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Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Background: Coronavirus disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in China in December 2019, was recently recognized as pandemic threat by the World Health Organization, with the potential of rapidly overloading health care systems and causing substantial mortality worldwide (www.who.int/dg/speeches/detail/who-director-general -s-opening-remarks-at-the-media-briefing-on-covid-19 —11-march -2020). Human-to-human transmission occurs mainly through respiratory droplets, but other routes are under investigation, because SARS-CoV-2 has been detected in several body fluids (1). So far, few data are available on ocular samples from patients with COVID-19, although conjunctivitis has been occasionally reported among COVID-19 symptoms, similar to infections caused by other human coronaviruses (2, 3). During the SARS epidemic, eye exposure to infectious fluids was associated with an increased risk for SARS-CoV transmission to health care workers (3, 4). Although SARS-CoV RNA was occasionally found in ocular specimens during the early phase of illness, its infectivity is unknown (2, 3). With regard to COVID-19, unprotected ocular exposure was thought to be responsible for infections that occurred in the Wuhan Fever Clinic in January 2020 (3, 4); in addition, SARS-CoV-2 RNA was detected in conjunctival secretions collected from the only patient with conjunctivitis out of 30 patients with COVID-19 from a hospital in China (5). However, further studies are needed to evaluate the infectious potential of the SARS-CoV-2 RNA detected in the ocular specimens and to determine whether transmission may occur through ocular secretions (3, 4). Objective: To present the early detection of infectious SARS-CoV-2 in ocular fluids from a patient with the first confirmed case of COVID-19 in Italy, who had been hospitalized at the National Institute for Infectious Diseases “L. Spallanzani” (INMI) in Rome. Methods and Findings: The patient, a 65-year-old woman, travelled from Wuhan, China, to Italy on 23 January 2020 and was admitted on 29 January 2020, 1 day after symptom onset. At admission to the high isolation unit at INMI, she presented with nonproductive cough, sore throat, coryza, and bilateral conjunctivitis. She had no fever until day 4, when fever (38 °C), nausea, and vomiting began. Infection with SARS-CoV-2 was confirmed by performing real-time reverse transcription polymerase chain reaction (RT-PCR) assay on sputum samples (cycle threshold value [Ct], 16.1) on the admission day, followed by viral M gene sequencing (GenBank accession number MT008022), and virus isolation on Vero E6 cell line (2019-nCoV/Italy-INMI1). The full genome sequence was obtained from either clinical sample or culture isolate (GISAID accession numbers EPI_ISL_410545 and EPI_ISL_410546). At admission, no other respiratory infections were detected (QIAstat-Dx Respiratory Panel; Qiagen).

Lo studio di idrogel supramolecolari da utilizzare in ambito biomedico è in continua espansione. Questo è dovuto al fatto che, così come gli idrogel polimerici, mostrano eccellenti proprietà meccaniche, ma possono anche essere sottoposti reversibilmente a rigonfiamento o a transizioni gel-sol in risposta a stimoli esterni (temperatura, pH, enzimi, agenti redox).1Ad esempio, la buona risposta degli idrogel supramolecolari agli stimoli fisiologici, insieme alla loro elevata biodegradabilità e biocompatibilità, ne ha permesso l’utilizzo per la diagnosi tumorale. Solitamente, questi materiali sono facilmente assimilati dalle cellule e hanno la funzione di carrier per le molecole attive nel bioimaging. 1Alla luce di queste premesse e della spiccata attività antimicrobica precedentemente riscontrata su idrogel formati da sali di imidazolio,2 si è pensato di sintetizzare nuovi sali organici di imidazolio fluorescenti, che potessero assolvere alla duplice funzione di gelator e di agente per il bioimaging. Sono stati ottenuti idrogel fluorescenti che hanno mostrato interessanti proprietà chimico-fisiche (temperatura di transizione gel-sol, risposta a stimoli esterni, reologia, morfologia, indagini spettrofluorimetriche) e biologiche (attività antiproliferativa, bioimaging su cellule tumorali in vitro e rilascio controllato del gelator in soluzione fisiologica).

Le ben note proprietà chimico-fisiche dei liquidi ionici (ILs), unite alla versatilità strutturale, sono alla base delle loro numerose e differenti applicazioni. In questo lavoro, si presenta un’interazione termocromica reversibile, sia in soluzione che in un film polimerico, tra un IL portante sul catione un residuo gluconammidico e il sale di cobalto Co(NTf2)2. I gruppi ossidrilici sul catione e l’anione bromuro dell’IL coordinano il Co al variare della temperatura applicata. A temperatura ambiente il complesso OH-Co risulta ottaedrico (rosa) mentre, intorno ai 60 °C, la geometria diviene tetraedrica con lo ione bromuro che coordina il Co (blu). Lo studio VT UV-vis (Figura 1) ha permesso di identificare le bande relative ai complessi e il loro andamento con la temperatura, determinando anche la temperatura di switch delle geometrie. Incorporando metallo e legante in un polimero, è stato ottenuto un film polimerico avente le stesse proprietà della soluzione. Il range di temperatura del fenomeno termocromico studiato (20-90m°C) è tale da rendere il sistema applicabile in device termosensibili

Neuroserpin (NS) is a serine protease inhibitor (SERPIN) involved in different neurological pathologies, including the Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB), related to the aberrant polymerization of NS mutants. Here we present an in vitro and in silico characterization of native NS and its dysfunctional conformation isoforms: the proteolytically cleaved conformer, the inactive latent conformer, and the polymeric conformer. Using circular dichroism and fluorescence spectroscopy, we present an experimental validation of the latent model and highlight the main structural features of the different conformers. In par- ticular, emission spectra of aromatic residues yield a distinct conformational fingerprint, that provides a novel and simple spectroscopic tool for selecting serpin conformers in vitro. Based on the analogy between cleaved and latent serpins, we propose a structural model for latent neuroserpin, for which an experimental crystallographic structure is lacking. Molecular Dynamics simulations suggest that NS conformational stability and flexibility arise from the spatial pattern of intramolecular salt-bridges and hydrogen bonds.

Chronic hemodialysis (HD) patients have a high risk to develop atherosclerotic cardiovascular disease. The available data, even though limited, suggest that some of the traditional cardiovascular risk factors do not play an important role in the HD population.1 Nonalcoholic fatty liver disease (NAFLD) is recognized as one of the leading causes of a wide spectrum of liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and end-stage liver failure.2,3 Despite the lack of conclusive results, it has been shown that steatosis accelerates the progression of chronic liver damage in hepatitis C (HCV) patients with specific HCV genotypes and in patients with visceral obesity,4 suggesting that severe liver fibrosis (caused by the progression of NAFLD) might reduce the survival in HD patients. Unfortunately, these studies are often limited by the lack of information about the pretransplant histological severity of the chronic hepatitis. Moreover, the spuriously low serum aminotransferase levels in HD patients may not serve as a reliable predictor of liver disease progression. In addition, NAFLD is closely related to several features of metabolic syndrome which is associated to an increased risk of cardiovascular disease and premature death. Recent studies have shown that the severity of liver histopathology among NAFLD patients is strongly associated with early carotid atherosclerosis,5 as assessed by intima-media thickness (IMT) ultrasound (US) examination. IMT is an independent predictor of cardiovascular mortality in the general population as well as in HD patients.6,7 To assess the possible relationship between NAFLD and increased IMT among patients undergoing HD, as a possible marker of subclinical atherosclerosis, independent on metabolic syndrome, insulin resistance, and classical cardiovascular risk factors, this prospective, cross-sectional study examined liver biochemical findings, liver histological features, and IMT measurements in a cohort of HD patients.

The definition of the secretome signature of a cancer cell line can be considered a potential tool to investigate tumor aggressiveness and a preclinical exploratory study required to optimize the search of cancer biomarkers. Dealing with a cell-specific secretome limits the contamination by the major components of the human serum and reduces the range of dynamic concentrations among the secreted proteins, thus favouring under-represented tissue-specific species. The aim of the present study is to characterize the secretome of two human colon carcinoma cell lines, CaCo-2 and HCT-GEO, in order to evaluate differences and similarities of two colorectal cancer model systems. In this study, we identified more than 170 protein species, 64 more expressed in the secretome of CaCo-2 cells and 54 more expressed in the secretome of HCT-GEO cells; 58 proteins were shared by the two systems. Among them, more than 50% were deemed to be secretory according to their Gene Ontology annotation and/or to their SignalP or SecretomeP scores. Such a characterization allowed corroborating the potential of a cell culture-based model in order to describe the cell-specific invasive properties and to provide a list of putative cancer biomarkers.

The polymerization of serpins is at the root of a large class of diseases; the molecular structure of serpin polymers has been recently debated. In this work, we study the polymerization kinetics of human neuroserpin by Fourier Transform Infra Red spectroscopy and by time-lapse Size Exclusion Chromatography. First, we show that two distinct neuroserpin polymers, formed at 45 and 85 °C, display the same isosbestic points in the Amide I band, and therefore share common secondary structure features. We also find a concentration independent polymerization rate at 45 °C suggesting that the polymerization rate limiting step is the formation of an activated monomeric species. The polymer structures are consistent with a model that predicts the bare insertion of portions of the reactive center loop into the A b-sheet of neighboring serpin molecule, although with different extents at 45 and 85 °C. Further studies are currently addressing the structure of monomeric neuroserpin conformers.