Pesticide exposure and increased breast cancer risk in women population studies.

Pesticide exposure is emerging as a risk factor for various human diseases. Breast cancer (BC) is a multifactorial disease with known genetic and non-genetic risk factors. Most BC cases are attibutable to non-genetic risk factors, with a history of adverse environmental exposures playing a significant role. Pesticide exposure can occur at higher levels in female populations participating in rural activities such as spraying of pesticides in the field, unprotected handling of pesticides at home, and washing of contaminated clothes. Exposure can also be significant in the drinking water of certain populations. Here, we reviewed the literature on women's exposure to pesticides and the risk of BC. We summarize the main links between pesticide exposure and BC and discuss the role of dose and exposure context, as well as potential mechanisms of toxicity. Overall, reports reviewed here have documented stronger associations between higher levels of exposure and BC risk, including documenting direct and acute pesticide exposure in certain female populations. However, discrepancies among studies regarding dose and mode of exposure may result in misunderstandings about the risks posed by pesticide exposure. Plausible mechanisms linking pesticides to breast cancer risk include their impacts as endocrine disruptors, as well as their roles as genotoxic agents, and modulators of the epigenome. Besides establishing links between pesticide exposure and breast cancer, the literature also highlights the critical need to understand the routes and doses of women's exposure to pesticides and the specific associations and mechanisms that are determinants of disease etiology and prognosis.

Evidence of reduced gestational age in response to in utero arsenic exposure and implications for aging trajectories of the newborn.

Arsenic exposure is associated with a plethora of age-related health outcomes of disparate etiology. However, evidence of the impact of arsenic on aging remains limited. Here, we investigated the utility of epigenetic clocks in two different populations and the impact of maternal arsenic exposure during pregnancy on epigenetic gestational age at birth. To do this, we examined publicly available DNA methylation data and estimated gestational age across five gestational clocks in two unrelated human populations. These populations also differ in the extent of arsenic exposure and the targeted tissue of analysis (cord blood and placental tissue). Our results indicate that same-tissue clocks produce gestational age estimates that are more highly correlated with clinical gestational age. Interestingly, our results also indicate that arsenic exposure is associated with gestational age, with higher arsenic exposures associated with decreased gestational age. We also applied two pediatric clocks to evaluate infant biological age in the same samples. The data is suggestive of higher pediatric age in infants exposed to higher arsenic levels during gestation. Taken altogether, our findings are consistent with past work indicating that that in utero arsenic exposure is associated with decreased gestational maturity as characterized by infant outcomes such as low birthweight and lung underdevelopment and dysfunction in arsenic exposed infants. The findings are also consistent with arsenic exposure setting infants on a trajectory of accelerated epigenetic aging that starts at birth.

Defining high confidence targets of differential CpG methylation in response to in utero arsenic exposure and implications for cancer risk.

Arsenic is a relatively abundant metalloid that impacts DNA methylation and has been implicated in various adverse health outcomes including several cancers and diabetes. However, uncertainty remains about the identity of genomic CpGs that are sensitive to arsenic exposure, in utero or otherwise. Here we identified a high confidence set of CpG sites whose methylation is sensitive to in utero arsenic exposure. To do so, we analyzed methylation of infant CpGs as a function of maternal urinary arsenic in cord blood and placenta from geographically and ancestrally distinct human populations. Independent analyses of these distinct populations were followed by combination of results across sexes and populations/tissue types. Following these analyses, we concluded that both sex and tissue type are important drivers of heterogeneity in methylation response at several CpGs. We also identified 17 high confidence CpGs that were hypermethylated across sex, tissue type and population; 11 of these were located within protein coding genes. This pattern is consistent with hypotheses that arsenic increases cancer risk by inducing the hypermethylation of genic regions. This study represents an opportunity to understand consistent, reproducible patterns of epigenomic responses after in utero arsenic exposure and may aid towards novel biomarkers or signatures of arsenic exposure. Identifying arsenic-responsive sites can also contribute to our understanding of the biological mechanisms by which arsenic exposure can affect biological function and increase risk of cancer and other age-related diseases.

The implications of DNA methylation for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a complex and serious neurodegenerative disorder that develops in consequence of the progressive loss of the upper and lower motor neurons. Cases of ALS are classified as sporadic (sALS), or familial (fALS). Over 90% of cases are sALS, while roughly 10% are related to inherited genetic mutations (fALS). Approximately 70% of the genetic mutations that contribute to fALS have been identified. On the other hand, the majority of the sALS cases have an undetermined genetic contributor and few mutations have been described, despite the advanced genetic analysis methods. Also, several factors contribute to the onset and progression of ALS. Numerous lines of evidence indicate that epigenetic changes are linked to aging, as well as neurodegenerative disorders, such as ALS. In most cases, they act as the heritable regulation of transcription by DNA methylation, histone modification and expression of noncoding RNAs. Mechanisms involving aberrant DNA methylation could be relevant to human ALS pathobiology and therapeutic targeting. Despite advances in research to find factors associated with ALS and more effective treatments, this disease remains complex and has low patient survival. Here, we provide a narrative review of the role of DNA methylation for this complex neurodegenerative disorder.

N6-methyladenosine upregulates ribosome biogenesis in environmental carcinogenesis.

Many trace metal pollutants in surface water, the atmosphere, and soil are carcinogenic, and ribosome biogenesis plays an important role in the carcinogenicity of heavy metals. However, the contradiction between upregulated ribosome biogenesis and decreased ribosomal DNA copy number in environmental carcinogenesis is not fully understood. Here, from a perspective of the most predominant and abundant RNA epigenetic modification, N6-methyladenosine (m6A), we explored the reason behind this contradiction at the post-transcriptional level using arsenite-induced skin carcinogenesis models both in vitro and in vivo. Based on the m6A microarray assay and a series of experiments, we found for the first time that the elevated m6A in arsenite-induced transformation is mainly enriched in the genes regulating ribosome biogenesis. m6A upregulates ribosome biogenesis post-transcriptionally by stabilizing ribosomal proteins and modulating non-coding RNAs targeting ribosomal RNAs and proteins, leading to arsenite-induced skin carcinogenesis. Using multi-omics analysis of human subjects and experimental validation, we identified an unconventional role of a well-known key proliferative signaling node AKT1 as a vital mediator between m6A and ribosome biogenesis in arsenic carcinogenesis. m6A activates AKT1 and transmits proliferative signals to ribosome biogenesis, exacerbating the upregulation of ribosome biogenesis in arsenite-transformed keratinocytes. Similarly, m6A promotes cell proliferation by upregulating ribosome biogenesis in cell transformation induced by carcinogenic heavy metals (chromium and nickel). Importantly, inhibiting m6A reduces ribosome biogenesis. Targeted inhibition of m6A-upregulated ribosome biogenesis effectively prevents cell transformation induced by trace metals (arsenic, chromium, and nickel). Our results reveal the mechanism of ribosome biogenesis upregulated by m6A in the carcinogenesis of trace metal pollutants. From the perspective of RNA epigenetics, our study improves our understanding of the contradiction between upregulated ribosome biogenesis and decreased ribosomal DNA copy number in the carcinogenesis of environmental carcinogens.

Y chromosome-linked variation affects locomotor activity in male Drosophila melanogaster and is robust to differences in thermal environment.

Although containing genes important for sex determination, genetic variation within the Y chromosome was traditionally predicted to contribute little to the expression of sexually dimorphic traits. This prediction was shaped by the assumption that the chromosome harbours few protein-coding genes, and that capacity for Y-linked variation to shape adaptation would be hindered by the chromosome's lack of recombination and holandric inheritance. Consequently, most studies exploring the genotypic contributions to sexually dimorphic traits have focused on the autosomes and X chromosome. Yet, several studies have now demonstrated that the Y chromosome harbours variation affecting male fitness, moderating the expression of hundreds of genes across the nuclear genome. Furthermore, emerging results have shown that expression of this Y-linked variation may be sensitive to environmental heterogeneity, leading to the prediction that Y-mediated gene-by-environment interactions will shape the expression of sexually dimorphic phenotypes. We tested this prediction, investigating whether genetic variation across six distinct Y chromosome haplotypes affects the expression of locomotor activity, at each of two temperatures (20 and 28 °C) in male fruit flies (Drosophila melanogaster). Locomotor activity is a sexually dimorphic trait in this species, previously demonstrated to be under intralocus sexual conflict. We demonstrate Y haplotype effects on male locomotor activity, but the rank order and magnitude of these effects were unaltered by differences in temperature. Our study contributes to a growing number of studies demonstrating Y-linked effects moderating expression of traits evolving under sexually antagonistic selection, suggesting a role for the Y chromosome in shaping outcomes of sexual conflict.

Novel Epigenetic Clock Biomarkers of Age-Related Macular Degeneration.

Age-Related Macular Degeneration (AMD) is a bilateral ocular condition resulting in irreversible vision impairment caused by the progressive loss of photoreceptors in the macula, a region at the center of the retina. The progressive loss of photoreceptor is a key feature of dry AMD but not always wet AMD, though both forms of AMD can lead to loss of vision. Regression-based biological age clocks are one of the most promising biomarkers of aging but have not yet been used in AMD. Here we conducted analyses to identify regression-based biological age clocks for the retina and explored their use in AMD using transcriptomic data consisting of a total of 453 retina samples including 105 Minnesota Grading System (MGS) level 1 samples, 175 MGS level 2, 112 MGS level 3 and 61 MGS level 4 samples, as well as 167 fibroblast samples. The clocks yielded good separation among AMD samples with increasing severity score viz., MGS1-4, regardless of whether clocks were trained in retina tissue, dermal fibroblasts, or in combined datasets. Clock application to cultured fibroblasts, embryonic stem cells, and induced Pluripotent Stem Cells (iPSCs) were consistent with age reprograming in iPSCs. Moreover, clock application to in vitro neuronal differentiation suggests broader applications. Interesting, many of the age clock genes identified include known targets mechanistically linked to AMD and aging, such as GDF11, C16ORF72, and FBN2. This study provides new observations for retina age clocks and suggests new applications for monitoring in vitro neuronal differentiation. These clocks could provide useful markers for AMD monitoring and possible intervention, as well as potential targets for in vitro screens.

Concordance of SARS-CoV-2 RNA in Aerosols From a Nurses Station and in Nurses and Patients During a Hospital Ward Outbreak.

Importance: Aerosol-borne SARS-CoV-2 has not been linked specifically to nosocomial outbreaks. Objective: To explore the genomic concordance of SARS-CoV-2 from aerosol particles of various sizes and infected nurses and patients during a nosocomial outbreak of COVID-19. Design, Setting, and Participants: This cohort study included patients and nursing staff in a US Department of Veterans Affairs inpatient hospital unit and long-term-care facility during a COVID-19 outbreak between December 27, 2020, and January 8, 2021. Outbreak contact tracing was conducted using exposure histories and screening with reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. Size-selective particle samplers were deployed in diverse clinical areas of a multicampus health care system from November 2020 to March 2021. Viral genomic sequences from infected nurses and patients were sequenced and compared with ward nurses station aerosol samples. Exposure: SARS-CoV-2. Main Outcomes and Measures: The primary outcome was positive RT-PCR results and genomic similarity between SARS-CoV-2 RNA in aerosols and human samples. Air samplers were used to detect SARS-CoV-2 RNA in aerosols on hospital units where health care personnel were or were not under routine surveillance for SARS-CoV-2 infection. Results: A total of 510 size-fractionated air particle samples were collected. Samples representing 3 size fractions (>10 µm, 2.5-10 µm, and <2.5 µm) obtained at the nurses station were positive for SARS-CoV-2 during the outbreak (3 of 30 samples [10%]) and negative during 9 other collection periods. SARS-CoV-2 partial genome sequences for the smallest particle fraction were 100% identical with all 3 human samples; the remaining size fractions shared >99.9% sequence identity with the human samples. Fragments of SARS-CoV-2 RNA were detected by RT-PCR in 24 of 300 samples (8.0%) in units where health care personnel were not under surveillance and 7 of 210 samples (3.3%; P = .03) where they were under surveillance. Conclusions and Relevance: In this cohort study, the finding of genetically identical SARS-CoV-2 RNA fragments in aerosols obtained from a nurses station and in human samples during a nosocomial outbreak suggests that aerosols may have contributed to hospital transmission. Surveillance, along with ventilation, masking, and distancing, may reduce the introduction of community-acquired SARS-CoV-2 into aerosols on hospital wards, thereby reducing the risk of hospital transmission.

Widespread pesticide contamination of drinking water and impact on cancer risk in Brazil.

Pesticides, which are associated with endocrine dysfunction, immunological dysregulation, and cancer, are widespread sources of drinking water contamination. The state of Paraná has a population of 11 million, is the second largest grain producer in Brazil and is a leading consumer of pesticides. In this study, we analyzed the extent of drinking water contamination from 11 proven, probable, or potentially carcinogenic pesticides (alachlor, aldrin-dieldrin, atrazine, chlordane, DDT-DDD-DDE, diuron, glyphosate-AMPA, lindane-γ-HCH, mancozeb-ETU, molinate, and trifluralin) in 127 grain-producing municipalities in the state of Paraná. Extensive contamination of drinking water was found, including legacy pesticides such as aldrin-dieldrin (mean 0.047 ppb), DDT-DDD-DDE (mean: 0.07), chlordane (mean: 0.181), and lindane-HCH (mean: 2.17). Most of the municipalities were significantly above the maximum limits for each one of the currently allowed pesticides (67% for alachlor, 9.44% for atrazine, 96.85% for diuron, 100% for glyphosate-AMPA, 80.31% for mancozeb-ETU, 91.33% for molinate, and 12.6% for trifluralin). Ninety-seven percent of municipalities presented a sum of all pesticides at levels significantly above (189.84 ppb) the European Union preconized limits (<0.5 ppb). Using the mean pesticide concentration in water (ppb), the exposed population for each municipality, and the benchmark cancer risk for pesticides, we estimated the minimum number of cancer cases attributable to pesticide-contaminated drinking water during the period (total of 542 cases). More than 80% were attributed to mancozeb-ETU and diuron. Glyphosate-AMPA and diuron-attributable cases strongly correlated with the total cancer cases in the same period (R = 0.8117 and 0.8138, respectively) as well as with breast cancer cases (R = 0.7695 and 0.7551, respectively). Water contamination was significantly correlated with the sum of the estimated cancer cases for all 11 pesticides detected in each city (R = 0.58 and p < 0.0001). These findings reveal extensive contamination of drinking water in the state of Paraná and suggest that contamination may increase the risk of cancer in this region.

Effect of the bileaflet inlet valve angle on the flow of a pediatric ventricular assist device: Experimental analysis.

BACKGROUND: Mechanical heart valves (MHV) and its fluid dynamics inside a pulsatile pediatric ventricular assist device (PVAD) can be associated with blood degradation. In this article, flow structures are analyzed and compared by an experimental investigation on the effect of bileaflet MHV positioned at varying angles in the inlet port orifice of a PVAD. METHODS: Time-resolved particle image velocimetry was applied to characterize the internal flow of the device. St Jude Medical bileaftlet valves were used on the inlet orifice and positioned at 0°, 15°, 30°, 45°, 60°, and 90° in relation to the centerline of the device. Three planes with bidimensional velocity magnitude fields were considered in the analysis with visualization of diastolic jets, device wall washing patterns and flow circulation during emptying or systole of the pump. Also, the washing vortex area, and vertical velocity probabilities of regurgitant flows in the inlet valve were evaluated. RESULTS: The results show that a variation in the angle of the MHV at the inlet port produced distinct velocities, fluid structures, and regurgitant flow probabilities within the device. MHV positioned at an angle of 0° generated the strongest inlet jet, larger vortex area during filling, more prominent outgoing flow, and less regurgitation compared to the angles studied. The presence of unfavorable fluid structures, such as small vortices, and/or sudden flow structure interruption, and/or regurgitation, were identified at 45° and 90° angles. CONCLUSIONS: The 0° inlet angle had better outcomes than other angles due to its consistency in the multiple parameters analyzed.

The role of H3K9 acetylation and gene expression in different brain regions of Alzheimer's disease patients.

Aims: To evaluate H3K9 acetylation and gene expression profiles in three brain regions of Alzheimer's disease (AD) patients and elderly controls, and to identify AD region-specific abnormalities. Methods: Brain samples of auditory cortex, hippocampus and cerebellum from AD patients and controls underwent chromatin immunoprecipitation sequencing, RNA sequencing and network analyses. Results: We found a hyperacetylation of AD cerebellum and a slight hypoacetylation of AD hippocampus. The transcriptome revealed differentially expressed genes in the hippocampus and auditory cortex. Network analysis revealed Rho GTPase-mediated mechanisms. Conclusions: These findings suggest that some crucial mechanisms, such as Rho GTPase activity and cytoskeletal organization, are differentially dysregulated in brain regions of AD patients at the epigenetic and transcriptomic levels, and might contribute toward future research on AD pathogenesis.

Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population. The onset and progression of AD are influenced by environmental factors, which are able to promote epigenetic changes on the DNA and/or the DNA-associated proteins called histones. We investigated a specific epigenetic modification of histones (H3K9 acetylation) in three brain regions of AD patients and compared them with elderly controls. We found increased levels of H3K9 acetylation in the cerebellum of AD patients, as well as a slight decrease of this modification in the hippocampus of the same patients. These brain tissues from AD patients showed abnormal gene expression patterns when compared with elderly controls. These findings contribute to understanding the molecular changes that occur in AD, and provide a basis for future research or drug development for AD treatment.

Post-transcriptional diversity in riboproteins and RNAs in aging and cancer.

Post-transcriptional (PtscM) and post-translational (PtrnM) modifications of nucleotides and amino acids are covalent modifications able to change physio-chemical properties of RNAs and proteins. In the ribosome, the adequate assembly of rRNAs and ribosomal protein subunits in the nucleolus ensures suitable translational activity, with protein synthesis tuned according to intracellular demands of energy production, replication, proliferation, and growth. Disruption in the regulatory control of PtscM and PtrnM can impair ribosome biogenesis and ribosome function. Ribosomal impairment may, in turn, impact the synthesis of proteins engaged in functions as varied as telomere maintenance, apoptosis, and DNA repair, as well as intersect with mitochondria and telomerase activity. These cellular processes often malfunction in carcinogenesis and senescence. Here we discuss regulatory mechanisms of PtscMs and PtrnMs on ribosomal function. We also address chemical modification in rRNAs and their impacts on cellular metabolism, replication control, and senescence. Further, we highlight similarities and differences of PtscMs and PtrnMs in ribosomal intermediates during aging and carcinogenesis. Understanding these regulatory mechanisms may uncover critical steps for the development of more efficient oncologic and anti-aging therapies.

High-Power LED Units Currently Available for Dental Resin-Based Materials-A Review.

The pursuit of less time-consuming procedures led to the development of high-power light-curing-units (LCU) to light-cure dental-resin-based-materials. This review aims to describe high-power light-emitting-diode (LED)-LCUs, by a bibliometric systematization of in vitro and in vivo studies. The research-question, by PICO model, aimed to assess the current knowledge on dentistry-based high-power LED-LCUs by analyzing to what extent their use can promote adverse events on materials and patients' oral condition when compared to low-power LED-LCUs, on daily dental practice. PubMed and B-on database search focused on high-power (≥2000 mW/cm2) LED-LCUs outputs. Studies assessing performance of high-power LED-LCUs for light-curing dental-resin-based-materials were included. From 1822 screened articles, 21 fulfilled the inclusion criteria. Thirty-two marketed units with high levels of radiant emittance (≥2000 mW/cm2 up to 6000 mW/cm2) were identified. Most output values vary on 2000-3000 mW/cm2. The highest output found was 6000 mW/cm2, in FlashMax™P3. Reports suggest that light-curing protocols with lower emittance irradiance and longer exposure outperforms all other combination, however in some clinical procedures high-power LED-LCUs are advocated when compared to low-power LED-LCUs. Moreover, long time exposures and over-curing can be dangerous to the biological vital pulp, and other oral tissues. Evidence showing that high-power LCUs are the best clinical option is still very scarce.

The association of epigenetic clocks in brain tissue with brain pathologies and common aging phenotypes.

Epigenetic clocks are calculated by combining DNA methylation states across select CpG sites to estimate biologic age, and have been noted as the most successful markers of biologic aging to date. Yet, limited research has considered epigenetic clocks calculated in brain tissue. We used DNA methylation states in dorsolateral prefrontal cortex specimens from 721 older participants of the Religious Orders Study and Rush Memory and Aging Project, to calculate DNA methylation age using four established epigenetic clocks: Hannum, Horvath, PhenoAge, GrimAge, and a new Cortical clock. The four established clocks were trained in blood samples (Hannum, PhenoAge, GrimAge) or using 51 human tissue and cell types (Horvath); the recent Cortical clock is the first trained in postmortem cortical tissue. Participants were recruited beginning in 1994 (Religious Orders Study) and 1997 (Memory and Aging Project), and followed annually with questionnaires and clinical evaluations; brain specimens were obtained for 80-90% of participants. Mean age at death was 88.0 (SD 6.7) years. We used linear regression, logistic regression, and linear mixed models, to examine relations of epigenetic clock ages to neuropathologic and clinical aging phenotypes, controlling for chronologic age, sex, education, and depressive symptomatology. Hannum, Horvath, PhenoAge and Cortical clock ages were related to pathologic diagnosis of Alzheimer's disease (AD), as well as to Aß load (a hallmark pathology of Alzheimer's disease). However, associations were substantially stronger for the Cortical than other clocks; for example, each standard deviation (SD) increase in Hannum, Horvath, and PhenoAge clock age was related to approximately 30% greater likelihood of pathologic AD (all p < 0.05), while each SD increase in Cortical age was related to 90% greater likelihood of pathologic AD (odds ratio = 1.91, 95% confidence interval 1.38, 2.62). Moreover, Cortical age was significantly related to other AD pathology (eg, mean tau tangle density, p = 0.003), and to odds of neocortical Lewy body pathology (for each SD increase in Cortical age, odds ratio = 2.00, 95% confidence 1.27, 3.17), although no clocks were related to cerebrovascular neuropathology. Cortical age was the only epigenetic clock significantly associated with the clinical phenotypes examined, from dementia to cognitive decline (5 specific cognitive systems, and a global cognitive measure averaging 17 tasks) to Parkinsonian signs. Overall, our findings provide evidence of the critical necessity for bespoke clocks of brain aging for advancing research to understand, and eventually prevent, neurodegenerative diseases of aging.

Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)].

Hexavalent Chromium [Cr (VI)] is an established toxicant, carcinogen, and a significant source of public health concern. The multicopy ribosomal DNA (rDNA) array is mechanistically linked to aging and cancer, is the most evolutionarily conserved segment of the human genome, and gives origin to nucleolus, a nuclear organelle where ribosomes are assembled. Here we show that exposure to Cr (VI) induces instability in the rDNA, triggering cycles of rapid, specific, and transient amplification and contraction of the array in human cells. The dynamic of environmentally responsive rDNA copy number (CN) amplification and contraction occurs at doses to which millions of individuals are regularly exposed. Finally, analyses of human populations occupationally exposed to Cr (VI) indicate that environmental exposure history and drinking habits but not age shape extensive naturally occurring rDNA copy number variation. Our observations identify a novel pathway of response to hexavalent chromium exposure and raise the prospect that a suite of environmental determinants of rDNA copy number remain to be discovered.

Characterization of hospital airborne SARS-CoV-2.

BACKGROUND: The mechanism for spread of SARS-CoV-2 has been attributed to large particles produced by coughing and sneezing. There is controversy whether smaller airborne particles may transport SARS-CoV-2. Smaller particles, particularly fine particulate matter (≤ 2.5 µm in diameter), can remain airborne for longer periods than larger particles and after inhalation will penetrate deeply into the lungs. Little is known about the size distribution and location of airborne SARS-CoV-2 RNA. METHODS: As a measure of hospital-related exposure, air samples of three particle sizes (> 10.0 µm, 10.0-2.5 µm, and ≤ 2.5 µm) were collected in a Boston, Massachusetts (USA) hospital from April to May 2020 (N = 90 size-fractionated samples). Locations included outside negative-pressure COVID-19 wards, a hospital ward not directly involved in COVID-19 patient care, and the emergency department. RESULTS: SARS-CoV-2 RNA was present in 9% of samples and in all size fractions at concentrations of 5 to 51 copies m-3. Locations outside COVID-19 wards had the fewest positive samples. A non-COVID-19 ward had the highest number of positive samples, likely reflecting staff congregation. The probability of a positive sample was positively associated (r = 0.95, p < 0.01) with the number of COVID-19 patients in the hospital. The number of COVID-19 patients in the hospital was positively associated (r = 0.99, p < 0.01) with the number of new daily cases in Massachusetts. CONCLUSIONS: More frequent detection of positive samples in non-COVID-19 than COVID-19 hospital areas indicates effectiveness of COVID-ward hospital controls in controlling air concentrations and suggests the potential for disease spread in areas without the strictest precautions. The positive associations regarding the probability of a positive sample, COVID-19 cases in the hospital, and cases in Massachusetts suggests that hospital air sample positivity was related to community burden. SARS-CoV-2 RNA with fine particulate matter supports the possibility of airborne transmission over distances greater than six feet. The findings support guidelines that limit exposure to airborne particles including fine particles capable of longer distance transport and greater lung penetration.

Digital Impressions in Implant Dentistry: A Literature Review.

INTRODUCTION: Digital impressions in implant dentistry rely on many variables, and their accuracy, particularly in complete edentulous patients, is not well understood. Aim. The purpose of this literature review was to determine which factors may influence the accuracy of digital impressions in implant dentistry. Emphasized attention was given to the design of the intra-oral scan body (ISB) and scanning techniques. MATERIALS AND METHODS: A Medline, PubMed and EBSCO Host databases search, complemented by a hand search, was performed in order to select relevant reports regarding the appliance of digital impressions in implant dentistry. The search subject included but was not limited to accuracy of digital impressions in implant dentistry, digital scanning techniques, the design and material of the ISBs, and the depth and angulation of the implant. The related titles and abstracts were screened, and the remaining articles that fulfilled the inclusion criteria were selected for full-text readings. RESULTS: The literature search conducted for this review initially resulted in 108 articles, among which only 21 articles fulfilled the criteria for inclusion. Studies were evaluated according to five subjects: accuracy of digital impressions in implant dentistry; the design and material of the intra-oral scan bodies; scanning technique; the influence of implants depth/angulations on the digital impression and accuracy of different intra-oral scanner devices. CONCLUSIONS: The accuracy of digital impressions in implant dentistry depends on several aspects. The depth/angulation of the implant, the experience of the operator, the intra-oral scanner used, and environmental conditions may influence the accuracy of digital impressions in implant dentistry. However, it seems that ISBs' design and material, as well as scanning technique, have a major impact on the trueness and precision of digital impressions in implant dentistry. Future research is suggested for the better understanding of this subject, focusing on the optimization of the ISB design and scanning protocols.

Effects of Different Undersizing Site Preparations on Implant Stability.

As immediate loading protocols are becoming more frequent, the primary stability of implants has become an essential criterion for the osseointegration of dental implants. Based on this, the objective of this study was to understand the influence of different undersized surgical preparation sites on the insertion torque (IT) and implant stability quotient (ISQ). Four different site-preparation protocols were performed on fresh humid type III bovine bone: one control, the standard protocol recommended by the manufacturer (P1), and three variations of undersized techniques (P2, P3 and P4). The implant used was VEGA by Klockner Implant System. The sample size was n = 40 for each of the four groups. A torquemeter was used to measure the IT, and the ISQ was measured with a Penguin RFA. Both variables showed a tendency to increase as the preparation technique was reduced, although not all the values were statistically significant (p < 0.05) when comparing with the standard preparation. The preparations without a cortical drill, P2 and P4, showed better results than those with a cortical drill. Given the limitations of this study, it can be concluded that reducing the implant preparation can increase both the IT and ISQ. Removing the cortical drill is an effective method for increasing implant stability, although it should be used carefully.

Exposure to microplastics cause gut damage, locomotor dysfunction, epigenetic silencing, and aggravate cadmium (Cd) toxicity in Drosophila.

The interactions of microplastics (MPs) with other chemicals and the range of outcomes are of great importance to enhance understanding of their environmental impacts and health risks. Cadmium (Cd) and cadmium compounds are widely used as pigments and stabilizers in plastics, but they readily leach out. Here we addressed the impacts of MPs, Cd, and their joint exposure in a tractable Drosophila melanogaster model. We show that exposure to MPs lead to extensive particle size depended gut damage early in life and an enhancement of Cd-induced inhibition of locomotor-behavioral function in adult flies. In addition, we show that Cd exposure induces epigenetic gene silencing via position-effect variegation (PEV) in somatic tissues that was dramatically enhanced by co-exposure with MPs. The results indicate that MPs can aggravate the toxicity of other environmental contaminants and induce adverse effects across a range of diverse outcomes in a tractable and widely used model organism. These observations raise the prospects of using Drosophila as a tool for the rapid assessment of MP-mediated toxicity.

Ganglioneuromas are driven by activated AKT and can be therapeutically targeted with mTOR inhibitors.

Peripheral sympathetic nervous system tumors are the most common extracranial solid tumors of childhood and include neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Surgery is the only effective therapy for ganglioneuroma, which may be challenging due to the location of the tumor and involvement of surrounding structures. Thus, there is a need for well-tolerated presurgical therapies that could reduce the size and extent of ganglioneuroma and therefore limit surgical morbidity. Here, we found that an AKT-mTOR-S6 pathway was active in human ganglioneuroma but not neuroblastoma samples. Zebrafish transgenic for constitutively activated myr-Akt2 in the sympathetic nervous system were found to develop ganglioneuroma without progression to neuroblastoma. Inhibition of the downstream AKT target, mTOR, in zebrafish with ganglioneuroma effectively reduced the tumor burden. Our results implicate activated AKT as a tumorigenic driver in ganglioneuroma. We propose a clinical trial of mTOR inhibitors as a means to shrink large ganglioneuromas before resection in order to reduce surgical morbidity.