Mucositis is an inflammatory condition of the gut, caused by an adverse effect of chemotherapy drugs, such as 5-fluorouracil (5-FU). In an attempt to develop alternative treatments for the disease, ...several research groups have proposed the use of probiotics, in particular, Lactic Acid Bacteria (LAB). In this context, the use of recombinant LAB, for delivering anti-inflammatory compounds has also been explored. In previous work, we demonstrated that either Lactococcus lactis NZ9000 or a recombinant strain expressing an antimicrobial peptide involved in human gut homeostasis, the Pancreatitis-associated Protein (PAP), could ameliorate 5-FU-induced mucositis in mice. However, the impact of these strains on the gut microbiota still needs to be elucidated. Therefore, in the present study, we aimed to characterize the effects of both Lactococci strains in the gut microbiome of mice through a 16 S rRNA gene sequencing metagenomic approach. Our data show 5-FU caused a significant decrease in protective bacteria and increase of several bacteria associated with pro-inflammatory traits. The Lactococci strains were shown to reduce several potential opportunistic microbes, while PAP delivery was able to suppress the growth of Enterobacteriaceae during inflammation. We conclude the strain secreting antimicrobial PAP was more effective in the control of 5-FU-dysbiosis.
Chronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin ...(IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE + PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-кB, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-β, tumor necrosis factor-α, neutrophils, IL-1β, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.
•We employ benchmark tests to analyze the inherent uncertainties of three flood routing models.•We test multiple model configurations against input data generated via Monte Carlo simulation.•The ...model outputs deviate from normality and exhibit negative skewness and fat tails.•Models are mainly sensitive against the inflow discharge and the channel friction.•Two real-world studies under limited data confirm the outcomes of benchmark analyses.
One-dimensional and quasi-two-dimensional hydraulic freeware models (HEC-RAS, LISFLOOD-FP and FLO-2d) are widely used for flood inundation mapping. These models are tested on a benchmark test with a mixed rectangular–triangular channel cross section. Using a Monte-Carlo approach, we employ extended sensitivity analysis by simultaneously varying the input discharge, longitudinal and lateral gradients and roughness coefficients, as well as the grid cell size. Based on statistical analysis of three output variables of interest, i.e. water depths at the inflow and outflow locations and total flood volume, we investigate the uncertainty enclosed in different model configurations and flow conditions, without the influence of errors and other assumptions on topography, channel geometry and boundary conditions. Moreover, we estimate the uncertainty associated to each input variable and we compare it to the overall one. The outcomes of the benchmark analysis are further highlighted by applying the three models to real-world flood propagation problems, in the context of two challenging case studies in Greece.
The presence of del(5q), either as the sole karyotypic abnormality or as part of a more complex karyotype, has distinct clinical implications for myelodysplastic syndromes (MDS) and acute myeloid ...leukemia. The 5q- syndrome, a subtype of low-risk MDS, is characterized by an isolated 5q deletion and <5% blasts in the bone marrow and can serve as a useful model for studying the role of 5q deletions in the pathogenesis and prognosis of myeloid malignancies. Recent clinical results with lenalidomide, an oral immunomodulatory drug, have shown durable erythroid responses, including transfusion independence and complete cytogenetic remissions in patients with del(5q) MDS with or without additional chromosomal abnormalities. These results indicate that lenalidomide can overcome the pathogenic effect of 5q deletion in MDS and restore bone marrow balance. The data provide important new insights into the pathobiology of 5q chromosomal deletions in myeloid malignancies.
•Framework for optimising sustainability, resilience, and cost (SRC) metrics is described and applied.•Traditional and low-carbon restoration strategies are compared on a bridge.•Fragility and ...restoration models are employed toward actionable SRC metrics.•Practical starting point for evaluating climate projections in adaptation strategies.
Climate change exacerbates natural hazards and continuously challenges the performance of critical infrastructure. Thus, climate resilience and sustainable adaptation of infrastructure are of paramount importance. This paper puts forward a novel framework and metrics for optimising sustainability (Greenhouse Gas emissions - GHG), climate resilience (restoration time), and cost. The framework aims to facilitate decision-making by operators and stakeholders and communicate actionable trade-offs between these principles. It describes approaches for quantifying ex-ante adaptation and ex-post recovery from the lenses of sustainability and resilience using relevant metrics. This paper concludes with an application of the framework on a bridge, where normalised metrics are integrated into one unique index (ISRC), which can be used in the recovery prioritisation for portfolios of similar assets. The optimisation program includes a bridge recovery, while reducing GHG emissions. The impact of climate change on the sustainability and resilience indexes is examined and the results show how the optimum solutions are adversely affected by different climate projections. In all scenarios examined, more sustainable solutions leading to reduced GHG emissions (tCO2e) are the optimum solutions when weighing resilience and cost. Based on the case study analysed in this paper, the low carbon restoration strategy resulted in up to 50% higher ISRC, which can justify investments for low GHG adaptation strategies in transport assets.
Lenalidomide leads to high rates of erythroid transfusion independence in low and intermediate-1 risk International Prognostic Scoring System (IPSS) del(5q) myelodysplastic syndromes (MDS), with a ...considerable number of patients achieving complete and partial cytogenetic remissions. The median duration of transfusion independence is 2 years, mainly at the expense of neutropenia and thrombocytopenia in the first courses of therapy. At present, the optimal initial treatment dose has been determined to be 10 mg administered orally daily for 21 out of 28 days. In general, the effects in non-del(5q) disease can be divided by 50%: non-del(5q) patients show 50% of erythroid response, 50% of duration of response, and 50% incidence of grade 3 and 4 neutropenia and thrombocytopenia compared to del(5q) patients. Recent data suggest that the risk of acute myeloid leukemia (AML) progression of del(5q) patients is dependent on their individual risk factors before treatment initiation, including World Health Organization (WHO) prognostic scoring system parameters and TP53 mutations. These data also indicate that lenalidomide per se is not leukemogenic. Length of treatment can be tailored according to response, and patients who relapse during treatment might restart after a period of drug holiday. This article will also discuss combination strategies with lenalidomide in higher risk disease.
This study presents U-Pb dating of detrital zircons from sandstones of the Araripe basin (NE Brazil) assisting in the reconstruction of the Mesozoic paleogeography. In particular, we focus in the ...seaway connection between the Proto-Atlantic ocean and this intracontinental basin in northwest Gondwana.The new U-Pb age spectra of detrital zircon grains from the pre-Jurassic and Mesozoic clastic sequences of the Araripe Basin, along with paleocurrent, stratigraphic and structural data, demonstrate a significant change in provenance during the Later Jurassic to mid-Cretaceous. Six distinct provenance patterns are identified in the sequences, which may reflect the rapid evolution of the paleogeographic scenarios during tectono-sedimentary history of the northwest Gondwana rift-related basins throughout the onset to the opening of the Atlantic Ocean. Here, we propose an alternative model for paleogeography of the northwest Gondwana. In the Later Jurassic, the main source of terrigenous clastics to the Araripe Basin was the Paleozoic-Triassic sedimentary rocks of the Parnaíba Basin, which formed a prominent barrier to separate the Araripe Basin from the Mesozoic units of the Parnaíba Basin. In the mid-Aptian, erosion led to the retraction of the Parnaíba Paleozoic sedimentary units to the west, as the Precambrian terranes from the Borborema Province, to the northwest, became the main source for the Araripe Basin. The rapid rifting evolution show that the Rio Salgado Belt, from NE region, became topographically depressed, potentially initiating a link between the Araripe and the Potiguar basins. During late-Aptian, the Araripe Basin probably connected to the Proto-Equatorial Atlantic Ocean from the northeast, through the Potiguar Basin and associated grabens on the north. The present paleogeographical reconstruction may explain the occurrence of warm water adapted Tethyan fauna in the Araripe Basin, more plausible than previous hypothesis of a connection to Proto-South Atlantic Ocean.
Over recent years, patient outcomes after colon cancer resection have not improved to the same degree as for rectal cancer. Japanese D3 resection and European complete mesocolic excision (CME) with ...central vascular ligation (CVL) are both based on sound oncologic principles. Expert surgeons using both techniques report impressive outcomes as compared with standard surgery. We aimed to independently compare the physical appearances and quality of specimens resected using both techniques in major institutions in Japan and Germany.
A series of resections for primary colon cancer from one European and two Japanese centers were independently assessed in terms of the plane of surgery, physical characteristics, and lymph node yields.
Mesocolic plane resection rates from both series were high; however, Japanese D3 specimens were significantly shorter (162 v 324 mm, P < .001), resulting in a smaller amount of mesentery (8,309 v 17,957 mm(2), P < .001) and nodal yield (median, 18 v 32, P < .001). The distance from the high vascular tie to the bowel wall (100 v 99 mm, P = .605) was equivalent.
Both techniques showed high mesocolic plane resection rates and long distances between the high tie and the bowel wall. The extended longitudinal resection after CME with CVL increased the nodal yield but did not increase the number of tumor involved nodes. Both series were oncologically superior to recently reported series from other countries and confirm the wide variation in colonic cancer surgery and the need for further standardization and optimization following the approach undertaken in improving rectal cancer outcomes.
The recognition of cytologic dysplasia in blood and bone marrow remains the cornerstone of myelodysplastic syndromes (MDS) diagnosis because it distinguishes MDS from clonal hematopoiesis of ...indeterminate potential or clonal cytopenia of undetermined significance. Expert morphologists achieve high concordance in the diagnosis of MDS if appropriate clinical information is provided. Because of the low prevalence of MDS, diagnostic approaches based solely on molecular diagnosis will likely be erroneous.
Corals live in close association with a diverse community of eukaryotes, bacteria, archaea and viruses that, together with the coral host, form the coral holobiont. Fungi are an important component ...of the coral holobiont; however, knowledge about their taxonomic diversity and the ecological functions these organisms play in reef corals is still scarce. In this study, we used metabarcoding to characterize the fungal community inhabiting the skeleton of eleven coral genera, as well as samples of crustose coralline algae, from Australia and Papua New Guinea. Most of the 24 distinct fungal genera identified were assigned to the phylum Ascomycota, followed by Basidiomycota.
Lulworthia
and
Lulwoana
(Ascomycota) were the most abundant and prevalent genera detected in our study. Besides these widely distributed genera, others never associated with corals or marine environments before, such as
Geranomyces
(Chytriomycota),
Flammulina
(Basidiomycota) and
Ophiosphaerella
(Ascomycota), were also detected. The predicted functional groups give insights into potential lifestyles and ecological functions of the fungal community in reef ecosystems. This study provides important observational data on a group of holobiont members that has received little attention.
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