Projections of UV radiation changes in the 21st century: impact of ozone recovery and cloud effects

Monthly averaged surface erythemal solar irradiance (UV-Ery) for local noon from 1960 to 2100 has been derived using radiative transfer calculations and projections of ozone, temperature and cloud change from 14 chemistry climate models (CCM), as part of the CCMVal-2 activity of SPARC. Our calculations show the influence of ozone depletion and recovery on erythemal irradiance. In addition, we investigate UV-Ery changes caused by climate change due to increasing greenhouse gas concentrations. The latter include effects of both stratospheric ozone and cloud changes. The derived estimates provide a global picture of the likely changes in erythemal irradiance during the 21st century. Uncertainties arise from the assumed scenarios, different parameterizations – particularly of cloud effects on UV-Ery – and the spread in the CCM projections. The calculations suggest that relative to 1980, annually mean UV-Ery in the 2090s will be on average 12% lower at high latitudes in both hemispheres, 3% lower at mid latitudes, and marginally higher (1 %) in the tropics. The largest reduction (16 %) is projected for Antarctica in October. Cloud effects are responsible for 2–3% of the reduction in UV-Ery at high latitudes, but they slightly moderate it at mid-latitudes (1 %). The year of return of erythemal irradiance to values of certain milestones (1965 and 1980) depends largely on the return of column ozone to the corresponding levels and is associated with large uncertainties mainly due to the spread of the model projections. The inclusion of cloud effects in the calculations has only a small effect of the return years. At mid and high latitudes, changes in clouds and stratospheric ozone transport by global circulation changes due to greenhouse gases will sustain the erythemal irradiance at levels below those in 1965, despite the removal of ozone depleting substances

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNF\u3b1 therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. Key messages: What are the new findings?Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy.The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody.Neutralization of eNAMPT ameliorates acute and chronic experimental colitis.Neutralization of eNAMPT limits the expression of IBD inflammatory signature.Neutralization of eNAMPT impairs immune cell infiltration in lamina propria

Lidocaine systemic infusion as an analgesic for perineal surgery in dogs : a postoperative study in comparison with fentanyl.

Aim of the study was to evaluate the postoperative analgesia obtained by systemic administration of lidocaine (LID) compared with those obtained by fentanyl (FEN) in 12 dogs undergoing perineal surgery. Systemic intra-operative lidocaine provides better postoperative analgesia than fentanyl after canine perineal surger

Effetto analgesico della somministrazione in infusione continua di lidocaina cloridrato nella chirurgia perineale del cane

Aim of the study was to evaluate the pre-emptive analgesic effect obtained by systemic continuous infusion of lidocaine (LID) in comparison with those obtained by systemic continuous infusion of fentanyl (FEN) during and after canine perineal surgery. Twelve male dogs undergoing perineal surgery were preanaesthetised with acepromazine (0.03 mg kg-1 IM), induced with propofol (4-6 mg kg-1 IV), and maintained with isoflurane in 100% oxygen. Fifteen minutes before perineal surgery, perineal herniorrhaphy or adenoma ( 8 3-5 cm) excission, all the animals were randomly assigned to receive a bolus followed by a systemic continuous infusion: lidocaine (1 mg kg-1 IV + 0.05 mg kg-1min-1 IV) in LID group(n=6) or fentanyl (5 mcg kg-1 IV + 0.05 mcg kg-1min-1 IV) in FEN group (n=6). Subjective pain score system, modified by Smith, was used for evaluation of pain at 0.5, 1, 2, 3, 4, 8, 16, and 24 hours after extubation (T0). All dogs showing pain score 65 9 (maximum=24) were treated with a rescue analgesic drug (buprenorphine 10 mcg kg-1 ) and excluded from further analysis. Physiological parameters during anaesthesia (HR, RR, NIBP, T\ub0, SpO2, ETCO2, ECG) and differences in pain scores in groups were analyzed using ANOVA, t test (P<0.05) and Wilcoxon\u2019s rank-sum test. Results: there was a significantly higher incidence of treatment failure in FEN group (83,3%) than in LID group (0%). After four hours, post-operative pain scores in LID group were significantly lower than those in FEN group. Monitored parameters during anaesthesia did not show significant differences between groups. Systemic intra-operative lidocaine provides better analgesia than fentanyl in canine post-perineal surgery, involving its potential role in pre-emptive and post-operative analgesia

Immune-tolerance to human iPS-derived neural progenitors xenografted into the immature cerebellum is overridden by species-specific differences in differentiation timing

We xeno-transplanted human neural precursor cells derived from induced pluripotent stem cells into the cerebellum and brainstem of mice and rats during prenatal development or the first postnatal week. The transplants survived and started to differentiate up to 1 month after birth when they were rejected by both species. Extended survival and differentiation of the same cells were obtained only when they were transplanted in NOD-SCID mice. Transplants of human neural precursor cells mixed with the same cells after partial in vitro differentiation or with a cellular extract obtained from adult rat cerebellum increased survival of the xeno-graft beyond one month. These findings are consistent with the hypothesis that the slower pace of differentiation of human neural precursors compared to that of rodents restricts induction of immune-tolerance to human antigens expressed before completion of maturation of the immune system. With further maturation the transplanted neural precursors expressed more mature antigens before the graft were rejected. Supplementation of the immature cells suspensions with more mature antigens may help to induce immune-tolerance for those antigens expressed only later by the engrafted cells

Explainable machine learning for early assessment of COVID-19 risk prediction in emergency departments

Between January and October of 2020, the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) virus has infected more than 34 million persons in a worldwide pandemic leading to overone million deaths worldwide (data from the Johns Hopkins University). Since the virus begun to spread,emergency departments were busy with COVID-19 patients for whom a quick decision regarding in- oroutpatient care was required. The virus can cause characteristic abnormalities in chest radiographs (CXR),but, due to the low sensitivity of CXR, additional variables and criteria are needed to accurately predictrisk. Here, we describe a computerized system primarily aimed at extracting the most relevant radiological,clinical, and laboratory variables for improving patient risk prediction, and secondarily at presenting anexplainable machine learning system, which may provide simple decision criteria to be used by cliniciansas a support for assessing patient risk. To achieve robust and reliable variable selection, Boruta and RandomForest (RF) are combined in a 10-fold cross-validation scheme to produce a variable importance estimate notbiased by the presence of surrogates. The most important variables are then selected to train a RF classifier,whose rules may be extracted, simplified, and pruned to finally build an associative tree, particularlyappealing for its simplicity. Results show that the radiological score automatically computed through aneural network is highly correlated with the score computed by radiologists, and that laboratory variables,together with the number of comorbidities, aid risk prediction. The prediction performance of our approachwas compared to that that of generalized linear models and shown to be effective and robust. The proposedmachine learning-based computational system can be easily deployed and used in emergency departmentsfor rapid and accurate risk prediction in COVID-19 patients

Antisense transcription at the TRPM2 locus as a novel prognostic marker and therapeutic target in prostate cancer

Overwhelming evidence indicates that cancer is a genetic disease caused by the accumulation of mutations in oncogenes and tumor suppressor genes. It is also increasingly apparent, however, that cancer depends not only on mutations in these coding genes but also on alterations in the large class of non-coding RNAs. Here, we report that one such long non-coding RNA, TRPM2-AS, an antisense transcript of TRPM2, which encodes an oxidative stress-activated ion channel, is overexpressed in prostate cancer (PCa). The high expression of TRPM2-AS and its related gene signature were found to be linked to poor clinical outcome, with the related gene signature working also independently of the patient's Gleason score. Mechanistically, TRPM2-AS knockdown led to PCa cell apoptosis, with a transcriptional profile that indicated an unbearable increase in cellular stress in the dying cells, which was coupled to cell cycle arrest, an increase in intracellular hydrogen peroxide and activation of the sense TRPM2 gene. Moreover, targets of existing drugs and treatments were found to be consistently associated with high TRPM2-AS levels in both targeted cells and patients, ultimately suggesting that the measurement of the expression levels of TRPM2-AS allows not only for the early identification of aggressive PCa tumors, but also identifies a subset of at-risk patients who would benefit from currently available, but mostly differently purposed, therapeutic agents

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis

Abstract: Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is increased in inflammatory bowel disease (IBD) patients, and its serum levels correlate with a worse prognosis. In the present manuscript, we show that eNAMPT serum levels are increased in IBD patients that fail to respond to anti-TNFα therapy (infliximab or adalimumab) and that its levels drop in patients that are responsive to these therapies, with values comparable with healthy subjects. Furthermore, eNAMPT administration in dinitrobenzene sulfonic acid (DNBS)-treated mice exacerbates the symptoms of colitis, suggesting a causative role of this protein in IBD. To determine the druggability of this cytokine, we developed a novel monoclonal antibody (C269) that neutralizes in vitro the cytokine-like action of eNAMPT and that reduces its serum levels in rodents. Of note, this newly generated antibody is able to significantly reduce acute and chronic colitis in both DNBS- and dextran sulfate sodium (DSS)-induced colitis. Importantly, C269 ameliorates the symptoms by reducing pro-inflammatory cytokines. Specifically, in the lamina propria, a reduced number of inflammatory monocytes, neutrophils, Th1, and cytotoxic T lymphocytes are found upon C269 treatment. Our data demonstrate that eNAMPT participates in IBD and, more importantly, that eNAMPT-neutralizing antibodies are endowed with a therapeutic potential in IBD. Key messages: What are the new findings?Higher serum eNAMPT levels in IBD patients might decrease response to anti-TNF therapy.The cytokine-like activity of eNAMPT may be neutralized with a monoclonal antibody.Neutralization of eNAMPT ameliorates acute and chronic experimental colitis.Neutralization of eNAMPT limits the expression of IBD inflammatory signature.Neutralization of eNAMPT impairs immune cell infiltration in lamina propria