Search

Azizi A Seixas,1,2 Arlener D Turner,2 Omonigho Michael Bubu,1,2 Girardin Jean-Louis,1,2 Mony J de Leon,3 Ricardo S Osorio,2 Lidia Glodzik3 1New York University Grossman School of Medicine, Department of Population Health, New York, NY, 10016, USA; 2New York University Grossman School of Medicine, Department of Psychiatry, New York, NY, 10016, USA; 3Weill Cornell Medicine, Department of Radiology, New York, NY, 10021, USACorrespondence: Azizi A SeixasDepartments of Population Health and Psychiatry, New York University Grossman School of Medicine, 180 Madison Avenue, Office # 715, New York, NY, 10016, USATel +1 646-501-3430Fax +1 212-263-4595Email Azizi.Seixas@nyulangone.orgObjective: Compared to European Americans, research indicates that African Americans have higher white matter hyperintensity (WMH) load; however, the clinical and biological bases underlying this higher burden are poorly understood. We hypothesize that obesity may explain differences in WMH between African and European Americans.Methods: Participants enrolled in longitudinal brain aging studies (n=292; 61% Female; 92% European American; mean age=69.6± 7.7) completed evaluations including medical exams, neuroimaging, and sociodemographic surveys. Overweight/obese status defined as body mass index ≥ 30 kg/m2, and WMH load, captured by FLAIR images, as sum of deep and periventricular volumes, scored using the Fazekas scale (0– 6), WMH≥ 4 considered high.Results: Logistic regression analyses, adjusted for age, sex, hypertension, and smoking history, indicated that age and interaction between race and obesity were significant predictors of WMH, demonstrating that obesity significantly moderated the relationship between race and WMH. Age independently increased the odds of high WMH by 16% (OR=1.16, 95% CI=1.09– 1.23, p< 0.001). Stratified analysis indicates that older European Americans had increased WMH (OR=1.17, 95% CI=1.09– 1.23, p< 0.001), while obese African Americans had increased WMH (OR=27.65, 95% CI=1.47– 519.13, p< 0.05). In a case controlled subgroup matched by age, sex, and education (n=48), African Americans had significantly higher WMH load (27% vs 4%, &KHgr;2=5.3, p=0.02).Conclusion: Results denote that age predicted WMH among European Americans, while obesity predicted WMH among African Americans. Matched sample analyses indicate that obesity increases the odds of WMH, though more pronounced in African Americans. These findings suggest that obesity may explain the differential burden of white matter hyperintensity load, signifying public health and clinical importance.Keywords: white matter hyperintensities, WMH, racial/ethnic differences, African American, obesity

Girardin Jean-Louis,1 Arlener D Turner,1 Peng Jin,2 Mengling Liu,2 Carla Boutin-Foster,3 Samy I McFarlane,3 Azizi Seixas1 1Departments of Population Health, Psychiatry, and Biostatistics, New York University Langone Health, New York, NY, USA; 2Department of Biostatistics, New York University Langone Health, New York, NY, USA; 3Departments of Medicine and Endocrinology, SUNY Downstate Medical Center, New York, NY, USACorrespondence: Girardin Jean-LouisNYU Grossman School of Medicine, 180 Madison Avenue, 7th Floor, New York, NY 10016, USATel +1 646.501.3431Email Girardin.Jean-Louis@nyulangone.orgAbstract: Mounting evidence shows a disproportionate COVID-19 burden among Blacks. Early findings indicate pre-existing metabolic burden (eg, obesity, hypertension and diabetes) as key drivers of COVID-19 severity. Since Blacks exhibit higher prevalence of metabolic burden, we examined the influence of metabolic syndrome on disparate COVID-19 burden. We analyzed data from a NIH-funded study to characterize metabolic burden among Blacks in New York (Metabolic Syndrome Outcome Study). Patients (n=1035) were recruited from outpatient clinics, where clinical and self-report data were obtained. The vast majority of the sample was overweight/obese (90%); diagnosed with hypertension (93%); dyslipidemia (72%); diabetes (61%); and nearly half of them were at risk for sleep apnea (48%). Older Blacks (age≥ 65 years) were characterized by higher levels of metabolic burden and co-morbidities (eg, heart disease, cancer). In multivariate-adjusted regression analyses, age was a significant (p≤ .001) independent predictor of hypertension (OR=1.06; 95% CI: 1.04– 1.09), diabetes (OR=1.03; 95% CI: 1.02– 1.04), and dyslipidemia (OR=0.98; 95% CI: 0.97– 0.99), but not obesity. Our study demonstrates an overwhelmingly high prevalence of the metabolic risk factors related to COVID-19 among Blacks in New York, highlighting disparate metabolic burden among Blacks as a possible mechanism conferring the greater burden of COVID-19 infection and mortality represented in published data.Keywords: COVID-19 burden, blacks, metabolic syndrome, metabolic risk factors, disparities

Fifth- and 6th-grade girls nominated by their teachers as having few friends participated in a manualized group treatment program for six sessions. Each treatment session consisted of three phases: a praise phase, interpersonal problem solving, and an activity phase. Pretest-posttest measurements included direct observations of target behaviors (conversing with others, initiating interaction, approached by another child, and being alone) and the Social Skills Rating System (Gresham & Elliot, 1988). Significant differences were noted between experimental participants and controls on three observational categories. At posttest, the treatment group spent less time alone, more time initiating conversations, and more time interacting with others than the control group. Suggestions are provided for enhancing programs similar to the one evaluated here. [ABSTRACT FROM AUTHOR]

Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging food safety concern. Although reports on spatial and temporal distribution have increased in recent years, processes leading to TTX accumulation in European bivalves are yet to be described. Here, we explored the hypothesis that the ribbon worm species Cephalothrix simula , known to contain high levels of TTX, could play a role in the trophic transfer of the toxin into shellfish. During a field study at a single location in southern England, we confirmed C. simula DNA in seawater adjacent to trestle-farmed Pacific oysters Magallana gigas (formerly Crassostrea gigas ) with a history of TTX occurrence. C. simula DNA in seawater was significantly higher in June and July during the active phase of toxin accumulation compared to periods of either no or continually decreasing TTX concentrations in M. gigas . In addition, C. simula DNA was detected in oyster digestive glands collected on 15 June 2021, the day with the highest recorded C. simula DNA abundance in seawater. These findings show evidence of a relationship between C. simula and TTX occurrence, providing support for the hypothesis that bivalves may acquire TTX through filter-feeding on microscopic life forms of C. simula present in the water column at particular periods each year. Although further evidence is needed to confirm such feeding activity, this study significantly contributes to discussions about the biological source of TTX in European bivalve shellfish.

Purpose: Sleep is an essential physiologic process, which is frequently disrupted in children with illness and/or injury. Accurate identification and quantification of sleep may provide insights to improve long-term clinical outcomes. Traditionally, however, the identification of sleep stages has relied on the resource-intensive and time-consuming gold standard polysomnogram. We sought to use limited EEG data, converted into density spectrum array EEG, to accurately identify sleep stages in a clinical pediatric population., Methods: We reviewed 87 clinically indicated pediatric polysomnographic studies with concurrent full montage EEG, between March 2017 and June 2020, of which 11 had normal polysomnogram and EEG interpretations. We then converted the EEG data of those normal studies into density spectral array EEG trends and had five blinded raters classify sleep stage (wakefulness, nonrapid eye movement [NREM] 1, NREM 2, NREM 3, and rapid eye movement) in 5-minute epochs. We compared the classified sleep stages from density spectral array EEG to the gold standard polysomnogram., Results: Inter-rater reliability was highest (κ = 0.745, P < 0.0001) when classifying state into wakefulness, NREM sleep, and rapid eye movement sleep. Agreement between group classification and polysomnogram was highest (κ = 0.873, [0.819, 0.926], P < 0.0001) when state was classified into wakefulness and sleep and was lowest (κ = 0.674 [0.645, 0.703], P < 0.0001) when classified into wakefulness, NREM 1, NREM 2, NREM 3, and rapid eye movement. The most common error that raters made was overscoring of NREM 1., Conclusions: Density spectral array EEG can be used to identify sleep stages in clinical pediatric patients without relying on traditional polysomnography., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 by the American Clinical Neurophysiology Society.)

Harmful algal bloom (HAB) toxins consumed by marine predators through fish prey can be lethal but studies on the resulting population consequences are lacking. Over the past approximately 20 years there have been large regional declines in some harbour seal populations around Scotland. Analyses of excreta (faeces and urine from live and dead seals and faecal samples from seal haulout sites) suggest widespread exposure to toxins through the ingestion of contaminated prey. A risk assessment model, incorporating concentrations of the two major HAB toxins found in seal prey around Scotland (domoic acid (DA), and saxitoxins (STX)), the seasonal persistence of the toxins in the fish and the foraging patterns of harbour seals were used to estimate the proportion of adults and juveniles likely to have ingested doses above various estimated toxicity thresholds. The results were highly dependent on toxin type, persistence, and foraging regime as well as age class, all of which affected the proportion of exposed animals exceeding toxicity thresholds. In this preliminary model STX exposure was unlikely to result in mortalities. Modelled DA exposure resulted in doses above an estimated lethal threshold of 1900 µg/kg body mass affecting up to 3.8 % of exposed juveniles and 5.3 % of exposed adults. Given the uncertainty in the model parameters and the limitations of the data these conclusions should be treated with caution, but they indicate that DA remains a potential factor involved in the regional declines of harbour seals. Similar risks may be experienced by other top predators, including small cetaceans and seabirds that feed on similar prey in Scottish waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

There are limited reports of neurobehavioral outcomes of children supported on extracorporeal membrane oxygenation (ECMO). This observational study aims to characterize the long-term (≥1 year) neurobehavioral outcomes, identify risk factors associated with neurobehavioral impairment, and evaluate the trajectory of functional status in pediatric ECMO survivors. Pediatric ECMO survivors ≥1-year postdecannulation and ≥3 years of age at follow-up were prospectively enrolled and completed assessments of adaptive behavior (Vineland Adaptive Behavior Scales, Third Edition [Vineland-3]) and functional status (Functional Status Scale [FSS]). Patient characteristics were retrospectively collected. Forty-one ECMO survivors cannulated at 0.0-19.8 years (median: 2.4 [IQR: 0.0, 13.1]) were enrolled at 1.3-12.8 years (median: 5.5 [IQR: 3.3, 6.5]) postdecannulation. ECMO survivors scored significantly lower than the normative population in the Vineland-3 Adaptive Behavior Composite (85 [IQR: 70, 99], P < 0.001) and all domains (Communication, Daily Living, Socialization, Motor). Independent risk factors for lower Vineland-3 composite scores included extracorporeal cardiopulmonary resuscitation, electrographic seizures during ECMO, congenital heart disease, and premorbid developmental delay. Of the 21 patients with impaired function at discharge (FSS ≥8), 86% reported an improved FSS at follow-up. Pediatric ECMO survivors have, on average, mild neurobehavioral impairment related to adaptive functioning years after decannulation. Continued functional recovery after hospital discharge is likely., (Copyright © ASAIO 2024.)

Pharmaceuticals are recognised as environmental contaminants of emerging concern (CECs) due to their increasing presence in the aquatic environment, along with high bioactivity linked to their therapeutic use. Therefore, information on environmental levels is urgently required. This study examined the presence of a range of common pharmaceuticals in oysters and mussels intended for human consumption from England and Wales using stable isotope dilution tandem mass spectrometry. A range of compounds were detected in bivalve tissue, with the Selective Serotonin Reuptake Inhibitor antidepressant sertraline being most abundant, reaching a maximum concentration of 22.1 ng/g wet weight shellfish tissue. Levels of all pharmaceuticals showed seasonal and geographical patterns. A dietary risk assessment revealed that the levels of pharmaceuticals identified in bivalve molluscs represent a clear hazard, but not a risk for the consumer. This study highlights the requirement for further monitoring of the presence of pharmaceuticals and other CECs in bivalve molluscs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the differences in internalizing symptoms between those who met criteria for Cannabis Use Disorder (CUD) and those who did not in young adults attending a Historically Black College or University (HBCU)., Participants: The sample included 619 undergraduate students, with 110 (18%) who met criteria for CUD., Methods: Participants completed an online survey, which included demographic, anxious and depressive symptomatology, and substance use assessment., Results: Those who met CUD criteria reported more depressive symptoms (M = 22.83 ± 10.74) and anxiety symptoms (M = 45.70 ± 12.82) than their non-CUD counterparts (M = 19.17 ± 10.58; M = 40.57 ± 14.11, respectively)., Conclusion: Differences between those who met criteria for CUD and those who did not are consistent with previous literature and may aid in characterizing internalizing behaviors in HBCU students with CUD. Future research should examine the subgroups that may cycle through withdrawal symptoms, despite not having severe CUD. This subgroup may be at higher risk for psychopathology than their severe counterparts.

The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida. We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida. Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species., (© 2023. Springer Nature Limited.)

Certain species of marine microalgae produce potent biotoxins that pose a risk to human health if contaminated seafood is consumed, particularly filter feeding bivalve shellfish. In regions where this is likely to occur water and seafood produce are regularly monitored for the presence of harmful algal cells and their associated toxins, but the current approach is flawed by a lengthy delay before results are available to local authorities. Quantitative Polymerase Chain Reaction (qPCR) can be used to measure phytoplankton DNA sequences in a shorter timeframe, however it is not currently used in official testing practices. In this study, samples were collected almost weekly over six months from three sites within a known HAB hotspot, St Austell Bay in Cornwall, England. The abundance of algal cells in water was measured using microscopy and qPCR, and lipophilic toxins were quantified in mussel flesh using LC-MS/MS, focusing on the okadaic acid group. An increase in algal cell abundance occurred alongside an increase in the concentration of okadaic acid group toxins in mussel tissue at all three study sites, during September and October 2021. This event corresponded to an increase in the measured levels of Dinophysis accuminata DNA, measured using qPCR. In the following spring, the qPCR detected an increase in D. accuminata DNA levels in water samples, which was not detected by microscopy. Harmful algal species belonging to Alexandrium spp. and Pseudo-nitzschia spp. were also measured using qPCR, finding a similar increase in abundance in Autumn and Spring. The results are discussed with consideration of the potential merits and limitations of the qPCR technique versus conventional microscopy analysis, and its potential future role in phytoplankton surveillance under the Official Controls Regulations pertaining to shellfish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Warming could facilitate the intensification of toxic algal blooms, two important stressors for marine organisms that are predicted to co-occur more frequently in the future. We investigated the immediate and delayed effects of a heatwave and a simulated bloom (3 × 10 6 cells L -1) of the diarrhetic shellfish toxin (DST)-producing benthic dinoflagellate Prorocentrum lima on the survival, physiology (oxygen consumption rate, condition index, immune parameters), and toxin accumulation in the Pacific rock oyster Magallana (Crassostrea) gigas. Oysters exposed to both stressors contained higher mean DST concentrations (mean ± 1 SE: 173.3 ± 19.78 μg kg -1 soft tissue) than those exposed to P. lima bloom alone (120.4 ± 20.90 μg kg -1 ) and exceeded the maximum permitted levels for human consumption. Exposure to individual stressors and their combination modified the physiology of M. gigas. Oysters exposed to heatwave alone had significantly higher oxygen consumption rates (0.7 ± 0.06 mg O 2 h -1  g -1 ) than the control (0.3 ± 0.06 mg O 2 h -1  g -1 ). However, this was not observed in oysters exposed to both heatwave and P. lima (0.5 ± 0.06 mg O 2 h -1  g -1 ). This alteration of the metabolic response to warming in the presence of P. lima may affect the ability of rock oysters to adapt to environmental stressors (i.e., a heatwave) to ensure survival. Immunomodulation, through changes in total hemocyte count, was observed in oysters exposed to P. lima alone and in combination with warming. Individual stressors and their combination did not influence the condition index, but one mortality was recorded in oysters exposed to both stressors. The findings of this study highlight the vulnerability of rock oysters to the predicted increased frequency of heatwaves and toxic algal blooms, and the increased likelihood of shellfish containing higher than regulatory levels of DST in warming coasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The farming of shellfish plays an important role in providing sustainable economic growth in coastal, rural communities in Scotland and acts as an anchor industry, supporting a range of ancillary jobs in the processing, distribution and exporting industries. The Scottish Government is encouraging shellfish farmers to double their economic contribution by 2030. These farmers face numerous challenges to reach this goal, among which is the problem caused by toxin-producing microplankton that can contaminate their shellfish, leading to harvesting site closure and the recall of product. Food Standards Scotland, a non-ministerial department of the Scottish Government, carries out a monitoring programme for both the toxin-producing microplankton and the toxins in shellfish flesh, with farms being closed when official thresholds for any toxin are breached. The farm remains closed until testing for the problematic toxin alone, often diarrhetic shellfish toxin (DST), shows the site to have dropped below the regulatory threshold. While this programme has proved to be robust, questions remain regarding the other toxins that may be present at a closed site. In this study, we tested archival material collected during site closures but only tested for DSTs as part of the official control monitoring. We found the presence of amnesic shellfish toxin (AST) in low concentrations in the majority of sites tested. In one case, the level of AST breached the official threshold. This finding has implications for AST monitoring programmes around Europe.

Study Objectives: Neurocognitive impairments in comorbid insomnia and sleep apnea (COMISA) are not well documented. We explored neurocognitive functioning and treatment effects in individuals with COMISA as an ancillary study to a randomized clinical trial., Methods: Participants with COMISA (n = 45; 51.1% female; mean age = 52.07 ± 13.29 years), from a 3-arm randomized clinical trial combining cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) concurrently (CBT-I+PAP) or sequentially, completed neurocognitive testing at baseline, and post-treatment. Using Bayesian linear mixed models, we estimated effects of CBT-I, PAP, or CBT-I+PAP, compared to baseline, and CBT-I+PAP compared to PAP on 12 metrics across five cognitive domains., Results: This COMISA sample had worse neurocognitive performance at baseline than reported for insomnia, sleep apnea, and controls in the literature, though short-term memory and psychomotor speed performance appears intact. When comparing PAP to baseline, performance on all measures was better after treatment. Performance after CBT-I was worse compared to baseline, and only performance in attention/vigilance, executive functioning via Stroop interference and verbal memory was better with moderate-high effect sizes and moderate probability of superiority (61-83). Comparisons of CBT-I+PAP to baseline generated results similar to PAP and comparing CBT-I+PAP to PAP revealed superior performance in only attention/vigilance via psychomotor vigilance task lapses and verbal memory for PAP., Conclusions: Treatment combinations involving CBT-I were associated with poorer neurocognitive performance. These potentially temporary effects may stem from sleep restriction, a component of CBT-I often accompanied by initially reduced total sleep time. Future studies should examine long-term effects of individual and combined COMISA treatment pathways to inform treatment recommendations., Clinical Trial: This was an ancillary study from a clinical trial (Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS), which was preregistered at www.clinicaltrials.gov (NCT01785303))., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tetrodotoxin (TTX), a potent neurotoxin mostly associated with pufferfish poisoning, is also found in bivalve shellfish. Recent studies into this emerging food safety threat reported TTX in a few, mainly estuarine, shellfish production areas in some European countries, including the United Kingdom. A pattern in occurrences has started to emerge, however the role of temperature on TTX has not been investigated in detail. Therefore, we conducted a large systematic TTX screening study, encompassing over 3500 bivalve samples collected throughout 2016 from 155 shellfish monitoring sites along the coast of Great Britain. Overall, we found that only 1.1 % of tested samples contained TTX above the reporting limit of 2 μg/kg whole shellfish flesh and these samples all originated from ten shellfish production sites in southern England. Subsequent continuous monitoring of selected areas over a five-year period showed a potential seasonal TTX accumulation in bivalves, starting in June when water temperatures reached around 15 °C. For the first time, satellite-derived data were also applied to investigate temperature differences between sites with and without confirmed presence of TTX in 2016. Although average annual temperatures were similar in both groups, daily mean values were higher in summer and lower in winter at sites where TTX was found. Here, temperature also increased significantly faster during late spring and early summer, the critical period for TTX. Our study supports the hypothesis that temperature is one of the key triggers of events leading to TTX accumulation in European bivalves. However, other factors are also likely to play an important role, including the presence or absence of a de novo biological source, which remains elusive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to describe enteral nutrition (EN) delivery in patients receiving postpyloric EN (PPEN) vs gastric EN (GEN)., Methods: Single-center retrospective study including patients aged <21 years admitted to an intensive care unit in a pediatric quaternary care hospital for ≧48 h who received PPEN or GEN as a first approach, as guided by a nutrition algorithm. PPEN patients were 1:1 propensity score matched to GEN patients on demographics, clinical characteristics, and disease severity. Days to EN initiation from admission, percentage of EN adequacy (delivered EN volume/prescribed EN volume) on days 1-3 and 7 after EN initiation, and time to achieving 60% of prescribed EN volume were compared between the two groups using Wilcoxon Mann-Whitney tests and a Cox proportional hazards model. Data are presented as median (IQR1, IQR3)., Results: Forty-six PPEN and 46 GEN patients were matched. Median time to EN initiation was 3.25 (2, 6.8) days for PPEN and 4.15 (1.5, 7.1) days for GEN (P = 0.6). Percentage of EN adequacy was greater for PPEN than GEN patients (day 1 PPEN 59.4% [18.8, 87.5] vs GEN 21.1% [7.8, 62.8], day 2 PPEN 54.3% [16.7, 95.8] vs GEN 24% [5.4, 56.7], day 3 PPEN 65.4% [14.7, 100] vs GEN 16% [0, 64.6], day 7 PPEN 77.8% [11.1, 100] vs GEN 13.8% [0, 74.5]; P < 0.05). PPEN patients had greater likelihood of achieving 60% of their prescribed EN volume than GEN patients (hazard ratio 1.84, 95% CI 1.07-3.15; P = 0.028)., Conclusion: PPEN was associated with greater EN delivery compared with GEN., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Tropical epibenthic dinoflagellate communities produce a plethora of bioactive secondary metabolites, including the toxins ciguatoxins (CTXs) and potentially gambierones, that can contaminate fishes, leading to ciguatera poisoning (CP) when consumed by humans. Many studies have assessed the cellular toxicity of causative dinoflagellate species to better understand the dynamics of CP outbreaks. However, few studies have explored extracellular toxin pools which may also enter the food web, including through alternative and unanticipated routes of exposure. Additionally, the extracellular exhibition of toxins would suggest an ecological function and may prove important to the ecology of the CP-associated dinoflagellate species. In this study, semi-purified extracts obtained from the media of a Coolia palmyrensis strain (DISL57) isolated from the U.S. Virgin Islands were assessed for bioactivity via a sodium channel specific mouse neuroblastoma cell viability assay and associated metabolites evaluated by targeted and non-targeted liquid chromatography tandem and high-resolution mass spectrometry. We found that extracts of C. palmyrensis media exhibit both veratrine enhancing bioactivity and non-specific bioactivity. LC-HR-MS analysis of the same extract fractions identified gambierone and multiple undescribed peaks with mass spectral characteristics suggestive of structural similarities to polyether compounds. These findings implicate C. palmyrensis as a potential contributor to CP and highlight extracellular toxin pools as a potentially significant source of toxins that may enter the food web through multiple exposure pathways.

The production, harvesting and safe consumption of bivalve molluscs can be disrupted by biological hazards that can be divided into three categories: (1) biotoxins produced by naturally occurring phytoplankton that are bioaccumulated by bivalves during filter-feeding, (2) human pathogens also bioaccumulated by bivalves and (3) bivalve pathogens responsible for disease outbreaks. Environmental changes caused by human activities, such as climate change, can further aggravate these challenges. Early detection and accurate quantification of these hazards are key to implementing measures to mitigate their impact on production and safeguard consumers. This review summarises the methods currently used and the technological advances in the detection of biological hazards affecting bivalves, for the screening of known hazards and discovery of new ones., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: Given the recent detection of tetrodotoxin (TTX) in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods., Objective: The aim was to conduct an interlaboratory study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods., Methods: Homogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data were used to calculate recoveries, repeatability, and reproducibility, together with participant acceptability z-scores., Results: Method performance characteristics were good, showing excellent sensitivity, recovery, and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC-MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC-MS/MS participants did not result in statistically different results. Method performance characteristics compared well with previously published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC-MS/MS., Conclusion: The results from this study demonstrate that current LC-MS/MS methods and ELISA are on the whole capable of sensitive, accurate, and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardize an LC-MS/MS protocol to further improve interlaboratory precision., Highlights: Multiple mass spectrometric methods and a commercial ELISA have been successfully assessed through an interlaboratory study, demonstrating excellent performance., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

Objective: We determined the interactive associations of apolipoprotein e4 (APOE-e4), and obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease and examined for racial/ethnic differences of this association., Methods: We used data from the National Alzheimer's Coordinating Center Uniform Dataset (NACC UDS). All participants undergo annual observations, including demographic survey, battery of neuropsychological tests, blood draw (with genotyping), and a clinical evaluation with medical and cognitive/dementia status assessment, while a subset of participants have cerebrospinal fluid (CSF) biomarkers and neuroimaging data. Biomarkers of AD were characterized as the presence of abnormally low amyloid in CSF, via validated Aβ 42 cut off protocols, and total segmented hippocampal volume, and volume of white matter hyper intensities (WMH). While clinical markers (to preview cognitive relationships) were characterized via the Montreal Cognitive Assessment (MOCA)., Results: Biomarker and clinical marker data were derived from 1,387 participants at baseline (mean age = 69.73 ± 8.32; 58.6% female; 13.7% Black/African American), 18.4% of the sample had sleep apnea, and 37.9% were APOE-e4 carriers. Our results confirmed previous reports that OSA and APOE-e4 were independently associated with AD through abnormal levels of amyloid ( F (1,306)  = 4.27; p  = 0.040; F (1,285)  = 60.88; p  < 0.000, respectively), WMH volume ( F (1,306)  = 4.27; p  = 0.040; F (1,285)  = 60.88; p  < 0.000, respectively), and MOCA scores ( F (1,306)  = 4.27; p  = 0.040; F (1,285)  = 60.88; p  < 0.000, respectively). No significant interaction between OSA and APOE-e4 relative to amyloid emerged, however, race stratified analyses indicated the interaction of OSA and APOE-e4 and was significantly associated with WMH and hippocampal volume in Black/African American, but not white participants., Conclusion: OSA and APOE-e4 are interactively associated with WHM in Black/African Americans. This interaction may partially explicate increased levels of risk in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with the authors AB and OB at the time of review., (Copyright © 2023 Turner, Locklear, Oruru, Briggs, Bubu and Seixas.)

Microcystins and nodularins, produced naturally by certain species of cyanobacteria, have been found to accumulate in aquatic foodstuffs such as fish and shellfish, resulting in a risk to the health of the seafood consumer. Monitoring of toxins in such organisms for risk management purposes requires the availability of certified matrix reference materials to aid method development, validation and routine quality assurance. This study consequently targeted the preparation of a mussel tissue reference material incurred with a range of microcystin analogues and nodularins. Nine targeted analogues were incorporated into the material as confirmed through liquid chromatography with tandem mass spectrometry (LC-MS/MS), with an additional 15 analogues detected using LC coupled to non-targeted high resolution mass spectrometry (LC-HRMS). Toxins in the reference material and additional source tissues were quantified using LC-MS/MS, two different enzyme-linked immunosorbent assay (ELISA) methods and with an oxidative-cleavage method quantifying 3-methoxy-2-methyl-4-phenylbutyric acid (MMPB). Correlations between the concentrations quantified using the different methods were variable, likely relating to differences in assay cross-reactivities and differences in the abilities of each method to detect bound toxins. A consensus concentration of total soluble toxins determined from the four independent test methods was 2425 ± 575 µg/kg wet weight. A mean 43 ± 9% of bound toxins were present in addition to the freely extractable soluble form (57 ± 9%). The reference material produced was homogenous and stable when stored in the freezer for six months without any post-production stabilization applied. Consequently, a cyanotoxin shellfish reference material has been produced which demonstrates the feasibility of developing certified seafood matrix reference materials for a large range of cyanotoxins and could provide a valuable future resource for cyanotoxin risk monitoring, management and mitigation.

Introduction: Asymptomatic patients with a remote history of transient ischemic attack (TIA) or stroke are not well studied as a separate population from asymptomatic patients with no prior history of TIA or stroke. We compared in-hospital outcomes after transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic patients, patients with a remote history of neurologic symptoms, and asymptomatic patients., Methods: Data from patients in the Vascular Quality Initiative database who underwent TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) were analyzed. Symptomatic status was defined as TIA and/or stroke occurring within 180 days before the procedure. Asymptomatic status was divided into patients with no history of TIA/stroke (asymptomatic) and patients with a history of TIA/stroke occurring more than 180 days before the procedure (remote history of neurologic symptoms). The Student t-test and Pearson χ 2 test were used to compare baseline patient characteristics and outcomes. Multivariate logistic regression was used to adjust for significant between-group differences in baseline characteristics., Results: There were 7158 patients who underwent TCAR (symptomatic: 2574, asymptomatic: 3689, and asymptomatic with a remote history of neurologic symptoms: 895) and 18,023 patients who underwent TFCAS (symptomatic: 6195, asymptomatic: 10,333, and asymptomatic with a remote history of neurologic symptoms: 1495). Regardless of symptom status, the mean patient age was 73 years for TCAR and 69 years for TFCAS. A total of 64% of patients in the study were male and 36% of patients were female. The mean long-term follow-up data ranged between 208 and 331 days within the three patient groups. Carotid stenosis patients with a remote history of neurologic symptoms had higher rates of TIA, stroke, TIA/stroke, stroke/death, and stroke/death/myocardial infarction than asymptomatic patients, and these rates were similar to those of symptomatic patients. Comparing TCAR and TFCAS among patients with a remote history of neurologic symptoms, there were statistically significant reductions in the odds of stroke/death (odds ratio: 0.46, 95% confidence interval: 0.27-0.84, P = .011) and stroke/death/myocardial infarction (odds ratio: 0.51, 95% confidence interval: 0.30-0.87, P = .013) after TCAR. This was likely driven by the increased rate of death after TFCAS in patients with a remote history of neurologic symptoms (0.9%) compared with asymptomatic patients (0.6%)., Conclusions: Asymptomatic patients with a remote history of TIA/stroke do not have the same outcomes as asymptomatic patients without a history of TIA/stroke and are at higher risk of adverse in-hospital events. Patients with a remote history of TIA/stroke have increased risk of in-hospital death after TFCAS and may benefit from TCAR., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Cyanobacterial blooms are often associated with the presence of harmful natural compounds which can cause adverse health effects in both humans and animals. One family of these compounds, known as anatoxins, have been linked to the rapid deaths of cattle and dogs through neurotoxicological action. Here, we report the findings resulting from the death of a dog at a freshwater reservoir in SW England. Poisoning was rapid following exposure to material at the side of the lake. Clinical signs included neurological distress, diaphragmatic paralysis and asphyxia prior to death after 45 min of exposure. Analysis by HILIC-MS/MS of urine and stomach content samples from the dog revealed the detection of anatoxin-a and dihydroanatoxin-a in both samples with higher concentrations of the latter quantified in both matrices. Detection and quantitative accuracy was further confirmed with use of accurate mass LC-HRMS. Additional anatoxin analogues were also detected by LC-HRMS, including 4-keto anatoxin-a, 4-keto-homo anatoxin-a, expoxy anatoxin-a and epoxy homo anatoxin-a. The conclusion of neurotoxicosis was confirmed with the use of two independent analytical methods showing positive detection and significantly high quantified concentrations of these neurotoxins in clinical samples. Together with the clinical signs observed, we have confirmed that anatoxins were responsible for the rapid death of the dog in this case.

In September and November 2016, eight marine sampling sites along the coast of the southeastern Gulf of Mexico were monitored for the presence of lipophilic and hydrophilic toxins. Water temperature, salinity, hydrogen potential, dissolved oxygen saturation, inorganic nutrients and phytoplankton abundance were also determined. Two samples filtered through glass fiber filters were used for the extraction and analysis of paralytic shellfish toxins (PSTs) by lateral flow immunochromatography (IFL), HPLC with post-column oxidation and fluorescent detection (FLD) and UHPLC coupled to tandem mass spectrometry (UHPLC-MS/MS). Elevated nutrient contents were associated with the sites of rainwater discharge or those near anthropogenic activities. A predominance of the dinoflagellate Pyrodinium bahamense was found with abundances of up to 10 4 cells L -1 . Identification of the dinoflagellate was corroborated by light and scanning electron microscopy. Samples for toxins were positive by IFL, and the analogs NeoSTX and STX were identified and quantified by HPLC-FLD and UHPLC-MS/MS, with a total PST concentration of 6.5 pg cell -1 . This study is the first report that confirms the presence of PSTs in P. bahamense in Mexican waters of the Gulf of Mexico.

Nearly one third of Americans experience poor sleep, which is associated with numerous deleterious health outcomes. Poor sleep may be exacerbated when an individual attends college, as they experience drastic shifts in lifestyle and sleep patterns. Previous research suggests cannabis has therapeutic potential for sleep disorders but may also impair sleep quality long-term. However, no study has examined the differences in sleep quality within individuals who meet criteria for Cannabis Use Disorder (CUD). The purpose of the current study was to determine differences in sleep quality among undergraduate students who met criteria for mild CUD (n = 18), moderate CUD (n = 22), severe CUD (n = 16) and students who did not meet criteria for CUD (n = 244). Participants included 300 predominantly Black/African American undergraduate students (79% female), aged between 18 and 25 years. Each participant completed an online survey that included measures assessing sleep quality and CUD criteria. Employing analysis of covariance, the moderate CUD subgroup (M = 9.00, SD = 3.32) reported poorer sleep quality than individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Interestingly, the severe CUD subgroup (M = 6.75, SD = 2.52) reported similar sleep quality to individuals who did not meet criteria for CUD (M = 6.93, SD = 3.03). Individuals meeting criteria for mild and moderate CUD reported the poorest sleep quality among the groups, suggesting a differentiation within CUD severity. Future research should assess withdrawal and cannabis use frequency among individuals who meet criteria for CUD to further elucidate disturbances in sleep quality among those with CUD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Harmful algal blooms are an increasing worldwide threat to the seafood industry and human health as a consequence of the natural production of biotoxins that can accumulate in shellfish. In the Argentine Sea, this has been identified as an issue for the offshore fisheries of Patagonian scallops ( Zygochlamys patagonica ), leading to potentially harmful effects on consumers. Here we assess spatial and temporal patterns in marine biotoxin concentrations in Patagonian scallops harvested in Argentinian waters between 2012-2017, based on analyses for paralytic shellfish toxins, lipophilic toxins, and amnesic shellfish toxins. There was no evidence for concentrations of lipophilic or amnesic toxins above regulatory acceptance thresholds, with trace concentrations of pectenotoxin 2, azaspiracid 2 and okadaic acid group toxins confirmed. Conversely, paralytic shellfish toxins were quantified in some scallops. Gonyautoxins 1 and 2 dominated the unusual toxin profiles (91%) in terms of saxitoxin equivalents with maximum concentrations reaching 3985 µg STX eq/kg and with changes in profiles linked in part to seasonal changes. Total toxin concentrations were compared between samples of the adductor muscle and whole tissue, with results showing the absence of toxins in the adductor muscle confirming toxin accumulation in the digestive tracts of the scallops and the absence of a human health threat following the processing of scallop adductor meat. These findings highlight that paralytic shellfish toxins with an unusual toxin profile can occur in relatively high concentrations in whole Patagonian scallops in specific regions and during particular time periods, also showing that the processing of scallops on board factory ships to obtain frozen adductor muscle is an effective management process that minimizes the risk of poisonings from final products destined for human consumption.

There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.

The use of biobanks may accelerate scientists' chances of developing cures and treatments that are tailored to individuals' biological makeup-a function of the precision medicine movement. However, given the underrepresentation of certain populations in biobanks, the benefits of these resources may not be equitable for all groups, including older, multi-ethnic populations. The objective of this study was to better understand older, multi-ethnic populations' (1) perceptions of the value of cancer biobanking research, (2) study design preferences, and (3) guidance on ways to promote and increase participation. This study was designed using a community-based participatory research (CBPR) approach and involved eight FGDs with 67 older (65-74 years old) black and white residents from Baltimore City and Prince George's County, MD. FGDs lasted between 90 and 120 min, and participants received a $25 Target gift card for their participation. Analysis involved an inductive approach in which we went through a series of open and axial coding techniques to generate themes and subthemes. Multiple themes emerged from the FGDs for the development of future cancer-related biobanking research including (1) expectations/anticipated benefits, (2) biobanking design preferences, and (3) ways to optimize participation. Overall, most participants were willing to provide biospecimens and favored cancer-related biobank. To increase participation of older, diverse participants in biobanking protocols, researchers need to engage older, diverse persons as consultants in order to better understand the value of biobanking research to individuals from the various populations. Scientists should also incorporate suggestions from the community on garnering trust and increasing comfort with study design., (© 2020. American Association for Cancer Education.)

Study Objectives: This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning., Methods: A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures., Results: A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring., Conclusions: Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303., Citation: Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med . 2022;18(3):789-800., (© 2022 American Academy of Sleep Medicine.)

Objective: The study objective was to examine predictors of sleep disturbance and strain among caregivers of persons living with dementia (PLWD)., Methods: This cross-sectional study utilized a sample of community-dwelling older adults and their family caregivers drawn from the 2017 National Health and Aging Trends Study and National Study of Caregiving. Multivariable logistic regression was used to assess the association between caregiver and PLWD characteristics and a composite measure of caregiving strain. High caregiving strain was defined as a total score of ≥ 5 on the 6 caregiving strain items (e.g., emotional difficulty, no time for self). We used multivariable proportional odds models to examine predictors of caregiver sleep-related outcomes (trouble falling back to sleep and interrupted sleep), after adjusting for other caregiver and PLWD factors., Results: Of the 1,142 family caregivers, 65.2% were female, 15% were Black, and 14% were Hispanic. Average age was 60 years old. Female caregivers were more likely to report high level of strain compared to male caregivers (OR: 2.61, 95% CI = 1.56, 4.39). Compared to non-Hispanic Whites, non-Hispanic Black and Hispanic caregivers had reduced odds of reporting greater trouble falling back asleep [OR = 0.55, CI (0.36, 0.82) and OR = 0.56, CI (0.34, 0.91), respectively]. The odds of reporting greater trouble falling back asleep was significantly greater among caregivers with high blood pressure vs. caregivers without high blood pressure [OR = 1.62, CI (1.12, 2.33)]., Conclusion: In this cross-sectional study, caregivers with greater sleep difficulty (trouble falling back asleep) were more likely to report having high blood pressure. We found no racial/ethnic differences in interrupted sleep among caregivers to PLWD. These results suggest that interventions to improve sleep among caregivers to PLWD may decrease poor cardiovascular outcomes in this group., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Osakwe, Senteio, Bubu, Obioha, Turner, Thawani, Saint Fleur-Calixte and Jean-Louis.)

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets., (© 2022. Crown.)

Although phytoplankton is ubiquitous in the world's oceans some species can produce compounds that cause damaging effects in other organisms. These include the toxins responsible for paralytic shellfish poisoning, which, in UK waters, are produced by dinoflagellates from the Alexandrium genus. Within Great Britain (GB) a monitoring programme exists to detect this harmful genus as well as the Paralytic Shellfish Poisoning (PSP) toxins in the flesh of shellfish from classified production areas. The techniques used for toxin analysis allow for detailed analysis of the toxin profiles present in contaminated shellfish. It is possible to compare the toxin profiles of contaminated shellfish with the profiles from toxin producing algae and use this information to infer the causative microalgal species responsible for the contamination. This study sought to evaluate the potential for this process within the GB monitoring framework. Two species of toxic Alexandrium, A. catenella from Scotland and A. minutum from Southern England, were fed to mussels (Mytilus sp.) under controlled conditions. The toxin profile in mussels derived from feeding on each species independently, when mixed and when introduced sequentially was analysed and compared to the source algal cultures using K means cluster analysis. Toxin profiles in contaminated shellfish clustered with those of the causative algae and separately from one another during toxin accumulation and, where A. catenella was the sole toxin source, during depuration. During depuration after feeding with A. minutum and where mixed or sequential feeding was undertaken deviant toxin profiles were observed. Finally, data generated within this experimental study were compared to monitoring data from the GB official control programme. These data indicated that the causative algal species in sole source contaminations could be inferred from toxin profile analysis. This technique will be of benefit within monitoring programmes to enhance the value of data with minimal additional expense, where the toxin profiles of causative microalgae have been well described., (Copyright © 2021. Published by Elsevier B.V.)

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer's disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers. Methods: Longitudinal data from the National Alzheimer's Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset ( n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis. Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p < 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p < 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aβ, T-tau, P-tau) and hippocampal volume ( n = 361) (aOR: 2.55, p < 0.01), and approximated risk-estimates of each biomarker in the sample where data was available. Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bubu, Williams, Umasabor-Bubu, Kaur, Turner, Blanc, Cejudo, Mullins, Parekh, Kam, Osakwe, Nguyen, Trammell, Mbah, de Leon, Rapoport, Ayappa, Ogedegbe, Jean-Louis, Masurkar, Varga and Osorio.)

Saxitoxins (STXs) are a family of potent neurotoxins produced naturally by certain species of phytoplankton and cyanobacteria which are extremely toxic to mammalian nervous systems. The accumulation of STXs in bivalve molluscs can significantly impact animal and human health. Recent work conducted in the North Sea highlighted the widespread presence of various saxitoxins in a range of benthic organisms, with the common sunstar ( Crossaster papposus ) demonstrating high concentrations of saxitoxins. In this study, an extensive sampling program was undertaken across multiple seas surrounding the UK, with 146 starfish and 5 brittlestars of multiple species analysed for STXs. All the common sunstars analysed ( n > 70) contained quantifiable levels of STXs, with the total concentrations ranging from 99 to 11,245 µg STX eq/kg. The common sunstars were statistically different in terms of toxin loading to all the other starfish species tested. Two distinct toxic profiles were observed in sunstars, a decarbomylsaxitoxin (dcSTX)-dominant profile which encompassed samples from most of the UK coast and an STX and gonyautoxin2 (GTX2) profile from the North Yorkshire coast of England. Compartmentalisation studies demonstrated that the female gonads exhibited the highest toxin concentrations of all the individual organs tested, with concentrations >40,000 µg STX eq/kg in one sample. All the sunstars, male or female, exhibited the presence of STXs in the skin, digestive glands and gonads. This study highlights that the common sunstar ubiquitously contains STXs, independent of the geographical location around the UK and often at concentrations many times higher than the current regulatory limits for STXs in molluscs; therefore, the common sunstar should be considered toxic hereafter.

A simple, rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed and optimized for the quantitation of a range of pharmaceuticals, metabolites, and related bioactive compounds in the bivalve mollusc species mussels (Mytilus edulis) and Pacific oysters (Crassostrea gigas). Shellfish tissues were extracted using a simple solvent-based extraction method prior to concentration and purification by pass-through solid-phase extraction and quantified using stable isotope dilution MS/MS. The analytes covered a range of therapeutic classes including antidepressants, anticonvulsants, beta-blockers, and antiplatelets. Of the 34 compounds included in the present study initially, 28 compounds were found to demonstrate acceptable performance. Performance was assessed by examining extraction efficiencies, matrix effects, sensitivity, and within- and between-batch precision. The results show that as indicated by acceptable HorRat and accuracy values, the method is fit for purpose. Application of this method to environmental mussel and oyster samples revealed the presence of 12 compounds at quantifiable concentrations, with the antidepressant sertraline being present at the highest level, reaching a concentration of 6.12 ng/g in mussel tissue. © 2021 Crown copyright. Environmental Toxicology and Chemistry 2021;40:3263-3274. © 2021 SETAC. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland., (© 2021 SETAC. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Harmful Algal Blooms (HAB) are natural atypical proliferations of micro or macro algae in either marine or freshwater environments which have significant impacts on human, animal and ecosystem health. The causative HAB organisms are primarily dinoflagellates and diatoms in marine and cyanobacteria within freshwater ecosystems. Several hundred species of HABs, most commonly marine dinoflagellates affect animal and ecosystem health either directly through physical, chemical or biological impacts on surrounding organisms or indirectly through production of algal toxins which transfer through lower-level trophic organisms to higher level predators. Traditionally, a major focus of HABs has concerned their natural production of toxins which bioaccumulate in filter-feeding invertebrates, which with subsequent trophic transfer and biomagnification cause issues throughout the food web, including the human health of seafood consumers. Whilst in many regions of the world, regulations, monitoring and risk management strategies help mitigate against the impacts from HAB/invertebrate toxins upon human health, there is ever-expanding evidence describing enormous impacts upon invertebrate health, as well as the health of higher trophic level organisms and marine ecosystems. This paper provides an overview of HABs and their relationships with aquatic invertebrates, together with a review of their combined impacts on animal, human and ecosystem health. With HAB/invertebrate outbreaks expected in some regions at higher frequency and intensity in the coming decades, we discuss the needs for new science, multi-disciplinary assessment and communication which will be essential for ensuring a continued increasing supply of aquaculture foodstuffs for further generations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220  GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8  μK&#95;{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r&#95;{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Background: Paralytic Shellfish Poison (PSP) toxins have been reported in non-bivalve shellfish species, including crustaceans and gastropods. Routine surveillance of these species is currently conducted in parts of England. To date, detection methods have not been validated for these matrices. Validation is required to ensure the test is fit for purpose, to give greater confidence in any results generated and ultimately facilitates accreditation., Objective: The aim was to test and validate two independent PSP toxin detection methods previously validated for bivalve shellfish matrices, for applicability to commercial non-bivalve species of interest., Methods: Matrices were shrimp (Crangon crangon), common whelk (Buccinum undatum), and edible crab (Cancer pagurus). The two methods assessed were the pre-column oxidation high-performance liquid chromatography-fluorescence detection AOAC 2005.06 Official Method of analysis and an internationally validated hydrophilic interaction chromatography-tandem mass spectrometry method. Brown and white crab meat were assessed separately., Results: A refined extraction protocol was implemented with an increased solvent to sample ratio. The same extraction protocol was utilized for both methods, allowing both methods to be run simultaneously. Method sensitivity, recovery, repeatability, and method uncertainty were characterized in all matrix/toxin combinations. Overall, both methods performed similarly to that previously reported in bivalve mollusks. Acceptability of the majority of toxin/matrix combinations was evidenced through comparison of method performance characteristics against specific performance criteria, including Horwitz ratio values., Conclusions: Both PSP toxin detection methods were found to provide acceptable performance for the monitoring of shrimp, whelk, and crab species., Highlights: Two PSP toxin detection methods have been single-laboratory validated successfully for three non-bivalve shellfish species., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia and sedation consistently identify sedative and opioid analgesic exposures as risk factors for both in-hospital delirium and post-discharge neurologic sequelae. Clinical observations are supported by animal models showing neuroinflammation, increased neuronal death, dysmyelination, and altered synaptic plasticity and neurotransmission. Additionally, intensive care sedation also contributes to sleep disruption, an important and overlooked variable during acute illness and post-discharge recovery. Because analgesia and sedation are potentially modifiable, understanding the underlying mechanisms could transform sedation strategies to improve outcomes. To move the needle on this, prospective clinical studies would benefit from cohesion with regard to datasets and core outcome assessments, including sleep quality. Analyses should also account for the wide range of diagnoses, heterogeneity of this population, and the dynamic nature of neurodevelopment in age cohorts. Much of the related preclinical evidence has been studied in comparatively brief anesthetic exposures in healthy animals during infancy and is not generalizable to critically ill children. Thus, complementary animal models that more accurately "reverse translate" critical illness paradigms and the effect of analgesia and sedation on neuropathology and functional outcomes are needed. This review explores the interactive role of sedatives and the neurologic vulnerability of critically ill children as it pertains to survivorship and functional outcomes, which is the next frontier in pediatric intensive care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Turner, Sullivan, Drury, Hall, Williams, Guilliams, Murphy and Iqbal O’Meara.)

A single laboratory method performance verification is reported for a rapid sensitive UHPLC-MS/MS method for the quantification of eight cyclic imine and two brevetoxin analogues in two bivalve shellfish matrices: mussel (Mytilus edulis) and Pacific oyster (Crassostrea gigas). Targeted cyclic imine analogues were from the spirolide, gymnodimine and pinnatoxin groups, namely 20-Me-SPX-C, 13-desMe-SPX-C, 13,19-didesMe-SPX-C, GYM-A, 12-Me-GYM, PnTx-E, PnTx-F and PnTx-G. Brevetoxin analogues consisted of the shellfish metabolites BTX-B5 and S-desoxy-BTX-B2. A rapid dispersive extraction was used as well as a fast six-minute UHPLC-MS/MS analysis. Mobile phase prepared using ammonium fluoride and methanol was optimised for both chromatographic separation and MS/MS response to suit all analytes. Method performance verification checks for both matrices were carried out. Matrix influence was acceptable for the majority of analogues with the MS response for all analogues being linear across an appropriate range of concentrations. In terms of limits of detection and quantitation the method was shown to be highly sensitive when compared with other methods. Acceptable recoveries were found with most analogues, with laboratory precision in terms of intra- and inter-batch precision deemed appropriate. The method was applied to environmental shellfish samples with results showing low concentrations of cyclic imines to be present. The method is fast and highly sensitive for the detection and quantification of all targeted analogues, in both mussel and oyster matrices. Consequently, the method has been shown to provide a useful tool for simultaneous monitoring for the presence or future emergence of these two toxin groups in shellfish., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)

Harmful algal bloom events are increasing in a number of water bodies around the world with significant economic impacts on the aquaculture, fishing and tourism industries. As well as their potential impacts on human health, toxin exposure from harmful algal blooms (HABs) has resulted in widespread morbidity and mortality in marine life, including top marine predators. There is therefore a need for an improved understanding of the trophic transfer, and persistence of toxins in marine food webs. For the first time, the concentrations of two toxin groups of commercial and environmental importance, domoic acid (DA) and saxitoxin (including Paralytic Shellfish Toxin (PST) analogues), were measured in the viscera of 40 different fish species caught in Scotland between February and November, 2012 to 2019. Overall, fish had higher concentrations of DA compared to PSTs, with a peak in the summer / autumn months. Whole fish concentrations were highest in pelagic species including Atlantic mackerel and herring, key forage fish for marine predators including seals, cetaceans and seabirds. The highest DA concentrations were measured along the east coast of Scotland and in Orkney. PSTs showed highest concentrations in early summer, consistent with phytoplankton bloom timings. The detection of multiple toxins in such a range of demersal, pelagic and benthic fish prey species suggests that both the fish, and by extension, piscivorous marine predators, experience multiple routes of toxin exposure. Risk assessment models to understand the impacts of exposure to HAB toxins on marine predators therefore need to consider how chronic, low-dose exposure to multiple toxins, as well as acute exposure during a bloom, could lead to potential long-term health effects ultimately contributing to mortalities. The potential synergistic, neurotoxic and physiological effects of long-term exposure to multiple toxins require investigation in order to appropriately assess the risks of HAB toxins to fish as well as their predators., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In the past twenty years marine biotoxin analysis in routine regulatory monitoring has advanced significantly in Europe (EU) and other regions from the use of the mouse bioassay (MBA) towards the high-end analytical techniques such as high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS). Previously, acceptance of these advanced methods, in progressing away from the MBA, was hindered by a lack of commercial certified analytical standards for method development and validation. This has now been addressed whereby the availability of a wide range of analytical standards from several companies in the EU, North America and Asia has enhanced the development and validation of methods to the required regulatory standards. However, the cost of the high-end analytical equipment, lengthy procedures and the need for qualified personnel to perform analysis can still be a challenge for routine monitoring laboratories. In developing regions, aquaculture production is increasing and alternative inexpensive Sensitive, Measurable, Accurate and Real-Time (SMART) rapid point-of-site testing (POST) methods suitable for novice end users that can be validated and internationally accepted remain an objective for both regulators and the industry. The range of commercial testing kits on the market for marine toxin analysis remains limited and even more so those meeting the requirements for use in regulatory control. Individual assays include enzyme-linked immunosorbent assays (ELISA) and lateral flow membrane-based immunoassays (LFIA) for EU-regulated toxins, such as okadaic acid (OA) and dinophysistoxins (DTXs), saxitoxin (STX) and its analogues and domoic acid (DA) in the form of three separate tests offering varying costs and benefits for the industry. It can be observed from the literature that not only are developments and improvements ongoing for these assays, but there are also novel assays being developed using upcoming state-of-the-art biosensor technology. This review focuses on both currently available methods and recent advances in innovative methods for marine biotoxin testing and the end-user practicalities that need to be observed. Furthermore, it highlights trends that are influencing assay developments such as multiplexing capabilities and rapid POST, indicating potential detection methods that will shape the future market.