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Copyright of Die Anaesthesiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Low back pain is a global health issue causing disability and missed work days. Commonly used MRI scans including T1-weighted and T2-weighted images provide detailed information of the spine and surrounding tissues. Artificial intelligence showed promise in improving image quality and simultaneously reducing scan time. This study evaluates the performance of deep learning (DL)-based T2 turbo spin-echo (TSE, T2DLR) and T1 TSE (T1DLR) in lumbar spine imaging regarding acquisition time, image quality, artifact resistance, and diagnostic confidence. Material and methods: This retrospective monocentric study included 60 patients with lower back pain who underwent lumbar spinal MRI between February and April 2023. MRI parameters and DL reconstruction (DLR) techniques were utilized to acquire images. Two neuroradiologists independently evaluated image datasets based on various parameters using a 4-point Likert scale. Results: Accelerated imaging showed significantly less image noise and artifacts, as well as better image sharpness, compared to standard imaging. Overall image quality and diagnostic confidence were higher in accelerated imaging. Relevant disk herniations and spinal fractures were detected in both DLR and conventional images. Both readers favored accelerated imaging in the majority of examinations. The lumbar spine examination time was cut by 61% in accelerated imaging compared to standard imaging. Conclusion: In conclusion, the utilization of deep learning-based image reconstruction techniques in lumbar spinal imaging resulted in significant time savings of up to 61% compared to standard imaging, while also improving image quality and diagnostic confidence. These findings highlight the potential of these techniques to enhance efficiency and accuracy in clinical practice for patients with lower back pain. [ABSTRACT FROM AUTHOR]

Purpose: Medial knee osteoarthritis can be treated with medial open wedge high tibial osteotomy (OWHTO). We sought to investigate osseous consolidation of the osteotomy with and without autologous bone grafts (ABG) to detect possible benefits of ABG in osseous healing and functional outcome. Methods: In this prospective study, patients without graft transplantation were compared to those receiving ABG after medial OWHTO. They were followed up 6 weeks, 12 weeks, 6 months and 12 months postoperatively. Radiographic progress of consolidation, clinical scores, contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were assessed at each appointment. Results: A total of 35 patients were enrolled, 20 without and 15 with graft transplantation. Radiologic evaluation showed a significantly earlier consolidation of the osteotomy gaps (p = 0.012) in patients with ABG, resulting in a significantly higher rate of consolidation 12 months after surgery (60% without bone graft vs. 100% with bone graft, p = 0.006). At 6 weeks as well as 6-month follow-up, a tendency of earlier consolidation with ABG was apparent, but not statistically significant (6 weeks: 50% vs. 80%, p = 0.089; 6 months: 30% vs. 60%, p = 0.097). CEUS and DCE-MRI showed physiological perfusion of the osteotomy gaps in both groups. A tendency to better function and less pain in patients with ABG was recognizable. Conclusion: In our study, autologous bone grafting evocated earlier osseous consolidation after medial OWHTO and showed a tendency to a better functional outcome. [ABSTRACT FROM AUTHOR]

Background: Nerve injuries are a frequent problem in routine clinical practice and require intensive interdisciplinary care. Objective: The current status of imaging to confirm the diagnosis of nerve injuries is described. The role of high-resolution ultrasound and magnetic resonance imaging (MRI) in the diagnostics and follow-up of peripheral nerve injuries is elaborated. Material and methods: Review of the current state of imaging to confirm the diagnosis of nerve injuries. Results: Depending on the suspected site of damage, the primary domain of magnetic resonance (MR) imaging (MR neurography) is injuries in the region of the spine, nerve roots, brachial plexus and lumbar plexus, pelvis and proximal thigh. In contrast, in other peripheral nerve lesions of the extremities the advantages of high-resolution nerve ultrasound in a dynamic setting predominate. The MR neurography is indicated here, especially in the frequent bottleneck syndromes and only in very isolated and selected cases. Conclusion: In addition to a correct anatomical assignment, the timely decision for a possible intervention and the appropriate concomitant treatment are an important basis for a favorable prognosis of nerve injuries. Imaging techniques should therefore be used early in the diagnostics and follow-up controls of peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic has led to changes in global health care. Medical societies had to update guidelines and enhance new services such as video consultations. Cancer treatment had to be modified. The aim of this study is to ensure optimal care for cancer patients with the help of high-quality training even in times of crisis. We therefore conducted a nationwide survey of physicians in training in oncological disciplines during the pandemic to assess the impact on their education. Methods: The survey was sent to tumour centres, hospitals, specialist societies, and working and junior research groups and distributed via newsletters and homepages. Interim results and a call for participation were published as a poster (DEGRO) [26] and in the German Cancer Society (DKG) journal FORUM [42]. The survey contained 53 questions on conditions of education and training and on clinical and scientific work. Statistics were carried out with LimeSurvey and SPSS (IBM Corp., Armonk, NY, USA). Results: Between February and November 2022, 450 participants answered the survey, with radio-oncologists being the largest group (28%). Most colleagues (63%) had access to digital training methods. Virtual sessions were rated as a good alternative, especially as multidisciplinary meetings (54%) as well as in-house and external training programs (48%, 47%). The time spent by training supervisors on education was rated as less than before the pandemic by 57%. Half of all participants perceived communication (54%), motivation (44%) and atmosphere (50%) in the team as bad. The participants felt strongly burdened by extra work (55%) and by a changed team atmosphere (49%). One third felt a change in the quality of training during the pandemic and rated it as negative (35%). According to 37% of the participants, this had little influence on their own quality of work. Additional subgroup analyses revealed significant differences in gender, specialty and education level. Conclusion: In order to improve oncology training in times of crisis, access to digital training options and meetings should be ensured. Participants wish for regular team meetings in person to enable good team spirit, compensation for overtime work and sufficient time for training supervisors for discussion and feedback. [ABSTRACT FROM AUTHOR]

Purpose: The WHO 2016 re-classification of myeloproliferative neoplasms resulted in a separation of essential thrombocythemia (ET) from the pre-fibrotic and fibrotic (overt) phases of primary myelofibrosis (MF). This study reports on a chart review conducted to evaluate the real life approach regarding clinical characteristics, diagnostic assessment, risk stratification and treatment decisions for MPN patients classified as ET or MF after implementation of the WHO 2016 classification. Methods: In this retrospective chart review, 31 office-based hematologists/oncologists and primary care centers in Germany participated between April 2021 and May 2022. Physicians reported available data obtained from patient charts via paper–pencil based survey (secondary use of data). Patient features were evaluated using descriptive analysis, also including diagnostic assessment, therapeutic strategies and risk stratification. Results: Data of 960 MPN patients diagnosed with essential thrombocythemia (ET) (n = 495) or myelofibrosis (MF) (n = 465) after implementation of the revised 2016 WHO classification of myeloid neoplasms was collected from the patient charts. While they met at least one minor WHO-criteria for primary myelofibrosis, 39.8% of those diagnosed with ET did not have histological BM testing at diagnosis. 63.4% of patients who were classified as having MF, however, did not obtain an early prognostic risk assessment. More than 50% of MF patients showed characteristics consistent with the pre-fibrotic phase, which was emphasized by the frequent use of cytoreductive therapy. Hydroxyurea was the most frequently used cytoreductive medication in 84.7% of ET and 53.1% of MF patients. While both ET and MF cohorts showed cardiovascular risk factors in more than 2/3 of the cases, the use of platelet inhibitors or anticoagulants varied between 56.8% in ET and 38.1% in MF patients. Conclusions: Improved histopathologic diagnostics, dynamic risk stratification including genetic risk factors for cases of suspected ET and MF are recommended for precise risk assessment and therapeutic stratification according to WHO criteria. [ABSTRACT FROM AUTHOR]

Nanocrystals have a great potential for future materials with tunable bandgap, due to their optical properties that are related with the material used, their sizes and their surface termination. Here, we concentrate on the silicon–tin alloy for photovoltaic applications due to their bandgap, lower than bulk Si, and also the possibility to activate direct band to band transition for high tin concentration. We synthesized silicon–tin alloy nanocrystals (SiSn-NCs) with diameter of about 2–3 nm by confined plasma technique employing a femtosecond laser irradiation on amorphous silicon–tin substrate submerged in liquid media. The tin concentration is estimated to be ∼ 17 % , being the highest Sn concentration for SiSn-NCs reported so far. Our SiSn-NCs have a well-defined zinc-blend structure and, contrary to pure tin NCs, also an excellent thermal stability comparable to highly stable silicon NCs. We demonstrate by means of high resolution synchrotron XRD analysis (SPring 8) that the SiSn-NCs remain stable from room temperature up to 400 ∘ C , with a relatively small expansion of the crystal lattice. The high thermal stability observed experimentally is rationalized by means of first-principle calculations. [ABSTRACT FROM AUTHOR]

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker. [ABSTRACT FROM AUTHOR]

PARP1 (aka ARTD1) acts as a prime sensor of cellular genotoxic stress response. PARP1 detects DNA strand breaks and subsequently catalyzes the formation of poly(ADP-ribose) (PAR), which leads to the recruitment of the scaffold protein XRCC1 during base excision and single strand break repair and the assembly of multi-protein complexes to promote DNA repair. Here, we reveal that the recruitment of either protein to sites of DNA damage is impeded in the absence of the other, indicating a strong reciprocal relationship between the two DNA repair factors during genotoxic stress response. We further analyzed several cellular and molecular endpoints in HeLa PARP1 KO, XRCC1 KO, and PARP1/XRCC1 double KO (DKO) cells after genotoxic treatments, i.e., PARylation response, NAD+ levels, clonogenic survival, cell cycle progression, cell death, and DNA repair. The analysis of NAD+ levels and cytotoxicity after treatment with the topoisomerase I inhibitor camptothecin revealed a hypersensitivity phenotype of XRCC1 KO cells compared to PARP1 KO cells—an effect that could be rescued by the additional genetic deletion of PARP1 as well as by pharmacological PARP inhibition. Moreover, impaired repair of hydrogen peroxide and CPT-induced DNA damage in XRCC1 KO cells could be partially rescued by additional deletion of PARP1. Our results therefore highlight important reciprocal regulatory functions of XRCC1 and PARP1 during genotoxic stress response. [ABSTRACT FROM AUTHOR]

Usage of MR imaging biomarkers is limited to experts. Automatic quantitative reports provide access for clinicians to data analysis. Automated data analysis was tested for usability in a small cohort of patients with hereditary spastic paraplegia type 4 (SPG4). We analyzed 3T MRI 3D-T1 datasets of n = 25 SPG4 patients and matched healthy controls using a commercial segmentation tool (AIRAscore structure 2.0.1) and standard VBM. In SPG4 total brain volume was reduced by 27.6 percentiles (p = 0.001) caused mainly by white matter loss (− 30.8th, p < 0.001) and stable total gray matter compared to controls. Brain volume loss occurred in: midbrain (− 41.5th, p = 0.001), pons (− 36.5th, p = 0.02), hippocampus (− 20.9th, p = 0.002), and gray matter of the cingulate gyrus (− 17.0th, p = 0.02). Ventricular volumes increased as indirect measures of atrophy. Group comparisons using percentiles aligned with results from VBM analyses. Quantitative imaging reports proved to work as an easily accessible, fully automatic screening tool for clinicians, even in a small cohort of a rare genetic disorder. We could delineate the involvement of white matter and specify involved brain regions. Group comparisons using percentiles provide comparable results to VBM analysis and are, therefore, a suitable and simple screening tool for all clinicians with and without in-depth knowledge of image processing. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is an important imaging modality in stroke. Computer based automated medical image processing is increasingly finding its way into clinical routine. The Ischemic Stroke Lesion Segmentation (ISLES) challenge is a continuous effort to develop and identify benchmark methods for acute and sub-acute ischemic stroke lesion segmentation. Here we introduce an expert-annotated, multicenter MRI dataset for segmentation of acute to subacute stroke lesions (https://doi.org/10.5281/zenodo.7153326). This dataset comprises 400 multi-vendor MRI cases with high variability in stroke lesion size, quantity and location. It is split into a training dataset of n = 250 and a test dataset of n = 150. All training data is publicly available. The test dataset will be used for model validation only and will not be released to the public. This dataset serves as the foundation of the ISLES 2022 challenge (https://www.isles-challenge.org/) with the goal of finding algorithmic methods to enable the development and benchmarking of automatic, robust and accurate segmentation methods for ischemic stroke. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) involves elevated levels of cellular oxidative stress which jeopardizes the integrity of essential cell compartments. Previously, we demonstrated higher levels of DNA lesions in peripheral blood mononuclear cells (PBMCs) in PTSD. Retaining vital levels of DNA integrity requires cells to mobilize compensatory efforts in elevating their DNA-repair capacity. Accordingly, we hypothesized to find increased expression rates of the DNA-repair genes X-ray repair cross complementing 1 (XRCC1), poly (ADP-ribose) polymerase 1 (PARP1), and polymerase β (Polβ) in PBMCs of PTSD patients as compared to controls, leading to functionally relevant changes in DNA-repair kinetics. In a cohort of 14 refugees with PTSD and 15 without PTSD, we found significantly higher XRCC1 expression in PTSD patients than controls (U = 161.0, p = 0.009, Cohen's r = 0.49), and positive correlations between the severity of PTSD symptoms and the expression of XRCC1 (rS = 0.57, p = 0.002) and PARP1 (rS = 0.43, p = 0.022). Higher XRCC1 (F = 2.39, p = 0.010, η2p = 0.10) and PARP1 (F = 2.15, p = 0.022, η2p = 0.09) expression accounted for slower repair of experimentally X-ray irradiation-induced DNA damage, highlighting the possible physiological relevance of altered DNA-repair gene expression in PTSD. Our study provides first evidence for a compensatory regulation of DNA-repair mechanisms in PTSD. We discuss the implications of increased DNA damage and altered DNA-repair mechanisms in immune senescence, premature aging, and increased physical morbidity in PTSD. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intensive care unit (ICU)-acquired delirium is associated with adverse outcome in trauma patients with concomitant traumatic brain injury (TBI), but diagnosis remains challenging. Quantifying circadian disruption by analyzing expression of the circadian gene period circadian regulator 2 (PER2) and heme oxygenase 1 (HO1), which determines heme turnover, may prove to be potential diagnostic tools. Expression of PER2 and HO1 was quantified using qPCR from blood samples 1 day and 7 days after trauma. Association analysis was performed comparing mRNA expression levels with parameters of trauma (ISS—injury severity score), delirium, acute kidney injury (AKI) and length of ICU stay. 48 polytraumatized patients were included (equal distribution of TBI versus non-TBI) corrected for ISS, age and gender using a matched pairs approach. Expression levels of PER2 and HO1 were independent of age (PER2: P = 0.935; HO1: P = 0.988), while expression levels were significantly correlated with trauma severity (PER2: P = 0.009; HO1: P < 0.001) and longer ICU length of stay (PER2: P = 0.018; HO1: P < 0.001). High expression levels increased the odds of delirium occurrence (PER2: OR = 4.32 [1.14–13.87]; HO1: OR = 4.50 [1.23–14.42]). Patients with TBI showed a trend towards elevated PER2 (OR = 3.00 [0.84–9.33], P = 0.125), but not towards delirium occurrence (P = 0.556). TBI patients were less likely to develop AKI compared to non-TBI (P = 0.022). Expression levels of PER2 and HO1 correlate with the incidence of delirium in an age-independent manner and may potentially improve diagnostic algorithms when used as delirium biomarkers. Trial registration: German Clinical Trials Register (Trial-ID DRKS00008981; Universal Trial Number U1111-1172-6077; Jan. 18, 2018). [ABSTRACT FROM AUTHOR]

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases. [ABSTRACT FROM AUTHOR]

The assessment of genotoxicity upon exposure to chemical and environmental agents plays an important role in basic research as well as in pharmaceutical, chemical, cosmetic and food industry. Low sensitivity and lack of inter-laboratory comparability are considered problematic issues in genotoxicity testing. Moreover, commonly used mutagenicity assays lack information about early and specific genotoxic events. Previously, we developed an automated version of the "Fluorimetric detection of Alkaline DNA Unwinding" (FADU) assay as a high-throughput screening method for the detection of DNA strand breaks in living cells. Here, we report an enzyme-modified version of the cell-based FADU assay (emFADU) for the determination of oxidative and methylation lesions in cellular DNA. Our method is based on the use of formamidopyrimidine DNA glycosylase or human alkyladenine DNA glycosylase for the detection of chemically-induced nucleobase modifications in lysates of immortalized cell lines, growing in suspension or as adherent cells, and in peripheral blood mononuclear cells. We could show that upon treatment with sub-cytotoxic doses of known genotoxins, oxidative and methylation lesions are readily detectable. This fast, inexpensive, and convenient method could be useful as a high-content screening approach for the sensitive and specific assessment of genotoxicity in human cells. Thus, when implemented in the early compound development in an industrial setting, the emFADU assay could help reduce the number of animals used for toxicity testing. Furthermore, as we established the method for different cell types, this new assay may provide an opportunity for population studies and/or mechanistic research into DNA repair pathways. [ABSTRACT FROM AUTHOR]

The Spix's Macaw (Cyanopsitta spixii) represents one of the four avian taxa, in which its global population is entirely captively managed. The species was declared "extinct in the wild" after several attempts failed to rediscover any remaining individuals in the wild since 2000. As an integral part of the ongoing ex situ conservation efforts, a long-term ethological study was conducted at the ACTP facility to investigate the behavioral repertoire of the largest subpopulation of this species in captivity. In this paper we provide an illustrated comprehensive ethogram with detailed description of the submission, displacement and agonistic behavior. The agonistic behavior is categorized in two subcategories, where qualitative aspects for distinct behavior elements for the intimidatory and conflict behavior are given. In addition, displacement displays are described in detail for the first time for a species of the genera. In total, 35 distinct behavior elements of the agonistic, displacement and submission behavioral repertoire are covered. Digital video images related to the article are available at http://www.momo-p.com/index-e.html, movieid:momo200417sm05a, momo200416sm01a, momo200417sm06a, momo200416sm06a, momo200416sm04a, momo200417sm03a, momo200417sm02a, momo200416sm05a, momo200417sm04a, momo200416sm02a, momo200416sm03a, and momo200417sm01a. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Poly-ADP-ribosylation (PARylation) is a fully reversible post-translational modification with key roles in cellular physiology. Due to the multi-domain structure of poly(ADP-ribose) polymerase-1 (PARP1) and the highly dynamic nature of the PARylation reaction, studies on the biochemical mechanism and structural dynamics remain challenging. Here, we report label-free, time-resolved monitoring of PARP1-dependent PARylation using ATR-FTIR spectroscopy. This includes PARP1 activation by binding to DNA strand break models, NAD+ substrate binding, PAR formation, and dissociation of automodified PARP1 from DNA. Analyses of PARP1 activation at different DNA models demonstrate a strong positive correlation of PARylation and PARP1 dissociation, with the strongest effects observed for DNA nicks and 3' phosphorylated ends. Moreover, by examining dynamic structural changes of PARP1, we reveal changes in the secondary structure of PARP1 induced by NAD+ and PARP inhibitor binding. In summary, this approach enables holistic and dynamic insights into PARP1-dependent PARylation with molecular and temporal resolution. The mechanism of PARP1-dependent poly-ADP-ribosylation in response to DNA damage is still under debate. Here, the authors use ATR-FTIR spectroscopy to provide time-resolved insights into the molecular details of this process under near physiological conditions. [ABSTRACT FROM AUTHOR]

Prenatal brain development is a complex and sensitive process, highly susceptible to environmental influences such as pollutants, stress, malnutrition, drugs, tobacco exposure, or ionizing radiation (IR). Disturbances in development may cause life-long disabilities and diseases, such as ADHD, childhood cancers, cognitive problems, depression, anxiety and more severe developmental disabilities. Due to increasing medical imaging, radiation therapy, natural terrestrial radiation, radioactive pollution and long-distance flights, humans are increasingly exposed to IR. However, data on impact of IR on very early human brain development are scarce, particularly in the very first weeks of gestation. Here we investigated the effects of low-dose X-ray IR (1 Gy) in a 3D early brain developmental model derived from human pluripotent stem cells. In this model very early neural stem cells, neuroectodermal progenitor cells (NEP), were exposed to low-dose IR and direct as well as delayed effects were investigated. Expression of 20 different marker genes crucial for normal neural development was determined 48 h and 9 days post IR (pIR). All but one of the analyzed marker genes were reduced 48 h after IR, and all but seven genes normalized their expression by day 9 pIR. Among the seven markers were genes involved in neurodevelopmental and growth abnormalities. Moreover, we could show that stemness of the NEP was reduced after IR. We were thus able to identify a significant impact of radiation in cells surviving low-dose IR, suggesting that low-dose IR could have a negative impact on the early developing human brain, with potential later detrimental effects. [ABSTRACT FROM AUTHOR]

Despite its worldwide ban, the warfare agent sulfur mustard (SM) still represents a realistic threat, due to potential release in terroristic attacks and asymmetric conflicts. Therefore, the rigorous and quantitative detection of SM exposure is crucial for diagnosis, health risk assessment, and surveillance of international law. Alkylation adducts of nucleic acids can serve as valuable toxicologically relevant 'biomarkers of SM exposure'. Here, we developed a robust and versatile bioanalytical platform based on isotope dilution UPLC-MS/MS to quantify major SM-induced DNA and RNA adducts, as well as adducts induced by the monofunctional mustard 2-chloroethyl ethyl sulfide. We synthesized 15N/13C-labeled standards, which allowed absolute quantitation with full chemical specificity and subfemtomole sensitivities. DNA and RNA mono-alkylation adducts and crosslinks were carefully analyzed in a dose- and time-dependent manner in various matrices, including human cancer and primary cells, derived of the main SM-target tissues. Nucleic acid adducts were detected up to 6 days post-exposure, indicating long persistence, which highlights their toxicological relevance and proves their suitability as forensic and medical biomarkers. Finally, we investigated ex vivo-treated rat skin biopsies and human blood samples, which set the basis for the implementation into the method portfolio of Organization for the Prohibition of Chemical Weapons-designated laboratories to analyze authentic samples from SM-exposed victims. [ABSTRACT FROM AUTHOR]

Background: Dural puncture, paraesthesia and vascular puncture are the most common complications of epidural catheter insertion. Their association with variation in midline needle insertion depth is unknown.Objective: This study evaluated the risk of dural and vascular punctures and the unwanted events paraesthesia and multiple skin punctures related to midline needle insertion depth.Material and Methods: A total of 14,503 epidural catheter insertions including lumbar (L1-L5; n = 5367), low thoracic (T7-T12, n = 8234) and upper thoracic (T1-T6, n = 902) insertions, were extracted from the German Network for Regional Anaesthesia registry between 2007 and 2015. The primary outcomes were compared with logistic regression and adjusted (adj) for confounders to determine the risk of complications/events. Results are presented as odds ratios (OR, [95% confidence interval]).Main Results: Midline insertion depth depended on body mass index, sex, and spinal level. After adjusting for confounders increased puncture depth (cm) remained an independent risk factor for vascular puncture (adjOR 1.27 [1.09-1.47], p = 0.002) and multiple skin punctures (adjOR 1.25 [1.21-1.29], p < 0.001). In contrast, dural punctures occurred at significantly shallower depths (adjOR 0.73 [0.60-0.89], p = 0.002). Paraesthesia was unrelated to insertion depth. Body mass index and sex had no influence on paraesthesia, dural and vascular punctures. Thoracic epidural insertion was associated with a lower risk of vascular puncture than at lumbar sites (adjOR 0.39 [0.18-0.84], p = 0.02).Conclusion: Variation in midline insertion depth is an independent risk factor for epidural complications; however, variability precludes use of depth as a reliable guide to insertion in individual patients. [ABSTRACT FROM AUTHOR]

For an improved understanding of the in-cylinder processes in internal combustion (IC) engines, advanced diagnostics are needed to measure the thermodynamic state of the in-cylinder fluid. This is essential to validate numerical simulations which aim at predicting the in-cylinder processes during motored engine operation. Here, knowledge of the in-cylinder temperature is essential, as it strongly influences in-cylinder gas viscosity as well as the in-cylinder mass and thus the peak pressure. This work presents temperature measurements at 2.3 ∘CA resolution of a motored, optically accessible engine by applying tunable diode laser absorption spectroscopy (TDLAS) to in-cylinder water vapor. The temperature was investigated in different heights along the cylinder axis for variations of intake temperature and engine speed. Temperature uncertainties of ± 2.3 K were achieved at various cycle phases, and the absolute temperatures are verified using thermodynamic calculations of simultaneously measured water vapor concentration. The measured temperature dependency is compared to isentropic and polytropic changes of state, the incylinder gas mass is calculated and an estimation of the heat transfer to the walls is given. Based on the in-cylinder mass, different numerical simulations of the engine found in literature are compared. [ABSTRACT FROM AUTHOR]

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Poly(ADP-ribosyl)ation (PARylation) is a complex and reversible posttranslational modification catalyzed by poly(ADP-ribose)polymerases (PARPs), which orchestrates protein function and subcellular localization. The function of PARP1 in genotoxic stress response upon induction of oxidative DNA lesions and strand breaks is firmly established, but its role in the response to chemical-induced, bulky DNA adducts is understood incompletely. To address the role of PARP1 in the response to bulky DNA adducts, we treated human cancer cells with benzo[a]pyrene 7,8-dihydrodiol-9,10-epoxide (BPDE), which represents the active metabolite of the environmental carcinogen benzo[a]pyrene [B(a)P], in nanomolar to low micromolar concentrations. Using a highly sensitive LC-MS/MS method, we revealed that BPDE induces cellular PAR formation in a time- and dose-dependent manner. Consistently, PARP1 activity significantly contributed to BPDE-induced genotoxic stress response. On one hand, PARP1 ablation rescued BPDE-induced NAD+ depletion and protected cells from BPDE-induced short-term toxicity. On the other hand, strong sensitization effects of PARP inhibition and PARP1 ablation were observed in long-term clonogenic survival assays. Furthermore, PARP1 ablation significantly affected BPDE-induced S- and G2-phase transitions. Together, these results point towards unresolved BPDE-DNA lesions triggering replicative stress. In line with this, BPDE exposure resulted in enhanced formation and persistence of DNA double-strand breaks in PARP1-deficient cells as evaluated by microscopic co-localization studies of 53BP1 and γH2A.X foci. Consistently, an HPRT mutation assay revealed that PARP inhibition potentiated the mutagenicity of BPDE. In conclusion, this study demonstrates a profound role of PARylation in BPDE-induced genotoxic stress response with significant functional consequences and potential relevance with regard to B[a]P-induced cancer risks. [ABSTRACT FROM AUTHOR]

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Copyright of HeilberufeSCIENCE is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

For improving the design of combustors, the knowledge of residence-time distributions (RTD) is important as they influence exhaust gas compositions. Measuring RTDs in combustors is challenging, due to high temperatures, chemical reactions, the presence of particles or corrosive species as well as high turbulence levels. This paper presents a technique for the in situ measurement of RTDs in combustors. Based on tunable diode laser absorption spectroscopy (TDLAS), the temporal evolution of the concentration of tracers is tracked simultaneously at the combustion chamber inlet and outlet. Using either air or mixtures of oxygen and carbon dioxide (oxy-fuel atmosphere) as oxidants, the method is applied to reacting and non-reacting operating conditions in a 20-kW methane combustor. For reacting conditions, hydrogen chloride is used as a tracer, whereas for non-reacting conditions methane was chosen. Depending on the tracer, for a repetition rate of approximately 2 kHz detection limits of 16-40 ppm are achieved. For deriving RTDs, low-pass filtering is compared to reactor network modeling. Different RTDs observed for varying operating conditions are discussed. [ABSTRACT FROM AUTHOR]

Halogen-free organophosphorus flame retardants are considered as replacements for the phased-out class of polybrominated diphenyl ethers (PBDEs). However, toxicological information on new flame retardants is still limited. Based on their excellent flame retardation potential, we have selected three novel 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivatives and assessed their toxicological profile using a battery of in vitro test systems in order to provide toxicological information before their large-scale production and use. PBDE-99, applied as a reference compound, exhibited distinct neuro-selective cytotoxicity at concentrations ≥10 µM. 6-(2-((6-oxido-6 H-dibenzo[ c,e][1,2]oxaphosphinin-6-yl)amino)ethoxy)-6 H-dibenzo[ c,e][1,2]oxaphosphinine 6-oxide (ETA-DOPO) and 6,6′-(ethane-1,2-diylbis(oxy))bis(6 H-dibenzo[ c,e][1,2]oxaphosphinine-6-oxide) (EG-DOPO) displayed adverse effects at concentrations >10 µM in test systems reflecting the properties of human central and peripheral nervous system neurons, as well as in a set of non-neuronal cell types. DOPO and its derivative 6,6′-(ethane-1,2-diylbis(azanediyl))bis(6 H-dibenzo[ c,e][1,2]oxaphosphinine-6-oxide) (EDA-DOPO) were neither neurotoxic, nor did they exhibit an influence on neural crest cell migration, or on the integrity of human skin equivalents. The two compounds furthermore displayed no inflammatory activation potential, nor did they affect algae growth or daphnia viability at concentrations ≤400 µM. Based on the superior flame retardation properties, biophysical features suited for use in polyurethane foams, and low cytotoxicity of EDA-DOPO, our results suggest that it is a candidate for the replacement of currently applied flame retardants. [ABSTRACT FROM AUTHOR]

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Copyright of Zeitschrift für die gesamte Versicherungswissenschaft is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The novel pandemic influenza A/H1N1v has also led to a rapid increase in the number of new cases in Germany. In the majority of patients the disease has taken a mild clinical course. However, in isolated cases severe complications requiring hospitalization or intensive care treatment have occurred. Most of the current recommendations refer to outpatients or mild diseases and are not always suitable and practicable for the management of a life-threatening influenza A/H1N1v infection in an intensive care setting. The aim of this review is to present a reliable diagnostic and therapeutic approach for critically ill patients, considering the current literature, case-based experiences from our own intensive care unit and including relevant recommendations of public health authorities. Initial measures regarding therapeutic, diagnostic and isolation precautions arise from past medical history, current anamnesis and characteristic symptoms and their progression. Patients suspected of having acquired an influenza A/H1N1v infection should be isolated. Early laboratory diagnosis of A/H1N1v infection ideally utilizes the reverse transcriptase polymerase chain reaction (RT-PCR) as the most sensitive diagnostic method. Emerging evidence suggests that incidence and severity of life-threatening influenza A/H1N1v infection increase with several risk factors (e.g. pregnancy, immunosuppression, obesity). Treatment decisions should not be delayed to await laboratory confirmation in these patients as early initiation of antiviral therapy is recommended. Elements of supportive care depend on the presentation of complications and secondary organ failure. If rapidly progressive lung dysfunction occurs, refractory to routine mechanical ventilation, early reporting to centers experienced in the use of extracorporeal membrane oxygenation (ECMO) should be established. [ABSTRACT FROM AUTHOR]

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In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option. [ABSTRACT FROM AUTHOR]

The paper describes the importance of toxicology as a discipline, its past achievements, current scientific challenges, and future development. Toxicological expertise is instrumental in the reduction of human health risks arising from chemicals and drugs. Toxicological assessment is needed to evaluate evidence and arguments, whether or not there is a scientific base for concern. The immense success already achieved by toxicological work is exemplified by reduced pollution of air, soil, water, and safer working places. Predominantly predictive toxicological testing is derived from the findings to assess risks to humans and the environment. Assessment of the adversity of molecular effects (including epigenetic effects), the effects of mixtures, and integration of exposure and biokinetics into in vitro testing are emerging challenges for toxicology. Toxicology is a translational science with its base in fundamental science. Academic institutions play an essential part by providing scientific innovation and education of young scientists. [ABSTRACT FROM AUTHOR]