Dental periodontal procedures: a systematic review of contamination (splatter, droplets and aerosol) in relation to COVID-19

Introduction The emergence of the SARS-CoV-2 virus and subsequent COVID-19 pandemic has had a significant effect on the delivery of routine dentistry; and in particular, periodontal care across the world. This systematic review examines the literature relating to splatter, droplet settle and aerosol for periodontal procedures and forms part of a wider body of research to understand the risk of contamination in relation to periodontal care procedures relevant to COVID-19. Methods A search of the literature was carried out using key terms and MeSH words relating to the review questions. Sources included Medline (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science and LILACS, ClinicalTrials.Gov. Studies meeting inclusion criteria were screened in duplicate and data extraction was carried out using a template. All studies were assessed for methodological quality and sensitivity. Narrative synthesis was undertaken. Results Fifty studies were included in the review with procedures including ultrasonic scaling (n = 44), air polishing (n = 4), prophylaxis (n = 2) and hand scaling (n = 3). Outcomes included bacterial (colony-forming units e.g. on settle plates) or blood contamination (e.g. visible splatter) and non bacterial, non blood (e.g. chemiluminescence or coloured dyes) contamination. All studies found contamination at all sites although the contamination associated with hand scaling was very low. Contamination was identified in all of the studies even where suction was used at baseline. Higher power settings created greater contamination. Distribution of contamination varied in relation to operator position and was found on the operator, patient and assistant with higher levels around the head of the operator and the mouth and chest of the patient. Settle was identified 30 min after treatments had finished but returned to background levels when measured at or after an hour. The evidence was generally low to medium quality and likely to underestimate contamination. Conclusion Ultrasonic scaling, air polishing and prophylaxis procedures produce contamination (splatter, droplets and aerosol) in the presence of suction, with a small amount of evidence showing droplets taking between 30 min and 1 h to settle. Consideration should be given to infection control, areas of cleaning particularly around the patient and appropriate personal protective equipment, with particular attention to respiratory, facial and body protection for these procedures. In addition, the use of lower power settings should be considered to reduce the amount and spread of contamination

Limbic-Predominant Age-Related TDP-43 Encephalopathy (LATE): Consensus Working Group Report

We describe a recently recognized disease entity, limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE neuropathological change (LATE-NC) is defined by a stereotypical TDP-43 proteinopathy in older adults, with or without coexisting hippocampal sclerosis pathology. LATE-NC is a common TDP-43 proteinopathy, associated with an amnestic dementia syndrome that mimicked Alzheimer’s-type dementia in retrospective autopsy studies. LATE is distinguished from frontotemporal lobar degeneration with TDP-43 pathology based on its epidemiology (LATE generally affects older subjects), and relatively restricted neuroanatomical distribution of TDP-43 proteinopathy. In community-based autopsy cohorts, ∼25% of brains had sufficient burden of LATE-NC to be associated with discernible cognitive impairment. Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-β plaques and tauopathy. Given that the ‘oldest-old’ are at greatest risk for LATE-NC, and subjects of advanced age constitute a rapidly growing demographic group in many countries, LATE has an expanding but under-recognized impact on public health. For these reasons, a working group was convened to develop diagnostic criteria for LATE, aiming both to stimulate research and to promote awareness of this pathway to dementia. We report consensus-based recommendations including guidelines for diagnosis and staging of LATE-NC. For routine autopsy workup of LATE-NC, an anatomically-based preliminary staging scheme is proposed with TDP-43 immunohistochemistry on tissue from three brain areas, reflecting a hierarchical pattern of brain involvement: amygdala, hippocampus, and middle frontal gyrus. LATE-NC appears to affect the medial temporal lobe structures preferentially, but other areas also are impacted. Neuroimaging studies demonstrated that subjects with LATE-NC also had atrophy in the medial temporal lobes, frontal cortex, and other brain regions. Genetic studies have thus far indicated five genes with risk alleles for LATE-NC: GRN, TMEM106B, ABCC9, KCNMB2, and APOE. The discovery of these genetic risk variants indicate that LATE shares pathogenetic mechanisms with both frontotemporal lobar degeneration and Alzheimer’s disease, but also suggests disease-specific underlying mechanisms. Large gaps remain in our understanding of LATE. For advances in prevention, diagnosis, and treatment, there is an urgent need for research focused on LATE, including in vitro and animal models. An obstacle to clinical progress is lack of diagnostic tools, such as biofluid or neuroimaging biomarkers, for ante-mortem detection of LATE. Development of a disease biomarker would augment observational studies seeking to further define the risk factors, natural history, and clinical features of LATE, as well as eventual subject recruitment for targeted therapies in clinical trials

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology

LATE-NC staging in routine neuropathologic diagnosis : an update

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.Peer reviewe

Peroxisome proliferators-activated receptor γ2 Pro12Ala variant is associated with body mass index in non-alcoholic fatty liver disease patients

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and commonly associated with insulin resistance and metabolic syndrome (MS). Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor abundantly expressed in adipocytes and plays a key role in the regulation of adipocyte differentiation, lipid and glucose homeostasis. Pro12Ala variant has been earlier associated with obesity, type 2 diabetes and MS. Aim: The present study aimed to determine the genotype frequencies of the Pro12Ala variant in NAFLD patients and any further association with other phenotype in the patients. Patients and methods: Ninety-eight NAFLD patients and 280 matched controls were genotyped for presence of the Pro12Ala variant. Genomic DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism using Bst-UI was performed for the detection of C-G change at codon 12 position of PPAR γ2 gene. Genotype and allele frequencies were compared between patients and controls. The Hardy-Weinberg equilibrium was tested by comparing expected/observed genotype frequencies by χ<SUP>2</SUP> test. Results: The frequencies of Pro/Ala genotype were comparable between NAFLD patients and controls. In the controls, 213 (75.7%) were homozygous for the wild-type (Pro/Pro) genotype and 67 (23.9%) were heterozygous (Pro/Ala). In NAFLD patients, genotypic distribution of wild type, heterozygous and homozygous were 63 (64.3%), 34 (34.7%) and 1 (1%), respectively. Heterozygous genotype was found to be significantly higher in the patients (P = 0.01). We also analyzed related phenotypic association of the patients with Pro12Ala genotype. We observed that the Pro12Ala (heterozygous) genotype was significantly higher in the patients who had body mass index &gt;25 kg/m<SUP>2</SUP> (P = 0.025). Conclusions: Pro12Ala variation of the PPAR γ2 gene is associated with NAFLD and might play a role in the pathogenesis of NAFLD

Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: (1) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and (2) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers. Keywords: cancer, circulating tumor cells, diagnostic nucleic acids, nucleases, diagnostic markers, breast cancer, liquid biops