Nitrogen concentrations in a small Mediterranean stream: 1. Nitrate 2. Ammonium

The importance of storm frequency as well as the groundwater and hyporheic inputs on nitrate (NO₃-N) and ammonium (NH₄-N) levels in stream water were studied in a small perennial Mediterranean catchment, Riera Major, in northeast Spain. NO₃-N concentrations ranged from 0.15 to 1.9 mg l^-1. Discharge explained 47% of the annual NO₃-N concentration variance, but this percentage increased to 97% when single floods were analysed. The rate of change in nitrate concentration with respect to flow, &#916;NO₃-N/&#916;Q, ranged widely from 0 to 20 &#956;g NO₃-N s l^-2. The &#916;NO₃-N/&#916;Q values fitted to a non linear model with respect to the storm flow magnitude (&#916;Q) (r²&#61;0.48, d.f.&#61;22, P<0.01). High values of &#916;NO₃-N/&#916;Q occurred at intermediate &#916;Q values, whereas low &#916;NO₃-N/&#916;Q values occurred during severe storms (&#916;Q > 400 l s^-1). N₃-N concentrations exhibit anticlockwise hysteresis patterns with changing flow and the patterns observed for autumnal and winter storms indicated that groundwater was the main N₃-N source for stream and hyporheic water. At baseflow, NO₃-N concentration in groundwater was higher (t&#61;4.75, d.f.&#61;29, P>0.001) and co-varied with concentrations in the stream (r&#61;0.91, d.f.&#61;28, P<0.001). In contrast, NO₃-N concentration in hyporheic water was identical to that in stream water. The role of the hyporheic zone as source or sink for ammonium was studied hyporheic was studied comparing its concentrations in stream and hyporheic zone before and after a major storm occurred in October 1994 that removed particulate organic matter stored in sediments. Results showed high ammonium concentrations (75&#177;28 s.d. &#956;g NH₄-N l^-1) before the storm flow in the hyporheic zone. After the storm, the ammonium concentration in the hyporheic dropped by 80% (13.6&#177;8 &#956;g N₄-N l^-1) and approached to the level found in stream water (11&#177;8 &#956;g NH₄-N l^-1) indicating that indisturbed hyporheic sediments act as a source for ammonium. After the storm, the ammonium concentrations in the stream, hyporheic and groundwater zones were very similar suggesting that stream ammonium concentrations are sustained mainly by input from groundwater. The present study provides evidence that storm flow magnitude is an important source of variability of nitrate concentration and fluxes in Mediterranean streams subjected to an irregular precipitation regime with prolonged dry periods

Modelling the inorganic nitrogen behaviour in a small Mediterranean forested catchment, Fuirosos (Catalonia)

The aim of this work was to couple a nitrogen (N) sub-model to already existent hydrological lumped (LU4-N) and semi-distributed (LU4-R-N and SD4-R-N) conceptual models, to improve our understanding of the factors and processes controlling nitrogen cycling and losses in Mediterranean catchments. The N model adopted provides a simplified conceptualization of the soil nitrogen cycle considering mineralization, nitrification, immobilization, denitrification, plant uptake, and ammonium adsorption/desorption. It also includes nitrification and denitrification in the shallow perched aquifer. We included a soil moisture threshold for all the considered soil biological processes. The results suggested that all the nitrogen processes were highly influenced by the rain episodes and that soil microbial processes occurred in pulses stimulated by soil moisture increasing after rain. Our simulation highlighted the riparian zone as a possible source of nitrate, especially after the summer drought period, but it can also act as an important sink of nitrate due to denitrification, in particular during the wettest period of the year. The riparian zone was a key element to simulate the catchment nitrate behaviour. The lumped LU4-N model (which does not include the riparian zone) could not be validated, while both the semi-distributed LU4-R-N and SD4-R-N model (which include the riparian zone) gave satisfactory results for the calibration process and acceptable results for the temporal validation process

Calibration of the INCA model in a Mediterranean forested catchment: the effect of hydrological inter-annual variability in an intermittent stream

International audienceMediterranean regions are characterised by a stream hydrology with a marked seasonal pattern and high inter-annual variability. Accordingly, soil N processes and leaching of solutes in Mediterranean regions also show a marked seasonality, occurring in pulses as soils re-wet following rain. The Integrated Nitrogen Catchment model (INCA) was applied to Fuirosos, a Mediterranean catchment located in NE Spain using hydrological data and streamwater nitrate and ammonium concentrations collected from 1999 to 2002. This study tested the model under Mediterranean climate conditions and assessed the effect of the high inter-annual variability on the ability of INCA to simulate discharge and N fluxes. The model was calibrated for the whole three-year period and the n coefficients of determinion (r2) between simulated and observed data were 0.54 and 0.1 for discharge and nitrate temporal dynamics, respectively. Ammonium dynamics were simulated poorly and the linear regression between observed and simulated data was not significant statistically. To assess the effect of inter-annual variability on INCA simulations, the calibration process was run separately for two contrasting hydrological years: a dry year with a total rainfall of 525 mm and a wet year with a total of 871 mm. The coefficients of determination for the correlation between observed and simulated discharge for these two periods were 0.67 (p2 = 0.13 p2 = 0.56 p Keywords: environmental modelling, intermittent stream, Mediterranean climate, Fuirosos, hydrology, nitrat

Co-design, co-learning, and co-production of an app for pancreatic cancer patients—the “Pancreas Plus” study protocol

Background: Pancreatic cancer is a malignant and complex tumor that often leads to an adverse prognosis. Patients need to face a challenging treatment path, which involves highly-specialized multidisciplinary professionals. The complexity of the disease requires the development of dedicated tools to support patients in their care journey. Co-production stands as a valuable strategy in oncological care to engage patients in understanding their care journey and behaving accordingly to get the best possible clinical outcome. Methods: The non-profit association Unipancreas, active in promoting the latest advances in pancreatic cancer care and in supporting pancreatic cancer patients, has partnered with a multidisciplinary group of professionals to conceive the brand new program “Pancreas Plus” to employ a co-design, co-learning, and co-production path to design an app devoted to pancreatic cancer patients to assist them during their treatment and follow-up journey. The app, which is the outcome of a multi-stakeholder engagement project, offers health information and medical advice specifically tailored on the pancreatic cancer disease. The article reports the research protocol, which may be replicated for the design of other e-health tools focusing on different conditions. Discussion: The study’s output will be an app that sees the pancreatic cancer patient as the main beneficiary but which can gather and address the interests and needs of all meaningful stakeholders, including clinicians, researchers, healthcare and educational institutions, and

Intermolecular disulfide bond influences unphosphorylated STAT3 dimerization and function

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated by the phosphorylation of tyrosine 705 in response to many cytokines and growth factors. Recently, the roles for unphosphorylated STAT3 (U-STAT3) have been described in response to cytokine stimulation, in cancers, and in the maintenance of heterochromatin stability. It has been reported that U-STAT3 dimerizes, shuttles between the cytoplasm and nucleus, and binds to DNA, thereby driving genes transcription. Although many reports describe the active role of U-STAT3 in oncogenesis in addition to phosphorylated STAT3, the U-STAT3 functional pathway remains elusive.In this report, we describe the molecular mechanism of U-STAT3 dimerization, and we identify the presence of two intermolecular disulfide bridges between Cys367 and Cys542 and Cys418 and Cys426, respectively. Recently, we reported that the same cysteines contribute to the redox regulation of STAT3 signaling pathway both in vitro and in vivo The presence of these disulfides is here demonstrated to largely contribute to the structure and the stability of U-STAT3 dimer as the dimeric form rapidly dissociates upon reduction in the S-S bonds. In particular, the Cys367-Cys542 disulfide bridge is shown to be critical for U-STAT3 DNA-binding activity. Mutation of the two Cys residues completely abolishes the DNA-binding capability of U-STAT3. Spectroscopic investigations confirm that the noncovalent interactions are sufficient for proper folding and dimer formation, but that the interchain disulfide bonds are crucial to preserve the functional dimer. Finally, we propose a reaction scheme of U-STAT3 dimerization with a first common step followed by stabilization through the formation of interchain disulfide bond

Pinus mugo essential oil impairs STAT3 activation through oxidative stress and induces apoptosis in prostate cancer cells

Essential oils (EOs) and their components have been reported to possess anticancer properties and to increase the sensitivity of cancer cells to chemotherapy. The aim of this work was to select EOs able to downregulate STAT3 signaling using Western blot and RT-PCR analyses. The molecular mechanism of anti-STAT3 activity was evaluated through spectrophotometric and fluorometric analyses, and the biological effect of STAT3 inhibition was analyzed by flow cytometry and wound healing assay. Herein, Pinus mugo EO (PMEO) is identified as an inhibitor of constitutive STAT3 phosphorylation in human prostate cancer cells, DU145. The down-modulation of the STAT3 signaling cascade decreased the expression of anti-proliferative as well as anti-apoptotic genes and proteins, leading to the inhibition of cell migration and apoptotic cell death. PMEO treatment induced a rapid drop in glutathione (GSH) levels and an increase in reactive oxygen species (ROS) concentration, resulting in mild oxidative stress. Pretreatment of cells with N-acetyl-cysteine (NAC), a cell-permeable ROS scavenger, reverted the inhibitory action of PMEO on STAT3 phosphorylation. Moreover, combination therapy revealed that PMEO treatment displayed synergism with cisplatin in inducing the cytotoxic effect. Overall, our data highlight the importance of STAT3 signaling in PMEO cytotoxic activity, as well as the possibility of developing adjuvant therapy or sensitizing cancer cells to conventional chemotherapy

Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

Background: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons’ preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI

FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer-related death. In cases with metastasis, the combination of 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine-based chemotherapy regimens are considered the standard of care. However, the optimal sequence of these regimens is unclear. Methods: This retrospective study initially evaluated 186 patients with locally advanced/metastatic pancreatic cancer at three Italian institutions between February 2013 and October 2019. All patients had progressed after receiving gemcitabine-based first-line chemotherapy and were subsequently offered second-line FOLFIRINOX, FOLFOX-6, or FOLFIRI treatment. This study evaluated progression-free survival (PFS), overall survival from the start of second-line treatment (OS2), overall survival from the start of first-line treatment (OS1), and safety outcomes. Results: A total of 77 patients received ⩾4 cycles of second-line chemotherapy and were considered eligible: 15 patients received FOLFIRINOX, 32 patients received FOLFOX-6, and 30 patients received FOLFIRI. The FOLFIRINOX group had median PFS of 26.29 weeks and median OS2 of 47.86 weeks, while the FOLFIRI group had median PFS of 10.57 weeks and median OS2 of 25.00 weeks (p = 0.038). No significant differences were observed between the FOLFIRINOX and FOLFOX-6 groups in terms of PFS (26.29 weeks versus 23.07 weeks) or OS2 (47.86 weeks versus 42.00 weeks). The most common grade 3–4 toxicities were anemia, neutropenia, and thrombocytopenia, which occurred more frequently in the FOLFIRINOX and FOLFOX-6 groups. Conclusion: Relative to the FOLFIRI regimen, the FOLFIRINOX regimen had a favorable toxicity profile and better survival outcomes. No significant differences were observed relative to the FOLFOX-6 regimen