Transfusion of Packed Red Cells: Indications, Triggers and Adverse Events.

Background: About four million units of packed red cells are transfused in Germany every year. The safety of blood transfusions is further improved by modern production methods and molecular diagnostic techniques.

Methods: This review is based on selected publications,including the German guidelines and regulations and the German Transfusion Act.

A global RNA-seq-driven analysis of CHO host and production cell lines reveals distinct differential expression patterns of genes contributing to recombinant antibody glycosylation.

Boehringer Ingelheim uses two CHO-DG44 lines for manufacturing biotherapeutics, BI-HEX-1 and BI-HEX-2, which produce distinct cell type-specific antibody glycosylation patterns. A recently established CHO-K1 descended host, BI-HEX-K1, generates antibodies with glycosylation profiles differing from CHO-DG44. Manufacturing process development is significantly influenced by these unique profiles.

Factors Governing P-Glycoprotein-Mediated Drug-Drug Interactions at the Blood-Brain Barrier Measured with Positron Emission Tomography.

The adenosine triphosphate-binding cassette transporter P-glycoprotein (ABCB1/Abcb1a) restricts at the blood-brain barrier (BBB) brain distribution of many drugs. ABCB1 may be involved in drug-drug interactions (DDIs) at the BBB, which may lead to changes in brain distribution and central nervous system side effects of drugs. Positron emission tomography (PET) with the ABCB1 substrates (R)-[(11)C]verapamil and [(11)C]-N-desmethyl-loperamide and the ABCB1 inhibitor tariquidar has allowed direct comparison of ABCB1-mediated DDIs at the rodent and human BBB.

Dynamics and Correlations among Soft Excitations in Marginally Stable Glasses.

Marginal stability is the notion that stability is achieved, but only barely so. This property constrains the ensemble of configurations explored at low temperature in a variety of systems, including spin, electron, and structural glasses. A key feature of marginal states is a (saturated) pseudogap in the distribution of soft excitations.

MzJava: An open source library for mass spectrometry data processing.

Mass spectrometry (MS) is a widely used and evolving technique for the high-throughput identification of molecules in biological samples. The need for sharing and reuse of code among bioinformaticians working with MS data prompted the design and implementation of MzJava, an open-source Java Application Programming Interface (API) for MS related data processing. MzJava provides data structures and algorithms for representing and processing mass spectra and their associated biological molecules, such as metabolites, glycans and peptides.

Age-dependent levels of 5-methyl-, 5-hydroxymethyl-, and 5-formylcytosine in human and mouse brain tissues.

The absolute levels of 5-hydroxymethylcytosine (hmC) and 5-methylcytosine (mC) in human brain tissues at various ages were determined. Additionally, absolute levels of 5-formylcytosine (fC) in adult individuals and cytosine modification levels in sorted neurons were quantified. These data were compared with age-related fC, hmC, and mC levels in mouse brain samples.

Patient blood management implementation strategies and their effect on physicians' risk perception, clinical knowledge and perioperative practice - the frankfurt experience.

Introduction: A multicomponent, evidence-based and interdisciplinary Patient Blood Management (PBM) program was introduced at the University Hospital Frankfurt in July 2013. The implementation strategy included practical and tactical components aimed to increase knowledge on the risks of preoperative anemia, to standardize hemotherapy, and to facilitate PBM components.

Methods: This article analyzes barriers to PBM implementation and outlines a strategy to introduce and manifest PBM.

Anomalous diffusion and griffiths effects near the many-body localization transition.

We explore the high-temperature dynamics of the disordered, one-dimensional XXZ model near the many-body localization (MBL) transition, focusing on the delocalized (i.e., "metallic") phase.

TET3 is recruited by REST for context-specific hydroxymethylation and induction of gene expression.

Ten-eleven translocation hydroxylases (TET1-3) oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In neurons, increased 5hmC levels within gene bodies correlate positively with gene expression. The mechanisms controlling TET activity and 5hmC levels are poorly understood.

Unrestricted modification search reveals lysine methylation as major modification induced by tissue formalin fixation and paraffin embedding.

Formalin-fixed paraffin-embedded (FFPE) tissue is considered as an appropriate alternative to frozen/fresh tissue for proteomic analysis. Here we study formalin-induced alternations on a proteome-wide level. We compared LC-MS/MS data of FFPE and frozen human kidney tissues by two methods.

Automated radiosynthesis of [(18)F]ciprofloxacin.

We transferred the previously published manual synthesis of [(18)F]ciprofloxacin (decay-corrected RCY: 5.5±1.0%) to an automated synthesis module (TRACERlab(TM) FXFDG, GE Healthcare) and observed a strong decrease in RCY (0.

Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.

As P-glycoprotein (Pgp) inhibition at the blood-brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate (R)-[(11)C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume (VT) of (R)-[(11)C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.

Anesthetic management of patients undergoing bariatric surgery: two year experience in a single institution in Switzerland.

Background: In the field of anesthesia for bariatric surgery, a wide variety of recommendations exist, but a general consensus on the perioperative management of such patients is missing. We outline the perioperative experiences that we gained in the first two years after introducing a bariatric program.

Methods: The perioperative approach was established together with all relevant disciplines.

Evaluation of metal artifacts in clinical MR images of patients with total hip arthroplasty using different metal artifact-reducing sequences.

Purpose: To evaluate the distortion and artifact area of metal in MR images and to compare artifact reduction using different metal artifact-reducing sequences in patients with metal-on-metal (MoM) and non-MoM total hip prostheses.

Materials And Methods: Thirty-six MoM and 15 non-MoM prostheses were examined in a 1.5-T MR scanner using T1-weighted (T1-w) sequences: turbo spin echo (TSE) high-readout bandwidth (hiBW), T1-w; TSE view angle tilting (VAT), T1-w; TSE VAT + slice encoding for metal artifact correction (SEMAC); short tau inversion recovery (STIR) hiBW or matched RF pulses (mRFp).

"Post-it" type connected DNA created with a reversible covalent cross-link.

We report the development of a new heterobase that is held together through reversible bonding. The so-formed cross-link adds strong stabilization to the DNA duplex. Despite this, the cross-link opens and closes through reversible imine bonding.

Intra-specific variations in expression of stress-related genes in beech progenies are stronger than drought-induced responses.

Rapidly decreasing water availability as a consequence of climate change is likely to endanger the range of long-lived tree species. A pressing question is, therefore, whether adaptation to drought exists in important temperate tree species like European beech (Fagus sylvatica L.), a wide-spread, dominant forest tree in Central Europe.

Processing strategies and software solutions for data-independent acquisition in mass spectrometry.

Data-independent acquisition (DIA) offers several advantages over data-dependent acquisition (DDA) schemes for characterizing complex protein digests analyzed by LC-MS/MS. In contrast to the sequential detection, selection, and analysis of individual ions during DDA, DIA systematically parallelizes the fragmentation of all detectable ions within a wide m/z range regardless of intensity, thereby providing broader dynamic range of detected signals, improved reproducibility for identification, better sensitivity, and accuracy for quantification, and, potentially, enhanced proteome coverage. To fully exploit these advantages, composite or multiplexed fragment ion spectra generated by DIA require more elaborate processing algorithms compared to DDA.

Survival of AIDS-related diffuse large B-cell lymphoma, Burkitt lymphoma, and plasmablastic lymphoma in the German HIV Lymphoma Cohort.

Overall survival (OS) of patients with acquired immunodeficiency syndrome (AIDS)-related Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and plasmablastic lymphoma (PBL) was analysed in the German AIDS-related-Lymphoma-Cohort-Study. Of 291 patients prospectively included between January 2005 and December 2012, 154 had DLBCL, 103 BL and 34 PBL. Two-year OS rates were similar between BL (69%) and DLBCL patients (63%) but lower for PBL patients (43%).

Deformable reconstruction of histology sections using structural probability maps.

The reconstruction of a 3D volume from a stack of 2D histology slices is still a challenging problem especially if no external references are available. Without a reference, standard registration approaches tend to align structures that should not be perfectly aligned. In this work we introduce a deformable, reference-free reconstruction method that uses an internal structural probability map (SPM) to regularize a free-form deformation.

In vivo P-glycoprotein function before and after epilepsy surgery.

Objectives: To study the functional activity of the multidrug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier of patients with temporal lobe epilepsy using (R)-[(11)C]verapamil (VPM)-PET before and after temporal lobe surgery to assess whether postoperative changes in seizure frequency and antiepileptic drug load are associated with changes in Pgp function.

Methods: Seven patients with drug-resistant temporal lobe epilepsy underwent VPM-PET scans pre- and postsurgery. Patients were followed up for a median of 6 years (range 4-7) after surgery.

Automatic ultrasound-MRI registration for neurosurgery using the 2D and 3D LC(2) Metric.

To enable image guided neurosurgery, the alignment of pre-interventional magnetic resonance imaging (MRI) and intra-operative ultrasound (US) is commonly required. We present two automatic image registration algorithms using the similarity measure Linear Correlation of Linear Combination (LC(2)) to align either freehand US slices or US volumes with MRI images. Both approaches allow an automatic and robust registration, while the three dimensional method yields a significantly improved percentage of optimally aligned registrations for randomly chosen clinically relevant initializations.

MR imaging with metal artifact-reducing sequences and gadolinium contrast agent in a case-control study of periprosthetic abnormalities in patients with metal-on-metal hip prostheses.

Objective: To apply and compare magnetic resonance imaging (MRI) metal artifact reducing sequences (MARS) including subtraction imaging after contrast application in patients with metal-on-metal (MoM) hip prostheses, investigate the prevalence and characteristics of periprosthetic abnormalities, as well as their relation with pain and risk factors.

Materials And Methods: Fifty-two MoM prostheses (35 cases with pain and or risk factors, and 17 controls) in 47 patients were examined in a 1.5-T MR scanner using MARS: turbo spin echo (TSE) with high readout bandwidth with and without view angle tilting (VAT), TSE with VAT and slice encoding for metal artifact correction (SEMAC), short tau inversion recovery (STIR) with matched RF pulses, and post-contrast imaging.