Aerosol and splatter generation with rotary handpieces used in restorative and orthodontic dentistry:a systematic review

Abstract: Introduction: The COVID-19 pandemic has caused major disruptions in dental care globally, in part due to the potential for contaminated aerosol to be generated by dental activities. This systematic review assesses the literature for changes in aerosol-contamination levels when rotary instruments are used, (1) as distance increases from patient’s mouth; (2) as time passes after the procedure; and (3) when using different types of handpieces. Methods: The review methods and reporting are in line with PRISMA statements. A structured search was conducted over five platforms (September 2021). Studies were assessed independently by two reviewers. To be eligible studies had to assess changes in levels of aerosol contamination over different distances, and time points, with rotary hand instruments. Studies’ methodologies and the sensitivity of the contamination-measurement approaches were evaluated. Results are presented descriptively. Results: From 422 papers identified, 23 studies were eligible. All investigated restorative procedures using rotary instruments and one study additionally looked at orthodontic bracket adhesive material removal. The results suggest contamination is significantly reduced over time and distance. However, for almost all studies that investigated these two factors, the sizes of the contaminated particles were not considered, and there were inconclusive findings regarding whether electric-driven handpieces generate lower levels of contaminated particles. Conclusion: Aerosol contamination levels reduce as distances, and post-procedure times increase. However, there was sparce and inconsistent evidence on the clearing time and no conclusions could be drawn. High-speed handpieces produce significantly higher levels of contamination than slow-speed ones, and to a lesser extent, micro-motor handpieces. However, when micro-motor handpieces were used with water, the contamination levels rose and were similar to high-speed handpiece contamination levels

Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages

To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium. SNCA Triplication pMac, but not A53T pMac, show significantly reduced phagocytosis capability and this can be phenocopied by adding monomeric αS to the cell culture medium of control pMac. Fibrillar αS is taken up by pMac by actin-rearrangement-dependent pathways, and monomeric αS by actin-independent pathways. Finally, pMac degrade αS and this can be arrested by blocking lysosomal and proteasomal pathways. Together, these results show that macrophages are capable of clearing αS, but that high levels of exogenous or endogenous αS compromise this ability, likely a vicious cycle scenario faced by microglia in Parkinson's disease

Weather in stellar atmosphere: the dynamics of mercury clouds in alpha Andromedae

The formation of long-lasting structures at the surfaces of stars is commonly ascribed to the action of strong magnetic fields. This paradigm is supported by observations of evolving cool spots in the Sun and active late-type stars, and stationary chemical spots in the early-type magnetic stars. However, results of our seven-year monitoring of mercury spots in non-magnetic early-type star alpha Andromedae show that the picture of magnetically-driven structure formation is fundamentally incomplete. Using an indirect stellar surface mapping technique, we construct a series of 2-D images of starspots and discover a secular evolution of the mercury cloud cover in this star. This remarkable structure formation process, observed for the first time in any star, is plausibly attributed to a non-equilibrium, dynamical evolution of the heavy-element clouds created by atomic diffusion and may have the same underlying physics as the weather patterns on terrestrial and giant planets.Comment: 10 pages, 2 figures; to be published in Nature Physic

UNCLES: Method for the identification of genes differentially consistently co-expressed in a specific subset of datasets

Background: Collective analysis of the increasingly emerging gene expression datasets are required. The recently proposed binarisation of consensus partition matrices (Bi-CoPaM) method can combine clustering results from multiple datasets to identify the subsets of genes which are consistently co-expressed in all of the provided datasets in a tuneable manner. However, results validation and parameter setting are issues that complicate the design of such methods. Moreover, although it is a common practice to test methods by application to synthetic datasets, the mathematical models used to synthesise such datasets are usually based on approximations which may not always be sufficiently representative of real datasets. Results: Here, we propose an unsupervised method for the unification of clustering results from multiple datasets using external specifications (UNCLES). This method has the ability to identify the subsets of genes consistently co-expressed in a subset of datasets while being poorly co-expressed in another subset of datasets, and to identify the subsets of genes consistently co-expressed in all given datasets. We also propose the M-N scatter plots validation technique and adopt it to set the parameters of UNCLES, such as the number of clusters, automatically. Additionally, we propose an approach for the synthesis of gene expression datasets using real data profiles in a way which combines the ground-truth-knowledge of synthetic data and the realistic expression values of real data, and therefore overcomes the problem of faithfulness of synthetic expression data modelling. By application to those datasets, we validate UNCLES while comparing it with other conventional clustering methods, and of particular relevance, biclustering methods. We further validate UNCLES by application to a set of 14 real genome-wide yeast datasets as it produces focused clusters that conform well to known biological facts. Furthermore, in-silico-based hypotheses regarding the function of a few previously unknown genes in those focused clusters are drawn. Conclusions: The UNCLES method, the M-N scatter plots technique, and the expression data synthesis approach will have wide application for the comprehensive analysis of genomic and other sources of multiple complex biological datasets. Moreover, the derived in-silico-based biological hypotheses represent subjects for future functional studies.The National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0310-1004)

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

A systematic review of droplet and aerosol generation in dentistry

Objectives This review aimed to identify which dental procedures generate droplets and aerosols with subsequent contamination, and for these, characterise their pattern, spread and settle. Data resources Medline(OVID), Embase(OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science and LILACS databases were searched for eligible studies from each database’s inception to May 2020 (search updated 11/08/20). Studies investigating clinical dental activities that generate aerosol using duplicate independent screening. Data extraction by one reviewer and verified by another. Risk of bias assessed through contamination measurement tool sensitivity assessment. Study selection A total eighty-three studies met the inclusion criteria and covered: ultrasonic scaling (USS, n = 44), highspeed air-rotor (HSAR, n = 31); oral surgery (n = 11), slow-speed handpiece (n = 4); air-water (triple) syringe (n = 4), air-polishing (n = 4), prophylaxis (n = 2) and hand-scaling (n = 2). Although no studies investigated respiratory viruses, those on bacteria, blood-splatter and aerosol showed activities using powered devices produced greatest contamination. Contamination was found for all activities, and at the furthest points studied. The operator’s torso, operator’s arm and patient’s body were especially affected. Heterogeneity precluded inter-study comparisons but intra-study comparisons allowed construction of a proposed hierarchy of procedure contamination risk: higher (USS, HSAR, air-water syringe, air polishing, extractions using motorised handpieces); moderate (slow-speed handpieces, prophylaxis, extractions) and lower (air-water syringe [water only] and hand scaling). Conclusion Gaps in evidence, low sensitivity of measures and variable quality limit conclusions around contamination for procedures. A hierarchy of contamination from procedures is proposed for challenge/verification by future research which should consider standardised methodologies to facilitate research synthesis. Clinical significance This manuscript addresses uncertainty around aerosol generating procedures (AGPs) in dentistry. Findings indicate a continuum of procedure-related aerosol generation rather than the common binary AGP or non-AGP perspective. The findings inform discussion around AGPs and direct future research to support knowledge and decision making around COVID-19 and dental procedures

Improved Outcome Prediction Using CT Angiography in Addition to Standard Ischemic Stroke Assessment: Results from the STOPStroke Study

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS.2. Strokes were classified as ‘‘major’ ’ by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was#7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores.10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p,0.0001). Combining NIHSS with BASIS was highly predictive: 77.6 % (114/147) classified as NIHSS.10/BASIS+ had poor outcomes, versus 21.5 % (77/358) with NIHSS#10/BASIS2 (p,0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95 % CI: 7.9 to 20.0