Forddougherty0301

Design Volumetric air flow was measured in a number of dental surgeries to calculate the air change rate per hour (ACHvent). In each surgery, measurements of aerosol removal by ventilation alone, and then with ventilation provided by a high-efficiency particulate air filter (PAC), were completed. The concentrations of aerosol particles of various sizes were recorded at baseline, after an initial period of incense burn, and then after 30 minutes of observation with and without the use of the PAC or ventilation system.Sample selection Ten dental surgeries with differing baseline ventilation rates had the concentrations of 0.3, 0.5 and 1.0 μm aerosol particles measured at 0 minutes, after 5 minutes of incense burn and then after 30 minutes of observation, firstly without the PAC system in operation and then with the PAC system in use.Data analysis For the 0.3 μm particles, velocities of aerosol removal were assessed by analysing the concentration decay constants with ventilation alone and ventilation with the PAHEPA filter significantly increased aerosol removal and lessened aerosol accumulation, particularly in rooms with low ventilation rates.Study design An experimental study design was used to investigate the spread of splatter/aerosol during simulated dental procedures on a mannequin in open plan clinic and dental clinical teaching laboratory settings. All experiments were based on crown preparation of an artificial maxillary central incisor using a high-speed air turbine over a ten-minute period. Fluorescein dye was introduced into the irrigation system of the handpiece (model 1) and the mannequin's mouth was used to simulate salivary flow (model 2) under varying experimental conditions (suction flow rate, cross ventilation and exposure time). Six experiments were conducted in the open plan clinic while three experiments were undertaken in the clinical laboratory. Customised rigs with collection platforms consisting of filter papers were placed in open plan bays and adjacent walkways. FIIN-2 concentration Samples were also collected from a 400 cm2 area in each of the eight adjacent bays. Time course experiments repeated the same procedures on three occasions in a cs. Risk of cross infection is small if the bays are >5 m apart and contamination can be minimised with the use of suction and cross ventilation.Design Cross-sectional, exploratory study collecting photographic referral data over three months.Sample selection Paediatric referrals to the orthodontic and maxillofacial department at Alder Hey Hospital during the COVID-19 pandemic.Data analysis Photographic referrals were analysed using Microsoft Excel to determine treatment outcomes, including 'not to see', 'plan to see' and 'need to see'. Demographic information collected and analysed were patient age, gender, referral source and presenting complaint.Results In total, 220 photographic referrals were received, with swelling (30%) and dental trauma (27%) being the most common presenting complaints. Fifty-seven percent of the referrals were not seen, 23% were seen semi-urgently and 20% booked for outpatient review. Of those seen, seven children were examined elsewhere, with 44 receiving face-to-face consultations at Alder Hey Children's Hospital, with eight being admitted.Conclusions Photographic triage has potential to be a useful adjunctive assessment tool for new patient referrals, with secondary benefits for training junior staff and for populations who already find access to dental services challenging. Feasibility studies on the application should be seriously considered. However, the unique circumstances which resulted in the development of a photographic triage method need to be considered when generalising its use to normal working conditions.Aim The aim of this retrospective cohort study was to determine and compare the seropositivity rates of SARS-CoV-2 among dental healthcare workers (HCWs) working in three different clinics using different types of aspirating systems. The study took place in Ekaterinburg (Russian Federation).Methods A total of 157 HCWs from three different clinics (56, 60 and 41 HCWs, respectively) who worked during the COVID-19 pandemic period (May to August 2020) constituted the cohort. All of the three chosen clinics had followed COVID-19 screening, triage and other recommendations for safe practice. In addition to using personal protective equipment and other common barrier methods to lower virus transmission, these clinics were equipped with different types of aspirating systems that included V6000 used in dry mode, V6000 used in semi-dry mode and VS900, respectively. All HCWs underwent serological testing once a week to detect immunoglobulin G and M antibodies against SARS-CoV-2 using SARS-CoV-2-IgG-EIA-BEST and SARS-CoV-2-IgM-EIA-BEST enzyme immunoassay kits (Vector-Best).Results An overall prevalence of seropositivity was observed to be 11.5% (19/157 HCWs) over a five-month follow-up. The prevalence of infection was not found to be associated with sex or the role of the member in the dental team (dentist/dental assistant). Significantly higher infection rates (p less then 0.001) were observed among HCWs working in the clinic equipped with the VS900 aspirating vacuum pump without HEPA filters, while the lowest infection rate was found among HCWs working in the clinic using the V6000 aspirating system in dry mode.Conclusions HCWs working in the clinic equipped with an aspirating system which has HEPA filters and released the air into an external environment (V6000) exhibited significantly lower seroprevalence rates compared to HCWs in the clinic using an aspirating system without HEPA filters which released air within the dental operatory away from the operation site (VS900).Data sources A search of electronic databases (PubMed and Google Scholar) was carried out, with publication being set from 2019 to October 2020.Study selection Titles and abstracts from the original search were reviewed by two reviewers independently. Overall, 17 studies were included in the final analysis.Data extraction and synthesis Data extraction was conducted independently by two reviewers. Studies that were chosen were examined and the following data parameters were included age and gender, COVID-19 polymerase chain reaction (PCR) test, COVID-19 manifestations, treatment for COVID-19, cutaneous lesions, oral manifestations, days after COVID-19 diagnosis, treat/healing or oral symptoms.Results Seventeen studies were included; 14 articles were case reports, two case series and one systematic review. The results showed that dry mouth, dysgeusia, oral ulcerations and opportunistic infections were among the most common oral manifestations expressed in COVID-19-positive patients.Conclusion The authors recommended carrying out careful clinical intraoral examinations on both COVID-19-positive patients or any patients requiring dental care, as oral symptoms can still be the only or initial symptom of COVID-19.

Pathogenic variants in Lysyl-tRNA synthetase 1 (KARS1) have increasingly been recognized as a cause of early-onset complex neurological phenotypes. To advance the timely diagnosis of KARS1-related disorders, we sought to delineate its phenotype and generate a disease model to understand its function in vivo.

Through international collaboration, we identified 22 affected individuals from 16 unrelated families harboring biallelic likely pathogenic or pathogenicin KARS1 variants. Sequencing approaches ranged from disease-specific panels to genome sequencing. We generated loss-of-function alleles in zebrafish.

We identify ten new and four known biallelic missense variants in KARS1 presenting with a moderate-to-severe developmental delay, progressive neurological and neurosensory abnormalities, and variable white matter involvement. We describe novel KARS1-associated signs such as autism, hyperactive behavior, pontine hypoplasia, and cerebellar atrophy with prevalent vermian involvement. Loss of kars1 leads to upregulation of p53, tissue-specific apoptosis, and downregulation of neurodevelopmental related genes, recapitulating key tissue-specific disease phenotypes of patients. Inhibition of p53 rescued several defects of kars1

knockouts.

Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets.

Our work delineates the clinical spectrum associated with KARS1 defects and provides a novel animal model for KARS1-related human diseases revealing p53 signaling components as potential therapeutic targets.

Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce. These data are important for counseling, therapies development, and improvement of outcome. The aim of this study is to gain knowledge on the natural history of ML by obtaining data on survival, symptom onset, presenting symptoms, diagnosis, and pathogenic variants associated with the MLII or MLIII phenotype.

A systematic review on all published MLII and MLIII cases between 1968 and August 2019 was performed.

Three hundred one articles provided data on 843 patients. Median age at diagnosis 0.7 for MLII and 9.0 years for MLIII. Median survival 5.0 for MLII and 62.0 years for MLIIIII. Median age of death 1.8 for MLII and 33.0 years for MLIII. Most frequent causes of death in all ML were pulmonary and/or cardiac complications. Pathogenic variants were described in 388 patients (GNPTAB 571, GNPTG 179).

This review provides unique insights into the natural history of MLII and MLIII, with a clear genotype-phenotype correlation with the most frequent pathogenic variant c.3503_3504del in MLII and in MLIII alpha/beta c.22A>G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.

G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our preclinical study included n = 49 xenografts generated from n = 9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification and clonal bone marrow evolution was reconstructed by serial whole-exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient-individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients' clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.The germline predisposition associated with the autosomal dominant inheritance of the 14q32 duplication implicating ATG2B/GSKIP genes is characterized by a wide clinical spectrum of myeloid neoplasms. We analyzed 12 asymptomatic carriers and 52 patients aged 18-74 years from six families, by targeted sequencing of 41 genes commonly mutated in myeloid malignancies. We found that 75% of healthy carriers displayed early clonal hematopoiesis mainly driven by TET2 mutations. Molecular landscapes of patients revealed two distinct routes of clonal expansion and leukemogenesis. The first route is characterized by the clonal dominance of myeloproliferative neoplasms (MPN)-driver events associated with TET2 mutations in half of cases and mutations affecting splicing and/or the RAS pathway in one-third of cases, leading to the early development of MPN, mostly essential thrombocythemia, with a high risk of transformation (50% after 10 years). The second route is distinguished by the absence of MPN-driver mutations and leads to AML without prior MPN.