Advanced patient age at diagnosis of diffuse large B-cell lymphoma is associated with molecular characteristics including ABC-subtype and high expression of MYC.

The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age being patient age at diagnosis an adverse prognostic factor. However, elderly patients are often underrepresented in common studies. To investigate the effect between age and biological characteristics in DLBCL, we analyzed data of 1534 patients encompassing all adult age groups, enriched for the age ≥75 years.

Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal.

Background: Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents.

Cell-of-origin classification by gene expression and MYC-rearrangements in diffuse large B-cell lymphoma of children and adolescents.

We present the largest series of diffuse large B-cell lymphoma (DLBCL) in patients younger than 18 years analysed to date by gene expression profiling using Nanostring technology to identify molecular subtypes and fluorescent in situ hybridization for translocations of MYC. We show that the activated B cell-like subtype of DLBCL is exceedingly rare in children and - in contrast to adults- not associated with outcome. Furthermore, we review the current literature and demonstrate that MYC translocations are not more frequent in paediatric compared to adult DLBCL.

Frequency of uterine sarcomas in patients admitted for uterine fibroid surgery.

Objective: To estimate the frequency of unsuspected uterine sarcoma identified postoperatively in women undergoing surgery for presumed benign uterine fibroids at a single university hospital.

Material And Methods: This was a retrospective single-center study; the records of all 2275 patients with uterine fibroids and uterine sarcomas from 2003 to 2015 were reviewed. Descriptive statistics were used to analyze demographic and clinical characteristics.

Role of dual bronchodilators in COPD: A review of the current evidence for indacaterol/glycopyrronium.

In this review, we summarize the rationale for combining long-acting bronchodilators in the management of chronic obstructive pulmonary disease (COPD), and the evidence for the long-acting bronchodilator combination indacaterol/glycopyrronium (IND/GLY). Clinical practice guidelines generally recommend the use of long-acting bronchodilators in the treatment of patients with all severities of COPD, either as a first-choice or alternative-choice therapy. Combining classes of long-acting bronchodilators can result in superior improvements in lung function and clinical outcomes compared with bronchodilator monotherapy, as observed in studies of free combinations of long-acting β-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs).

IL-26 Confers Proinflammatory Properties to Extracellular DNA.

In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors.

Immune stimulatory effects of neutrophil extracellular traps in granulomatosis with polyangiitis.

Objectives: The aim of this study was to analyse the role of netting neutrophils in the pathogenesis of granulomatosis with polyangiitis (GPA), especially their interplay with peripheral blood mononuclear cells (PBMCs).

Methods: The amount of cell-free DNA (cfDNA) was determined in sera from GPA patients (pairs active/inactive state of disease, n=18) and from healthy controls (HCs, n=10). Furthermore, we performed in vitro incubation experiments using PBMCs and NETs from patients and HCs for accessing the effect of NETs on PBMC behaviour.

Association between MRI-derived hepatic fat fraction and blood pressure in participants without history of cardiovascular disease.

Objectives: We assessed whether liver fat content, as determined by MRI, correlates with blood pressure (BP), a major vascular risk factor, in individuals from the general population without history of stroke and coronary or peripheral artery disease.

Methods: Cross-sectional data from 384 participants (161 women; aged 39-73 years) of a MRI substudy of the KORA FF4 survey were used. Hepatic fat fraction (HFF) was measured in the left and right lobe of the liver using single voxel multiecho H-spectroscopy and at the level of the portal vein using a multiecho Dixon-sequence.

Sleep-Dependent Consolidation of Rewarded Behavior Is Diminished in Children with Attention Deficit Hyperactivity Disorder and a Comorbid Disorder of Social Behavior.

Children suffering from attention-deficit hyperactivity disorder (ADHD) often also display impaired learning and memory. Previous research has documented aberrant reward processing in ADHD as well as impaired sleep-dependent consolidation of declarative memory. We investigated whether sleep also fosters the consolidation of behavior learned by probabilistic reward and whether ADHD patients with a comorbid disorder of social behavior show deficits in this memory domain, too.

Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the non-Hodgkin Lymphoma Berlin-Frankfurt-Münster protocols.

Mature B-cell non-Hodgkin lymphoma is the most common subtype of non-Hodgkin lymphoma in childhood and adolescence. B-cell non-Hodgkin lymphomas are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the oncogene are known as relevant but not sufficient for Burkitt lymphoma pathogenesis.

Development and validation of the deep brain stimulation impairment scale (DBS-IS).

Background: Bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) has considerable influence on motor and non-motor symptoms in Parkinson's disease (PD). While improvements in motor functioning can be easily assessed with general quality of life questionnaires, the measurement of specific STN-DBS-associated impairments often remains insufficient. Hence, we aimed to develop a questionnaire that measures STN-DBS-related impairments.

Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial.

Background: Filgotinib (GLPG0634, GS-6034) is a once-daily, orally administered, Janus kinase 1 (JAK1)-selective inhibitor. The FITZROY study examined the efficacy and safety of filgotinib for the treatment of moderate-to-severe Crohn's disease.

Methods: We did a randomised, double-blind, placebo-controlled phase 2 study, which recruited patients from 52 centres in nine European countries.

Transcranial direct current stimulation improves clinical symptoms in adolescents with attention deficit hyperactivity disorder.

Anodal transcranial direct current stimulation (tDCS) of the prefrontal cortex has repeatedly been shown to improve working memory. As patients with attention deficit hyperactivity disorder (ADHD) are characterized by both underactivation of the prefrontal cortex and deficits in working memory that correlate with clinical symptoms, it is hypothesized that the modulation of prefrontal activity with tDCS in patients with ADHD increases performance in working memory and reduces symptoms of ADHD. To test this hypothesis, fifteen adolescents with ADHD (12-16 years old, three girls and 12 boys) were treated according to the randomized, double-blinded, sham-controlled, crossover design with either 1 mA anodal tDCS over the left dorsolateral prefrontal cortex or with the sham protocol 5 days each with a 2 weeks pause between these conditions.

Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage.

We analyzed the in silico purified DNA methylation signatures of 82 mantle cell lymphomas (MCL) in comparison with cell subpopulations spanning the entire B cell lineage. We identified two MCL subgroups, respectively carrying epigenetic imprints of germinal-center-inexperienced and germinal-center-experienced B cells, and we found that DNA methylation profiles during lymphomagenesis are largely influenced by the methylation dynamics in normal B cells. An integrative epigenomic approach revealed 10,504 differentially methylated regions in regulatory elements marked by H3K27ac in MCL primary cases, including a distant enhancer showing de novo looping to the MCL oncogene SOX11.

Sleep at baseline and after electroconvulsive therapy in patients with major depression.

Sleep in major depressive disorder is frequently altered and possibly indicative for treatment outcomes. For example, increased rapid eye movement (REM-) sleep density seems to predict worse treatment outcomes of psychotherapy. We therefore investigated pre-treatment sleep and sleep changes after termination of electroconvulsive therapy (ECT).

Extracellular K rapidly controls NaCl cotransporter phosphorylation in the native distal convoluted tubule by Cl -dependent and independent mechanisms.

Key Points: High dietary potassium (K ) intake dephosphorylates and inactivates the NaCl cotransporter (NCC) in the renal distal convoluted tubule (DCT). Using several ex vivo models, we show that physiological changes in extracellular K , similar to those occurring after a K rich diet, are sufficient to promote a very rapid dephosphorylation of NCC in native DCT cells. Although the increase of NCC phosphorylation upon decreased extracellular K appears to depend on cellular Cl fluxes, the rapid NCC dephosphorylation in response to increased extracellular K is not Cl -dependent.

A severe pediatric infection with a novel enterovirus A71 strain, Thuringia, Germany.

Infection by Enterovirus A71 (EV-A71) is an important cause of hand, foot, and mouth disease (HFMD). Outbreaks including severe cases with neurological and cardiopulmonary complications have been reported particularly from Southeast Asia. In Europe, the epidemiology of EV-A71 is not well understood.

Autologous co-culture of primary human alveolar macrophages and epithelial cells for investigating aerosol medicines. Part I: model characterisation.

The development of new formulations for pulmonary drug delivery is a challenge on its own. New in vitro models which address the lung are aimed at predicting and optimising the quality, efficacy and safety of inhaled drugs, to facilitate the more rapid translation of such products into the clinic. Reducing the complexity of the in vivo situation requires that such models reproducibly reflect essential physiological factors in vitro.

Angiopoietin-2, its soluble receptor Tie-2, and metabolic syndrome components in a population-based sample.

Objective: Since angiopoietin-2 (Ang-2) levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang-2 and its soluble receptor (sTie-2) were associated with the metabolic syndrome (MetS) and individual MetS components.

Methods: Within the population-based Study of Health in Pomerania, two sets of analyses were performed. First, Ang-2 and sTie-2 were related to the prevalence of MetS and its components cross-sectionally (n = 3,205).

Recurrent mutations in NF-κB pathway components, KMT2D, and NOTCH1/2 in ocular adnexal MALT-type marginal zone lymphomas.

The pathogenesis of ocular adnexal marginal zone lymphomas of mucosa-associated lymphatic tissue-type (OAML) is still poorly understood. We analyzed 63 cases of such lymphomas for non-synonymous mutations in 24 candidate genes by amplicon sequencing. We validated frequent mutations in the NF-κB regulators MYD88, TNFAIP3 and TNIP1 in OAML, but also identified recurrent mutations in several additional components of the NF-κB pathway, including BCL10 and NFKBIA.

Current concepts of essential tremor.

Essential tremor is clinically defined but there is increasing evidence that it is not a unique entity. Its pathophysiology has been studied with many methods but may also vary between subtypes. Neurophysiologically, there is strong evidence that a specific cerebello-thalamo-cortical loop is abnormally oscillating.

Recombinant herpes simplex virus type 1 strains with targeted mutations relevant for aciclovir susceptibility.

Here, we describe a novel reliable method to assess the significance of individual mutations within the thymidine kinase (TK) gene of herpes simplex virus type 1 (HSV-1) to nucleoside analogue resistance. Eleven defined single nucleotide polymorphisms that occur in the TK gene of clinical HSV-1 isolates and a fluorescence reporter were introduced into the HSV-1 strain 17(+) that had been cloned into a bacterial artificial chromosome. The susceptibility of these different strains to aciclovir, penciclovir, brivudin, and foscarnet was determined with a modified cytopathic effect reduction assay.

Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer.

Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth factor receptor signaling. However, the function of myotubularin-related protein 7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated with increasing tumor grade (G), size (T) and stage (UICC) in patients with colorectal cancer (CRC) (n=1786).