Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Central Neck Dissection Cannot Be Avoided In Medullary Thyroid Cancer (MTC) On The Basis Of Presurgical Serum Calcitonin (CT)

Objectives: While it is well known that lymphnode metastases (LNF- mets) have never found in RET gene carriers with a basal presurgical CT <30-40 pg/ml, to our knowledge there are no studies about this issue in spo- radic adult MTC patients. The aim of the study was to look for a pre-operative serum CT value able to predict the absence of central nodes metastases, in order to avoid the lymphadenectomy of the central neck compartment (CCL) which is affected by a higher prevalence of complications. Methods: We retrospectively analyzed the clinico-pathological and molecular features of MTC patients underwent surgery at our Department between 2005 and 2015. In this period we changed the laboratory assay for CT assessment: before September 2013 we used an immunometric assay [ELSA- hCT; Cis-BioInternational, Gif sur Yvette, France, normal value <10 pg/ml both in males and females], after September 2013 we used an immunoassay method [Immulite 2000, DPC, LA, USA, normal values <11.5 pg/ml and <18.2 pg/ml in females and males respectively]. Results: A total of 306 MTC patients underwent total thyroidectomy (TTX) and CCL in this study period. They were divided into 2 subgroups according to the assay used: group I (n=200) (CT assay ELSA-hCT) and group II (n=50) (CT assay Immulite). Thirty-seven/200 patients of group I and 13/50 of group II had LFN-mets at histology. The highest value of CT able to iden- tify all negative cases was 14 pg/ml in group I and 12.6 pg/ml (for female) and 18.6 pg/ml (for males) in group II which are, in both assays, very close to the upper limit of normal values. Conclusions: We didn’t find a preoperative CT cut-off able to identify MTC patients certainly not complicated by LNF-mets. According to our results all MTC adults patients should underwent at least TTX+CCL

Experimental study of the propagation of scintillation light in Liquid Argon

Properties of the propagation of scintillation light in liquid argon (LAr), at $\lambda$ ~128 nm wavelength, have been experimentally investigated in a dedicated setup at CERN. The speed of scintillation photons has been measured for the first time in this medium, refractive index and the Rayleigh scattering are being studied as well. Such measurement provides a key ingredient for the interpretation of data from the current and next generation large mass LAr detectors as those dedicated to the search for rare events such as neutrinos or Dark Matter. Furthermore the improvement on the understanding of the scintillation light propagation represent a benchmark for the multiple theoretical models and simulations for the next generation of detectors which are now based on still incomplete measurements and calculations.Properties of the propagation of scintillation light in liquid argon (LAr), at λ∼ 128 nm wavelength, have been experimentally investigated in a dedicated setup at CERN. The speed of scintillation photons has been measured for the first time in this medium, refractive index and the Rayleigh scattering are being studied as well. Such measurement provides a key ingredient for the interpretation of data from the current and next generation large mass LAr detectors as those dedicated to the search for rare events such as neutrinos or Dark Matter. Furthermore the improvement on the understanding of the scintillation light propagation represent a benchmark for the multiple theoretical models and simulations for the next generation of detectors which are now based on still incomplete measurements and calculations

Propagation of scintillation light in Liquid Argon

The properties of the propagation of scintillations light in the liquid argon, at $\lambda$=128 $nm$ wavelength, has been experimentally investigated in a dedicated setup at CERN. The velocity of scintillation photons has been measured for the first time in the liquid argon. The obtained result, $\frac{1}{v_{g}}$ = 7.5 $\pm$ 0.1 ns/m, is then used to derive the refractive index and the Rayleigh scattering of the liquid argon at VUV region. Such measurement provides a key ingredient for the interpretation of data from the current and next generation large mass liquid argon detectors as those dedicated to the search for rare events such as neutrinos or Dark Matter. Furthermore the improvement on the understanding of the scintillation light propagation represent a benchmark for the multiple theoretical models and simulations for the next generation of detectors

Human milk and donkey milk, compared to cow milk, reduce inflammatory mediators and modulate glucose and lipid metabolism, acting on mitochondrial function and oleylethanolamide levels in rat skeletal muscle

Scope: Milk from various species differs in nutrient composition. In particular, human milk (HM) and donkey milk (DM) are characterized by a relative high level of triacylglycerol enriched in palmitic acid in sn-2 position. These dietary fats seem to exert beneficial nutritional properties through N-acylethanolamine tissue modulation. The aim of this study is to compare the effects of cow milk (CM), DM, and HM on inflammation and glucose and lipid metabolism, focusing on mitochondrial function, efficiency, and dynamics in skeletal muscle, which is the major determinant of resting metabolic rate. Moreover, we also evaluated the levels of endocannabinoids and N-acylethanolamines in liver and skeletal muscle, since tissue fatty acid profiles can be modulated by nutrient intervention. Procedures: To this aim, rats were fed with CM, DM, or HM for 4 weeks. Then, glucose tolerance and insulin resistance were analyzed. Pro-inflammatory and anti-inflammatory cytokines were evaluated in serum and skeletal muscle. Skeletal muscle was also processed to estimate mitochondrial function, efficiency, and dynamics, oxidative stress, and antioxidant/detoxifying enzyme activities. Fatty acid profiles, endocannabinoids, and N-acylethanolamine congeners were determined in liver and skeletal muscle tissue. Results: We demonstrated that DM or HM administration reducing inflammation status, improves glucose disposal and insulin resistance and reduces lipid accumulation in skeletal muscle. Moreover, HM or DM administration increases redox status, and mitochondrial uncoupling, affecting mitochondrial dynamics in the skeletal muscle. Interestingly, HM and DM supplementation increase liver and muscle levels of the N-oleoylethanolamine (OEA), a key regulator of lipid metabolism and inflammation. Conclusions: HM and DM have a healthy nutritional effect, acting on inflammatory factors and glucose and lipid metabolism. This beneficial effect is associated to a modulation of mitochondrial function, efficiency, and dynamics and to an increase of OEA levels in skeletal muscle

Post-translational selective intracellular silencing of acetylated proteins with de novo selected intrabodies

The ability to selectively interfere with post-translationally modified proteins would have many biological and therapeutic applications. However, post-translational modifications cannot be selectively targeted by nucleic-acid-based interference approaches. Here we describe post-translational intracellular silencing antibody technology (PISA), a method for selecting intrabodies against post-translationally modified proteins. We demonstrate our method by generating intrabodies against native acetylated proteins and showing functional interference in living cells