Crucial Role of Nucleic Acid Sensing via Endosomal Toll-Like Receptors for the Defense of and .

is a major human pathogen causing a variety of diseases ranging from common pharyngitis to life-threatening soft tissue infections and sepsis. Microbial nucleic acids, especially bacterial RNA, have recently been recognized as a major group of pathogen-associated molecular patterns (PAMPs) involved in the detection of via endosomal Toll-like receptors (TLRs) . However, the individual contribution and cooperation between TLRs as well as cell-type and strain specific differences in dependency on nucleic acid detection during infection have not been clarified in detail.

New approaches for the detection of invasive fungal diseases in patients following liver transplantation-results of an observational clinical pilot study.

Purpose: Despite antifungal prophylaxis following liver transplantation (LTX), patients are at risk for the development of subsequent opportunistic infections, such as an invasive fungal disease (IFD). However, culture-based diagnostic procedures are associated with relevant weaknesses.

Methods: Culture and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of ß-D-glucan (BDG), galactomannan (GM), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A and mid-regional proadrenomedullin (MR-proADM) were evaluated in 93 patients at 6 consecutive time points within 28 days following LTX.

Personalized medicine with IgGAM compared with standard of care for treatment of peritonitis after infectious source control (the PEPPER trial): study protocol for a randomized controlled trial.

Background: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator.

Emission and propagation of 1D and 2D spin waves with nanoscale wavelengths in anisotropic spin textures.

Spin waves offer intriguing perspectives for computing and signal processing, because their damping can be lower than the ohmic losses in conventional complementary metal-oxide-semiconductor (CMOS) circuits. Magnetic domain walls show considerable potential as magnonic waveguides for on-chip control of the spatial extent and propagation of spin waves. However, low-loss guidance of spin waves with nanoscale wavelengths and around angled tracks remains to be shown.

Gut microbiome patterns correlate with higher postoperative complication rates after pancreatic surgery.

Background: Postoperative complications are of great relevance in daily clinical practice, and the gut microbiome might play an important role by preventing pathogens from crossing the intestinal barrier. The two aims of this prospective clinical pilot study were: (1) to examine changes in the gut microbiome following pancreatic surgery, and (2) to correlate these changes with the postoperative course of the patient.

Results: In total, 116 stool samples of 32 patients undergoing pancreatic surgery were analysed by 16S-rRNA gene next-generation sequencing.

Anatomy of Skyrmionic Textures in Magnetic Multilayers.

Room temperature magnetic skyrmions in magnetic multilayers are considered as information carriers for future spintronic applications. Currently, a detailed understanding of the skyrmion stabilization mechanisms is still lacking in these systems. To gain more insight, it is first and foremost essential to determine the full real-space spin configuration.

Enhanced Performance of Next-Generation Sequencing Diagnostics Compared With Standard of Care Microbiological Diagnostics in Patients Suffering From Septic Shock.

Objectives: Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Within the presented investigation, higher performance of next-generation sequencing-based diagnostics was validated by comparison to matched blood cultures.

Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study.

Background: Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined.

Methods: In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled.

[Diagnostic Approaches in Sepsis - Part 2: Pathogen Detection].

Despite the dissemination of innovative, molecular biology-based and commercially available devices for pathogen detection, culture-based methods with susceptibility testing remain the key principles for guiding antimicrobial treatment of patients suffering from sepsis or septic shock on the ICU. Culture-based methods are able to facilitate pathogen detection from a diversity of specimen (respiratory secretion, intraoperatively obtained smears, aspirates, and so forth). However, the latency from obtainment of the specimen up to pathogen detection with susceptibility testing is a major disadvantage of culture-based methods in critical illness.

[Diagnostic Approaches in Sepsis - Part 1: General Diagnostic Principles, Focus Identification and Source Control].

Sepsis and septic shock represent medical emergencies with persistently high mortality rates. According to the lately revised Surviving Sepsis Campaign (SSC) guidelines, focus identification/pathogen detection and the initial administration of broad-spectrum antibiotics are to be secluded within one hour after recognition of the symptoms of sepsis. However, there is dispute concerning the so called hour-1 bundle.

Sepsis Induces a Long-Lasting State of Trained Immunity in Bone Marrow Monocytes.

Innate immune memory describes the functional reprogramming of innate immune cells after pathogen contact, leading to either a boosted (trained immunity) or a diminished (immune tolerance) response to a secondary stimulus. Immune tolerance or "sepsis-induced immunosuppression" is a typical hallmark of patients after sepsis survival, characterized by hypo-responsiveness of the host's immune system. This condition renders the host vulnerable for a persisting infection or the occurrence of secondary, often opportunistic infections, along with an increased mortality rate.

Sepsis in mechanically ventilated patients with spinal cord injury: a retrospective analysis.

Study Design: Retrospective analysis.

Objectives: Sepsis, one of the most frequent and life-threatening complications on intensive care units (ICUs), is associated with a need for mechanical ventilation (MV) as well as adverse respiratory outcomes in hospitalized individuals. However, it has poorly been investigated in patients with spinal cord injury (SCI); a population at high risk for pulmonary and infectious complications.

Current-Induced Skyrmion Generation through Morphological Thermal Transitions in Chiral Ferromagnetic Heterostructures.

Magnetic skyrmions promise breakthroughs in future memory and computing devices due to their inherent stability and small size. Their creation and current driven motion have been recently observed at room temperature, but the key mechanisms of their formation are not yet well-understood. Here it is shown that in heavy metal/ferromagnet heterostructures, pulsed currents can drive morphological transitions between labyrinth-like, stripe-like, and skyrmionic states.

Postoperative pancreatic fistula: Microbial growth determines outcome.

Background: Postoperative pancreatic fistula is a dangerous complication in pancreatic surgery. This study assessed the impact of microbiologic pathogens detected in postoperative pancreatic fistula on clinical outcomes after partial pancreatoduodenectomy and distal pancreatectomy.

Methods: Microorganisms in postoperative pancreatic fistula were identified by microbiologic analyses from abdominal drains or intraoperative swabs during relaparotomy.

Impact of human sepsis on CCCTC-binding factor associated monocyte transcriptional response of Major Histocompatibility Complex II components.

Background: Antigen presentation on monocyte surface to T-cells by Major Histocompatibility Complex, Class II (MHC-II) molecules is fundamental for pathogen recognition and efficient host response. Accordingly, loss of Major Histocompatibility Complex, Class II, DR (HLA-DR) surface expression indicates impaired monocyte functionality in patients suffering from sepsis-induced immunosuppression. Besides the impact of Class II Major Histocompatibility Complex Transactivator (CIITA) on MHC-II gene expression, X box-like (XL) sequences have been proposed as further regulatory elements.

Caspofungin Modulates Ryanodine Receptor-Mediated Calcium Release in Human Cardiac Myocytes.

Recent studies showed that critically ill patients might be at risk for hemodynamic impairment during caspofungin (CAS) therapy. The aim of our present study was to examine the mechanisms behind CAS-induced cardiac alterations. We revealed a dose-dependent increase in intracellular Ca concentration ([Ca]) after CAS treatment.

Association of Immune Cell Subtypes and Phenotype With Subsequent Invasive Candidiasis in Patients With Abdominal Sepsis.

Background: In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis.

Methods: The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis.

High-throughput synthesis of modified Fresnel zone plate arrays via ion beam lithography.

Fresnel zone plates (FZP) are diffractive photonic devices used for high-resolution imaging and lithography at short wavelengths. Their fabrication requires nano-machining capabilities with exceptional precision and strict tolerances such as those enabled by modern lithography methods. In particular, ion beam lithography (IBL) is a noteworthy method thanks to its robust direct writing/milling capability.

The Interplay of Notch Signaling and STAT3 in TLR-Activated Human Primary Monocytes.

The highly conserved Notch signaling pathway essentially participates in immunity through regulation of developmental processes and immune cell activity. In the adaptive immune system, the impact of the Notch cascade in T and B differentiation is well studied. In contrast, the function, and regulation of Notch signaling in the myeloid lineage during infection is poorly understood.

3D Nanoprinted Plastic Kinoform X-Ray Optics.

High-performance focusing of X-rays requires the realization of very challenging 3D geometries with nanoscale features, sub-millimeter-scale apertures, and high aspect ratios. A particularly difficult structure is the profile of an ideal zone plate called a kinoform, which is manufactured in nonideal approximated patterns, nonetheless requires complicated multistep fabrication processes. Here, 3D fabrication of high-performance kinoforms with unprecedented aspect ratios out of low-loss plastics using femtosecond two-photon 3D nanoprinting is presented.

In-depth characterization of the neuroinflammatory reaction induced by peripheral surgery in an animal model.

Delirium is a common complication seen after surgery and anesthesia, in particular in older patients. Although the etiology of postoperative delirium is only incompletely understood, various lines of evidence suggest that proinflammatory signaling from the peripheral site of inflammation to central nervous system results in a decrease of cerebral acetylcholine (ACh) levels thereby inducing neuroinflammation. To corroborate this theory, we applied an animal model for characterization of the neuroinflammatory response after partial hepatectomy (HPx).

Paternal sepsis induces alterations of the sperm methylome and dampens offspring immune responses-an animal study.

Background: Sepsis represents the utmost severe consequence of infection, involving a dysregulated and self-damaging immune response of the host. While different environmental exposures like chronic stress or malnutrition have been well described to reprogram the germline and subsequently offspring attributes, the intergenerational impact of sepsis as a tremendous immunological stressor has not been examined yet.

Methods: Polymicrobial sepsis in 12-week-old male C57BL/6 mice was induced by cecal ligation and puncture (CLP), followed by a mating of the male survivors (or appropriate sham control animals) 6 weeks later with healthy females.

Applying the human factors analysis and classification system to critical incident reports in anaesthesiology.

Background: The Human Factors Analysis and Classification System (HFACS) was developed as a practical taxonomy to investigate and analyse the human contribution to accidents and incidents. Based on Reason's "Swiss Cheese Model", it considers individual, environmental, leadership and organizational contributing factors in four hierarchical levels. The aim of this study was to assess the applicability of a modified HFACS taxonomy to incident reports from a large, anonymous critical incident database with the goal of gaining valuable insight into underlying, more systemic conditions and recurring schemes that might add important information for future incident avoidance.

The immunosuppressive face of sepsis early on intensive care unit-A large-scale microarray meta-analysis.

Background: Sepsis is defined as a life-threatening condition, resulting from a dysregulated and harmful response of the hosts' immune system to infection. Apart from this, the (over-)compensating mechanisms counterbalancing the inflammatory response have been proven to render the host susceptible to further infections and increase delayed mortality. Our study aimed to unravel the heterogeneity of immune response in early sepsis and to explain the biology behind it.