Activation of SGK1 in Endometrial Epithelial Cells in Response to PI3K/AKT Inhibition Impairs Embryo Implantation.

Background: Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation.

Methods/results: Here, we report that treatment of endometrial epithelial cells with specific inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT activity pathway results in reciprocal activation of SGK1.

Conjugative DNA-transfer in Streptomyces, a mycelial organism.

Conjugative DNA-transfer in the Gram-positive mycelial soil bacterium Streptomyces, well known for the production of numerous antibiotics, is a unique process involving the transfer of a double-stranded DNA molecule. Apparently it does not depend on a type IV secretion system but resembles the segregation of chromosomes during bacterial cell division. A single plasmid-encoded protein, TraB, directs the transfer from the plasmid-carrying donor to the recipient.

Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma.

Background: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.

Methods: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group).

Polydiglycosylphosphate Transferase PdtA (SCO2578) of Streptomyces coelicolor A3(2) Is Crucial for Proper Sporulation and Apical Tip Extension under Stress Conditions.

Unlabelled: Although anionic glycopolymers are crucial components of the Gram-positive cell envelope, the relevance of anionic glycopolymers for vegetative growth and morphological differentiation of Streptomyces coelicolor A3(2) is unknown. Here, we show that the LytR-CpsA-Psr (LCP) protein PdtA (SCO2578), a TagV-like glycopolymer transferase, has a dual function in the S. coelicolor A3(2) life cycle.

Clinical outcome and paravalvular leakage of the new balloon-expandable Edwards Sapien 3 valve in comparison to its predecessor model (Edwards Sapien XT) in patients undergoing transfemoral aortic valve replacement.

Objectives: The aim of this study was to compare the 30-day procedural, clinical and echocardiographic outcome of the new balloon-expandable Edwards Sapien 3 (ES3) valve with the Edwards Sapien XT (ESXT).

Background: Post-implant paravalvular leaks (PVL) after transfemoral aortic valve replacement (TAVR) resulting in residual aortic regurgitation (AR) are a major limitation for long term outcome. New TAVR-devices have to eliminate this problem.

Balloon-guided inflation osteoplasty in the treatment of Hill-Sachs lesions of the humeral head: case report of a new technique.

Background: The use of the extra-vertebral balloon osteoplasty is increasing and in the meanwhile it has become a safe surgical technique in the treatment of tibial head, distal radius and calcaneus fractures. In addition, we already could show in a biomechanical setup that the balloon osteoplasty might be a safe tool for reduction in the treatment of Hill-Sachs lesions, but clinical application has not been performed so far.

Case Presentation: We report the case of a 53 year- old male patient who was referred to our Trauma department (level I trauma center) after the first manifestation of a posterior shoulder dislocation due to an epileptic seizure, originated in a- up to this date unknown -glioblastoma.

Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

Background And Purpose: Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation.

Fluorescence microscopy of Streptomyces conjugation suggests DNA-transfer at the lateral walls and reveals the spreading of the plasmid in the recipient mycelium.

Conjugative DNA-transfer in mycelial streptomycetes is a unique process, manifested on agar plates by the formation of circular growth retardation zones called pocks. Because pock size correlates with the extent of the transconjugant zone, it was suggested that pocks reflect the spreading of the transferred plasmid in the recipient mycelium. However, this concept has not been experimentally proven yet.

A Multiprotein DNA Translocation Complex Directs Intramycelial Plasmid Spreading during Streptomyces Conjugation.

Unlabelled: Conjugative DNA transfer in mycelial Streptomyces is a unique process involving the transfer of a double-stranded plasmid from the donor into the recipient and the subsequent spreading of the transferred plasmid within the recipient mycelium. This process is associated with growth retardation of the recipient and manifested by the formation of circular inhibition zones, named pocks. To characterize the unique Streptomyces DNA transfer machinery, we replaced each gene of the conjugative 12.

Control of Morphological Differentiation of Streptomyces coelicolor A3(2) by Phosphorylation of MreC and PBP2.

During morphological differentiation of Streptomyces coelicolor A3(2), the sporogenic aerial hyphae are transformed into a chain of more than fifty spores in a highly coordinated manner. Synthesis of the thickened spore envelope is directed by the Streptomyces spore wall synthesizing complex SSSC which resembles the elongasome of rod-shaped bacteria. The SSSC includes the eukaryotic type serine/threonine protein kinase (eSTPK) PkaI, encoded within a cluster of five independently transcribed eSTPK genes (SCO4775-4779).

Self-resistance mechanisms of actinomycetes producing lipid II-targeting antibiotics.

Glycopeptides and several lantibiotics are lipid II-targeting antibiotics produced by actinomycetes. To protect themselves from their own product, antibiotic producers developed self-resistance mechanisms. Inspection of different producer strains revealed that their resistance is not only based on a single determinant but on the synergistic action of different factors.

Synthesis of the spore envelope in the developmental life cycle of Streptomyces coelicolor.

Members of the family of Streptomycetaceae, the main producer of antibiotics and other secondary metabolites, are Gram-positive multi-cellular soil bacteria with a complex life cycle. By apical tip extension Streptomyces coelicolor forms a multiply branching vegetative mycelium penetrating the substrate. Upon nutrient limitation, a hydrophobic aerial mycelium is erected, which eventually develops into a regular chain of spores that are able to survive detrimental environmental conditions.

Dynamic-locking-screw (DLS)-leads to less secondary screw perforations in proximal humerus fractures.

Background: Loss of reduction and screw perforation causes high failure rates in the treatment of proximal humerus fractures. The purpose of the present study was to evaluate the early postoperative complications using modern Dynamic Locking Screws (DLS 3.7) for plating of proximal humerus fractures.

DLS 5.0--the biomechanical effects of dynamic locking screws.

Introduction: Indirect reduction of dia-/metaphyseal fractures with minimally invasive implant application bridges the fracture zone in order to protect the soft-tissue and blood supply. The goal of this fixation strategy is to allow stable motion at the fracture site to achieve indirect bone healing with callus formation. However, concerns have arisen that the high axial stiffness and eccentric position of locked plating constructs may suppress interfragmentary motion and callus formation, particularly under the plate.

Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial.

Background: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.

A septal chromosome segregator protein evolved into a conjugative DNA-translocator protein.

Streptomycetes, Gram-positive soil bacteria well known for the production of antibiotics feature a unique conjugative DNA transfer system. In contrast to classical conjugation which is characterized by the secretion of a pilot protein covalently linked to a single-stranded DNA molecule, in Streptomyces a double-stranded DNA molecule is translocated during conjugative transfer. This transfer involves a single plasmid encoded protein, TraB.

Conjugal plasmid transfer in Streptomyces resembles bacterial chromosome segregation by FtsK/SpoIIIE.

Conjugation is a major route of horizontal gene transfer, the driving force in the evolution of bacterial genomes. Antibiotic producing soil bacteria of the genus Streptomyces transfer DNA in a unique process involving a single plasmid-encoded protein TraB and a double-stranded DNA molecule. However, the molecular function of TraB in directing DNA transfer from a donor into a recipient cell is unknown.

Local catheter-based delivery of antithrombotic or antiproliferative drugs: a new concept for prevention of restenosis.

Background: Drug eluting stents have reduced the incidence of restenosis after percutaneous coronary interventions significantly, but cause concern about long term safety. Local drug delivery using special application catheters is an alternative approach for intracoronary pharmacotherapy. Besides the fact, that no problematic coating as drug carrier has to be used, a local delivery independent of the stent itself by using catheter techniques offers further advantages - such as the possibility to treat the whole vessel wall, stent edges and adjacent vessel segments and not only the area close to the stent struts.

Catheter-based local antiproliferative therapy in kissing balloon technique for in-stent stenosis of coronary artery bifurcation lesions.

There is currently no promising interventional solution for in-stent stenosis in previously stented bifurcation lesions, even with drug-eluting stents. Rather than being restricted to stent struts, catheter-based local antiproliferative therapy offers the advantage of homogenous drug transfer to the whole vessel wall, and thereby allows for intracoronary pharmacotherapy without adding additional layers of metal into an already stented lesion. The newly developed GENIE catheter (Acrostak Corp, Switzerland), applied in the kissing balloon technique, allows for delivery of liquid paclitaxel into whole bifurcation lesions without repeat stent implantation.

Melanoma of the nose: prognostic factors, three-dimensional histology, and surgical strategies.

Objectives: The prominent position of the nose in the face accounts for its constant exposure to sunlight and thus its high incidence of malignant involvement. The aim of this prospective study was to define prognostic factors for nasal melanomas and to evaluate surgical strategies.

Methods: Forty-five patients with stage I/II melanoma were included.

Unique conjugation mechanism in mycelial streptomycetes: a DNA-binding ATPase translocates unprocessed plasmid DNA at the hyphal tip.

A single plasmid-encoded protein, the septal DNA translocator TraB, is sufficient to promote conjugal plasmid transfer in mycelial streptomycetes. To analyse the molecular mechanism of conjugation the closely related TraB proteins from plasmids pSG5 of Streptomyces ghanaensis and pSVH1 of Streptomyces venezuelae were characterized. TraB of pSG5 was expressed as a fusion protein with eGFP and found to be localized at the hyphal tips of Streptomyces lividans by fluorescence microscopy, which strongly indicates that conjugation takes place at the tips of the mating mycelium.

Testing two accounts of pain underestimation.

Two important influences on pain underestimation by health care professionals were investigated by varying specific cues with reference to underestimation of patients' pain: when observers are not allowed to talk to patients and when observers expect social cheating. One hundred and twenty health care professionals watched videotaped facial expressions of pain patients and estimated their pain. The first group only saw the faces, the second group was given patients' self-reports in addition and the last group was given a context cue priming them to expect cheating in addition to faces and patients' ratings.

Micrometastasis of a sentinel lymph node in cutaneous melanoma is a significant prognostic factor for disease-free survival, distant-metastasis-free survival, and overall survival.

Objective: Sentinel lymph node biopsy (SLNB) has been proposed as a minimally invasive procedure for the histopathologic staging of the regional lymph node basin. The aim of this work was to investigate the prognostic value of detection of micrometastasis by SLNB.

Methods: In the period from January 1996 to March 2000, a sentinel lymph node (SLN) was identified in 283 patients at the Department Dermatology, University of Tuebingen.

Clinical risk factors and prognostic significance of local recurrence in cutaneous melanoma.

Background: True local recurrence (LR) means clinically detectable regrowth of parts of the tumour which were not completely excised. In the literature the term 'LR' has been used in a vague and inconsistent manner that may include satellite and in-transit metastasis.

Objective: The aim of this study was to establish clinical, histological and surgical risk factors for the manifestation of LR and to evaluate the prognostic significance of LR.