Modelling the SARS-CoV-2 vaccination campaign in Italy: the fundamental role of unreported cases.

In Italy and around the world, the year 2021 was dedicated to vaccination campaigns against the COVID-19 epidemic arising after the outbreak of SARS-CoV-2 in China in 2019. In December 2020, we proposed a model prediction for the effects of vaccination, and now, after more than 9 months of the vaccination campaign, a comparison of those predictions with the actual data is mandatory. Surprising evidences emerge suggesting new strategies to consider regarding the spread of the virus and to protect frail people.

Modelling SARS-CoV-2 unreported cases in Italy: Analysis of serological survey and vaccination scenarios.

Objectives: Aim of the present paper is the study of the large unreported component, characterizing the SARS-CoV-2 epidemic event in Italy, taking advantage of the Istat survey. Particular attention is devoted to the sensitivity and specificity of the serological test and their effects.

Methods: The model satisfactory reproduces the data of the Italian survey showing a relevant predictive power and relegating in a secondary position models which do not include, in the simulation, the presence of asymptomatic groups.

Rapid Release of Interleukin-1β from Human Platelets Is Independent of NLRP3 and Caspase.

Objective:  Platelets are critical in mediating both rapid responses to injury and the development and progression of coronary disease. Several studies have shown that, after prolonged exposure to agonists, they produce and release inflammatory mediators including interleukin-1β (IL-1β), via the classical pathway (NLRP3 inflammasome and caspase-1 cleavage to release active IL-1β) as described for leukocytes. This study aimed to determine whether there is rapid release of IL-1β in response to soluble platelet agonists and whether such rapid release is NLRP3- and caspase-1-dependent.

Colchicine inhibits ROS generation in response to glycoprotein VI stimulation.

Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (HDCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist).

Factors Associated With the Risk of Progression of Low-Risk Branch-Duct Intraductal Papillary Mucinous Neoplasms.

Importance: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are common pancreatic preneoplastic lesions, but their surveillance is not personalized.

Objective: To investigate patient- and cyst-related factors associated with progression into worrisome features (WFs) or high-risk stigmata (HRS) categories of BD-IPMNs.

Design, Setting, And Participants: Cyst- and patient-related factors of consecutive BD-IPMNs without WFs or HRS in 540 patients diagnosed from 2009 to 2018 with at least 12 months' surveillance until February 28, 2020, were registered in a 2-center ambispective cohort study in Italy.

A study of SARS-CoV-2 epidemiology in Italy: from early days to secondary effects after social distancing.

Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 101,739 confirmed cases, in Italy, as of March 30th, 2020. While the analogous event in China appears to be under control at the moment, the outbreaks in western countries are still at an early stage of development. Italy, at present, is playing a major role in understanding the transmission dynamics of these new infections and evaluating the effectiveness of control measures in a western social context.

Remote ischemic preconditioning inhibits platelet α β activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial.

Objectives: We investigated whether remote ischemic preconditioning (RIPC) inhibits agonist-induced conformational activation of platelet α β in patients with coronary artery disease already receiving conventional antiplatelet therapy.

Patients/methods: Consecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham.

Needle-knife fistulotomy vs. standard biliary sphincterotomy for choledocholithiasis: common bile duct stone recurrence and complication rate.

 With common bile duct (CBD) stones, access to the CBD can be achieved through the papilla orifice followed by standard biliary sphincterotomy (SBS), or through precut fistulotomy (PF) in case of difficult cannulation. The two methods alter papilla anatomy differently, potentially leading to a different rate of stone recurrence. No data have been published on stone recurrence after PF in patients with CBD stones.

Exocrine pancreatic insufficiency: prevalence, diagnosis, and management.

Exocrine pancreatic insufficiency (EPI) is a condition caused by reduced or inappropriate secretion or activity of pancreatic juice and its digestive enzymes, pancreatic lipase in particular. EPI can result in clinical manifestation and biochemical alterations causing reduced quality of life and life-threating complications. EPI is common in pancreatic disorders, where it should be suspected and actively investigated, and in many extrapancreatic conditions.

Correction: Long-term follow-up of low-risk branchduct IPMNs of the pancreas: is main pancreatic duct dilatation the most worrisome feature?

In the HTML version of this paper Pietro Magnoni was incorrectly tagged as the corresponding author. The corresponding author should have been Maria Chiara Petrone. This has now been corrected in the HTML version of the paper.

Long-term follow-up of low-risk branch-duct IPMNs of the pancreas: is main pancreatic duct dilatation the most worrisome feature?

Objectives: The management of branch-duct IPMN remains controversial due to the relatively low rate of malignant degeneration and the uncertain predictive role of high-risk stigmata (HRS) and worrisome features (WFs) identified by the 2012 International Consensus Guidelines. Our aim was to evaluate the evolution of originally low-risk (Fukuoka-negative) BD-IPMNs during a long follow-up period in order to determine whether the appearance of any clinical or morphological variables may be independently associated with the development of malignancy over time.

Methods: A prospectively collected database of all patients with BD-IPMN referring to our Institute between 2002 and 2016 was retrospectively analyzed.

Cell-specific production, secretion, and function of apolipoprotein E.

Apolipoprotein E (apoE) is a 34-kDa glycoprotein that is secreted from many cells throughout the body. ApoE is best known for its role in lipoprotein metabolism. Recent studies underline the association of circulating lipoprotein-associated apoE levels and the development for cardiovascular disease (CVD).

N-glycosylation of human sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is essential for stability, secretion and activity.

Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a recently identified phosphodiesterase, which is a secreted -linked glycoprotein. SMPDL3A is highly homologous to acid sphingomyelinase (aSMase), but unlike aSMase cannot cleave sphingomyelin. Rather, SMPDL3A hydrolyzes nucleotide tri- and diphosphates and their derivatives.

Human macrophage cathepsin B-mediated C-terminal cleavage of apolipoprotein A-I at Ser228 severely impairs antiatherogenic capacity.

Apolipoprotein A-I (apoA-I) is the major component of HDL and central to the ability of HDL to stimulate ATP-binding cassette transporter A1 (ABCA1)-dependent, antiatherogenic export of cholesterol from macrophage foam cells, a key player in the pathology of atherosclerosis. Cell-mediated modifications of apoA-I, such as chlorination, nitration, oxidation, and proteolysis, can impair its antiatherogenic function, although it is unknown whether macrophages themselves contribute to such modifications. To investigate this, human monocyte-derived macrophages (HMDMs) were incubated with human apoA-I under conditions used to induce cholesterol export.

Pharmacological inhibition of dynamin II reduces constitutive protein secretion from primary human macrophages.

Dynamins are fission proteins that mediate endocytic and exocytic membrane events and are pharmacological therapeutic targets. These studies investigate whether dynamin II regulates constitutive protein secretion and show for the first time that pharmacological inhibition of dynamin decreases secretion of apolipoprotein E (apoE) and several other proteins constitutively secreted from primary human macrophages. Inhibitors that target recruitment of dynamin to membranes (MiTMABs) or directly target the GTPase domain (Dyngo or Dynole series), dose- and time- dependently reduced the secretion of apoE.

Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages.

Cholesterol-loaded foam cell macrophages are prominent in atherosclerotic lesions and play complex roles in both inflammatory signaling and lipid metabolism, which are underpinned by large scale reprogramming of gene expression. We performed a microarray study of primary human macrophages that showed that transcription of the sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) gene is up-regulated after cholesterol loading. SMPDL3A protein expression in and secretion from primary macrophages are stimulated by cholesterol loading, liver X receptor ligands, and cyclic AMP, and N-glycosylated SMPDL3A protein is detectable in circulating blood.

Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-β42: importance of lipid homeostasis.

Amyloid-β (Aβ)-containing plaques are a major neuropathological feature of Alzheimer's disease (AD). The two major isoforms of Aβ peptide associated with AD are Aβ40 and Aβ42, of which the latter is highly prone to aggregation. Increased presence and aggregation of intracellular Aβ42 peptides is an early event in AD progression.

Comparison of capillary versus aspiration technique in endoscopic ultrasound-guided fine-needle aspiration: A preliminary report.

Introduction: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used to diagnose pancreatic malignancies. Different EUS-FNA techniques have been described to improve sample quality. Recently, a new technique, using capillarity, has been proposed.

Cellular cholesterol regulates ubiquitination and degradation of the cholesterol export proteins ABCA1 and ABCG1.

The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins.

Left ventricular "diverticulum" in a patient affected by galactosialidosis.

We present the case of a 35-year-old man affected by the late juvenile form of galactosialidosis. He was known for a moderate pericardial effusion which remained unchanged in the last 12 months. Last follow-up transthoracic echocardiographic examination showed a bulging of the posterior and lateral wall of the left ventricle.

Exploring sterol and lipid biology in the functional genomic era.

The growing prevalence of disorders of lipid and sterol homeostasis such as obesity and atherosclerosis in Western societies has increased demand for the development of therapies for their prevention and treatment. Crucial for this development is an understanding of the underlying cellular mechanisms which are involved in both healthy and diseased states. However, gaps remain in our knowledge of fundamental processes, such as intracellular sterol transport, lipid storage and mobilisation.

Cyclosporin A decreases apolipoprotein E secretion from human macrophages via a protein phosphatase 2B-dependent and ATP-binding cassette transporter A1 (ABCA1)-independent pathway.

Cyclosporin A (CsA) is an immunosuppressant that inhibits protein phosphatase 2B (PP2B/calcineurin) and is associated with hyperlipidemia, decreased cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1), and increased risk of atherosclerosis. Apolipoprotein E (apoE) is an important regulator of lipid metabolism and atherosclerosis, the secretion of which from human macrophages is regulated by the serine/threonine protein kinase A (PKA) and intracellular calcium (Ca(2+)) (Kockx, M., Guo, D.

Rapid purification method for the 26S proteasome from the filamentous fungus Trichoderma reesei.

We have developed a fast and simple two column chromatographic method for the purification of the 26S proteasome from the filamentous fungus Trichoderma reesei that simplifies the overall procedure and reduces the purification time from 5 to 2.5 days. The combination of only the anionic exchange POROS HQ column (Applied Biosystems) together with a size exclusion column has not been used previously for proteasome purification.

Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae.

Background: Arsenic and cadmium are widely distributed in nature and pose serious threats to the environment and human health. Exposure to these nonessential toxic metals may result in a variety of human diseases including cancer. However, arsenic and cadmium toxicity targets and the cellular systems contributing to tolerance acquisition are not fully known.