β-Glucan Antigenemia Assay for the Diagnosis of Invasive Fungal Infections in Patients With Hematological Malignancies: A Systematic Review and Meta-Analysis of Cohort Studies From the Third European Conference on Infections in Leukemia (ECIL-3)

This Third European Conference on Infections in Leukemia meta-analysis of high-quality hemato-oncological cohort studies shows that 2 consecutive positive 1,3-β-D-glucan assays have high specificity and both positive and negative predictive values but low sensitivity for diagnosis of invasive fungal infectio

Efficacy of three different irrigation techniques in the removal of smear layer and organic debris from root canal wall: A scanning electron microscope study

Abstract Aim Aim of this study was to compare the removal of smear layer and organic debris within the tooth canal among conventional needle irrigation, EndoVac and Endoactivator. Methodology Eighty single-rooted extracted human teeth were prepared with rotary NiTi instrumentation and randomly separated into 4 groups. Twenty teeth were used as positive control (Group 1), irrigated with only saline. Teeth assigned to Group 2 ( n = 20) received irrigation with a conventional syringe and a 30-gauge needle (NaviTip, Ultradent, South Jordan, UT); samples in Group 3 ( n = 20) were rinsed with an irrigation device based on apical negative pressure (EndoVac, Discus Dental, Culver City, CA) and teeth in Group 4 ( n = 20) were treated with a sonic irrigation system (EndoActivator, Dentsply Tulsa Dental, Tulsa, OK, USA). The amount of residual smear layer and debris was evaluated under a scanning electron microscope, and a semi-quantitative score was assigned to each root at the coronal, middle and apical thirds; the chi-square test was used to compare the results of the S.E.M. analysis. Results EndoActivator performed the best cleansing for both smear layer and organic debris in all root canal thirds, followed by EndoVac and conventional irrigation ( p > 0.001). EndoVac and conventional irrigation showed better cleaning in the coronal area, whereas EndoActivator performed an homogeneous cleansing at all levels. Conclusions The EndoVac system and the EndoActivator system demonstrated significantly more efficacy in cleansing root canal walls than conventional needle irrigation

Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer's Disease Patients

Cystatin B is a small, multifunctional protein involved in the regulation of inflammation, innate immune response, and neuronal protection and found highly abundant in the brains of patients with Alzheimer's disease (AD). Recently, our study demonstrated a significant association between the level of salivary cystatin B and AD. Since the protein is able to establish protein-protein interaction (PPI) in different contexts and aggregation-prone proteins and the PPI networks are relevant for AD pathogenesis, and due to the relevance of finding new AD markers in peripheral biofluids, we thought it was interesting to study the possible involvement of cystatin B in PPIs in saliva and to evaluate differences and similarities between AD and age-matched elderly healthy controls (HC). For this purpose, we applied a co-immunoprecipitation procedure and a bottom-up proteomics analysis to purify, identify, and quantify cystatin B interactors. Results demonstrated for the first time the existence of a salivary cystatin B-linked multi-protein complex composed by 82 interactors and largely expressed in the body. Interactors are involved in neutrophil activation, antimicrobial activity, modulation of the cytoskeleton and extra-cellular matrix (ECM), and glucose metabolism. Preliminary quantitative data showed significantly lower levels of triosophosphate isomerase 1 and higher levels of mucin 7, BPI, and matrix Gla protein in AD with respect to HC, suggesting implications associated with AD of altered glucose metabolism, antibacterial activities, and calcification-associated processes. Data are available via ProteomeXchange with identifiers PXD039286 and PXD030679

A top-down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls

Parkinson's disease (PD) is a complex neurodegenerative disease with motor and non-motor symptoms. Diagnosis is complicated by lack of reliable biomarkers. To individuate peptides and/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top-down platform based on HPLC-ESI-IT-MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin & beta;4, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of & alpha;-defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S-cysteinylated and S-glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. & alpha;-defensins, histatin 1, oxidized S100A9, and P-B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin & beta;4 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate-immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

Central nervous system relapse occurs in about 5% of cases of acute promyelocytic leukaemia

In this report, we present images from a patient with acute promyelocytic leukemia who experienced several central nervous system relapses

Identification of an HSP90 modulated multi-step process for ERBB2 degradation in breast cancer cells

open6noISSN: 1949-2553The receptor tyrosine kinase ERBB2 interacts with HSP90 and is overexpressed in aggressive breast cancers.Therapeutic HSP90 inhibitors, i.e. Geldanamycin (GA), target ERBB2 to degradation. We have previously shown that HSP90 is responsible for the missorting of recycling ERBB2 to degradation compartments. In this study, we used biochemical, immunofluorescence and electron microscopy techniques to demonstrate that in SKBR3 human breast cancer cells, GA strongly induces polyubiquitination and internalization of the full-length p185-ERBB2, and promotes its cleavage, with the formation of a p116-ERBB2 form in EEA1-positive endosomes (EE). p116-ERBB2 corresponds to a non-ubiquitinated, signaling-impaired, membranebound fragment, which is readily sorted to lysosomes and degraded. To define the sequence of events leading to p116-ERBB2 degradation, we first blocked the EE maturation/trafficking to late endosomes/lysosomes with wortmannin, and found an increase in GA-dependent formation of p116-ERBB2; we then inhibited the proteasome activity with MG-132 or lactacystin, and observed an efficient block of p185-ERBB2 cleavage, and its accumulation in EE, suggesting that p185-ERBB2 polyubiquitination is necessary for proteasome-dependent p116-ERBB2 generation occurring in EE. As polyubiquitination has also been implicated in autophagy-mediated degradation of ERBB2 under different experimental conditions, we exploited this possibility and demonstrate that GA strongly inhibits early autophagy, and reduces the levels of the autophagy markers atg5-12 and LC3-II, irrespective of GA-induced ERBB2 polyubiquitination, ruling out a GA-dependent autophagic degradation of ERBB2. In conclusion, we propose that HSP90 inhibition fosters ERBB2 polyubiquitination and proteasome-dependent generation of a non-ubiquitinated and inactive p116-ERBB2 form in EE, which is trafficked from altered EE to lysosomes.openCastagnola,Patrizio; Bellese,Grazia; Birocchi,Filippo; Gagliani,Maria Cristina; Tacchetti,Carlo; Cortese,KatiaCastagnola, Patrizio; Bellese, Grazia; Birocchi, Filippo; Gagliani, MARIA CRISTINA; Tacchetti, Carlo; Cortese, Kati