[Perioperative pain therapy in minimally invasive thoracic surgery]. / Perioperative Schmerztherapie bei minimal-invasiver Thoraxchirurgie.

Thoracic surgery is often associated with severe postoperative pain levels. Even though these are less pronounced in thoracoscopic approaches, mechanical irritation, compression or injury of intercostal nerves and placement of chest tubes can cause pain levels, which must be treated. An adequate pain therapy in thoracic surgery is essential as insufficient inspiration due to inadequate analgesia may result in postoperative complications. Epidural anesthesia was considered the gold standard in thoracotomy for a long time. For video-assisted thoracoscopy, however, it is sometimes no longer recommended due to its benefit-risk ratio. Alternative thoracic blocks are the paravertebral block, the erector spinae plane block and the serratus anterior block, for which research has found heterogeneous results.This article summarizes the current recommendations for perioperative management of thoracoscopic surgery and gives an overview of the PROSPECT recommendations as well as the current Association of the Scientific Medical Societies in Germany (AWMF) guidelines for perioperative and postoperative pain therapy. In particular, individual regional anesthesia techniques and their current evidence are reviewed.

A chromosome-scale reference genome assembly of the great sand eel, Hyperoplus lanceolatus.

Despite increasing sequencing efforts, numerous fish families still lack a reference genome, which complicates genetic research. One such understudied family is the sand lances (Ammodytidae, literally: "sand burrower"), a globally distributed clade of over 30 fish species that tend to avoid tidal currents by burrowing into the sand. Here, we present the first annotated chromosome-level genome assembly of the great sand eel (Hyperoplus lanceolatus). The genome assembly was generated using Oxford Nanopore Technologies long sequencing reads and Illumina short reads for polishing. The final assembly has a total length of 808.5 Mbp, of which 97.1% were anchored into 24 chromosome-scale scaffolds using proximity-ligation scaffolding. It is highly contiguous with a scaffold and contig N50 of 33.7 and 31.3 Mbp, respectively, and has a BUSCO completeness score of 96.9%. The presented genome assembly is a valuable resource for future studies of sand lances, as this family is of great ecological and commercial importance and may also contribute to studies aiming to resolve the suprafamiliar taxonomy of bony fishes.

Performance of the eazyplex® BloodScreen GN as a simple and rapid molecular test for identification of Gram-negative bacteria from positive blood cultures.

The LAMP-based eazyplex® BloodScreen GN was evaluated for the detection of frequent Gram-negatives directly from positive blood culture (BC) bottles. A total of 449 BCs were analyzed. Sensitivities and specificities were 100% and 100% for Escherichia coli, 95.7% and 100% for Klebsiella pneumoniae, 100% and 100% for blaCTX-M, 100% and 100% for Klebsiella oxytoca, 100% and 99% for Proteus mirabilis, and 100% and 99.8% for Pseudomonas aeruginosa, respectively. The time to result ranged from 8 to 16 min, plus about 6 min for sample preparation. The eazyplex® BloodScreen GN is a reliable molecular assay for rapid BC testing.

Interactive effects of microplastic pollution and heat stress on reef-building corals.

Plastic pollution is an emerging stressor that increases pressure on ecosystems such as coral reefs that are already challenged by climate change. However, the effects of plastic pollution in combination with global warming are largely unknown. Thus, the goal of this study was to determine the cumulative effects of microplastic pollution with that of global warming on reef-building coral species and to compare the severity of both stressors. For this, we conducted a series of three controlled laboratory experiments and exposed a broad range of coral species (Acropora muricata, Montipora digitata, Porites lutea, Pocillopora verrucosa, and Stylophora pistillata) to microplastic particles in a range of concentrations (2.5-2500 particles L-1) and mixtures (from different industrial sectors) at ambient temperatures and in combination with heat stress. We show that microplastic can occasionally have both aggravating or mitigating effects on the corals' thermal tolerance. In comparison to heat stress, however, microplastic constitutes a minor stressor. While heat stress led to decreased photosynthetic efficiency of algal symbionts, and increased bleaching, tissue necrosis, and mortality, treatment with microplastic particles had only minor effects on the physiology and health of the tested coral species at ambient temperatures. These findings underline that while efforts to reduce plastic pollution should continue, they should not replace more urgent efforts to halt global warming, which are immediately needed to preserve remaining coral reef ecosystems.

Blue and Long-Wave Ultraviolet Light Induce in vitro Neutrophil Extracellular Trap (NET) Formation.

Neutrophil Extracellular Traps (NETs) are produced by neutrophilic granulocytes and consist of decondensed chromatin decorated with antimicrobial peptides. They defend the organism against intruders and are released upon various stimuli including pathogens, mediators of inflammation, or chemical triggers. NET formation is also involved in inflammatory, cardiovascular, malignant diseases, and autoimmune disorders like rheumatoid arthritis, psoriasis, or systemic lupus erythematosus (SLE). In many autoimmune diseases like SLE or dermatomyositis, light of the ultraviolet-visible (UV-VIS) spectrum is well-known to trigger and aggravate disease severity. However, the underlying connection between NET formation, light exposure, and disease exacerbation remains elusive. We studied the effect of UVA (375 nm), blue (470 nm) and green (565 nm) light on NETosis in human neutrophils ex vivo. Our results show a dose- and wavelength-dependent induction of NETosis. Light-induced NETosis depended on the generation of extracellular reactive oxygen species (ROS) induced by riboflavin excitation and its subsequent reaction with tryptophan. The light-induced NETosis required both neutrophil elastase (NE) as well as myeloperoxidase (MPO) activation and induced histone citrullination. These findings suggest that NET formation as a response to light could be the hitherto missing link between elevated susceptibility to NET formation in autoimmune patients and photosensitivity for example in SLE and dermatomyositis patients. This novel connection could provide a clue for a deeper understanding of light-sensitive diseases in general and for the development of new pharmacological strategies to avoid disease exacerbation upon light exposure.

Inhibition of the hyaluronan matrix enhances metabolic anticancer therapy by dichloroacetate in vitro and in vivo.

BACKGROUND AND PURPOSE: Aerobic glycolysis is a unique feature of tumour cells that entails several advantages for cancer progression such as resistance to apoptosis. The low MW compound, dichloroacetate, is a pyruvate dehydrogenase kinase inhibitor, which restores oxidative phosphorylation and induces apoptosis in a variety of cancer entities. However, its therapeutic effectiveness is limited by resistance mechanisms. This study aimed to examine the role of the anti-apoptotic hyaluronan (HA) matrix in this context and to identify a potential add-on treatment option to overcome this limitation. EXPERIMENTAL APPROACH: The metabolic connection between dichloroacetate treatment and HA matrix augmentation was analysed in vitro by quantitative PCR and affinity cytochemistry. Metabolic pathways were analysed using Seahorse, HPLC, fluorophore-assisted carbohydrate electrophoresis, colourimetry, immunoblots, and immunochemistry. The effects of combining dichloroacetate with the HA synthesis inhibitor 4-methylumbelliferone was evaluated in 2D and 3D cell cultures and in a nude mouse tumour xenograft regression model by immunoblot, immunochemistry, and FACS analysis. KEY RESULTS: Mitochondrial reactivation induced by dichloroacetate metabolically activated HA synthesis by augmenting precursors as well as O-GlcNAcylation. This process was blocked by 4-methylumbelliferone, resulting in enhanced anti-tumour efficacy in 2D and 3D cell culture and in a nude mouse tumour xenograft regression model. CONCLUSIONS AND IMPLICATIONS: The HA rich tumour micro-environment represents a metabolic factor contributing to chemotherapy resistance. HA synthesis inhibition exhibited pronounced synergistic actions with dichloroacetate treatment on oesophageal tumour cell proliferation and survival in vitro and in vivo suggesting the combination of these two strategies is an effective anticancer therapy.