Expression and Temperature-Dependent Regulation of the Beta2-Microglobulin (Cyca-B2m) Gene in a Cold-Blooded Vertebrate, the Common Carp (Cyprinus carpio L.)

Expression of beta2-microglobulin (β 2m) in the common carp was studied using a polyclonal antibody raised against a recombinant protein obtained from eukaryotic expression of the Cyca-B2m gene. β 2m is expressed on peripheral blood Ig+ and Ig- lymphocytes, but not on erythrocytes and thrombocytes. In spleen and pronephros, dull- and bright-positive populations could be identified correlating with the presence of erythrocytes, thrombocytes, and mature leucocytes or immature and mature cells from the lympho-myeloid lineage, respectively. Thymocytes were shown to be comprised of a single bright-positive population. The Cyca-B2m polyclonal antiserum was used in conjunction with a similarly produced polyclonal antiserum to an MHC class I (Cyca-UA) α chain to investigate the expression of class I molecules on peripheral blood leucocytes (PBL) at different permissive temperatures. At 12℃, a temporary downregulation of class I molecules was demonstrated, which recovered to normal levels within 3 days. However, at 6℃, a lasting absence of class I cell-surface expression was observed, which could be restored slowly by transfer to 12C. The expression of immunoglobulin molecules on B cells was unaffected by temperature changes. The absence of the class cell-surface expression was shown to be the result of a lack of sufficient Cyca-B2m gene transcription, although Cyca-UA mRNA was present at comparable levels at all temperatures. This suggests that class I expression is regulated by a temperature-sensitive transcription of the Cyca-B2m gene

Local recurrence and survival after treatment of oral squamous cell carcinoma of the maxilla: A systematic review and meta-analysis

OBJECTIVE: Oral squamous cell carcinoma involving the maxilla (MSCC) is a rare malignancy. The aim was to perform a systematic review and meta-analysis of available literature on local recurrence (LR), overall survival (OS), and associated risk factors of MSCC. STUDY DESIGN: The Cochrane, PubMed, and EMBASE databases were searched with related keywords and synonyms. The pooled proportions of both LR and OS were subsequently calculated with 95% confidence intervals. RESULTS: In total, 2638 articles were screened on title and abstract, 131 articles were screened on full text, and 20 were included. The pooled 5-year LR rate was 19.3%, and the 5-year OS rate was 53.7%. The subgroup analysis between surgery only and surgery with (neo)adjuvant treatment resulted in an odds ratio (OR) of .76 (95% confidence interval [CI]; .41-1.40). CONCLUSIONS: Postoperative (chemo)radiotherapy or preoperative intra-arterial chemoradiotherapy improves survival when adverse tumor characteristics are present. Posterior tumor extension into the soft palate, pterygoid muscle, pterygoid process, and infratemporal fossa was significantly associated with decreased OS in multiple studies. More research into the risk-reduction of local recurrence is warranted

Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients - insights from the PRoVENT-COVID study:a national, multicenter, observational cohort analysis

BACKGROUND: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: We analyzed data from the multicenter observational 'PRactice of VENTilation in COVID-19 patients' study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. RESULTS: Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27-7.72 L), 0.78 L (0.26-1.27 L), and - 0.35 L (- 6.52-0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77-0.95, P = 0.0047). Sensitivity analyses showed similar results. CONCLUSIONS: In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020

European Sea Bass (Dicentrarchus labrax) immune status and disease resistance are impaired by arginine dietary supplementation

Infectious diseases and fish feeds management are probably the major expenses in the aquaculture business. Hence, it is a priority to define sustainable strategies which simultaneously avoid therapeutic procedures and reinforce fish immunity. Currently, one preferred approach is the use of immunostimulants which can be supplemented to the fish diets. Arginine is a versatile amino acid with important mechanisms closely related to the immune response. Aiming at finding out how arginine affects the innate immune status or improve disease resistance of European seabass (Dicentrarchus labrax) against vibriosis, fish were fed two arginine-supplemented diets (1% and 2% arginine supplementation). A third diet meeting arginine requirement level for seabass served as control diet. Following 15 or 29 days of feeding, fish were sampled for blood, spleen and gut to assess cell-mediated immune parameters and immune-related gene expression. At the same time, fish from each dietary group were challenged against Vibrio anguillarum and survival was monitored. Cell-mediated immune parameters such as the extracellular superoxide and nitric oxide decreased in fish fed arginine-supplemented diets. Interleukins and immune-cell marker transcripts were down-regulated by the highest supplementation level. Disease resistance data were in accordance with a generally depressed immune status, with increased susceptibility to vibriosis in fish fed arginine supplemented diets. Altogether, these results suggest a general inhibitory effect of arginine on the immune defences and disease resistance of European seabass. Still, further research will certainly clarify arginine immunomodulation pathways thereby allowing the validation of its potential as a prophylactic strategy.European Union's Seventh Framework Programme AQUAEXCEL (Aquaculture Infrastructures for Excellence in European Fish Research) [262336]; AQUAIMPROV [NORTE-07-0124-FEDER-000038]; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte) , under the National Strategic Reference Framework, through the European Regional Development Fund; North Portugal Regional Operational Programme (ON. 2 - O Novo Norte), under the National Strategic Reference Framework through the COMPETE - Operational Competitiveness Programme; Fundacao para a Ciencia e Tecnologia; Fundacao para a Ciencia e Tecnologia [SFRH/BD/89457/2012, SFRH/BPD/77210/2011]; Generalitat Valenciana through the project REVIDPAQUA [ISIC/2012/003]; [PEst-C/MAR/LA0015/2013]; [UID/Multi/04423/2013]info:eu-repo/semantics/publishedVersio

Controls on natural gas migration in the western Nile Delta fan

The aim of this study is to combine petrophysical and geochemical data in order to reconstruct the migration history and pathways of mixed microbial-thermogenic gases drilled on the Nile Delta fan, offshore Egypt. While general interest lies in understanding migration routes, rates and mechanisms special attention is dedicated to understanding (1) the origin of gas in both reservoir and non-reservoir units using chemical and isotopic fingerprints and (2) whether a free gas phase supports relatively rapid leakage via bulk flow in non-reservoir units, both above and below commercial accumulations. The Pilocene section in this study is a classic slope environment comprising channels, mud-rich turbidites, mass transport complexes and hemipelagites. Data from seismic and drilled wells suggest that the channel and levee reservoirs are rarely full to spill, implying either a lack of charge and leakage rates which precludes complete filling of the structures. The provided data set enables a quantitative assessment of gas distribution and its genetic fingerprint in the context of both stratigraphic position and lithology. Data is reported from 25 wells, each provided with a conventional wireline log suite and some with borehole images and high-quality core images. Gas concentration data, plus compositional and isotope data are available for isotubes and headspace gas for both reservoir and non-reservoir units. Small-to-medium scale linear and non-linear depth shifts between different techniques (core recovery, core logging, wireline logging) in conjunction with scale and resolution issues demanded logical/stochastic depth synchronisation and well as harmonisation of signal resolution (typically up-scaling). Accordingly, great care was taken to depth-match core, log and gas data. In general, there is evidence of leaking thermogenic and partly biodegraded gas from the reservoirs under investigation, while some microbial methane appears to be retained in the cap rock. Careful assessment of the maturity of the thermogenic gas charge suggests that in a given structure, maturities are similar throughout the sampled section of underseal, reservoir and top seal. Furthermore, compositional temperature stratification suggests a balance between influx of fresh gas and microbial metabolism rates, supporting the concept of a dynamic charge-leak scenario that is sustaining hydrocarbon fermenting microbial communities in the deep biosphere. It was found that microbial recycling of hydrocarbons at depth enables the identification of diffusive gas mixing pathways in the combined analysis of methane and ethane compositional and isotopic data. The proposed diffusion pattern supports the idea of a widely present coupling between both methanogenic and biodegrading microbial communities that exhibit strong carbon isotopic dis-balances at gas-water contacts (GWC) where nutrient supply is in favour of the biodegrading metabolism. Although the hypothesis of coupled diffusive/microbial gas overprints complies with (1) various literature reports that microbial attack on free gas phases is hindered by restricted physical access and (2) segregative isotope fractionation as a consequence of differences on methane and ethane diffusivity, it is conditional to the nature of gas mixing patterns along borehole trajectories in the context of lithology and pore fluid saturations. Undoubtedly, the ubiquitous presence of microbial gas has consequences for vertical net leakage. As classic empirical wireline models for hydrocarbon saturation (i.e. free gas phase volumetrics) are not suited for clay-dominated cap rock sections, an alternative approach presented in this study is based on total gas (TG) modelling from nuclear logs and its solubility in the formation of brine. The calibrated saturation model is scale-independent and implies that free gas occurs on the most of the clay-dominated non-reservoir sections. However, model resolution is not sufficient to capture the suspected filamentary network of free gas phase within the mudrock pore space that enables relatively rapid leakage via Darcy flow. In an unique attempt to validate manual and thereby subjective lithofacies allocations to core images a subset of rock sample properties such as grain size fractions and porosity were successfully modelled using quantitative core image properties. However, model validity appears to be restricted to clay-rich lithofacies due to both an absence of calibration data for sands and occurrence of abnormally dark sandstone units. Further, an artificial neural network (ANN) was trained to propagate the calibrated core fancies along the entire wireline logged borehole section to set the lithological context for a detailed fluid flow analysis. Reproducibility of input (core) facies by output (wireline) facies is similar to the reproducibility by fellow geoscientists but could not be significantly improved to 60-80% of reliability by reduction of facies types. The study shows that a combination of geochemical data with lithological and petro-physical information generates detailed insights into rates, mechanisms, and pathways of two phase flow through the deep biosphere of gas-charged basins. Vertical, geologically rapid flow through mud-rich sequences is a viable migration route for gas if the influence of cap rock bypass systems (permeable faults, sandstone intrusions, mud volcanoes etc.) is restricted. It was found that an adequate quantification of both thermogenic gas fraction and diffusive gas mixing fingerprints is crucial to identity stratigraphic intervals that are not dominated by advective leakage through the pore space and are consequently bypassed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes—an international multicentre retrospective study

Background Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to noncancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population

Poly-β-hydroxybutyrate administration during early life: effects on performance, immunity and microbial community of European sea bass yolk-sac larvae

The reliable production of marine fish larvae is one of the major bottlenecks in aquaculture due to high mortalities mainly caused by infectious diseases. To evaluate if the compound poly-β-hydroxybutyrate (PHB) might be a suitable immunoprophylactic measure in fish larviculture, its capacity to improve immunity and performance in European sea bass (Dicentrarchus labrax) yolk-sac larvae was explored. PHB was applied from mouth opening onwards to stimulate the developing larval immune system at the earliest possible point in time. Larval survival, growth, microbiota composition, gene expression profiles and disease resistance were assessed. PHB administration improved larval survival and, furthermore, altered the larva-associated microbiota composition. The bacterial challenge test using pathogenic Vibrio anguillarum revealed that the larval disease resistance was not influenced by PHB. The expression profiles of 26 genes involved e.g. in the immune response showed that PHB affected the expression of the antimicrobial peptides ferritin (fer) and dicentracin (dic), however, the response to PHB was inconsistent and weaker than previously demonstrated for sea bass post-larvae. Hence, the present study highlights the need for more research focusing on the immunostimulation of different early developmental stages for gaining a more comprehensive picture and advancing a sustainable production of high quality fry

Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies

The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state‐of‐the‐art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful "tips and tricks" along the analytical workflow