Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Efficient Discrete Element Modeling of Particle Dampers

Particle dampers’ dissipative characteristics can be difficult to predict because of their highly non-linear behavior. The application of such devices in deformable vibrating systems can require extensive experimental and numerical analyses; therefore, improving the efficiency when simulating particle dampers would help in this regard. Two techniques often proposed to speed up the simulation, namely the adoption of a simplified frictional moment and the reduction of the contact stiffness, are considered; their effect on the simulation run-time, on the ability of the particle bed to sustain shear deformation, and on the prediction of the dissipation performance is investigated for different numerical case studies. The reduction in contact stiffness is studied in relation to the maximum overlap between particles, as well as the contacts’ duration. These numerical simulations are carried out over a wide range of motion regimes, frequencies, and amplitude levels. Experimental results are considered as well. All the simulations are performed using a GPU-based discrete element simulation tool coupled with the multi-body code MBDyn; the results and execution time are compared with those of other solvers

Prevention of Bacterial Infiltration in Class 1 Temporary Restorations Using Zinc Oxide/Calcium Sulphate Filling Materials: An In Vitro Study

This study evaluated sealing properties of zinc oxide/calcium sulphate filling material (Plastor©) to prevent bacterial infiltration in simulated Class 1 cavities with and without the presence of a spacer apically the restoration. Twenty-eight experimental Eppendorf tubes containing Tryptic Soy Agar were prepared and divided into seven groups: group A (Plastor©), group B (Plastor© + cotton pellet), group C (Plastor© + cotton pellet soaked of m-cresyl acetate), group D (Plastor© + cotton pellet soaked of eugenol), group E (Plastor© + PTFE pellet), group F (positive control), and group G (negative control). All prepared vials were individually immersed in tubes containing 5 mL of a suspension of Streptococcus mutans (105 CFU/mL) previously prepared and then incubated at 37 °C for 5 and 10 days. Subsequently, agar was collected and tested for S.mutans using real-time PCR. Aliquots of each agar samples were separately seeded on TSA for S. mutans isolation. The real-time PCR tests were negative for S. mutans on all the vials at both T5 and T10, except for positive control resulted positive at both T5 and T10. The isolation tests showed bacterial growth of S. mutans only with the agar samples collected from the vials of positive control, confirming real-time PCR tests. This in vitro study evidenced complete sealing ability of zinc oxide/calcium sulphate in temporary restorations of Class 1 cavities without mechanical loading at 10 days and complete immersion in a bacterial suspension. Moreover, sealing ability is not influenced by presence of spacers

Bartonella henselae mitral valve endocarditis associated with multi‐resistant Enterococcus faecalis bacteraemia in a cat

Feline infective endocarditis is a difficult condition to detect and diagnose early, with a poor long-term prognosis. This case report describes the clinical, laboratory, instrumen- tal and histological findings in a 12-year-old cat with Bartonella henselae endocarditis associated with multi-resistant Enterococcus faecalis bacteraemia. The latter pathogen recently emerged as deadly nosocomial bacteria in humans and is considered a com- mon cause of infective endocarditis. The prolonged corticosteroid therapy administered in the cat probably played a role in the onset of B. henselae endocarditis and E. fae- calis intestinal translocation and bacteraemia. Echocardiography remains the tool of choice to suspect infective endocarditis, as it can detect vegetative lesions consistent with this condition. Feline infective endocarditis should always be considered as a differen- tial diagnosis in cats, especially when there are signs of systemic disease, a history of prolonged corticosteroid treatment or concomitant infections

Prevention of Bacterial Infiltration in Class 1 Temporary Restorations Using Zinc Oxide/Calcium Sulphate Filling Materials: An In Vitro Study

This study evaluated sealing properties of zinc oxide/calcium sulphate filling material (Plastor©) to prevent bacterial infiltration in simulated Class 1 cavities with and without the presence of a spacer apically the restoration. Twenty-eight experimental Eppendorf tubes containing Tryptic Soy Agar were prepared and divided into seven groups: group A (Plastor©), group B (Plastor© + cotton pellet), group C (Plastor© + cotton pellet soaked of m-cresyl acetate), group D (Plastor© + cotton pellet soaked of eugenol), group E (Plastor© + PTFE pellet), group F (positive control), and group G (negative control). All prepared vials were individually immersed in tubes containing 5 mL of a suspension of Streptococcus mutans (105 CFU/mL) previously prepared and then incubated at 37 °C for 5 and 10 days. Subsequently, agar was collected and tested for S.mutans using real-time PCR. Aliquots of each agar samples were separately seeded on TSA for S. mutans isolation. The real-time PCR tests were negative for S. mutans on all the vials at both T5 and T10, except for positive control resulted positive at both T5 and T10. The isolation tests showed bacterial growth of S. mutans only with the agar samples collected from the vials of positive control, confirming real-time PCR tests. This in vitro study evidenced complete sealing ability of zinc oxide/calcium sulphate in temporary restorations of Class 1 cavities without mechanical loading at 10 days and complete immersion in a bacterial suspension. Moreover, sealing ability is not influenced by presence of spacers

Alveolar osteitis associated with methicillin-resistant Staphylococcus epidermidis

A critical point in dentistry is the empiric prescription of broad-spectrum antibiotics that could increase the levels of antimicrobial resistance. Alveolar osteitis is one of the most common post-op- erative complications in which antibiotic use is controversial. A 35-year-old female, with pain in the right mandibular region and treated with cefixime, was diagnosed with cracked tooth syndrome and pulpitis. The tooth was extracted and a massive purulent bleeding drainage was observed. Irrigation of the socket and a new therapy with azithromycin were done. Bacteriological analysis, a specific mecA gene PCR for the methicillin resistance, and the antimicrobial susceptibility test were per- formed on the bacterial isolate. A Staphylococcus epidermidis isolate was methicillin-resistant and showed resistance to erythromycin, azithromycin, clarithromycin, and sulfamethoxazole + trimeth- oprim. After 7 days, intraoral examination showed a complete resolution. The aim of this report is to suggest that systemic antibiotics may provide insufficient efficacy during alveolar osteitis, especially when caused by a multidrug-resistant organism

<i>Streptococcus mutans</i> Associated with Endo-Periodontal Lesions in Intact Teeth

A massive periodontal destruction can affect the root canal (RC) system and potentially expose the pulpo-dentinal complex to opportunistic bacteria. Streptococcus mutans is a major pathogen of human caries and periodontal diseases, and its virulence mostly resides in the ability to adhere to collagen and form biofilms, due to collagen-binding proteins (CBPs) Cnm and Cbm. Seventeen patients affected by severe endo-periodontal lesions without caries and/or exposure of pulpal tissue were subjected to tooth extraction and samples for microbiological investigation were collected from the root surface (RS) and RC. The collected swabs were cultivated and subjected to the quantitative real-time PCR (qPCR) for the detection of S. mutans and to the PCR for the cnm/cbm genes investigation, followed by next-generation sequencing (NGS). S. mutans DNA was detected in 12/17 (70.5%) RS samples and in 8/17 (47.0%) RC samples. In the CBPs screening of positive samples, the cnm gene was detected in 4/12 (33.3%) RS and in 1/8 (12.5%) RC samples, whilst all the samples tested negative for the cbm gene. The presence of the cnm gene could enhance the local virulence of the pathogens. Therefore, S. mutans have to be included as potential periodontopathogen bacterium in severe or refractory forms of periodontal diseases

African Swine Fever&mdash;How to Unravel Fake News in Veterinary Medicine

In recent years, fake scientific news has spread much faster through the Internet and social media within the so-called &ldquo;infodemic&rdquo;. African Swine Fever (ASF) is a perfect case study to prove how fake news can undermine the public health response, even in the veterinary field. ASF is a highly contagious infective disease affecting exclusively domestic and wild pigs such as wild boars. ASF can cause social damage and economic losses both directly (due to the high mortality rate) and indirectly (due to international sanctions). Although ASF is not a threat to human health, since 2018 newspapers have often reported false or misleading news, ranging from misinterpreted findings/data to fake or alarmistic news. In some cases, fake news was spread, such as the use of snipers at the border of nations to kill wild boars, or those reports concerning possible risks to human health. In order to provide real and fact-based news on epidemics, some organizations have created easy-to-read infographic and iconographic materials, available on their websites, to help the readers identifying the fake news. Indeed, it is crucial that governments and scientific organizations work against fear and anxiety, using simple and clear communication