Awake versus Asleep Anesthesia in Deep Brain Stimulation Surgery for Parkinson's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Deep brain stimulation (DBS) is a well-established surgical therapy for patients with Parkinsons' Disease (PD). Traditionally, DBS surgery for PD is performed under local anesthesia, whereby the patient is awake to facilitate intraoperative neurophysiological confirmation of the intended target using microelectrode recordings. General anesthesia allows for improved patient comfort without sacrificing anatomic precision and clinical outcomes. METHODS: We performed a systemic review and meta-analysis on patients undergoing DBS for PD. Published randomized controlled trials, prospective and retrospective studies, and case series which compared asleep and awake techniques for patients undergoing DBS for PD were included. A total of 19 studies and 1,900 patients were included in the analysis. RESULTS: We analyzed the (i) clinical effectiveness - postoperative UPDRS III score, levodopa equivalent daily doses and DBS stimulation requirements. (ii) Surgical and anesthesia related complications, number of lead insertions and operative time (iii) patient's quality of life, mood and cognitive measures using PDQ-39, MDRS, and MMSE scores. There was no significant difference in results between the awake and asleep groups, other than for operative time, for which there was significant heterogeneity. CONCLUSION: With the advent of newer technology, there is likely to have narrowing differences in outcomes between awake or asleep DBS. What would therefore be more important would be to consider the patient's comfort and clinical status as well as the operative team's familiarity with the procedure to ensure seamless transition and care.

Case series: Fundus autofluorescence abnormalities in a family of ocular albinism carriers.

SIGNIFICANCE: Carriers of ocular albinism demonstrate signs of retinal mosaicism with unique features on fundus autofluorescence testing, which differentiate this condition from other x-linked retinal disorders in carrier patients. Distinctive findings include a mud-splattered fundus with peripheral hyperpigmented streaks, which correlate with areas of hyperautofluorescence and hypoautofluorescence. PURPOSE: This is the first reported case series of a family that demonstrates diagnostic retinal and fundus autofluorescence abnormalities related to retinal mosaicism in three sisters who were unaware they were carriers of ocular albinism type 1. Multimodal imaging, electrodiagnostic testing, and genetic testing can be used to confirm the diagnosis and differentiate this clinical presentation from other sight-threatening hereditary retinal diseases. CASE REPORTS: Three sisters, aged 21, 17, and 13 years, were referred to determine the cause of abnormal retinal pigmentation. All presented with normal vision, and anterior segment examination was unremarkable without iris transillumination. They denied family history of ocular disease. Fundus examination of all three sisters revealed a mud-splattered pattern of pigmentation in the posterior pole and radial pigmentary streaks. Fundus autofluorescence showed a pattern of hyperautofluorescence and hypoautofluorescence corresponding to this pigmentary pattern. Spectral domain optical coherence tomography, electro-oculogram, and electroretinogram were normal in all three sisters. Genetic testing of their father, who was unaware of any disorder, tested positive for ocular albinism. CONCLUSIONS: Ocular albinism carriers have abnormal retinal pigmentation in a characteristic pattern. Fundus autofluorescence shows a correlative pattern that can confirm carrier status of ocular albinism in individuals unaware of their status and rule out other retinal degenerations.

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Personal health behaviors and physical activity and nutrition counseling by nurse practitioners: An online survey.

BACKGROUND: Healthy lifestyle counseling improves nutritional intake and participation in exercise, yet the rate of patient counseling varies and clinicians' personal behaviors can influence counseling practices. PURPOSE: This cross-sectional study evaluated lifestyle counseling by nurse practitioners (NPs) and the relationship between their personal behaviors and patient counseling. METHODOLOGY: Practicing NPs ( N = 1,220) completed an online survey regarding personal behaviors and counseling for healthy body weight, moderate-vigorous physical activity, muscle strengthening, fruit and vegetable consumption, and dietary protein. RESULTS: The majority reported counseling "usually" or "often" for healthy weight (54%), moderate-vigorous physical activity (53%), and fruits/vegetables (57%), whereas only 44% and 17% reported "usually" or "often" counseling for dietary protein and muscle strengthening. When NPs did not personally engage in the behavior, the odds for counseling were significantly reduced: NPs were 21% less likely to counsel for moderate-vigorous physical activity (odds ratio [OR] = 0.79 [0.65-0.97], p = .026), 27% less likely to counsel for muscle strengthening (OR = 0.73 [0.60-0.90], p = .004), 57% less likely to counsel for fruit/vegetable consumption (OR = 0.43 [0.35-0.54], p < .001), and 72% less likely to counsel for dietary protein (OR = 0.28 [0.18-0.45], p < .001). Personal body mass index did not predict counseling for a healthy weight. CONCLUSION: Although NPs report regular patient counseling regarding healthy lifestyle behaviors, the odds for counseling are increased approximately 20-75% when they engage in the behaviors themselves. IMPLICATIONS: Promotion of healthy behaviors during professional education may have long-term implications for preventive health counseling.

Evaluating the effects of antimicrobial drug use on the ecology of antimicrobial resistance and microbial community structure in beef feedlot cattle.

Introduction: Use of antimicrobial drugs (AMDs) in food producing animals has received increasing scrutiny because of concerns about antimicrobial resistance (AMR) that might affect consumers. Previously, investigations regarding AMR have focused largely on phenotypes of selected pathogens and indicator bacteria, such as Salmonella enterica or Escherichia coli. However, genes conferring AMR are known to be distributed and shared throughout microbial communities. The objectives of this study were to employ target-enriched metagenomic sequencing and 16S rRNA gene amplicon sequencing to investigate the effects of AMD use, in the context of other management and environmental factors, on the resistome and microbiome in beef feedlot cattle. Methods: This study leveraged samples collected during a previous longitudinal study of cattle at beef feedlots in Canada. This included fecal samples collected from randomly selected individual cattle, as well as composite-fecal samples from randomly selected pens of cattle. All AMD use was recorded and characterized across different drug classes using animal defined daily dose (ADD) metrics. Results: Overall, fecal resistome composition was dominated by genes conferring resistance to tetracycline and macrolide-lincosamide-streptogramin (MLS) drug classes. The diversity of bacterial phyla was greater early in the feeding period and decreased over time in the feedlot. This decrease in diversity occurred concurrently as the microbiome represented in different individuals and different pens shifted toward a similar composition dominated by Proteobacteria and Firmicutes. Some antimicrobial drug exposures in individuals and groups were associated with explaining a statistically significant proportion of the variance in the resistome, but the amount of variance explained by these important factors was very small (<0.6% variance each), and smaller than associations with other factors measured in this study such as time and feedlot ID. Time in the feedlot was associated with greater changes in the resistome for both individual animals and composite pen-floor samples, although the proportion of the variance associated with this factor was small (2.4% and 1.2%, respectively). Discussion: Results of this study are consistent with other investigations showing that, compared to other factors, AMD exposures did not have strong effects on antimicrobial resistance or the fecal microbial ecology of beef cattle.

Genomic Characterization of Enterococcus hirae From Beef Cattle Feedlots and Associated Environmental Continuum.

Enterococci are commensal bacteria of the gastrointestinal tract of humans, animals, and insects. They are also found in soil, water, and plant ecosystems. The presence of enterococci in human, animal, and environmental settings makes these bacteria ideal candidates to study antimicrobial resistance in the One-Health continuum. This study focused on Enterococcus hirae isolates (n = 4,601) predominantly isolated from beef production systems including bovine feces (n = 4,117, 89.5%), catch-basin water (n = 306, 66.5%), stockpiled bovine manure (n = 24, 0.5%), and natural water sources near feedlots (n = 145, 32%), and a few isolates from urban wastewater (n = 9, 0.2%) denoted as human-associated environmental samples. Antimicrobial susceptibility profiling of a subset (n = 1,319) of E. hirae isolates originating from beef production systems (n = 1,308) showed high resistance to tetracycline (65%) and erythromycin (57%) with 50.4% isolates harboring multi-drug resistance, whereas urban wastewater isolates (n = 9) were resistant to nitrofurantoin (44.5%) and tigecycline (44.5%) followed by linezolid (33.3%). Genes for tetracycline (tetL, M, S/M, and O/32/O) and macrolide resistance erm(B) were frequently found in beef production isolates. Antimicrobial resistance profiles of E. hirae isolates recovered from different environmental settings appeared to reflect the kind of antimicrobial usage in beef and human sectors. Comparative genomic analysis of E. hirae isolates showed an open pan-genome that consisted of 1,427 core genes, 358 soft core genes, 1701 shell genes, and 7,969 cloud genes. Across species comparative genomic analysis conducted on E. hirae, Enterococcus faecalis and Enterococcus faecium genomes revealed that E. hirae had unique genes associated with vitamin production, cellulose, and pectin degradation, traits which may support its adaptation to the bovine digestive tract. E. faecium and E. faecalis more frequently harbored virulence genes associated with biofilm formation, iron transport, and cell adhesion, suggesting niche specificity within these species.

Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Paediatric brain tumours in Singapore: A 15-year epidemiological and outcome study.

Paediatric brain tumours (PBTs) are the most common solid tumours in children. Previous publications reflect variations in incidence rates and frequency of histological types in different global populations. However, there are limited studies on the epidemiology of PBTs in Singapore. This study aims to summarise the epidemiology of paediatric brain tumours managed in Singapore. This is an ethics-approved retrospective study of all patients below 19 years old diagnosed with PBTs managed by Singapore's 2 tertiary paediatric neurosurgical centres, KK Women's and Children's Hospital (KKH) and the National University Hospital (NUH) over a 15-year period from 01 January 2002 to 31 December 2017. Data collected was analysed for age, gender, tumour characteristics, presenting complaints, location, treatment modalities, 1-year and 5-year overall survival (OS). A total of 396 patients were included. The mean age of diagnosis was 7.05 years (0.25-18; ± 4.83) and male-to-female ratio was 1.41:1. Top histological groups were astrocytic (30.6%), embryonal (26.0%), germ cell (11.1%), ependymoma (30, 7.58%) and craniopharyngioma (27, 6.82%). Outcomes included recurrence rate (31.2%), 1-year OS (89.5%) and 5-year OS (72.2%). Poorer 5-year OS were noted in embryonal tumours (47.0%; p < 0.001) and ependymoma (50.0%; p = 0.0074) patients. Of note, the following cohorts also had poorer OS at 5 years: supratentorial tumours (76.2%; p = 0.0426), radiotherapy (67.4%; p = 0.0467) and surgery (74.9%, HR; p < 0.001). Overall, our data reflects patient demographics, presenting complaints, treatment modalities and survival outcomes, that are comparable to other international paediatric neurosurgical centres.

Environmental performance of commercial beef production systems utilizing conventional productivity-enhancing technologies.

The objective of this study was to evaluate the effects of using conventional productivity-enhancing technologies (PETs) with or without other natural PETs on the growth performance, carcass traits, and environmental impacts of feedlot cattle. A total of 768 cross-bred yearling steers (499 ±â€…28.6 kg; n = 384) and heifers (390 ±â€…34.9 kg; n = 384) were offered a barley grain-based basal diet and divided into implanted or non-implanted groups. Steers were then allocated to diets that contained either: (i) no additive (control); natural feed additives including (ii) fibrolytic enzymes (Enz), (iii) essential oil (Oleo), (iv) direct-fed microbial (DFM), (v) DFM + Enz + Oleo combination; conventional feed additives including (vi) Conv (monensin, tylosin, and beta-adrenergic agonists [ßAA]); or Conv with natural feed additives including (vii) Conv + DFM + Enz; (viii) Conv + DFM + Enz + Oleo. Heifers received one of the first three dietary treatments or the following: (iv) probiotic (Citr); (v) Oleo + Citr; (vi) Melengesterol acetate (MGA) + Oleo + ßAA; (vii) Conv (monensin, tylosin, ßAA, and MGA); or (viii) Conv + Oleo (ConvOleo). Data were used to estimate greenhouse gas (GHG) and ammonia (NH3) emissions, as well as land and water use. Implant and Conv-treated cattle exhibited improvements in growth and carcass traits as compared to the other treatments (P < 0.05). Improvements in the performance of Conv-cattle illustrated that replacing conventional feed additives with natural feed additives would increase both the land and water required to satisfy the feed demand of steers and heifers by 7.9% and 10.5%, respectively. Further, GHG emission intensity for steers and heifers increased by 5.8% and 6.7%, and NH3 emission intensity by 4.3% and 6.7%, respectively. Eliminating the use of implants in cattle increased both land and water use by 14.6% and 19.5%, GHG emission intensity by 10.5% and 15.8%, and NH3 emission intensity by 3.4% and 11.0% for heifers and steers, respectively. These results demonstrate that the use of conventional PETs increases animal performance while reducing the environmental impacts of beef production. Restricting use would increase the environmental footprint of beef produced for both domestic and international markets.

A heavy-ion production channel of 149Tb via 63Cu bombardment of 89Y.

The radionuclide 149Tb (t1/2 = 4.1 h) is a potential theranostic isotope which can simultaneously be used for targeted-alpha-particle therapy and positron-emission tomography. Feasibility experiments were performed to test a near-symmetric heavy-ion reaction of 63Cu bombardment on monoisotopic 89Y. The indirect reaction was studied to avoid isomer production. Offline gamma spectroscopy was used to quantify thick-target physical yields and experimental results show modest agreement to the fusion-evaporation code PACE4. A near-symmetric fission yield was also observed.

A neuronal mechanism controlling the choice between feeding and sexual behaviors in Drosophila.

Animals must express the appropriate behavior that meets their most pressing physiological needs and their environmental context. However, it is currently unclear how alternative behavioral options are evaluated and appropriate actions are prioritized. Here, we describe how fruit flies choose between feeding and courtship; two behaviors necessary for survival and reproduction. We show that sex- and food-deprived male flies prioritize feeding over courtship initiation, and manipulation of food quality or the animal's internal state fine-tunes this decision. We identify the tyramine signaling pathway as an essential mediator of this decision. Tyramine biosynthesis is regulated by the fly's nutritional state and acts as a satiety signal, favoring courtship over feeding. Tyramine inhibits a subset of feeding-promoting tyramine receptor (TyrR)-expressing neurons and activates P1 neurons, a known command center for courtship. Conversely, the perception of a nutritious food source activates TyrR neurons and inhibits P1 neurons. Therefore, TyrR and P1 neurons are oppositely modulated by starvation, via tyramine levels, and food availability. We propose that antagonistic co-regulation of neurons controlling alternative actions is key to prioritizing competing drives in a context- dependent manner.

Prevalence and Risk Factors Associated With Antimicrobial Resistance in Bacteria Related to Bovine Respiratory Disease-A Broad Cross-Sectional Study of Beef Cattle at Entry Into Canadian Feedlots.

A broad, cross-sectional study of beef cattle at entry into Canadian feedlots investigated the prevalence and epidemiology of antimicrobial resistance (AMR) in Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, bacterial members of the bovine respiratory disease (BRD) complex. Upon feedlot arrival and before antimicrobials were administered at the feedlot, deep nasopharyngeal swabs were collected from 2,824 feedlot cattle in southern and central Alberta, Canada. Data on the date of feedlot arrival, cattle type (beef, dairy), sex (heifer, bull, steer), weight (kg), age class (calf, yearling), source (ranch direct, auction barn, backgrounding operations), risk of developing BRD (high, low), and weather conditions at arrival (temperature, precipitation, and estimated wind speed) were obtained. Mannheimia haemolytica, P. multocida, and H. somni isolates with multidrug-resistant (MDR) profiles associated with the presence of integrative and conjugative elements were isolated more often from dairy-type than from beef-type cattle. Our results showed that beef-type cattle from backgrounding operations presented higher odds of AMR bacteria as compared to auction-derived calves. Oxytetracycline resistance was the most frequently observed resistance across all Pasteurellaceae species and cattle types. Mycoplasma bovis exhibited high macrolide minimum inhibitory concentrations in both cattle types. Whether these MDR isolates establish and persist within the feedlot environment, requires further evaluation.

METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes.

The methylase METTL3 is the writer enzyme of the N6 -methyladenosine (m6 A) modification of RNA. Using a structure-based drug discovery approach, we identified a METTL3 inhibitor with potency in a biochemical assay of 280 nM, while its enantiomer is 100 times less active. We observed a dose-dependent reduction in the m6 A methylation level of mRNA in several cell lines treated with the inhibitor already after 16 h of treatment, which lasted for at least 6 days. Importantly, the prolonged incubation (up to 6 days) with the METTL3 inhibitor did not alter levels of other RNA modifications (i. e., m1 A, m6 Am , m7 G), suggesting selectivity of the developed compound towards other RNA methyltransferases.

Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.

OBJECTIVES: Efforts to develop and deploy effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue at pace. Here, we describe rational antigen design through to manufacturability and vaccine efficacy of a prefusion-stabilised spike (S) protein, Sclamp, in combination with the licensed adjuvant MF59 'MF59C.1' (Seqirus, Parkville, Australia). METHODS: A panel recombinant Sclamp proteins were produced in Chinese hamster ovary and screened in vitro to select a lead vaccine candidate. The structure of this antigen was determined by cryo-electron microscopy and assessed in mouse immunogenicity studies, hamster challenge studies and safety and toxicology studies in rat. RESULTS: In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. CONCLUSION: The SARS-CoV-2 Sclamp vaccine candidate is compatible with large-scale commercial manufacture, stable at 2-8°C. When formulated with MF59 adjuvant, it elicits neutralising antibodies and T-cell responses and provides protection in animal challenge models.

Feedlot Cattle Antimicrobial Use Surveillance Network: A Canadian Journey.

Antimicrobial drugs are important tools for maintaining human and animal health. Globally, antimicrobial use (AMU) in food-producing animals is under increasing scrutiny due to its potential to promote antimicrobial resistance (AMR). Historically, comprehensive Canadian data related to the types of antimicrobial drugs used, extent of use, common indicators of use and the demographics of the cattle populations receiving antimicrobial drugs have been limited, in part due to segmentation in the cattle industry and fragmentation of the drug distribution system. Appropriate AMU estimates are required to understand AMU practices, to interpret AMR levels and patterns, to meaningfully assess associated public health risks, and to inform stewardship activities. The Canadian beef cattle industry has a long history of collaboration in AMU and AMR research. Prior research projects identified both opportunities and challenges in the collection of AMU data. Cornerstone projects provided insight into the complexity of collecting AMU data in Canada's feedlot sector. This paper will discuss how the lessons learned from past work have contributed to the formation of a Canadian fed-cattle antimicrobial surveillance program that was initiated in 2019. This important surveillance program will allow feedlot cattle AMU to improve management decisions and support AMU best practices in the evolving Canadian AMR landscape.

Multidrug Resistance in Pasteurellaceae Associated With Bovine Respiratory Disease Mortalities in North America From 2011 to 2016.

Multidrug-resistant (MDR; resistance to ≥3 antimicrobial classes) members of the Pasteurellaceae family may compromise the efficacy of therapies used to prevent and treat bovine respiratory disease (BRD) in feedlot cattle. This study examined the prevalence of multidrug resistance in strains of Mannheimia haemolytica and Pasteurella multocida collected from BRD cattle mortalities in North America. Isolates of M. haemolytica (n = 147) and P. multocida (n = 70) spanning 69 Alberta feedlots from 2011 to 2016 and two United States feedlots from 2011 to 2012 were examined for antimicrobial resistance (AMR) in association with integrative and conjugative elements (ICEs). Overall, resistance was high in both bacterial species with an increase in the prevalence of MDR isolates between 2011 and 2016. Resistance to >7 antimicrobial drugs occurred in 31% of M. haemolytica and 83% of P. multocida isolates. Resistance to sulfadimethoxine, trimethoprim/sulfamethoxazole, neomycin, clindamycin oxytetracycline, spectinomycin, tylosin, tilmicosin, and tulathromycin was most common. Although >80% of strains harbored three or more ICE-associated genes, only 12% of M. haemolytica and 77% of P. multocida contained all six, reflecting the diversity of ICEs. There was evidence of clonal spread as P. multocida and M. haemolytica isolates with the same pulsed-field gel electrophoresis profile from the United States in 2011 were isolated in Alberta in 2015-2016. This work highlights that MDR strains of Pasteurellaceae containing ICEs are widespread and may be contributing to BRD therapy failure in feedlot cattle. Given the antimicrobial resistance gene profiles identified, these MDR isolates may be selected for by the use of macrolides, tetracyclines, and/or in-feed supplements containing heavy metals.

Astatine partitioning between nitric acid and conventional solvents: indication of covalency in ketone complexation of AtO.

Astatine-211 has been produced at Texas A&M University on the K150 cyclotron, with a yield of 890 ± 80 MBq through the 209Bi(α,2n)211At reaction via an 8 h bombardment with a beam current of 4-8 µA and an α-particle beam energy of 28.8 MeV. The target was then dissolved in HNO3 and the extraction of 211At was investigated into a variety of organic solvents in 1-3 M HNO3. Extraction of 211At with distribution ratios as high as 11.3 ± 0.6, 12.3 ± 0.8, 42.2 ± 2.2, 69 ± 4, and 95 ± 6 were observed for diisopropyl ether, 1-decanol, 1-octanol, 3-octanone, and methyl isobutyl ketone, respectively, while the distribution ratios for 207Bi were ≤0.05 in all cases. The extraction of 211At into both methyl isobutyl ketone and 3-octanone showed a strong, linear dependence on the HNO3 initial aqueous concentration and better extraction than other solvents. DFT calculations show stronger binding between the carbonyl oxygen of the ketone and the At metal center.

Dioxin-like compound exposures and DNA methylation in the Anniston Community Health Survey Phase II.

The Anniston Community Health Survey (ACHS-I) was initially conducted from 2005 to 2007 to assess polychlorinated biphenyl (PCB) exposures in Anniston, Alabama residents. In 2014, a follow-up study (ACHS-II) was conducted to measure the same PCBs as in ACHS-I and additional compounds e.g., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like non-ortho (cPCBs) substituted PCBs. In this epigenome-wide association study (EWAS), we examined the associations between PCDD, PCDF, and PCB exposures and DNA methylation. Whole blood DNA methylation was measured using Illumina EPIC arrays (n=292). We modeled lipid-adjusted toxic equivalencies (TEQs) for: ΣDioxins (sum of 28 PCDDs, PCDFs, cPCBs, and mPCBs), PCDDs, PCDFs, cPCBs, and mPCBs using robust multivariable linear regression adjusting for age, race, sex, smoking, bisulfite conversion batch, and estimated percentages of six blood cell types. Among all exposures we identified 10 genome-wide (Bonferroni p≤6.74E-08) and 116 FDR (p≤5.00E-02) significant associations representing 10 and 113 unique CpGs, respectively. Of the 10 genome-wide associations, seven (70%) occurred in the PCDDs and four (40%) of these associations had an absolute differential methylation ≥1.00%, based on the methylation difference between the highest and lowest exposure quartiles. Most of the associations (six, 60%) represented hypomethylation changes. Of the 10 unique CpGs, eight (80%) were in genes shown to be associated with dioxins and/or PCBs based on data from the 2019 Comparative Toxicogenomics Database. In this study, we have identified a set of CpGs in blood DNA that may be particularly susceptible to dioxin, furan, and dioxin-like PCB exposures.