3He in the Bransfield Strait waters: indication for local injection from back-arc rifting

Helium data from the waters of the Bransfield Strait, the southern Drake Passage and the northwestern shelf of the Weddell Sea are presented. The 3He profiles from the eastern and central basins of the Bransfield Strait show maxima (δ3He ≈ 7%) below the sill depths that separate the strait from the surrounding open ocean. The 3He excess is interpreted as a local injection of a 3He-rich helium component into the deep waters of the Bransfield Strait from backarc rifting. Tritiogenic 3He and excess 3He from mixing with Circumpolar Deep Water are excluded as possible sources. The estimated 3He/4He ratio of the injected helium component (2.4–5.0 × 10−6) is less than that of pure mantle helium and may contain radiogenic helium from continental crustal material which underlies the Bransfield Strait

The endocannabinoid, anandamide, induces cannabinoid receptor-independent cell death in renal proximal tubule cells

Background: The endocannabinoid (EC) system is well characterized in the central nervous system but scarcely studied in peripheral organs. In this paper, we newly identify the effect of the EC anandamide (AEA) upon renal proximal tubule cells. Methods: Measurement of lactate dehydrogenase (LDH) release after treatment of primary renal proximal tubule cells (RPTEC) and renal carcinoma cell line (Caki-1) with AEA, arachidonic acid (AA), ethanolamide (EtAm), EC receptor CB1 antagonist (AM251), CB2 receptor antagonist (SR144528), TRPV1 receptor antagonist (capsazepine), degradation enzyme fatty acid amide hydrolase (FAAH) antagonist (URB597), antioxidants GSH-EE; Trolox, GSH depletor BSO, membrane cholesterol depletor (MCD), apoptosis inhibitor zVAD, necroptosis inhibitor Nec-1 or ferroptosis inhibitor Fer-1. Western blot and qRT-PCR analysis plus determination of reactive oxygen species (ROS) via H2-DCFDA were performed. Histology for EC enzymes, N-acetylphosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) and FAAH, as well as the determination of physiological levels of ECs in human and rat renal tissue via liquid chromatography were conducted. Results: AEA both dose- and time-dependently induces cell death in RPTEC and Caki-1 within hours, characterized by cell blebbing, not influenced by blocking the described EC receptors by AM251, SR144528, capsaze pine or FAAH by URB597 or MCD. Cell death is mediated via ROS. There is no difference found in the histology of the enzymes FAAH and NAPE-PLD in human renal tissue with interstitial nephritis. Blocking of apoptotic, necroptotic or ferroptotic cell death does not lead to a reduction in LDH release in vitro. Conclusion: The endocannabinoid anandamide induces cell death in renal proximal tubule cell in a time- and dose-dependent manner. This pathway is mediated via ROS and is independent of cannabinoid receptors, membrane cholesterol or FAAH activity

The temporal evolution of the tracer signal in the Deep Western Boundary Current, Tropical Atlantic

Four World Ocean Circulation Experiment (WOCE) repeat cruises (October 1990 to March 1994) in the tropical Atlantic off Brazil are used to study the spatial and temporal evolution of the chlorofluorocarbon (CFC) (components CFC-11 and CFC-12) and tritium signal in the upper North Atlantic Deep Water (NADW). Its shallowest part, located in the tropical Atlantic around 1600-m depth, is the shallow upper North Atlantic Deep Water (SUNADW). It is characterized by a distinct tracer maximum, which is presumably received through winter time convection in the subpolar North Atlantic. Here we discuss the tracer fields and the temporal evolution of the tracer signal of the SUNADW in the tropical Atlantic along two meridional sections at 44 degrees and 35 degrees W and two zonal sections at 5 degrees and 10 degrees S off Brazil. The spatial and temporal development of the tracer field in the tropical Atlantic as well as the correlation with hydrographic parameters show that the temporal tracer change being due to the arrival of "younger" water is disturbed by other processes. In particular, the impact of variable mixing and spreading pathways on the observed tracer variability in the SUNADW is evident in the observations

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Background Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P  = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Kardiopulmonale Leistungsfähigkeit vor und unter nCPAP-Therapie bei Patienten mit obstruktivem Schlafapnoe-Syndrom

$\bf {EINLEITUNG:}$ Das obstruktive Schlafapnoe-Syndrom (OSAS) wirkt sich negativ auf den gesamten menschlichen Organismus aus. Zur Therapiebewertung wurde die kardiopulmonale Leistungsfähigkeit bei Patienten vor und unter nCPAP-Therapie untersucht. $\bf {METHODIK:}$ Insgesamt wurden 36 Patienten (19 mit und 17 Patienten ohne arterieller Hypertonie) spiroergometrisch untersucht. Davon wurden 17 Patienten therapiert, acht standen ohne Behandlung als Kontrollpatienten zur Verfügung. $\bf {ERGEBNISSE:}$ Insgesamt zeigten die 36 Patienten und besonders die Patienten mit zusätzlichem Hypertonus eine Einschränkung ihrer kardiopulmonalen Leistungsfähigkeit. Unter nCPAP konnte im Vergleich zu den Kontrollpatienten eine Steigerung der spiroergomerischen Werte verzeichnet werden. $\bf {DISKUSSION:}$ Die eingeschränkte kardiopulmonale Leistungsfähigkeit bei Patienten mit OSAS kann durch eine suffiziente nCPAP-Therapie deutlich gesteigert werden

Time course of PSS depolymerisation by whole cells <i>G</i>. <i>trabeum</i> DSM 1398.

<p>Cultures in regular Wetzstein medium (■) were compared to those supplemented with 500 μM 2,5-DMBQ (▲), without iron (♦), and cultures inactivated by sodium azide (control; ●). Symbols represent means ± standard deviations for triplicate cultures; standard deviations smaller than symbol size are not shown.</p

Potential of Wood-Rotting Fungi to Attack Polystyrene Sulfonate and Its Depolymerisation by <i>Gloeophyllum trabeum</i> via Hydroquinone-Driven Fenton Chemistry

<div><p>Synthetic polymers often pose environmental hazards due to low biodegradation rates and resulting accumulation. In this study, a selection of wood-rotting fungi representing different lignocellulose decay types was screened for oxidative biodegradation of the polymer polystyrene sulfonate (PSS). Brown-rot basidiomycetes showed PSS depolymerisation of up to 50 % reduction in number-average molecular mass (M_n) within 20 days. In-depth investigations with the most efficient depolymeriser, a <i>Gloeophyllum trabeum</i> strain, pointed at extracellular hydroquinone-driven Fenton chemistry responsible for depolymerisation. Detection of hydroxyl radicals present in the culture supernatants showed good compliance with depolymerisation over the time course of PSS degradation. 2,5-Dimethoxy-1,4-hydroquinone (2,5-DMHQ), which was detected in supernatants of active cultures via liquid chromatography and mass spectrometry, was demonstrated to drive the Fenton processes in <i>G</i>. <i>trabeum</i> cultures. Up to 80% reduction in M_n of PSS where observed when fungal cultures were additionally supplemented with 2,5-dimethoxy benzoquinone, the oxidized from of 2,5-DMHQ. Furthermore, 2,5-DMHQ could initiate the Fenton's reagent-mediated PSS depolymerisation in cell-free systems. In contrast, white-rot fungi were unable to cause substantial depolymerising effects despite the expression of lignin-modifying exo-enzymes. Detailed investigations with laccase from <i>Trametes versicolor</i> revealed that only in presence of certain redox mediators limited PSS depolymerisation occurred. Our results indicate that brown-rot fungi might be suitable organisms for the biodegradation of recalcitrant synthetic polymeric pollutants.</p></div