Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

AIMS: Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca2+ transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. MAIN METHODS: PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca2+-ATPase pump inhibitors. The role of Na+/Ca2+ exchanger was examined in experiments performed in zero Na+ medium. NO release and intracellular Ca2+ were measured through specific probes. KEY FINDINGS: In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca2+]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca2+ mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na+/Ca2+ exchanger and Ca2+-ATPase pump in restoring Ca2+ was found. SIGNIFICANCE: Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca2+ transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved

Some observations on the relationship of manifest and hidden esca to rainfall

This paper reports observations on the relationship between the yearly incidence of manifest esca (i.e. diseased plants which show foliar symptoms), hidden esca (that which remains asymptomatic throughout a growing season) and rainfall. Data from three vineyards (two in Tuscany and one in Emilia-Romagna, Italy) showed that rainfall in May-July or only in July was inversely related with hidden esca. For two vineyards, TB in Emilia-Romagna and CAR-3 in Tuscany, the spatial pattern of diseased vines in the first year of appearance of the foliar esca symp-toms was also determined. The maps of the vines in these vineyards indicated that diseased plants mostly occurred alone. This suggests that the disease had its origin in infected rooted cuttings or was triggered by inoculum aerially dispersed from distant sources and/or occurring, at least in hypothesis, in the soil

Has Xylella fastidiosa "chosen" olive trees to establish in the Mediterranean basin?

<p>Severe decline of olive trees was observed in the Lecce province, Apulia (Italy), and received the name ‘complesso del disseccamento rapido dell’olivo’ (olive rapid decline complex). Affected plants showed leaf scorch symptoms and dieback of twigs, branches and even of the whole plant. Similar symptoms, unusual for the area, have also been observed in other Apulian localities (Cerignola, Foggia, Canosa di Puglia, and Andria). Three fungal species were associated with the symptoms: Phaeoacremonium aleophilum, Neofusicoccum parvum, and Pleurostomophora richardsiae. The latter is the first report of this fungal species infecting olives. In the Lecce province, the bacterium Xylella fastidiosa also was detected from affected olive trees. Xylella fastidiosa is a quarantine agent in Europe that had been previously reported in the Mediterranean region, but did not spread probably because of the lack of a vector. Present findings suggest that this fundamental condition has now been met.</p

Obstetrics and Gynecology Emergency Department Activity during Lockdown in a Teaching Hospital, Hub Center, for COVID-19

Background. The lockdown related to the SARS-CoV-2 pandemic has imposed profound changes in the interaction of the population with hospitals and emergency departments. The main aim of this research was to evaluate the impact of lockdown on the activity of obstetrics and gynecology emergency department (OGED) in a teaching hospital, hub center, for COVID-19. Methods. The study considers all visits to the OGED with their different triage color codes that represent the clinical severity of each case (from the most severe to the least one: red, yellow, green, white). Data were selected through the "PSNet"triage program and collected anonymously. We analyzed frequency distributions of the variables separately for each woman and calculated mean and standard deviations for continuous variables. We then analyzed the association between factors and outcomes for categorical variables (expressed as a number and percentage of the total) using the chi-square test (χ2). The level of significance was established with p<0.05. Statistical analysis was performed using SPSS Statistics V20.0. Given the fact that the study has a retrospective observational nature and it is based on an anonymous routine database, approval by the Local Ethics Committee was not necessary. Results. The relative decrease of patients presenting to OGED in 2020 was -50.96%. The percentage of nonpregnant women was significantly lower in 2020 compared to 2019 (p≤0.0001; Δ = -79.46%). Regarding the obstetric group, we saw an important decrease of visits in 2020 compared to 2019 (p<0.0001; Δ = -40%). The prevalence of yellow codes was significantly higher in 2020 (Δ = +29.72%), while that of white (Δ = -61.58%) and green (Δ = -52.22%) codes was significantly lower (p≤0.0001). Comparing the diagnoses at discharge, we could highlight significant reductions in 2020 for more than one diagnosis: bleeding (p≤0.0001; Δ = -70.42%), pain (p≤0.0001; Δ = -81.22%), urinary diseases (p=0.004; Δ = -75.64%), and gastrointestinal diseases (p≤0.0001; Δ = -87.50%). Conclusions. An evident change emerged in relation to the dynamics between the local obstetrical and gynecological population, and OGED resources. The COVID-19 lockdown greatly reduced the rate of admission to OGED without time-related obstetric and gynecological complications. The reduction of admissions suggests a more appropriate use of the ED by patients that may inspire future policies for the implementation of emergency services

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab