Practical Consequences Resulting from the Analysis of a 21-Multigene Array in the Interdisciplinary Conference of a Breast Cancer Center.

During the multidisciplinary planning of postoperative therapy after breast cancer, borderline cases can arise with no clear rationale for or against adjuvant chemotherapy. In 50 hormone- receptor-positive, Her2neu-negative carcinomas of the breast with no or only minimal lymph node involvement (max. pT1a) we initiated an Oncotype DX® multigene assay in addition to the evaluation of usual parameters.

Outcomes after cochlear implant provision in children with cochlear nerve hypoplasia or aplasia.

Introduction: Cochlear nerve aplasia or hypoplasia is found in up to a half of patients with unilateral or bilateral hearing loss. There is an ongoing discussion regarding the indication of cochlear implants for hearing rehabilitation in cases with radiologically-defined aplasia or hypoplasia of the cochlear nerve in those patients, especially in children. At present there is conflicting evidence whether the audiological outcomes of those children with a CI are comparable to those of children with a CI and a radiologically-normal cochlear nerve.

Large-scale self-organized gold nanostructures with bidirectional plasmon resonances for SERS.

Efficient substrates for surface-enhanced Raman spectroscopy (SERS) are under constant development, since time-consuming and costly fabrication routines are often an issue for high-throughput spectroscopy applications. In this research, we use a two-step fabrication method to produce self-organized parallel-oriented plasmonic gold nanostructures. The fabrication routine is ready for wafer-scale production involving only low-energy ion beam irradiation and metal deposition.

Metabolic conversion of CI-1040 turns a cellular MEK-inhibitor into an antibacterial compound.

Influenza virus (IV) infections cause severe respiratory illnesses that can be complicated by bacterial super-infections. Previously, we identified the cellular Raf-MEK-ERK cascade as a promising antiviral target. Inhibitors of MEK, such as CI-1040, showed potent antiviral activity.

The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma.

Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis.

Novel insights into neuroinflammation: bacterial lipopolysaccharide, tumor necrosis factor α, and Ureaplasma species differentially modulate atypical chemokine receptor 3 responses in human brain microvascular endothelial cells.

Background: Atypical chemokine receptor 3 (ACKR3, synonym CXCR7) is increasingly considered relevant in neuroinflammatory conditions, in which its upregulation contributes to compromised endothelial barrier function and may ultimately allow inflammatory brain injury. While an impact of ACKR3 has been recognized in several neurological autoimmune diseases, neuroinflammation may also result from infectious agents, including Ureaplasma species (spp.).

CRISPR RNA-Dependent Binding and Cleavage of Endogenous RNAs by the Campylobacter jejuni Cas9.

Cas9 nucleases naturally utilize CRISPR RNAs (crRNAs) to silence foreign double-stranded DNA. While recent work has shown that some Cas9 nucleases can also target RNA, RNA recognition has required nuclease modifications or accessory factors. Here, we show that the Campylobacter jejuni Cas9 (CjCas9) can bind and cleave complementary endogenous mRNAs in a crRNA-dependent manner.

Effects of a partially supervised conditioning programme in cystic fibrosis: an international multi-centre randomised controlled trial (ACTIVATE-CF): study protocol.

Background: Physical activity (PA) and exercise have become an accepted and valued component of cystic fibrosis (CF) care. Regular PA and exercise can positively impact pulmonary function, improve physical fitness, and enhance health-related quality of life (HRQoL). However, motivating people to be more active is challenging.

Is sweat testing for cystic fibrosis feasible in patients with down syndrome?

Background: Recurrent airway infections are common in patients with Down's syndrome (DS). Hence, ruling out Cystic Fibrosis (CF) in these patients is often required. In the past, the value of sweat testing - the gold standard to diagnose CF - has been questioned in DS as false positive results have been reported.

Evaluation of a software module for adaptive treatment planning and re-irradiation.

Background: The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow.

Methods: The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk.

[Significance of the doctorate in scientific medical education].

According to European and German law, the medical education of physicians must take place in a scientific degree program at a university or under the supervision of a university. To keep up the ideal of a scientific degree program, various organizations and associations, such as the German Research Foundation, the German Council of Science and Humanities and the German Medical Faculty Association, see the need for an even stronger anchoring of academic learning content in the course of study. Traditionally, a scientific project, which is carried out during the studies, provides the basis for the Doctor of Medicine (Dr.

Postoperative endophthalmitis - a case report highlighting the additive value of molecular testing.

is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms.

Improving anti-trypanosomal activity of alkamides isolated from Achillea fragrantissima.

In previous studies the aerial parts of Achillea fragrantissima were found to have substantial antileishmanial and antitrypanosomal activity. A bioassay-guided fractionation of a dichloromethane extract yielded the isolation of the essential anti-trypanosomal compounds of the plant. Seven sesquiterpene lactones (including Achillolide-A), two flavonoids, chrysosplenol-D and chrysosplenetine, and four alkamides (including pellitorine) were identified.

Ndrg1 promotes adipocyte differentiation and sustains their function.

Adipocytes play a central role in maintaining metabolic homeostasis in the body. Differentiation of adipocyte precursor cells requires the transcriptional activity of peroxisome proliferator-activated receptor-γ (Pparγ) and CCAAT/enhancer binding proteins (C/Ebps). Transcriptional activity is regulated by signaling modules activated by a plethora of hormones and nutrients.

Thrombopoiesis is spatially regulated by the bone marrow vasculature.

In mammals, megakaryocytes (MKs) in the bone marrow (BM) produce blood platelets, required for hemostasis and thrombosis. MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Through imaging of MKs in the intact BM, here we show that MKs can be found within the entire BM, without a bias towards bone-distant regions.

Image-based modeling and scoring of Howell-Jolly Bodies in human erythrocytes.

The spleen selectively removes cells with intracellular inclusions, for example, detached nuclear fragments in circulating erythrocytes, called Howell-Jolly Bodies (HJBs). With absent or deficient splenic function HJBs appear in the peripheral blood and can be used as a simple and non-invasive risk-indicator for fulminant potentially life-threatening infection after spleenectomy. However, it is still under debate whether counting of the rare HJBs is a reliable measure of splenic function.

Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of Neuronal Ceroid Lipofuscinosis.

CLN diseases are rare lysosomal storage diseases characterized by progressive axonal degeneration and neuron loss in the CNS, manifesting in disability, blindness, and premature death. We have previously demonstrated that, in animal models of infantile and juvenile forms of CLN disease (CLN1 and CLN3, respectively), secondary neuroinflammation in the CNS substantially amplifies neural damage, opening the possibility that immunomodulatory treatment might improve disease outcome. First, we recapitulated the inflammatory phenotype, originally seen in mice in autopsies of CLN patients.

Stem cell-derived organoids and their application for medical research and patient treatment.

3D culture has allowed the initiation and expansion of organ-like structures, called organoids, from either tissue-resident adult stem cells or pluripotent stem cells. Today, organoids can be grown to resemble a wide variety of organs, exhibiting remarkable similarity to their in vivo counterparts. As successful organoid generation is possible from virtually every patient, organoids hold a great promise for medical research and the development of new treatments.

Caffeine modulates glucocorticoid-induced expression of CTGF in lung epithelial cells and fibroblasts.

Background: Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling.

Stroke unit care in germany: the german stroke registers study group (ADSR).

Background: Factors influencing access to stroke unit (SU) care and data on quality of SU care in Germany are scarce. We investigated characteristics of patients directly admitted to a SU as well as patient-related and structural factors influencing adherence to predefined indicators of quality of acute stroke care across hospitals providing SU care.

Methods: Data were derived from the German Stroke Registers Study Group (ADSR), a voluntary network of 9 regional registers for monitoring quality of acute stroke care in Germany.

Proteomic Analysis of the Mediator Complex Interactome in Saccharomyces cerevisiae.

Here we present the most comprehensive analysis of the yeast Mediator complex interactome to date. Particularly gentle cell lysis and co-immunopurification conditions allowed us to preserve even transient protein-protein interactions and to comprehensively probe the molecular environment of the Mediator complex in the cell. Metabolic N-labeling thereby enabled stringent discrimination between bona fide interaction partners and nonspecifically captured proteins.