Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus.

The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear.

Crystal structure of 5,11-di-hydro-pyrido[2,3-b][1,4]benzodiazepin-6-one.

The title compound, C12H9N3O, is an inter-mediate in the synthesis of the muscarinic M2 receptor antagonist AFDX-384. The seven-membered ring adopts a boat conformation and the dihedral angle between the planes of the aromatic rings is 41.51 (9)°.

Long-term disease control by pomalidomide-/dexamethasone-based therapy in a patient with advanced multiple myeloma: a case report and review of the literature.

Background: Therapy for multiple myeloma (MM) has substantially improved in the era of immunomodulatory drugs and bortezomib. However, the prognosis of patients with progressive disease despite treatment with these 'novel agents' remains poor. Recently, pomalidomide was approved in this setting, but a median progression-free survival of <4 months still leaves room for improvement.

A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma.

AFM13 is a bispecific, tetravalent chimeric antibody construct (TandAb) designed for the treatment of CD30-expressing malignancies. AFM13 recruits natural killer (NK) cells via binding to CD16A as immune effector cells. In this phase 1 dose-escalation study, 28 patients with heavily pretreated relapsed or refractory Hodgkin lymphoma received AFM13 at doses of 0.

Multiple mechanisms of MYCN dysregulation in Wilms tumour.

Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies.

Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors.

Blastemal histology in chemotherapy-treated pediatric Wilms tumors (nephroblastoma) is associated with adverse prognosis. To uncover the underlying tumor biology and find therapeutic leads for this subgroup, we analyzed 58 blastemal type Wilms tumors by exome and transcriptome sequencing and validated our findings in a large replication cohort. Recurrent mutations included a hotspot mutation (Q177R) in the homeo-domain of SIX1 and SIX2 in tumors with high proliferative potential (18.

Diagnosis and treatment of cytomegalovirus 2013.

Purpose Of Review: Despite significant improvements in the management of patients undergoing allogeneic stem cell transplantation, including anticytomegalovirus (CMV) prophylaxis and treatment, clinical handling of CMV infection remains challenging in the light of high morbidity and mortality rates. Thus, novel strategies and agents to control CMV infection and disease will be discussed.

Recent Findings: Novel assays to quantify viral load and detect antiviral resistance mechanisms on the basis of next-generation sequencing have been described and will help to earlier and more effectively control CMV infection.

Hey bHLH transcription factors.

Hey bHLH transcription factors are direct targets of canonical Notch signaling. The three mammalian Hey proteins are closely related to Hes proteins and they primarily repress target genes by either directly binding to core promoters or by inhibiting other transcriptional activators. Individual candidate gene approaches and systematic screens identified a number of Hey target genes, which often encode other transcription factors involved in various developmental processes.

Tensile strength of flexor tendon repair using barbed suture material in a dynamic ex vivo model.

The purpose of this study was to compare two sutures; a knotted polydioxane with a knotless barbed in a 4-strand Kirchmayr-Kessler suture technique. Human flexor digitorum tendons were separated into four groups. Group 1 - polydioxane; Group 2 - barbed suture; Group 3 and 4 - same as group 1 and 2 with an additional peripheral running suture.

Medium-term results after complex intra-articular fractures of the tibial plateau.

Background: To present the medium-term results of intra-articular, bicondylar AO/OTA classification type C fractures of the tibial plateau in a retrospective study at a level-1 trauma center in 22 patients with 23 fractures.

Methods: Demographic data for the patients and details of current clinical and radiological follow-up findings were obtained to assess range of motion, clinical stability and alignment of the knee, and posttraumatic arthrosis (Kellgren/Lawrence score). Functional outcomes were assessed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) form.

Cost analysis for computer supported multiple-choice paper examinations.

Introduction: Multiple-choice-examinations are still fundamental for assessment in medical degree programs. In addition to content related research, the optimization of the technical procedure is an important question. Medical examiners face three options: paper-based examinations with or without computer support or completely electronic examinations.

MR-based analysis of regional cardiac function in relation to cellular integrity in Fabry disease.

Background: Fabry cardiomyopathy is characterized by left ventricular (LV) hypertrophy and regional fibrosis. Recent high-end echocardiography studies of selected LV sections suggest an interrelation between regional fibrosis, impaired function, and hypertrophy possibly changing under specific enzyme replacement therapy (ERT).

Methods: Magnetic resonance imaging (MRI) was used for a region dependent study of cardiac function, morphology and late enhancement (LE) in 25 Fabry patients before and after 12 months of ERT in comparison to 43 healthy volunteers.

Biomechanical evaluation of flexor tendon repair using barbed suture material: a comparative ex vivo study.

Purpose: Barbed suture material for tendon repair opens up the possibility of a knotless reconstruction due to an increased suture-tendon interaction. The aim of this study was to compare the tensile strength of a knotted technique with a monofilament polydioxane suture to that of a knotless technique with a barbed suture material, by using a multistrand, modified Kirchmayr-Kessler tenorrhaphy.

Methods: Sixty human flexor digitorum tendons were randomized into 4 groups.

Outcome after resection of one hundred gastrointestinal stromal tumors.

Aims: To evaluate the outcome after surgical resection in patients with gastrointestinal stromal tumors and to determine the factors influencing local tumor recurrence or distant metastatic disease after locally complete tumor resection (R0).

Methods: Outcomes of 100 patients with primary gastrointestinal stromal tumors (GIST) surgically managed between 1997 and 2006 at a single institution were reviewed. Univariate and bivariate analyses were used to determine factors affecting recurrence-free and tumor-free survival.

A novel post-and-core restoration system--results of three years of clinical application of the "Wuerzburg Post".

The Wuerzburg Post is a new post-and-core restoration system designed to eliminate the weak parts of post-and-core restorations and the associated problems, respectively. In contrast to conventional posts, the Wuerzburg Post is a short and thick post, which no longer relies on cementation or luting for retention in the root, but on stress-free positive locking, which it achieves by means of a post which can be spread into a predefined and form-congruent undercut cavity. The second key feature is an annular groove which runs in the dentin, girded by a corresponding structure, ensuring regular force transmission and stress dissipation, as opposed to the classic ferrule design.

Comparison of arterial and central venous cannulations using ultrasound guidance in pigs.

Objective: To evaluate the feasibility of ultrasound guided vascular access in pigs by comparing central venous and arterial cannulation techniques.

Animals: Twenty-two healthy female Pietrain pigs, 14-18 weeks old and weighing 51.1 +/- 4.

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease.

Aims/hypothesis: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD.

Methods: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism.

Attitudes of mothers towards their child with Down syndrome before and after the introduction of prenatal diagnosis.

In 1970, before the introduction of prenatal diagnosis of chromosome anomalies, an unpublished questionnaire study concerning the social and emotional situation of mothers of children with Down syndrome was conducted in southern Germany. To assess the psychosocial impact of the availability of prenatal diagnosis on parents of genetically handicapped children, we re-evaluated and repeated the 1970 study over 30 years later. Although mothers' feelings of guilt for having a child with disabilities remained on a low level, today's mothers have a stronger feeling of being involuntarily segregated in society.

A new case of Carney triad: gastrointestinal stromal tumours and leiomyoma of the oesophagus do not show activating mutations of KIT and platelet-derived growth factor receptor alpha.

The Carney triad is a rare syndrome of unknown aetiology, with synchronous or metachronous appearance of rare neoplasms: gastrointestinal stromal tumours (GISTs), pulmonary chondromas and extra-adrenal paragangliomas. In most cases, the Carney triad is incomplete. The combination encountered typically, GISTs and pulmonary chondromas, was also seen in our patient, a 22-year-old woman.

Interlocking nailing of forearm fractures.

Introduction: With the exception of forearm fractures, intramedullary techniques are preferred for osteosynthesis in the case of long-bone fractures. For the latter, however, the main problem remains insufficient stability against torsional forces resulting in high rates of non-union. This is why plate osteosynthesis by means of a DCP 3.

OKT3 muromonab as second-line and subsequent treatment in recipients of stem cell allografts with steroid-resistant acute graft-versus-host disease.

We retrospectively evaluated response to monoclonal antibody directed against CD3 (OKT3) treatment in 43 patients with steroid-resistant acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic cell transplantation. Median duration of OKT3 therapy was 9 (range, 1-20) days. In all, 20 cycles were administered as second-line and 28 as third-plus line treatment.

Skill dependence of radiation exposure for the orthopaedic surgeon during interlocking nailing of long-bone shaft fractures: a clinical study.

Introduction: The objective of this clinical trial was to determine whether there is a skill dependence for the total amount of radiation exposure to orthopaedic surgeons caused by fluoroscopy during intramedullary fracture fixation.

Materials And Methods: Surgical teams were assigned to either the 'Senior group' or the 'Junior group' according to their professional qualification and clinical appointment. Twenty-two long-bone shaft fractures were stabilized with intramedullary nails.