Lifetime prediction of encapsulated CdSexS1-x quantum platelets for color conversion in high luminance LED microdisplays.

The LED technology is seen today as the most promising approach to manufacture high luminance color microdisplays for augmented reality application. So far, it mostly involves blue micro-LED technology and quantum dots-based layers for green and red color generation by light down-conversion. Despite significant progress, the viability of this technology still raises many questions. Among them, the stability of the color conversion layer under nominal display operating conditions is still an issue which has not been thoroughly addressed yet. This paper provides experimental data on the aging behavior of CdSexS1-x quantum platelets (QP) for blue-to-red conversion, under a wide range of blue irradiation power. A modeling of the photoluminescence (PL) decrease versus aging time is proposed, that enables to reliably predict the lifetime of a color LED microdisplay in real operating conditions. At room temperature, the alumina encapsulated CdSexS1-x QPs exhibit a lifetime (t70) of 35,000 h under operating conditions representative of a microdisplay emitting 100,000 nits white light, in video mode. With an average daily use of 3 hours, it would represent for a microdisplay more than 30 years. In addition, the study highlights that display heating induces a lifetime decrease related to a thermally activated enhancement of the annihilation rate of PL emission centers. As a result, a display operated at 100,000 nits and 45°C would see its lifetime t70 reduced by a factor 4 (∼8 years), which remains acceptable for most micro-display applications.

Experimental and theoretical investigation of 2D nanoplatelet-based conversion layers for color LED microdisplays.

In the field of augmented reality, there is a need for very bright color microdisplays to meet the user specifications. Today, one of the most promising technology to manufacture such displays involves a blue micro-LED technology and quantum dots-based color conversion layers. Despite recent progress, the external power conversion efficiencies (EPCE) of these layers remain under ∼25%, below the needs (>40%) to reach a white luminance of 100,000 cd/m2. In this work, we have synthesized CdSexS1-x nanoplatelet-based conversion layers for red and green conversion, and measured their absorption properties and EPCE performances with respect to layer thickness. On this basis, a model was developed that reliably predicts the layer EPCE while using only few input data, namely the layer absorption coefficients and the photoluminescence quantum yield (PLQY) of color photoresist. It brings a new insight into the conversion process at play at a micro-LED level and provides a simple method for extensive optimization of conversion materials. Finally, this study highlights the outstanding red conversion efficiency of photoresist layers made of core-double shell CdSexS1-x nanoplatelets with 31% EPCE (45% external PLQY) for 8 µm-thick conversion layer.

Corrigendum to "Activation of Melanocortin Receptors MC1 and MC5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy".

[This corrects the article DOI: 10.1155/2016/7368389.].

Role of comorbidities on therapeutic persistence of biological agents in rheumatoid arthritis: results from the RECord-linkage On Rheumatic Disease study on administrative healthcare databases.

Objectives: This study aimed to evaluate the impact of different comorbidities on thereflecting its safety profile persistence of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), taking advantage of a retrospective analysis of administrative healthcare databases (AHDs).Method: A retrospective observational study was conducted on AHDs of the Lombardy region, Italy (2004-2013). Among RA patients treated with bDMARDs, drug survival was estimated using Cox proportional hazard models [hazard ratio (HR), 95% confidence interval (CI)], crude and adjusted for prespecified confounders (gender, age, disease duration, concomitant use of non-steroidal anti-inflammatory drugs, glucocorticoids, conventional DMARDs, specific bDMARDs), in first-line and subsequent lines of treatment. The role of comorbidities in administration of specific bDMARDs was analysed through multinomial logistic models.Results: The study included 4657 RA patients. In the first-line treatment strategy, the Charlson Comorbidity Index (CCI) (RA excluded) was significantly associated with an increased rate of bDMARD failure (CCI = 1: HR 1.28, 95% CI 1.13-1.46; CCI ≥ 2: HR 1.26, 95% CI 1.03-1.53). Among selected comorbidities, chronic obstructive pulmonary disease (HR 1.38, 95% CI 1.01-1.91), diabetes (HR 1.18, 95% CI 1.01-1.37), and previous-year bacterial infections (HR 1.18, 95% CI 1.07-1.30) were slightly associated with risk of bDMARD failure, while acute myocardial infarction (HR 1.30, 95% CI 0.97-1.75), mild liver disease (HR 1.21, 95% CI 0.91-1.60), and solid tumours (HR 1.19, 95% CI 0.93-1.53) were not. In the following treatment lines, neoplasms were associated with reduced risk of failure (HR 0.64, 95% CI 0.41-0.99). Multiple comorbidities were associated with first-line abatacept and rituximab administration.Conclusions: Comorbidities affect treatment decisions in RA and influence bDMARD failure, and should be considered when analysing the persistence of biological therapy.

Public health and clinical approach to proactive management of frailty in multidimensional arena.

Background: Demographic changes have forced communities and people themselves to reshape ageing concepts and approaches and try to develop actions towards active and healthy ageing. In this context, the European Commission launched different private-public partnerships to develop new solutions and answers on questions related to this topic. The European Innovation Partnership on Active and Healthy Ageing, including topic related action groups as well reference sites committed towards a common action to facilitate active and healthy ageing, has contributed key elements for interventions, scaled up best practices and evaluated impact of their action to drive innovation across many regions in Europe over the past years. Methods: This paper describes action taken by A3 action group in the European Innovation Partnership on Active and Healthy Ageing. This paper gives an overview of how the partnership combined the view on frailty coming from public health as well as the clinical management. Results: Within different European regions, to tackle frailty, EIPonAHA partners have conceptualized functional decline and frailty, making use of good practice models working well on community programs. The A3 Group of EIPonAHA has worked alongside a process of innovation, targeting all ageing citizens with the clear goal of involving communities in the preventive approach. Conclusion: Engagement needs of older people with a focus on functionally rather than disease management as primary objective is considered as an overarching concept, also embracing adherence, compliance, empowerment, health literacy, shared decision-making, and activation. Furthermore, training of staff working with ageing people across all sectors needs to be implemented and evaluated in future studies.

Eculizumab treatment in patients with COVID-19: preliminary results from real life ASL Napoli 2 Nord experience.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)-related pneumonia, referred to as COVID-19 (Coronavirus Disease 19), is a public health emergency as it carries high morbidity, mortality, and has no approved specific pharmacological treatments. In this case series, we aimed to report preliminary data obtained with anti-complement C5 therapy with eculizumab in COVID-19 patients admitted to intensive care unit (ICU) of ASL Napoli 2 Nord. PATIENTS AND METHODS: This is a case series of patients with a confirmed diagnosis of SARS-CoV2 infection and severe pneumonia or ARDS who were treated with up to 4 infusions of eculizumab as an off-label agent. Patients were also treated with anticoagulant therapy with Enoxaparin 4000 IU/day via subcutaneous injection, antiviral therapy with Lopinavir 800 mg/day + Ritonavir 200 mg/day, hydroxychloroquine 400 mg/day, ceftriaxone 2 g/day IV, vitamine C 6 g/day for 4 days, and were on Non-Invasive Ventilation (NIV). RESULTS: We treated four COVID-19 patients admitted to the intensive care unit because of severe pneumonia or ARDS. All patients successfully recovered after treatment with eculizumab. Eculizumab induced a drop in inflammatory markers. Mean C Reactive Protein levels dropped from 14.6 mg/dl to 3.5 mg/dl and the mean duration of the disease was 12.8 days. CONCLUSIONS: Eculizumab has the potential to be a key player in treatment of severe cases of COVID-19. Our results support eculizumab use as an off-label treatment of COVID-19, pending confirmation from the ongoing SOLID-C19 trial.

Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases.

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.

Nordic walking increases circulating VEGF more than traditional walking training in postmenopause.

OBJECTIVES: Nordic walking (NW) is widely practiced by postmenopausal women. Its effects are peculiar owing to the involvement of more muscle groups than in traditional walking training (WT). Since mechanical load promotes secretion of vascular endothelial growth factor (VEGF) from both skeletal muscle and muscle endothelium, the aim of the study was to compare the effect of NW and WT on VEGF levels. METHOD: Thirty postmenopausal women were randomly assigned to NW or WT. Both groups trained 40-50 min/day, three times per week, at a mean intensity of 12 on a 15-category scale of the ratings of perceived exertion. Since VEGF is also released from adipocytes, anthropometric parameters were assessed. RESULTS: NW increased circulating VEGF more than WT (p = 0.041). Furthermore, both study groups exhibited an average decrease in weight (p = 0.023), body mass index (p = 0.024), hip circumference (p = 0.001), and arm fat index, although WT participants had higher values for this index at baseline (p < 0.001) and thus exhibited a greater net decrease compared with the NW participants (p < 0.011). CONCLUSIONS: These data imply that NW increases the level of circulating VEGF more than does traditional walking when the intensity of training is equivalent.

Participation in clinical trials improves outcomes in women's health: a systematic review and meta-analysis.

BACKGROUND: Previous reviews examining the effect of participation in trials on outcomes have not consistently shown benefit. Obstetrics and gynaecology is a unique disease area posing challenges for both researchers and patients. OBJECTIVES: To determine whether participation in randomised controlled trials (RCTs), compared with non-participation, has a beneficial effect on women's health. SEARCH STRATEGY: Medline, Embase, the Cochrane Library, and PsycInfo were searched up to December 2015. SELECTION CRITERIA: We selected studies that reported the same clinical outcomes for participants in a women's health RCT and a comparable non-participant cohort. DATA COLLECTION AND ANALYSIS: Data were extracted on quality, characteristics and study results. Outcomes were compared using logistic regression. MAIN RESULTS: There were 21 relevant studies (20 160 women, 4759 outcome events). Trial participants, compared with non-participants, had 25% better odds of improved outcomes on average (OR 0.75; 95% CI 0.64-0.87; I2  = 64.3%). The beneficial effect of participating in a trial was larger in comparisons where: RCTs were of high quality (OR 0.62; 95% CI 0.50-0.76) versus low (OR 0.92; 95% CI 0.74-1.16); and RCT intervention was not available to non-participants (OR 0.57; 95% CI 0.47-0.69) versus when it was (OR 1.13; 95% CI 0.89-1.44). The effect of trial participation was not influenced by effect size within the RCT (P = 0.48), whether funding was received or not (P = 0.13), whether non-participants received any treatment or not (P = 0.49), and the quality of the comparison of RCT participants with non-participants (P = 0.88). CONCLUSIONS: Women participating in RCTs on average experienced better outcomes compared with those outside trials. TWEETABLE ABSTRACT: Participants in obstetric and gynaecology RCTs experience better outcomes compared with non-participants.

Thermal degradation of driftwood: Determination of the concentration of sodium, calcium, magnesium, chlorine and sulfur containing compounds.

The annual production of driftwood in Italy has been estimated to be more than 60,000 tonnes. This wood can be used as an energy source. Particular attention should be paid to its content of alkali and alkaline earth metals, sulfur and chlorine. Few works are available in the literature on this topic. For this reason, the authors propose experimental tests of combustion, gasification and pyrolysis, to evaluate the fate of alkali and alkaline earth metals, sulfur and chlorine in the solid residues and compare the three thermal degradation technologies. The results show a release of alkaline earth metals of about 45% of the initial quantity for gasification and a release of 55% of the initial quantity for combustion (while pyrolysis at 600°C has a very low release). The release of sodium is about 65% for gasification and 80% for combustion. It can be seen that the release of sodium is higher than that of alkaline earth metals; this is due to the divalency of the last ones. Dealing with the release of major elements (chlorine, sulfur and AAEMs) the tests have shown that pyrolysis process is a low emitting technology.

Activation of Melanocortin Receptors MC 1 and MC 5 Attenuates Retinal Damage in Experimental Diabetic Retinopathy.

We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12-16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 µL) of the selective MC1 small molecule agonist BMS-470539 (33 µmol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1α, IL-1ß, IL-6, MIP-1α, MIP-2α, MIP-3α, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment.

Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure.

This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 µM, 0.05 µM, and 0.1 µM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 ± 12 ms and 110 ± 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D-glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 µM, 0.05 µM, and 0.1 µM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 µM and by 32% for BF-5m 0.1 µM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 µM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP.

Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey.

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.

Vitamin a decreases after a maximal incremental stress test in non-professional male runners with low aerobic performance.

The data on the effects of aerobic training on plasma antioxidant vitamins are conflicting. Additionally, most studies focus on the oxidative profiles of professional athletes, but limited information is available for amateur athlete populations. The aim of this study was to evaluate the effects of high-intensity exercise on antioxidant vitamins in non-professional runners with varying levels of aerobic power. Eighty-one male runners underwent an incremental test to exhaustion. The study population was then divided into the following tertiles according to VO2max: Group L (LowVO2max, less than 44.2 mLkg-1min-1), Group M (MediumVO2max, 44.2-49.7 mLkg-1min-1) and Group H (HighVO2max, >49.7). Comparative analyses were performed between Groups L and H. The total antioxidant capacity (TAC), Vitamin (Vit) E, Vitamin A, ß-carotene, lycopene and thiobarbituric acid-reactive substances (TBARS) were determined before and 60 min after exercise testing. After the stress test, Vit A decreased and TBARS increased in Group L, whereas no changes in the vitamin concentrations, TAC induction and TBARS reduction were observed in group H. In individuals with low VO2max, an incremental test determined lipid-peroxidation and Vitamin A consumption, whereas H Group increases TAC that buffer TBARS production.

Daily Oxygen/O3 Treatment Reduces Muscular Fatigue and Improves Cardiac Performance in Rats Subjected to Prolonged High Intensity Physical Exercise.

Rats receiving daily intraperitoneal administration of O2 and running on a treadmill covered an average distance of 482.8 ± 21.8 m/week as calculated during 5-week observation. This distance was increased in rats receiving daily intraperitoneal administration of an oxygen/O3 mixture at a dose of 100; 150; and 300 µg/kg with the maximum increase being +34.5% at 300 µg/kg and still present after stopping the administration of oxygen/O3. Oxygen/O3 decreased the mean arterial blood pressure (-13%), the heart rate (-6%), the gastrocnemius and cardiac hypertrophy, and fibrosis and reduced by 49% the left ventricular mass and relative wall thickness measurements. Systolic and diastolic functions were improved in exercised oxygen/O3 rats compared to O2 rats. Oxygen/O3 treatment led to higher MPI index starting from the dose of 150 µg/kg (p < 0.05) and more effective (+14%) at a dose of 300 µg/kg oxygen/O3. Oxygen/O3 dose-dependently increased the expression of the antioxidant enzymes Mn-SOD and GPx1 and of eNOS compared to the exercised O2 rats. The same doses resulted in decrease of LDH levels, CPK, TnI, and nitrotyrosine concentration in the heart and gastrocnemius tissues, arguing a beneficial effect of the ozone molecule against the fatigue induced by a prolonged high intensity exercise.

Interplay between Intravitreal RvD1 and Local Endogenous Sirtuin-1 in the Protection from Endotoxin-Induced Uveitis in Rats.

Rat endotoxin-induced uveitis (EIU) is a well-established model of human uveitis. In this model, intravitreal injection of resolvin D1 (RvD1, 10-100-1000 ng/kg) 1 hour after subcutaneous treatment of Sprague-Dawley rats with lipopolysaccharide (LPS, 200 µg/rat) significantly prevented the development of uveitis into the eye. RvD1 dose-dependently increased the expression of sirtuin-1 (SIRT1) within the eye, while it decreased the expression of acetyl-p53 and acetyl-FOXO1. These effects were accompanied by local downregulation of some microRNAs related to the expression and activity of SIRT1. These were miR-195-5p, miR-200a-3p, miR-34a-5p, and miR-145-5p. An increase of manganese superoxide dismutase and decrease of caspase 3 were evident after RvD1 treatment. In another set of experiments, the protective effects of RvD1 (1000 ng/kg) were partly abolished by the pretreatment of the rats with EX527 (10 mg/kg/day, i.p.), a specific inhibitor of SIRT1 activity, for 7 days prior to the induction of EIU in rats. Similarly, the effects of RvD1 (1000 ng/kg) on the SIRT1 protein expression were abolished by Boc2, N-t-butoxycarbonyl-PLPLP, a specific formyl-peptide receptor type 2/lipoxin A receptor antagonist. Therefore, an interplay of the SIRT1 activity on the RvD1 mediated resolution of EIU is argued.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest.

BACKGROUND: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line trials of chemotherapy ± anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC). These associations and the predictive accuracy of response measurements for survival parameters were investigated in the phase III TRIBE trial of FOLFOXIRI plus bevacizumab (bev) versus FOLFIRI plus bev. PATIENTS AND METHODS: A landmark approach was adopted to define the assessable population. The distribution of RECIST response rate, ETS and DoR was compared in the two arms. Associations between response measurements and progression-free survival (PFS), post-progression survival (PPS) and OS were tested by univariate and multivariate Cox models. Prediction performance of each factor was estimated by C-index. RESULTS: A significantly higher percentage of patients in the FOLFOXIRI plus bev arm achieved ETS ≥20%, when compared with the control arm (62.7% versus 51.9%, P = 0.025). Also the DoR was significantly higher in the triplet plus bev arm (43.4% versus 37.8%, P = 0.003). Both ETS and DoR were associated with PFS, PPS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. Both ETS and DoR were able to predict survival as accurately as RECIST response. CONCLUSION: FOLFOXIRI plus bev improves ETS and DoR when compared with FOLFIRI plus bev. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus bev. ETS is a promising and valuable end point for clinical trials' design deserving further investigation.

Protection from endotoxic uveitis by intravitreal Resolvin D1: involvement of lymphocytes, miRNAs, ubiquitin-proteasome, and M1/M2 macrophages.

This study investigated the protective effects of intravitreal Resolvin D1 (RvD1) against LPS-induced rat endotoxic uveitis (EIU). RvD1 was administered into the right eye at a single injection of 5 µL volume containing 10-100-1000 ng/kg RvD1 1 h post-LPS injection (200 µg, Salmonella minnesota) into thefootpad of Sprague-Dawley rats. 24 h later, the eye was enucleated and examined for clinical, biochemical, and immunohistochemical evaluations. RvD1 significantly and dose-dependently decreased the clinical score attributed to EIU, starting from the dose of 10 ng/kg and further decreased by 100 and 1000 ng/kg. These effects were accompanied by changes in four important determinants of the immune-inflammatory response within the eye: (i) the B and T lymphocytes, (ii) the miRNAs pattern, (iii) the ubiquitin-proteasome system (UPS), and (iv) the M1/M2 macrophage phenotype. LPS+RvD1 treated rats showed reduced presence of B and T lymphocytes and upregulation of miR-200c-3p, miR 203a-3p, miR 29b-3p, and miR 21-5p into the eye compared to the LPS alone. This was paralleled by decreases of the ubiquitin, 20S and 26S proteasome subunits, reduced presence of macrophage M1, and increased presence of macrophage M2 in the ocular tissues. Accordingly, the levels of the cytokine TNF-α, the chemokines MIP1-α and NF-κB were reduced.