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Biodegradability testing in soil helps to identify safe synthetic organic chemicals but is still obscured by the formation of soil-bound 'non-extractable' residues (NERs). Present-day methodologies using radiocarbon or stable ( 13 C, 15 N) isotope labeling cannot easily differentiate soil-bound parent chemicals or transformation products (xenoNERs) from harmless soil-bound biomolecules of microbial degraders (bioNERs). Hypothesizing a minimal retention of hydrogen in biomolecules, we here apply stable hydrogen isotope - deuterium (D) - labeling to unravel the origin of NERs. Soil biodegradation tests with D- and 13 C-labeled 2,4-D, glyphosate and sulfamethoxazole reveal consistently lower proportions of applied D than 13 C in total NERs and in amino acids, a quantitative biomarker for bioNERs. Soil-bound D thus mostly represents xenoNERs and not bioNERs, enabling an efficient quantification of xenoNERs by just measuring the total bound D. D or tritium (T) labeling could thus improve the value of biodegradability testing results for diverse organic chemicals forming soil-bound residues., (© 2024. The Author(s).)

Aims: To create and validate a weakly supervised artificial intelligence (AI) model for detection of abnormal colorectal histology, including dysplasia and cancer, and prioritise biopsies according to clinical significance (severity of diagnosis)., Materials and Methods: Triagnexia Colorectal, a weakly supervised deep learning model, was developed for the classification of colorectal samples from haematoxylin and eosin (H&E)-stained whole slide images. The model was trained on 24 983 digitised images and assessed by multiple pathologists in a simulated digital pathology environment. The AI application was implemented as part of a point and click graphical user interface to streamline decision-making. Pathologists assessed the accuracy of the AI tool, its value, ease of use and integration into the digital pathology workflow., Results: Validation of the model was conducted on two cohorts: the first, on 100 single-slide cases, achieved micro-average model specificity of 0.984, micro-average model sensitivity of 0.949 and micro-average model F1 score of 0.949 across all classes. A secondary multi-institutional validation cohort, of 101 single-slide cases, achieved micro-average model specificity of 0.978, micro-average model sensitivity of 0.931 and micro-average model F1 score of 0.931 across all classes. Pathologists reflected their positive impressions on the overall accuracy of the AI in detecting colorectal pathology abnormalities., Conclusions: We have developed a high-performing colorectal biopsy AI triage model that can be integrated into a routine digital pathology workflow to assist pathologists in prioritising cases and identifying cases with dysplasia/cancer versus non-neoplastic biopsies., (© 2024 John Wiley & Sons Ltd.)

Glyphosate and nitrogen (N) or (P) phosphorus fertilizers are often applied in combination to agricultural fields. The additional P or N supply to microorganisms might drive glyphosate degradation towards sarcosine/glycine or aminomethylphosphonic acid (AMPA), and consequently determine the speciation of non-extractable residues (NERs): harmless biogenic NERs (bioNERs) or potentially hazardous xenobiotic NERs (xenoNERs). We therefore investigated the effect of P or N-fertilizers on microbial degradation of glyphosate and bioNER formation in an agricultural soil. Four different treatments were incubated at 20 °C for 75 days as follows; I: no fertilizer (2- 13 C, 15 N-glyphosate only, control), II: P-fertilizer (superphosphate + 2- 13 C, 15 N-glyphosate, effect of P-supply), III: N-fertilizer (ammonium nitrate + 2- 13 C, 15 N-glyphosate, effect of N-supply) and IV: 15 N-fertilizer ( 15 N-ammonium nitrate + 2- 13 C-glyphosate, differentiation between microbial assimilations of 15 N: 15 N-fertilizer versus 15 N-glyphosate). We quantified 13 C or 15 N in mineralization, extractable residues, NERs and in amino acids (AAs). At the end, mineralization (36-41 % of the 13 C), extractable 2- 13 C, 15 N-glyphosate/2- 13 C-glyphosate (0.42-0.49 %) & 15 N-AMPA (1.2 %), and 13 C/ 15 N-NERs (40-43 % of the 13 C, 40-50 % of the 15 N) were comparable among treatments. Contrastingly, the 15 N-NERs from 15 N-fertlizer amounted to only 6.6 % of the 15 N. Notably, N-fertilizer promoted an incorporation of 13 C/ 15 N from 2- 13 C, 15 N-glyphosate into AAs and thus the formation of 13 C/ 15 N-bioNERs. The 13 C/ 15 N-AAs were as follows: 16-21 % (N-fertilizer) > 11-13 % (control) > 7.2-7.3 % (P-fertilizer) of the initially added isotope. 2- 13 C, 15 N-glyphosate was degraded via the sarcosine/glycine and AMPA simultaneously in all treatments, regardless of the treatment type. The percentage share of bioNERs within the NERs in the N-fertilized soil was highest ( 13 C: 80-82 %, 15 N: 100 %) compared to 53 % ( 13 C & 15 N, control) and to only 30 % ( 13 C & 15 N, P-fertilizer). We thus concluded simultaneous N & glyphosate addition to soils could be beneficial for the environment due to the enhanced bioNER formation, while P & glyphosate application disadvantageous since it promoted xenoNER formation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karolina M. Nowak reports financial support was provided by German Research Foundation. Sohaib Aslam reports was provided by Alexander von Humboldt Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tumours of the gastrointestinal tract represent nearly a quarter of all newly diagnosed tumours diagnosed in 2019. Various treatment modalities for gastrointestinal cancers exist, some of which may be guided by biomarkers. Biomarkers act as gauges of either normal or pathogenic processes or responses to an exposure or intervention. They come in many forms. This review explores established and potential molecular/immunohistochemical (IHC) predictive and prognostic biomarkers of the gastrointestinal tract., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Glyphosate can be biodegraded via the aminomethylphosponic acid (AMPA) and the sarcosine/glycine pathway leading to the formation of three intermediate products AMPA, sarcosine or glycine. The fate of the three intermediate compounds of glyphosate biodegradation including nature of non-extractable residues (NERs; harmless biogenic [NERs biogenic ] versus hazardous xenobiotic [NERs xenobiotic ]) in soils has not been investigated yet. This information is crucial for an assessment of environmental risks related to the speciation of glyphosate-derived NERs which may stem from glyphosate intermediates. Therefore, we incubated 13 C- and 15 N-labeled glyphosate (2- 13 C, 15 N-glyphosate) and its degradation product AMPA ( 13 C, 15 N-AMPA), sarcosine ( 13 C 3 , 15 N-sarcosine) or glycine ( 13 C 2 , 15 N-glycine) in an agricultural soil separately for a period of 75 days. 13 C 2 -glycine and 13 C 3 -sarcosine mineralized rapidly compared to 2- 13 C-glyphosate and 13 C-AMPA. The mineralization of 13 C-AMPA was lowest among all four compounds due to its persistent nature. Only 0.5% of the initially added 2- 13 C, 15 N-glyphosate and still about 30% of the initially added 13 C, 15 N-AMPA was extracted from soil after 75 days. The NERs formed from 13 C, 15 N-AMPA were mostly NERs xenobiotic as compared to other three compounds for which significant amounts of NERs biogenic were determined. We noticed 2- 13 C, 15 N-glyphosate was biodegraded via two biodegradation pathways simultaneously; however, the sarcosine/glycine pathway with the formation of harmless NERs biogenic presumably dominated., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karolina Nowak reports financial support was provided by Helmholtz Centre for Environmental Research - UFZ. Karolina Nowak reports financial support was provided by German Research Foundation. Sohaib Aslam reports was provided by Alexander von Humboldt Foundation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The partner and localiser of BRCA2 (PALB2) gene, located on chromosome 16, functions as a tumour suppressor that plays a critical role in homologous recombination repair after DNA double-strand breaks. It encodes proteins involved in the BRCA2 and BRCA1, and RAD51 pathways. Heterozygous germline mutations in PALB2 have been implicated in the development of breast, pancreatic and ovarian cancers. Whereas biallelic mutations of PALB2 have been associated with Fanconi anaaemia. Currently, 604 distinct PALB2 variants have been discovered. However, only 140 variants are thought to be pathogenic and approximately 400 are variants of unknown significance. Further studies are needed before the presence of PLAB2 mutations can be implemented as a routine clinical biomarker., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The blood brain barrier (BBB) plays a critically important role in the regulation of central nervous system (CNS) homeostasis, but also represents a major limitation to treatments of brain pathologies. In recent years, focused ultrasound (FUS) in conjunction with gas-filled microbubble contrast agents has emerged as a powerful tool for transiently and non-invasively disrupting the BBB in a targeted and image-guided manner, allowing for localized delivery of drugs, genes, or other therapeutic agents. Beyond the delivery of known therapeutics, FUS-mediated BBB opening also demonstrates the potential for use in neuromodulation and the stimulation of a range of cell- and tissue-level physiological responses that may prove beneficial in disease contexts. Clinical trials investigating the safety and efficacy of FUS-mediated BBB opening are well underway, and offer promising non-surgical approaches to treatment of devastating pathologies. This article reviews a range of pre-clinical and clinical studies demonstrating the tremendous potential of FUS to fundamentally change the paradigm of treatment for CNS diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Planted filters are often used to remove pesticides from runoff water. However, the detailed fate of pesticides in the planted filters still remains elusive. This hampers an accurate assessment of environmental risks of the pesticides related to their fate and thereby development of proper mitigation strategies. In addition, a test system for the chemical fate analysis including plants and in particular for planted filters is not well established yet. Therefore, we developed a microcosm test to simulate the fate of pesticide in planted filters, and applied 2- 13 C, 15 N-glyphosate as a model pesticide. The fate of 2- 13 C, 15 N-glyphosate in the planted microcosms over 31 day-incubation period was balanced and compared with that in the unplanted microcosms. The mass balance of 2- 13 C, 15 N-glyphosate turnover included 13 C mineralization, degradation products, and the 13 C and 15 N incorporation into the rhizosphere microbial biomass and plants. We observed high removal of glyphosate (> 88%) from the water mainly due to adsorption on gravel in both microcosms. More glyphosate was degraded in the planted microcosms with 4.1% of 13 C being mineralized, 1.5% of 13 C and 3.8% of 15 N being incorporated into microbial biomass. In the unplanted microcosms, 1.1% of 13 C from 2- 13 C, 15 N-glyphosate was mineralized, and only 0.2% of 13 C and 0.1% of 15 N were assimilated into microbial biomass. The total recovery of 13 C and 15 N was 81% and 85% in planted microcosms, and 91% and 93% in unplanted counterparts, respectively. The microcosm test was thus proven to be feasible for mass balance assessments of the fate of non-volatile chemicals in planted filters. The results of such studies could help better manage and design planted filters for pesticide removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Perioperative care of patients undergoing liver transplantation (LT) is very complex. Metabolic derangements, hypothermia, coagulopathy and thromboses, severe infections, and graft dysfunction can affect outcomes. In this manuscript, we discuss several perioperative problems that can be encountered in LT recipients. The authors present the most up-to-date information regarding predicting and treating hemodynamic instability, coagulation monitoring and management, postoperative ventilation strategies and early extubation, management of infections, and ESLD-related pulmonary complications. In addition, early post-transplant allograft dysfunction will be discussed.

Solid tumor treatment relies heavily upon chemotherapies, radiation, surgical resection, and/or immunotherapies. Although many alternative non-invasive solid tumor therapies have been proposed through the years and continue to be tested in various contexts, tumor cell eradication remains a daunting task for the current cancer armamentarium. Indeed, solid tumors exhibit physically and biochemically heterogenous microenvironments, allowing them to easily acquire resistance mechanisms. Progress in sonodynamic therapy (SDT), a treatment modality capable of controlling tumor growth while limiting off-target effects and toxicities, has accelerated in recent years. SDT combines "sonosensitizing" agents with the non-invasive application of focused acoustic energy [i.e. focused ultrasound (FUS)] to drive highly localized formation of tumor cell-killing reactive oxygen species (ROS). Sonosensitizers selectively accumulate in tumor cells, after which FUS radiation eliminates the tumor by forcing the tumor cells to undergo cell death. In this article, we comprehensively review recent studies wherein SDT has been applied to treat primary and metastatic tumors. We discuss sonosensitizers, combination therapies with SDT, developments in defining the mechanism of SDT-induced cell cytotoxicity, and the promise SDT offers as a modulator of anti-tumor immunity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glyphosate can be degraded by soil microorganisms rapidly and is impacted by temperature and soil properties. Enhanced temperature and total organic carbon (TOC) as well as reduced pH increased the rate of 13 C 3 15 N-glyphosate conversion to CO 2 and biogenic non-extractable residues (bioNERs) in a Haplic Chernozem (Muskus et al., 2019) and in a Humic Cambisol (Muskus et al., 2020). To date; however, the combined effect of temperature and TOC or pH on microbial community composition and glyphosate degraders in these two soils has not been investigated. Phospholipid fatty acid [PLFA] biomarker analysis combined with 13 C labeling was employed to investigate the effect of two soil properties (pH, TOC) and of three temperatures (10 °C, 20 °C, 30 °C) on soil microorganisms. Before incubation, the properties of a Haplic Chernozem and a Humic Cambisol were adjusted to obtain five treatments: (a) Control (Haplic Chernozem: 2.1% TOC and pH 6.6; Humic Cambisol: 3% TOC and pH 7.0), (b) 3% TOC (Haplic Chernozem) or 4% TOC (Humic Cambisol), (c) 4% TOC (Haplic Chernozem) or 5% TOC (Humic Cambisol), (d) pH 6.0 (Haplic Chernozem) or pH 6.5 (Humic Cambisol), and (e) pH 5.5 for both soils. All treatments were amended with 50 mg kg -1 glyphosate and incubated at 10 °C, 20 °C or 30 °C. We observed an increase in respiration, microbial biomass and glyphosate mineralization with incubation temperature. Although respiration and microbial biomass in the Humic Cambisol was higher, the microorganisms in the Haplic Chernozem were more active in glyphosate degradation. Increased TOC shifted the microbiome and the 13 C-glyphosate degraders towards Gram-positive bacteria in both soils. However, the abundance of 13 C-PLFAs indicative for the starvation of Gram-negative bacteria increased with increasing TOC or decreasing pH at higher temperatures. Gram-negative bacteria thus may have been involved in earlier stages of glyphosate degradation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Surface water runoff can export pesticides from agricultural fields into adjacent aquatic ecosystems, where they may pose adverse effects to organisms. Constructed wetlands (CWs) are widely used to treat agricultural runoff contaminated by pesticides, but the removal of hydrophilic pesticides is usually low. In this study, we suggest superabsorbent polymer (SAP), a cross-linked hydrophilic polymer, as a supplement to substrates of CWs and tested the hypothesis that SAP results in an enhanced removal of hydrophilic pesticides. Therefore, batch experiments were conducted to study the retention capacity of water-saturated SAP (w-SAP) for several hydrophilic pesticides. Retention of the pesticides on w-SAP was related to the ionization state and water solubility of the pesticides. The retention of neutral pesticides, imidacloprid, metalaxyl and propiconazole, was about 20% higher than that measured for anionic pesticides, bentazone, glyphosate and MCPA. The retention of the pesticides by w-SAP mainly resulted from their distribution in the gel-water phase of w-SAP, while less water soluble pesticides might have also been adsorbed on the molecular backbone of SAP. Furthermore, we tested the efficacy of w-SAP for treatment of runoff water contaminated by pesticides in lab-scale horizontal subsurface flow CWs. SAP in CWs improved the removal of the pesticides, including the recalcitrant ones. The removal enhancement was owing to the increase of hydraulic retention time and improvement of biodegradation. The removal of the pesticides in SAP containing CWs was > 93% for MCPA, glyphosate, and propiconazole, 62 - 99% for imidacloprid, 50 - 84% for metalaxyl, and 38 - 73% for bentazone. In the control gravel CWs, the removal was > 98% for glyphosate, generally > 83% for MCPA and propiconazole, 46 - 98% for imidacloprid, 32 - 97% for metalaxyl, and 9 - 96% for bentazone., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP)., Design: We identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS))., Results: 12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4 , but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1 . MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity., Conclusions: MMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Pesticides in agricultural surface water runoff cause a major threat to freshwater systems. Installation of filter systems or constructed wetlands in areas of preferential run-off is a possible measure for pesticides abatement. To develop such systems, combinations of filter materials suitable for retention of both hydrophilic and hydrophobic organic pesticides were tested for pesticide removal in planted microcosms. The retention of six pesticides frequently detected in surface waters (bentazone, MCPA, metalaxyl, propiconazole, pencycuron, and imidacloprid) was evaluated in unplanted and planted pot experiments with novel bed material mixtures consisting of pumice, vermiculite, water super-absorbent polymer (SAP) for retention of ionic and water soluble pesticides, and synthetic hydrophobic wool for adsorption of hydrophobic pesticides. The novel materials were compared to soil with high organic matter content. The highest retention of the pesticides was observed in the soil, with a considerable translocation of pesticides into the plants, and low leaching potential, in particular for the hydrophobic compounds. However, due to the high retention of pesticides in soil, environmental risks related to their long term mobilization cannot be excluded. Mixtures of pumice and vermiculite with SAP resulted in high retention of i) water and ii) both hydrophilic and hydrophobic pesticides but with much lower leaching potential compared to the mineral systems without SAP. Mixtures of such materials may provide near natural treatment options in riparian strips and also for treatment of rainwater runoff without the need for water containment systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

To identify therapeutic targets for KRAS mutant pancreatic cancer, we conduct a druggable genome small interfering RNA (siRNA) screen and determine that suppression of BCAR1 sensitizes pancreatic cancer cells to ERK inhibition. Integrative analysis of genome-scale CRISPR-Cas9 screens also identify BCAR1 as a top synthetic lethal interactor with mutant KRAS. BCAR1 encodes the SRC substrate p130Cas. We determine that SRC-inhibitor-mediated suppression of p130Cas phosphorylation impairs MYC transcription through a DOCK1-RAC1-β-catenin-dependent mechanism. Additionally, genetic suppression of TUBB3, encoding the βIII-tubulin subunit of microtubules, or pharmacological inhibition of microtubule function decreases levels of MYC protein in a calpain-dependent manner and potently sensitizes pancreatic cancer cells to ERK inhibition. Accordingly, the combination of a dual SRC/tubulin inhibitor with an ERK inhibitor cooperates to reduce MYC protein and synergistically suppress the growth of KRAS mutant pancreatic cancer. Thus, we demonstrate that mechanistically diverse combinations with ERK inhibition suppress MYC to impair pancreatic cancer proliferation., Competing Interests: Declaration of interests C.J.D. has received funding from and is a consultant for and advisory board member of Mirati Therapeutics and Deciphera Pharmaceuticals. C.J.D. has consulted for Eli Lilly, Jazz Therapeutics, Revolution Medicines, Ribometrix, and Turning Point Therapeutics. A.D.C. has consulted for Eli Lilly and Mirati Therapeutics. A.J.A. has consulted for Oncorus, Arrakis Therapeutics, and Merck & Co. A.J.A. has received research funding support from Mirati Therapeutics and Deerfield. W.C.H. is a consultant for Thermo Fisher, Solvasta Ventures, MPM Capital, KSQ Therapeutics, iTeos, Tyra Biosciences, Frontier Medicine, and Paraxel., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the prevalence and risk factors of new-onset glucose metabolism impairment using an oral glucose tolerance test (OGTT) in patients with normal fasting glycaemia on long-term glucocorticoid (GC) treatment., Methods: An OGTT was performed in 150 patients without a previous history of pre-diabetes or diabetes who were diagnosed with inflammatory rheumatic diseases and treated with GCs >3 months. All participants underwent clinical and biochemical evaluation for risk factors of diabetes: age, sex, current and cumulative dose of steroids, treatment duration, waist circumference, BMI, Homeostatic Model Assessment for Insulin Resistance, fasting insulin concentration, family history of diabetes, CRP, 28-joint DAS with CRP, type of connective tissue disease and trunk fat percentage measured by DXA. Logistic regression analysis was conducted to evaluate the association between the presence of impaired glucose tolerance (IGT) in the OGTT and analysed risk factors., Results: A total of 102 patients (68%) had fully normal glucose tolerance. Diabetes, isolated impaired fasting glucose, isolated IGT and combined impaired fasting glucose + IGT was diagnosed in 3.3, 4.67, 19.33 and 4.67% of patients, respectively; 20% of participants had IGT or diabetes despite normal fasting glucose concentration. The median cumulative dose and current dose (5 mg) of GCs and treatment duration were similar compared with the normal glucose tolerance group. In a multivariate logistic regression model, only older age (particularly ≥50 years of age) and trunk fat percentage remained significant factors predicting IGT or diabetes in the OGTT., Conclusion: New-onset GC-induced glucose intolerance, even in patients on long-term low-dose treatment, is prevalent despite normal fasting glucose concentration and patients should be screened with an OGTT despite the absence of classic risk factors of diabetes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The SWItch Sucrose non-fermentable (SWI/SNF) complex is a large, multi-subunit ATP-dependent nucleosome remodeling complex that acts as a tumor suppressor by modulating transcription. Mutations of SWI/SNF subunits have been described in relation to developmental disorders, hereditary SWI/SNF deficiency syndromes, as well as malignancies. In this review we summarize the current literature in regards to SWI/SNF-deficient tumors of the luminal gastrointestinal tract (GIT) and pancreas. As a group they range from moderately to undifferentiated tumors composed of monotonous anaplastic cells, prominent macronucleoli and a variable rhabdoid cell component. Deficiency of a SWI/SNF subunit is typified by complete loss of nuclear staining by immunohistochemistry for respective subunit., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The herbicide metamitron is frequently detected in the environment, and its degradation in soil differs from that in aquatic sediments. In this study, we applied 13 C 6 -metamitron to investigate the differences in microbial activity, metamitron mineralization and metamitron degrading microbial communities between soil and water-sediment systems. Metamitron increased soil respiration, whereas it suppressed respiration in the water-sediment system as compared to controls. Metamitron was mineralized two-fold faster in soil than in the water-sediment. Incorporation of 13 C from 13 C 6 -metamitron into Phospholipid fatty acids (PLFAs) was higher in soil than in sediment, suggesting higher activity of metamitron-degrading microorganisms in soil. During the accelerated mineralization of metamitron, biomarkers for Gram-negative, Gram-positive bacteria and actinobacteria dominated within the 13 C-PLFAs in soil. Gram-negative bacteria dominated among the metamitron degraders in sediment throughout the incubation period. Actinobacteria, and actinobacteria and fungi were the main consumers of necromass of primary degraders in soil and water-sediment, respectively. This study clearly showed that microbial groups involved in metamitron degradation depend on the system (soil vs. water-sediment) and on time. It also indicated that the turnover of organic chemicals in complex environments is driven by different groups of synthropic degraders (primary degraders and necromass degraders) rather than by a single degrader., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.

One important route of degradation of herbicide pendimethalin in soil leads to formation of non-extractable residues (NER). To investigate NER nature (irreversibly, chemically bound, including possible biogenic NER, or strongly sorbed and entrapped) residues of 14 C-labelled pendimethalin in soil were investigated after conventional extraction with organic solvents by silylation. After 400 days of incubation, 32.0% of applied radioactivity (AR) was transformed into NER, 39.9% AR remained extractable. Mineralization reached 26.2% AR. Additionally, 14 C-pendimethalin was incubated in soil amended with compost for 217 days to investigate the influence of organic amendments on NER formation. NER amounted to 37.8% AR, with 57.9% AR remaining extractable. Mineralization was negligible (1.4% AR). For all sampling times only low amounts of radioactivity were entrapped (<5% AR) in soil without compost amendment. Pendimethalin was present only in trace amounts (ca. 0.4% AR), other released residues consisted of undefined fractions (sum ≈2% AR). In soil amended with compost, silylation overall resulted in release of higher amounts of radioactivity (19% AR). Addition of compost led to an increase in potential entrapment and sorption sites for pendimethalin, forming higher amounts of strongly sorbed, entrapped residues. Furthermore, potential release of non-extractable pendimethalin residues was investigated by incubation of solvent-extracted soil (without compost amendment) mixed with fresh soil for additional 3 months. NER were partly mineralized (7% AR) and 20% became extractable with organic solvents. However, no pendimethalin or any known metabolites were found. It can be concluded that no parent pendimethalin was found and NER of pendimethalin in soil are mainly formed by covalent binding to organic matrix with only low potential of remobilization under natural conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Hernia sacs with pathological evaluation over a 19-year period were analysed with regards to pathological diagnoses, full costing and the impact on patient management., Materials and Methods: The database of the Department of Pathology were searched over the study period (2001 to 2019 inclusive) for hernia sacs. The total cost of complete pathology examination was calculated on average numbers and rates of pay that existed over the study period., Results: A total of 3619 hernia sacs from the abdominal, hiatus/diaphragmatic, inguinal and femoral hernias were retrieved. Of these 3592 cases (99.25%) had sections taken for histological evaluation. A total of 3437 cases representing 95.7% of all hernia sacs did not show any pathological abnormality. If non-neoplastic clinically insignificant lesions seen in hernia sacs is included, then 3552 of 3592 (98.9%) hernia sacs underwent full pathological evaluation for no patient benefit.On average two blocks or tissue sections per case were processed incurring a technical cost of $53 175.00. The total pathologist cost in reporting the 3592 cases was approximately $39 870.00 and rose to $40 410.00 when interpretation of ancillary tests was factored in. $95 328.90 (average $26.90 per specimen with a yearly average total cost of $5 017.31) was spent over the 19-year period in full pathological examination of 3592 hernia sacs., Conclusion: Given the low return on investment and the difficult to quantify time savings and reallocation, we do not advocate the routine sampling of hernia sacs. Gross examination will suffice in 99% of the cases. Selective cases may be sampled if clinically indicated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Amendment of soils with plant residues is common practice for improving soil quality. In addition to stimulated microbial activity, the supply of fresh soluble organic (C) from litter may accelerate the microbial degradation of chemicals in soils. Therefore, the aim of this study was to test whether the maize litter enhances degradation of 4-chloro-2-methylphenoxyacetic acid (MCPA) and increases formation of non-toxic biogenic non-extractable residues (bioNERs). Soil was amended with 13 C 6 -MCPA and incubated with or without litter addition on the top. Three soil layers were sampled with increasing distance from the top: 0-2 mm, 2-5 mm and 5-20 mm; and the mass balance of 13 C 6 -MCPA transformation determined. Maize litter promoted microbial activity, mineralization of 13 C 6 -MCPA and bioNER formation in the upper two layers (0-2 and 2-5 mm). The mineralization of 13 C 6 -MCPA in soil with litter increased to 27% compared to only 6% in the control. Accordingly, maize addition reduced the amount of extractable residual MCPA in soil from 77% (control) to 35% of initially applied 13 C 6 -MCPA. While non-extractable residues (NERs) were <6% in control soil, litter addition raised NERs to 21%. Thereby, bioNERs comprised 14% of 13 C 6 -MCPA equivalents. We found characteristic differences of bioNER formation with distance to litter. While total NERs in soil at a distance of 2-5 mm were mostly identified as 13 C-bioNERs (97%), only 45-46% of total NERs were assigned to bioNERs in the 0-2 and 5-20 mm layers. Phospholipid fatty acid analysis indicated that fungi and Gram-negative bacteria were mainly involved in MCPA degradation. Maize-C particularly stimulated fungal activity in the adjacent soil, which presumably facilitated non-biogenic NER formation. The plant litter accelerated formation of both non-toxic bioNERs and non-biogenic NERs. More studies on the structural composition of non-biogenic NERs with toxicity potential are needed for future recommendations on litter addition in agriculture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glyphosate is one of the most used herbicides in the world. The fate of glyphosate in tropical soils may be different from that in soils from temperate regions. In particular, the amounts and types of non-extractable residues (NER) may differ considerably, resulting in different relative contributions of xenoNER (sorbed and sequestered parent compound) and bioNER (biomass residues of degraders). In addition, environmental conditions and agricultural practices leading to total organic carbon (TOC) or pH variation can alter the degradation of glyphosate. The aim of this study is thus to investigate how the glyphosate degradation and turnover are influenced by varying temperature, pH and TOC of sandy loam soil from Colombia. The pH or TOC of a Colombian soil was modified to yield five treatments: control (pH 7.0, TOC 3%), 4% TOC, 5% TOC, pH 6.5, and pH 5.5. Each treatment received 50 mg kg -1 of 13 C 3 15 N-glyphosate and was incubated at 10 °C, 20 °C and 30 °C for 40 days. Rising temperature increased the mineralization of 13 C 3 15 N-glyphosate from 13 to 20% (10 °C) to 32-39% (20 °C) and 41-51% (30 °C) and decreased the amounts of extractable 13 C 3 15 N-glyphosate after 40 days of incubation from 13 to 26% (10 °C) to 4.6-12% (20 °C) and 1.2-3.2% (30 °C). Extractable 13 C 3 15 N-glyphosate increased with higher TOC and higher pH. Total 13 C-NER were similar in all treatments and at all temperatures (47%-60%), indicating that none of the factors studied affected the amount of total 13 C-NER. However, 13 C-bioNER dominated within the 13 C-NER pool in the control and the 4% TOC treatment (76-88% of total 13 C-NER at 20 °C and 30 °C), whereas in soil with 5% TOC and pH 6.5 or 5.5 13 C-bioNER were lower (47-61% at 20 °C and 30 °C). In contrast, the 15 N-bioNER pool was small (between 14 and 39% of the 15 N-NER). Thus, more than 60% of 15 N-NER is potentially hazardous xenobiotic NER which need careful attention in the future., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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Stethoscopes are used to transmit body sounds related to various physiological processes to ears of a physician, providing basic or supportive information for eventual diagnosis. Unfavorably, the dominant frequency components of most of the auscultation signals are localized close to the lower frequency limits of the human auditory system, restricting the achievable selectivity and specificity. The present study introduces an approach that aims at overcoming the existing limitations. A signal processing scheme utilizing knock rejection, dynamic compressor, and pseudo-stereo synthesizer blocks is described, along with hardware implementation and results of the initial subjective evaluation.

Current medical healthcare has no sufficient innovative drug delivery formulations for treating patients with alveolar osteitis. This study presents a portion of research conducted to design, fabricate, and characterize systems for the treatment of alveolar osteitis. The results demonstrate that intra-alveolar formulations can be designed to function as drug carriers, facilitate wound dressing, and promote tissue regeneration. Our aim was to design cone-shaped implants made of microcrystalline chitosan filled with sodium meloxicam, i.e., a nonsteroidal anti-inflammatory agent. SEM analysis revealed the porous structure and monophasic characteristic of the formulation. Moreover, textural analysis demonstrated the effect of different factors (shape, hydration, addition of an active substance) on the hardness, springiness and cohesiveness of the studied systems. The active substance was released in a two-phase process. In vitro biocompatibility tests performed according to ISO 10993-5 confirmed the lack of cytotoxicity of the tested formulations. The designed formulations did not stimulate human THP1-XBlue™ monocytes to activate the transcription nuclear factor NF-κB, which ensures that the performed systems do not induce local inflammation. These initial results indicate that the innovative sodium meloxicam release system can improve safety and efficacy in clinical settings., (Copyright © 2019. Published by Elsevier B.V.)

Environmental fate assessment of chemicals involves standardized simulation tests with isotope-labeled molecules to balance transformation, mineralization, and formation of nonextractable residues (NER). Methods to predict microbial turnover and biogenic NER have been developed, having limited use when metabolites accumulate, the chemicals are not the only C source, or provide for other macroelements. To improve predictive capability, we extended a recently developed method for microbial growth yield estimation to account for incomplete degradation and multiple-element assimilation and combined it with a dynamic model for fate description in soils and sediments. We evaluated the results against the unique experimental data of 13 C 3 - 15 N co-labeled glyphosate turnover with AMPA formation in water-sediment systems (OECD 308). Balancing 13 C- and 15 N- fluxes to biomass showed a pronounced shift of glyphosate transformation from full mineralization to AMPA formation. This may be explained by various hypotheses, for example, the limited substrate turnover inherent to the batch conditions of the test system causing microbial starvation or inhibition by P release. Modeling results indicate initial N overload due to the lower C/N ratio in glyphosate compared to average cell composition leading to subsequent C demand and accumulation of AMPA.

Glyphosate is the best-selling and the most-used broad-spectrum herbicide worldwide. Microbial conversion of glyphosate to CO 2 and biogenic non-extractable residues (bioNER) leads to its complete degradation. The degradation of glyphosate may vary in different soils and it depends on environmental conditions and soil properties. To date, the influence of temperature, soil pH and total organic carbon (TOC) on microbial conversion of glyphosate to bioNER has not been investigated yet. The pH or TOC of an agricultural original soil (pH 6.6, TOC 2.1%) was modified using sulfuric acid or farmyard manure (FYM), respectively. Each treatment: original (I), 3% TOC (II), 4% TOC (III), pH 6.0 (IV) and pH 5.5 (V) was amended with 13 C 3 15 N-glyphosate and incubated at 10 °C, 20 °C and 30 °C for 39 days. The temperature was the main factor controlling the mineralization and the extractable 13 C 3 15 N-glyphosate, whereas higher TOC content and lower pH resulted in enhanced formation of 13 C-bioNER. After 39 days the cumulative mineralization of 13 C-glyphosate was in the range of 12-22% (10 °C), 37-47% (20 °C) and 43-54% (30 °C). Extractable residues of 13 C-glyphosate were in the range of 10-21% (10 °C) and 4-10% (20 °C and 30 °C); whereas those of 15 N-glyphosate were as follows 20-32% (10 °C) and 12-25% (20 °C and 30 °C). The 13 C-NER comprised about 53-69% of 13 C-mass balance in soils incubated at 10 °C, but 40-50% in soils incubated at 20 °C and 30 °C. The 15 N-NER were higher than the 13 C-NER and varied between 62% and 74% at 10 °C, between 53% and 81% at 20 °C and 30 °C. A major formation of 13 C-bioNER (72-88% of 13 C-NER) at 20 °C and 30 °C was noted in soil amended with FYM. An increased formation of 15 N-bioNER (14-17% of 15 N-NER) was also observed in FYM-amended soil. The xenobiotic 15 N-NER had a major share within the 15 N-NER and thus need to be considered when assessing the environmental risk of glyphosate-NER., (Copyright © 2018. Published by Elsevier B.V.)

Background: Vasoplegia is a clinical condition typically manifested by cardiovascular instability unresponsive to the usual doses of inotropes or vasopressors. It can occur in a variety of clinical settings including liver transplantation (LT). Immunoglobulins have been used to treat sepsis-related vasoplegia. We performed a retrospective study to evaluate the efficacy of IgM-enriched immunoglobulin (IgMIg) on 30-day mortality and its ability to reverse vasoplegia in patients undergoing LT., Methods: Between May 2013 and November 2017, 473 LT were performed at our institution. We identified 21 patients who received IgMIg for 3 days to treat vasoplegia. Patients included in the study met the criteria for having vasoplegia and required noradrenaline administration greater than 1 μg·kg·min for more than 24 hours to maintain a mean arterial pressure of 70 mm Hg or greater. Procalcitonin and interleukin-6 (IL-6) levels were used as surrogate markers for inflammation and were measured at the beginning and end of IgM treatment., Results: After IgMIg administration, median noradrenaline infusion rates could be significantly reduced from 1.6 μg·kg·min (1.3-2 μg·kg·min) to 0.16 μg·kg·min (0.08-0.34 μg·kg·min) (P < 0.001). In addition, after treatment, procalcitonin levels decreased significantly from 44 ng/mL (24-158) to 26.1 ng/mL (10.9-48.7) (P < 0.001) and IL-6 levels decreased significantly from 63 pg/mL (29-102) to 20 pg/mL (11-20) (P < 0.001). Thirty-day morality was 14.3%., Conclusions: The administration of IgMIg in patients with vasoplegia after LT is associated with a return of hemodynamic stability. Despite a predicted mortality of over 90% by Sepsis-Related Organ Failure Assessment score, the mortality rate of patients receiving IgMIg in our study was less than 20%.

Bromoxynil is a widely used nitrile herbicide applied to maize and other cereals in many countries. To date, still little is known about bromoxynil turnover and the structural identity of bromoxynil non-extractable residues (NER) which are reported to occur in high amounts. Therefore, we investigated the microbial turnover of 13 C-labeled bromoxynil for 32 days. A focus was laid on the estimation of biogenic NER based on the turnover of 13 C into amino acids (AA). At the end, 25% of 13 C 6 -bromoxynil equivalents were mineralized, 2% assigned to extractable residues and 72.5% to NER. Based on 12% in the 13 C-total AA and an assumed share of AA of 50% in microbial biomass we arrived at 24% of total 13 C-biogenic NER. About 33% of the total 13 C-NER could thus be explained by 13 C-biogenic NER; 67% was unknown and by definition xenobiotic NER with potential for toxicity. The 13 C label from 13 C 6 -bromoxynil was mainly detected in the humic acids (28.5%), but significant amounts were also found in non-humics (17.6%), fulvic acids (13.2%) and humins (12.7%). The 13 C-total amino acids hydrolyzed from humic acids, humins and fulvic acids amounted to 5.2%, 6.1% and 1.2% of 13 C 6 -bromoxynil equivalents, respectively, corresponding to total 13 C-biogenic NER amounts of 10.4%, 12.2% and 2.4%. The humins contained mostly 13 C-biogenic NER, whereas the humic and fulvic acids may be dominated by the xenobiotic NER. Due to the high proportion of unknown 13 C-NER and particularly in the humic and fulvic acids, future studies should focus on the detailed characterization of these fractions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The area of application of electronic stethoscopes in medical diagnostics covers the scope of usability of the acoustic stethoscopes, from which they have evolved and which they could potentially replace. However, the principle of operation of these two groups of diagnostic devices is substantially different. Thus, an important question arises, regarding the differences in parameters of the transmitted sound and their potential diagnostic consequences in clinical practice., Methods: In order to answer this question, heart auscultation signals are recorded using various stethoscopes and divided into short fragments based on the analysis of the synchronized recordings of electrocardiogram signals. Next, a dedicated algorithm is used to extract representative datasets for each case, which are then analyzed for their acoustic parameters. Four different electronic stethoscopes were investigated, together with an acoustic stethoscope as a reference point., Results: The determined acoustic characteristics of the considered stethoscopes differ significantly between each other., Conclusions: The differences in sound transmitted by various stethoscope models may translate into significant differences in quality of the obtained diagnosis. It is also pointed out, that the terminology and application guidelines regarding the electronic stethoscopes are misleading and should be changed.

Introduction Adrenocortical carcinoma (ACC) is a rare malignancy, associated with poor outcome and few therapeutic options. Despite increasing attention, the knowledge about the clinical course and treatment of these tumors is limited. Objectives Survival rates in ACC are still low and the percentage of relapse is high. Thus, it is crucial to identify the prognostic factors of overall survival (OS) and recurrence‑free survival (RFS). Patients and methods This was a retrospective analysis of 66 patients diagnosed with ACC between 2002 and 2015. Results The median OS was 43.5 months, 78.19 months for stage I + II, 22.95 months for stage III, and 19.54 months for stage IV ACC. Older age, stage IV ACC, margin status R2, and no mitotane treatment were associated with poor OS. Low Ki67 and mitotic indices were related to improved OS in a univariate analysis. The median RFS was 101.1 months. Disease recurrence after potentially curative surgery was reported in 1 patient (25%) with stage I, 12 patients (46%) with stage II, and 9 patients (45%) with stage III ACC. Male sex and no mitotane treatment were associated with a reduced RFS in a multivariate analysis and higher Ki67 and mitotic indices in the univariate analysis. Conclusions Ki67 and mitotic indices should be considered as prognostic factors when planning the adjuvant treatment of ACC. Mitotane treatment may be independently associated with better outcomes regardless of the tumor stage.

Purpose: The force with which the diaphragm chestpiece of a stethoscope is pressed against the body of a patient during an auscultation examination introduces the initial stress and deformation to the diaphragm and the underlying tissues, thus altering the acoustic parameters of the sound transmission path. If the examination is performed by an experienced physician, he will intuitively adjust the amount of the force in order to achieve the optimal sound quality. However, in case of becoming increasingly popular auto-diagnosis and telemedicine auscultation devices with no such feedback mechanisms, the question arises regarding the influence of the possible force mismatch on the parameters of the recorded signal., Design: The present study describes the results of the experimental investigations on the relation between pressure applied to the chestpiece of a stethoscope and parameters of the transmitted bioacoustic signals. The experiments were carried out using various stethoscopes connected to a force measurement system, which allowed to maintain fixed pressure during auscultation examinations. The signals were recorded during examinations of different volunteers, at various auscultation sites., Results: The obtained results reveal strong individual and auscultation-site variability., Conclusions: It is concluded that the underlying tissue deformation is the primary factor that alters the parameters of the recorded signals., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The present study introduces a detailed methodology which can be applied for objective evaluation and comparison of the acoustic parameters of medical stethoscopes using auscultation sounds as test signals. The described approach allows taking into account the acoustic coupling between the body of an auscultated patient and the chest piece of a stethoscope. Information obtained from additional, synchronized electrocardiography measurements is used to extract short, specific fragments of recordings, defined as acoustic events. Analysis of the spectral characteristics of many acoustic events allows us to compare the acoustic properties of various stethoscopes and to estimate the measurement uncertainty. The exemplary results of the comparative evaluation of acoustic properties of bell and diaphragm-type chest pieces of a single stethoscope are presented. The results show that the frequency characteristics of the signals obtained using both examined chest pieces under the conditions of the performed examinations are very similar.

Metamitron and its main metabolite desamino-metamitron are frequently detected in surface waters. To date, there are no studies targeting metamitron degradation in water-sediment systems. Therefore, the aim of this study was to trace the fate of metamitron in a water-sediment system using 13 C-isotope labeling. Mineralization of metamitron was high and accounted for 49% of 13 C 6 -metamitron equivalents at the end. In contrast, only 8.7% of 13 C 6 -metamitron equivalents were mineralized in the water only system demonstrating the key role of sediment for biodegradation. Metamitron disappeared from the water on day 40 and was completely removed from the sediment on day 80. This agrochemical was utilized as carbon source by microorganisms as shown by the incorporation of the 13 C label into microbial amino acids and finally into biogenic residues. The latter amounted to 24% of 13 C 6 -metamitron equivalents at the end. However, 17% of 13 C 6 -metamitron equivalents were detected in xenobiotic non-extractable residues (NER) with a release potential and delayed risk for the environment. Metamitron was degraded via two pathways, initially via 4-(dimethylimino)-3-methyl-6-phenyl-1,2,4-triazin-5(4H)-one, which might be related to growth, and later via desamino-metamitron, which can be attributed to starvation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Metamitron is one of the most commonly used herbicide in sugar beet and flower bulb cultures. Numerous laboratory and field studies on sorption and degradation of metamitron were performed. Detailed biodegradation studies in soil using 13 C-isotope labeling are still missing. Therefore, we aimed at providing a detailed turnover mass balance of 13 C 6 -metamitron in soil microcosms over 80 days. In the biotic system, metamitron mineralized rapidly, and 13 CO 2 finally constituted 60% of the initial 13 C 6 -metamitron equivalents. In abiotic control experiments CO 2 rose to only 7.4% of the initial 13 C 6 -metamitron equivalents. The 13 C label from 13 C 6 -metamitron was incorporated into microbial amino acids that were ultimately stabilized in the soil organic matter forming presumably harmless biogenic residues. Finally, 13 C label from 13 C 6 -metamitron was distributed between the 13 CO 2 and the 13 C-biogenic residues indicating nearly complete biodegradation. The parallel increase of 13 C-alanine, 13 C-glutamate and 13 CO 2 indicates that metamitron was initially biodegraded via the desamino-metamitron route suggesting its relevance in the growth metabolism. In later phases of biodegradation, the "Rhodococcus route" was indicated by the low 13 CO 2 evolution and the high relevance of the pyruvate pathway, which aims at biomolecule synthesis and seems to be related to starvation. This is a first report on the detailed degradation route of metamitron in soil., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Because of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors., Methods: Between September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected., Results: There were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%., Discussion: Organs from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients.

Procedures for the analysis of turnover of chemicals (and of natural compounds) are well developed using radio or stable isotope labelled tracer compounds in various standardized OECD tests. Due to the analytical focus on the isotope label the chemical speciation of the so-called non-extractable residues (NER) in soils and sediments often remains unknown. These NER may stem from parent compounds, metabolites, microbial biomass, or from precipitated carbonates after productive microbial degradation. Fate studies mostly do not describe the link to phylogenetic assignment of degraders and microbial ecology although in these fields various isotope tracer applications are well developed, too. We present several options for integrating both approaches in environmental biotechnology and how they can be used to improve knowledge in microbial ecology., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Glyphosate and its metabolite aminomethylphosphonic acid (AMPA) are frequently detected in water and sediments. Up to date, there are no comprehensive studies on the fate of glyphosate in water-sediment microcosms according to OECD 308 guideline. Stable isotope co-labeled (13)C3(15)N-glyphosate was used to determine the turnover mass balance, formation of metabolites, and formation of residues over a period of 80 days. In the water-sediment system, 56% of the initial (13)C3-glyphosate equivalents was ultimately mineralized, whereas the mineralization in the water system (without sediment) was low, reaching only 2% of (13)C-glyphosate equivalents. This finding demonstrates the key role of sediments in its degradation. Glyphosate was detected below detection limit in the water compartment on day 40, but could still be detected in the sediments, ultimately reaching 5% of (13)C3(15)N-glyphosate equivalents. A rapid increase in (13)C(15)N-AMPA was noted after 10 days, and these transformation products ultimately constituted 26% of the (13)C3-glyphosate equivalents and 79% of the (15)N-glyphosate equivalents. In total, 10% of the (13)C label and 12% of the (15)N label were incorporated into amino acids, indicating no risk bearing biogenic residue formation from (13)C3(15)N-glyphosate. Initially, glyphosate was biodegraded via the sarcosine pathway related to microbial growth, as shown by co-labeled (13)C(15)N-glycine and biogenic residue formation. Later, degradation via AMPA dominated under starvation conditions, as shown by the contents of (13)C-glycine. The presented data provide the first evidence of the speciation of the non-extractable residues as well as the utilization of glyphosate as a carbon and nitrogen source in the water-sediment system. This study also highlights the contribution of both the sarcosine and the AMPA degradation pathways under these conditions., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

One of the unique features of the quantum-cascade-laser-seeded, nanosecond-pulse CO 2 laser, invented for the purpose of generation of extreme UV by laser-produced-plasma, is a robust synthesis of arbitrary pulse waveforms. In the present Letter we report on experimental results that are, to our best knowledge, the first demonstration of such functionality obtainable from nanosecond-pulse CO 2 laser technology. An online pulse duration adjustment within 10-40 ns was demonstrated, and a few exemplary pulse waveforms were synthesized, such as "tophat," "tailspike," and "leadspike" shapes. Such output characteristics may be useful to optimize the performance of LPP EUV source.

The introduction of new test methods and the modification of existing ones are crucial for obtaining reliable results, which contributes to the development of innovative materials that may have clinical applications. Today, silicone is commonly used in medicine and the diversity of its applications are continually growing. The aim of this study is to evaluate the mucoadhesiveness of polymeric membranes by a method that modifies the existing test methods through the introduction of silicone discs. The matrices were designed for clinical application in the management of diseases within the oral cavity. The use of silicone discs allows reliable and reproducible results to be obtained, which allows us to make various tensometric measurements. In this study, different types of polymeric matrices were examined, as well as their crosslinking and the presence for the active pharmaceutical ingredient were compared to the pure dosage form. The lidocaine hydrochloride (Lid(HCl)) was used as a model active substance, due to its use in dentistry and clinical safety. The results were characterized by a high repeatability (RSD < 10.6%). The advantage of silicone material due to its mechanical strength, chemical and physical resistance, allowed a new test method using a texture analyzer to be proposed.

This paper reports the development of an analytical model, with supporting experimental data, which quite accurately describes the key features of CO 2 laser ablation of fused silica glass. The quantitative model of nonexplosive, evaporative material removal is shown to match the experimental data very well, to the extent that it can be used as a tool for ablative measurements of absorption coefficient and vaporization energy. The experimental results indicated that a minimum of 12  MJ kg -1 is required to fully vaporize fused quartz initially held at room temperature, which is in good agreement with the prediction of the model supplied with input data available in the literature. An optimal window for the machining of fused quartz was revealed in terms of pulse duration 20-80 μs and CO 2 laser wavelength optimized for maximum absorption coefficient. Material removal rates of 0.33 μm per J cm -2 allow for a high-precision depth control with modest laser stability. The model may also be used as a parameter selection guide for CO 2 laser ablation of fused silica or other materials of similar thermophysical properties.