efficacious than the equivalent amount of Cassia bark. A decrease in blood glucose levels was observed in a glucose tolerance test (GTT), whereas it was not obvious in rats that were not challenged by a glucose load. The elevation in plasma insulin was direct since a stimulatory in vitro effect of insulin release from INS-1 cells (an insulin secreting cell line) was observed. Thus the cassia extract has a direct antidiabetic potency.

This study investigated the effects of procedural justice perceptions on employee responses to an organizational merger. On the basis of research on organizational justice and the social psychological theory of intergroup relations, our main hypothesis was that perceived justice of the merger implementation is positively related to post-merger organizational identification and perceptions of common ingroup identity. post-merger identification and common ingroup identity, in turn, were hypothesized to be related to positive attitudes towards the employees of the merger partner and to extra-role behaviour. Results based on a sample of 189 employees from a merged organization indicated partial support for our hypotheses. Implications for further research and merger management are discussed.

Background Neurofeedback (NF) in children with ADHD has been investigated in a series of studies over the last years. Previous studies did not unanimously support NF as a treatment in ADHD. Most studies did not control for unspecific treatment effects and did not demonstrate that self-regulation took place. The present study examined the efficacy of NF in comparison to electromyographic feedback (EMG) to control for unspecific effects of the treatment, and assessed self-regulation of slow cortical potentials (SCP). Methods A total of 150 children aged 7 - 9 years diagnosed with ADHD (82% male; 43% medicated) were randomized to 25 sessions of feedback of slow cortical potentials (NF) or feedback of coordination of the supraspinatus muscles (EMG). The primary endpoint was the change in parents’ ratings of ADHD core symptoms four weeks after the end of treatment compared to pre-tests. Results Children in both groups showed reduced ADHD-core symptoms (NF – 0.3, 95% CI -0.42 / -0.18; EMG – 0.13, 95% CI -0.26 / -0.01). NF showed a significant superiority over EMG (treatment difference 0.17, 95% CI 0.02 / 0.3), p=0.02). This yielded an ES of d=0.57 without and 0.40 with Baseline observation carried forward (BOCF). The sensitivity analysis confirmed the primary result. Successful self-regulation of brain activity was observed only in NF. As a secondary result teachers reported no superior improvement from NF compared to EMG, but within-group analysis revealed effects of NF on the global ADHD score, inattention, and impulsivity. In contrast, EMG feedback did not result in changes despite more pronounced self-regulation learning. Conclusions Based on the primary parent-rated outcome NF proved to be superior to a semi-active EMG feedback treatment. The study supports the feasibility and efficacy of NF in a large sample of children with ADHD, based on both specific and unspecific effects. Trial Register Current controlled trials ISRCTN76187185, registered 5 February 2009.

The structure and magnetic properties of nano-sized (1.6 to 4.4 nm) ferrihydrite samples are systematically investigated through a combination of X-ray diffraction (XRD), X-ray pair distribution function (PDF), X-ray absorption spectroscopy (XAS) and magnetic analyses.

INTRODUCTION: Little is known about the contribution of impulsivity, inattention and comorbid attention deficit/hyperactivity disorder (ADHD) in the development and maintenance of bulimia nervosa (BN). In particular, their specific contribution to disordered eating symptoms and whether they have additive effects to the general psychopathological burden remains unclear. METHODS: Fifty-seven female patients seeking treatment for BN and 40 healthy controls completed diagnostic questionnaires and interviews that investigated: a) ADHD, b) impulsivity, c) eating disorders and d) general psychopathology. Attentional processes and impulsivity were assessed by a comprehensive computer-based neuropsychological battery. RESULTS: Twenty-one percent of patients with BN met the clinical cut-off for previous childhood ADHD compared to 2.5% of healthy controls. Adult ADHD according to DSM IV was also more prevalent in patients with BN, with an odds ratio of 4.2. Patients with BN and previous childhood ADHD were more impulsive and inattentive than patients with BN alone. These patients also displayed more severely disordered eating patterns and more general psychopathological symptoms compared with those without ADHD. Severity of eating disorder symptoms was better explained by inattentiveness than by either impulsivity or hyperactivity. DISCUSSION: Our data suggest an elevated rate of former childhood and current ADHD-symptoms in treatment-seeking patients with BN. Stronger impulsivity and inattention associated with more severe neuropsychological deficits and eating disorder symptoms indicate an additive risk that is clinically relevant for these patients. Thus, clinicians should identify comorbid patients who might profit from additional ADHD-specific treatments.

This narrative, single-case study examines how liaison librarians at the University of Minnesota (UMN) came to include advocating for reform of the scholarly communication system among their core responsibilities. While other libraries may hire a coordinator or rely on a committee to undertake outreach programs, UMN has defined baseline expertise in scholarly communication for all librarians who serve as liaisons to disciplinary faculty members. By “mainstreaming” scholarly communication duties, UMN is declaring these issues central to the profession.1 This intrinsic study uses evidence gathered from open-ended interviews with three participants, supplemented by documentation. It explores the context of these changes, systems thinking, and new mental models.

While cognitive impairments are well documented for the acute episode of major depressive disorder (MDD), less is known about cognitive functioning in the euthymic state. For working memory, dysfunctional activation of lateral prefrontal and cingulate cortex has been reported in the acute episode. This study investigates working-memory function and its neurobiological correlate in euthymic MDD patients, particularly whether dysfunctional activation persists when depressive symptoms improve. We investigated 56 subjects with functional magnetic resonance imaging (fMRI) at 3 Tesla. To challenge working-memory function, a classical verbal n-back task (0-, 1-, and 2-back) was used in 28 well-characterized, euthymic, unipolar MDD patients and 28 healthy control subjects matched according to age, sex, and educational level. Data were analyzed using SPM5. In the absence of significant behavioral differences, we observed comparable overall patterns of brain activation in both groups. As expected, both groups showed stronger activation of the typical working-memory network with increasing memory load. However, significant hyperactivation of the cingulate cortex was observed in euthymic patients, while lateral prefrontal activation was comparable between patients and controls. Working-memory challenge in the euthymic state of MDD revealed a dissociation of lateral prefrontal and cingulate brain function. Cingulate function, which is important for both emotional and cognitive processing and their integration, is still abnormal when mood is restored. This could reflect a different speed of normalization in prefrontal and limbic cortices, persistent systematic changes in neuronal networks after an episode of MDD, or a compensatory mechanism to maintain working-memory performance.

Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options.

Several pesticides have been hypothesized to act as endocrine-disrupting compounds, exhibiting hormonal activity and perturbing normal physiological functions. Among these, especially s-triazine herbicides have received increased attention. Despite being banned in many countries, including the European Union, atrazine is still the world's most widely used herbicide. Despite its discontinued use, considerable concentrations of atrazine and its degradation products, mainly desethylatrazine (DEA) and deisopropylatrazine (DIA), are still found in the environment, including drinking water sources. The aim of this investigation was to study concentrations of especially s-triazine herbicides and major degradation products in drinking water, including spring water, tap water and bottled water in Luxembourg. Spring water (2007/2008/2009, n = 69/69/69), tap water (2008/2009, n = 19/26), and bottled water (2007/2008/2009, n = 5/13/7) were sampled at locations in Luxembourg and investigated for pesticides by LC-ESI-MS/MS. Atrazine was the predominant triazine, detectable in many spring water locations, tap and bottled water, ranging (mean) from 0-57 (9), 0-44 (4), and 0-4 (1) ng l(-1), respectively. DEA and DIA in spring water ranged (mean) from 0-120 (19) and 0-27 (3) ng l(-1), with higher concentrations from agricultural areas and low molar ratios of DEA:atrazine <0.5 and high ratios of atrazine:nitrate suggesting point-source contamination. Levels (mean) of DEA and DIA in tap water were 0-62 (14) and 0-6 (<1) ng l(-1) and in bottled water 0-11 (2) and 0-7 (2) ng l(-1). Simazine and other triazines were detected in traces (<5 ng l(-1)). Thus, the conducted monitoring suggested the presence of low concentrations of s-triazines in raw and finished water, presumably partly due to non-agricultural contamination, with concentrations being below thresholds advocated by the European Union Directive 98/83/EC.

Fusarium culmorum is one of the most harmful pathogens of durum wheat and is the causal agent of foot and root rot (FRR) disease. F. culmorum produces the mycotoxin deoxynivalenol (DON) that is involved in the pathogenic process. The role of the gene FcStuA, a StuA ortholog protein with an APSES domain sharing 98.5% homology to the FgStuA protein (FGSG10129), was determined by functional characterisation of deletion mutants obtained from two F. culmorum wild-type strains, FcUk99 (a highly pathogenic DON producer) and Fc233B (unable to produce toxin and with a mild pathogenic behavior). The ΔFcStuA mutants originating from both strains showed common phenotypic characters including stunted vegetative growth, loss of hydrophobicity of the mycelium, altered pigmentation, decreased activity of polygalacturonic enzymes and catalases, altered and reduced conidiation, delayed conidial germination patterns and complete loss of pathogenicity towards wheat stem base/root tissue. Glycolytic process efficiency [measured as growth on glucose as sole carbon (C) source] was strongly impaired and growth was partially restored on glutamic acid. Growth on pectin-like sources ranked in between glucose and glutamic acid with the following order (the lowest to the highest growth): beechwood xylan, sugarbeet arabinan, polygalacturonic acid, citrus pectin, apple pectin, potato azogalactan. DON production in the mutants originating from FcUK99 strain was significantly decreased (-95%) in vitro. Moreover, both sets of mutants were unable to colonise non-cereal plant tissues, i.e. apple and tomato fruits and potato tubers. No differences between mutants, ectopic and wild-type strains were observed concerning the level of resistance towards four fungicides belonging to three classes, the demethylase inhibitors epoxiconazole and tebuconzole, the succinate dehydrogenase inhibitor isopyrazam and the cytochrome bc1 inhibitor trifloxystrobin. StuA, given its multiple functions in cell regulation and pathogenicity control, is proposed as a potential target for novel disease management strategies.

Background: Treatment algorithms are considered as key to improve outcomes by enhancing the quality of care. This is the first randomized controlled study to evaluate the clinical effect of algorithm-guided treatment in inpatients with major depressive disorder. Methods: Inpatients, aged 18 to 70 years with major depressive disorder from 10 German psychiatric departments were randomized to 5 different treatment arms (from 2000 to 2005), 3 of which were standardized stepwise drug treatment algorithms (ALGO). The fourth arm proposed medications and provided less specific recommendations based on a computerized documentation and expert system (CDES), the fifth arm received treatment as usual (TAU). ALGO included 3 different second-step strategies: lithium augmentation (ALGO LA), antidepressant dose-escalation (ALGO DE), and switch to a different antidepressant (ALGO SW). Time to remission (21-item Hamilton Depression Rating Scale ≤9) was the primary outcome. Results: Time to remission was significantly shorter for ALGO DE (n=91) compared with both TAU (n=84) (HR=1.67; P=.014) and CDES (n=79) (HR=1.59; P=.031) and ALGO SW (n=89) compared with both TAU (HR=1.64; P=.018) and CDES (HR=1.56; P=.038). For both ALGO LA (n=86) and ALGO DE, fewer antidepressant medications were needed to achieve remission than for CDES or TAU (P<.001). Remission rates at discharge differed across groups; ALGO DE had the highest (89.2%) and TAU the lowest rates (66.2%). Conclusions: A highly structured algorithm-guided treatment is associated with shorter times and fewer medication changes to achieve remission with depressed inpatients than treatment as usual or computerized medication choice guidance.

BACKGROUND: Disease stage is the most important prognostic parameter in allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia, but other factors such as donor/host histocompatibility and gender combination, recipient age, performance status and comorbidities need to be considered. Several scoring systems are available to predict outcome in HCT recipients; however, their prognostic relevance in acute lymphoblastic leukemia is not well defined. DESIGN AND METHODS: In the present study we evaluated a modified EBMT risk score (mEBMT) and the HCT-specific comorbidity index (HCT-CI) in 151 adult acute lymphoblastic leukemia patients who received allogeneic HCT from 1995 until 2007 at our center. RESULTS: Disease status was first complete remission (CR1) (47%), CR>1 (21%) or no CR (32%). Overall survival (OS) at one, two and five years was 62%, 51% and 40% and non-relapse mortality (NRM) was 21%, 24% and 32%. Median mEBMT was 3 (0-6). Higher mEBMT was associated with inferior OS (hazard ratio per score unit (HR): 1.50, P<0.001), higher NRM (HR: 1.36, P=0.042) and higher relapse mortality (HR: 1.68, P<0.001). Disease stage was the predominant prognostic factor in this score. Comorbidities were present in 71% of patients with mild hepatic disease (29%), moderate pulmonary disease (28%) and infections (23%) being the most common. Median HCT-CI was 1 (0-9). In univariate analysis a trend for inferior OS (HR: 1.08, P=0.20) and higher NRM (HR: 1.14, P=0.11) with increasing HCT-CI was observed but the level of significance was not reached. In additional analyses we found that reduced Karnofsky Performance Status (KPS) was associated with inferior OS (HR: 1.34, P=0.023) and higher relapse mortality (HR: 1.71, P=0.001) when analyzed univariately. However, KPS was associated with disease stage and significance was lost in multivariate analysis. CONCLUSIONS: The mEBMT was prognostic in our patient cohort with predominant influence of disease stage, whereas a trend but no significant prognostic value was observed for the HCT-CI.

New theoretical models of nonsuicidal self-injury (NSSI) postulate that symptoms subsequent to childhood maltreatment rather than childhood maltreatment itself may lead to engagement in NSSI. However, little is known concerning which specific syndromes serve as underlying mechanisms. In this study we sought to examine the mediating effects of dissociative, posttraumatic, and depressive symptoms, 3 often comorbid syndromes following childhood trauma. In addition, we aimed to assess differences between women with and without NSSI. A sample of 87 female inpatients with a history of childhood abuse and neglect was divided into 2 subgroups (NSSI: n = 42, no NSSI: n = 45). The assessment included measures of NSSI characteristics; adverse childhood experiences; and posttraumatic, dissociative, and depressive symptoms. The NSSI group reported significantly more cases of childhood maltreatment and higher levels of current dissociative, posttraumatic, and depressive symptoms than patients without NSSI. The results of a path analysis showed that only dissociation mediated the relationship between a history of child maltreatment and NSSI when all 3 psychopathological variables were included in the model. The findings point toward a strong and rather specific association between dissociative experiences and NSSI and therefore have important implications for clinical practice.

Uncontrolled use of the internet has been reported to affect the lives of some users in a negative way. According to epidemiological studies, about 1% of the general population is showing signs of internet addiction. Since internet addiction is becoming a growing health concern, research on potential risk factors is becoming more important in order to develop strategies for prevention and to adopt therapeutic treatment. Although there are some studies investigating personality traits in internet addiction, most of these studies are based on samples of healthy subjects. In this research project, we compared personality profiles of a sample of patients in different rehabilitation centers. 70 patients with an addiction disorder that additionally met the criteria for internet addiction were compared to 48 patients suffering from alcohol dependence. Besides Big Five personality traits, we also assessed depressive symptoms. It was shown that patients with comorbid internet addiction can be discriminated from other patients by higher neuroticism and lower extraversion as well as lower conscientiousness. After controlling for depressive symptoms, lower conscientiousness especially turned out to be a disorder-specific risk factor. As internet addiction is related to unique patterns of personality traits and can be discriminated from alcohol dependence, treatment approaches are needed that meet the specific requirements of patients with internet addiction.

IIntroduction Aggression and violence are highly complex problems in acute psychiatry that often lead to the coercive interventions. The Safewards Model is an evidence-informed conflict-reduction strategy to prevent and reduce such incidents. The aim of this study was to evaluate the implementation of this model with regards to coercive interventions in inpatient care. Materials and Method We evaluated outcomes of the implementation of the Safewards Model in two locked psychiatric wards in Germany. Frequency and duration of coercive interventions applied during a period of ten weeks before and ten weeks after the implementation period were assessed through routine data. Fidelity to the Safewards Model was assessed by the Organization Fidelity Checklist. Results Fidelity to the Safewards Model was high in both wards. The overall use of coercive measures differed significantly between wards (case-wise: χ2 (1, n = 250) = 35.34, p ≤ 0.001; patient-wise: χ2 (1, n = 103) = 21.45, p ≤ 0.001) and decreased post implementation. In one ward, the number of patients exposed to coercive interventions in relation to the overall number of admissions decreased significantly (χ2 (1, 182) = 9.30, p = 0.003). Furthermore, the mean duration of coercive interventions overall declined significantly (U(55,21) = -2.142, p = 0.032) with an effect size of Cohen’s d = -0.282 (95% CI: -0.787, 0.222) in that ward. Both aspects declined as well in the other ward, but not significantly. Discussion Results indicate that the implementation of the Safewards interventions according to the model in acute psychiatric care can reduce coercive measures. They also show the role of enabling factors as well as of obstacles for the implementation process.