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The identification of the genetic cause of vascular malformations is improving understanding of pathogenesis of these lesions and also informing potential opportunities for treatment. Somatic activating mutations affecting RAS/MAPK and PIK3/AKT/mTor pathways are implicated in all types of vascular malformations. Pathogenic variants associated with vascular lesions may be germline or somatic. Next-generation sequencing technologies allow identification of lower level mosaic mutations than was achievable with standard Sanger sequencing. Best practice strategies to identify underlying genetic mutations in vascular malformations are influenced by the tissues involved and the type of vascular lesion.

Objective:The variability of findings in studies examining the effects of chronic cannabis use on neuropsychological functioning highlights the importance of examining contributing factors. Few studies examine the role of sex in the relationship between cannabis and neuropsychological functioning, despite known neurobiological structural differences between males and females. This study examined whether males and females experience differential cognitive effects of chronic cannabis use.Method:Chronic cannabis users (3+ days per week for >12 months, n = 110, 72% male) and non-users (n = 71, 39% male) completed a neuropsychological test battery. Two multivariate analyses of covariance (MANCOVAs) examined for sex differences in performance within users and non-users on neuropsychological tests, controlling for potential confounding variables. Bonferroni corrections were applied to adjust for multiple comparisons.Results:Male and female cannabis users did not differ in cannabis use variables. Female cannabis users performed better than males on multiple subtests of the California Verbal Learning Test-II (CVLT-II), a verbal learning and memory test. Male cannabis users performed better than female users on Trial 1 of the CVLT-II (p = .002), and Trail Making Test B (p = .001), which measure attention and cognitive flexibility, respectively. Non-user males and females performed comparably, with the exception of Trail Making Test B (p = .001).Conclusions:Results suggest that chronic cannabis use differentially impacts males and females, with females exhibiting better verbal learning and memory despite males demonstrating better attention and cognitive flexibility. Further research is needed to understand the potential protective mechanism of female sex on learning and memory effects of cannabis use.

Depression is a risk factor for cardiovascular disease (CVD), and subgroups of people with depression may be at particularly elevated CVD risk. Lower high-frequency heart rate variability (HF HRV), which reflects diminished parasympathetic activation, is a candidate mechanism underlying the depression-CVD relationship and predicts cardiovascular events. Few studies have examined whether certain depression subgroups - such as those with co-occurring affective factors - exhibit lower HF HRV. The present study sought to assess associations between co-occurring affective factors and HF HRV in people with depression.Utilizing baseline data from the 216 primary care patients with depression in the eIMPACT trial, we examined cross-sectional associations of depression's co-occurring affective factors (i.e., anxiety symptoms, hostility/anger, and trait positive affect) with HF HRV. HF HRV estimates were derived by spectral analysis from electrocardiographic data obtained during a supine rest period.Individual regression models adjusted for demographics and depressive symptoms revealed that anxiety symptoms (standardized regression coefficient β = -0.24, p = .002) were negatively associated with HF HRV; however, hostility/anger (β = 0.02, p = .78) and trait positive affect (β = -0.05, p = .49) were not. In a model further adjusted for hypercholesterolemia, hypertension, diabetes, body mass index, current smoking, CVD prevention medication use, and antidepressant medication use, anxiety symptoms remained negatively associated with HF HRV (β = -0.19, p = .02).Our findings suggest that, in adults with depression, those with comorbid anxiety symptoms have lower HF HRV than those without. Co-occurring anxiety may indicate a depression subgroup at elevated CVD risk on account of diminished parasympathetic activation.

Objective Ongoing environmental changes increasingly require public health nurses to understand how environmental factors impact the health of populations. One approach to researching these impacts is incorporating environmental research methods to determine associations between harmful exposures and health. We use the Salton Sea in Southern California as a demonstration of how environmental exposure can be examined using air parcel trajectory analysis. Design We demonstrate a methodology for public health nurses to better understand and apply data from the Hybrid Single-Particle Lagrangian Integrated Trajectory meteorological model to estimate the effect of airborne particulate matter from a single source. Measurements We explain a method for tracking air parcel trajectories to populations: selection of meterological data to identify air parcels, geographic identification of population centers, generation of trajectories, classification of trajectory dispersions, adjusting for atmospheric stability, and merging environmental variables with health data. Conclusions Climate change-related environmental events are expected to become more commonplace and disproportionately affect those populations impacted by health disparities. Public health nurses can identify communities at risk so that public health nursing researchers can use these techniques in collaboration with environmental science to robustly examine health effects of proximal air pollution sources for communities at risk.

Background: Informal electronic waste (e-waste) recycling is an increasingly important industry worldwide. However, few studies have studied the health risks in this group of workers. Objective: To assess the associations between occupational exposures to metals and genetic instability and renal markers among e-waste recycling workers. Methods: We recruited informal e-waste recycling workers from a community in northeastern Thailand. Participants completed a questionnaire, several health measurements, and provided urine and blood samples, which we then analyzed for a number of metals including lead (Pb), cadmium (Cd), and manganese (Mn). Samples were analyzed for a marker of RNA and DNA damage (ie, oxidative stress), 8-hydroxy-2'-deoxyguanosine (8-OHdG). Glomerular filtration rate (GFR) and fractional excretion of calcium (FECa%) were measured as markers of renal function. Correlations and regression models were used to assess associations between these various factors. Results: We found significantly higher levels of Cd and Pb in blood of men compared with those in women. Men who worked >48 hours/week had significantly higher levels of 8-OHdG compared with men who worked ≤48 hours/week. Smoking was significantly associated with higher blood Pb and Cd concentrations among men. Conclusion: Our results suggest gender differences in both blood concentrations of metals associated with e-waste recycling and smoking and highlight potentially elevated oxidative stress associated with longer work hours. Health promotion efforts are needed among informal e-waste recyclers to reduce possible risks of renal damage and cancer

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1–3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4–7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas., Zika virus vaccination elicits Zika and dengue virus cross-neutralizing antibodies in flavivirus-exposed individuals, potentially enhancing the protective efficacy of the vaccine in flavivirus-endemic regions.

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.

ObjectivesPaediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.DesignA multicentre, international, collaborative cohort study.Setting91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.ParticipantsPatients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measureAll-cause mortality at 30 days and 90 days.Results1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (pConclusionsThe COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.

The somatic depressive symptom cluster (including appetite and sleep disturbances) is more strongly associated with insulin resistance (a diabetes risk marker) than other depressive symptom clusters. Utilizing baseline data from 129 primary care patients with depression but no diabetes in the eIMPACT trial (M

IntroductionChildhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality.MethodsProspective cohort study in 109 institutions in 41 countries. Inclusion criteria: children ResultsAll-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3–11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); pConclusionsChildren with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer.

Objectives Examinations of cultural variations in caregiving experiences and practices tend to focus on racially and ethnically diverse family caregivers. We extended this research by exploring the role of place-based cultural constructs on care decisions of family caregivers for persons living with dementia in rural Appalachia whose experiences and backgrounds dwell outside the lines of dominant culture. Methods Guided by our sociocultural conceptual model of service use and a descriptive qualitative study design, we conducted in-depth interviews with 30 caregivers for persons living with dementia to understand how predisposing and enabling factors influence caregiving decisions, including the use of services to care for persons living with dementia. Results Three predisposing factors reflecting the culture of rural Appalachian counties in Virginia (reasons for becoming a caregiver, previous caregiving experience, and deference to the person living with dementia) shaped decisions about caregiving responsibilities and service use. Three place-based enabling factors (a personal sense of belonging, knowledge of services, and family support for service use) played an important role in facilitating access to services. Discussion Findings revealed subtle variation across caregivers in this study and in comparison, to caregivers’ experiences more generally. We interpret these variations in light of culturally influenced attitudes, family norms, and sources of information about formal services. Place-based cultural experience influenced dementia family caregivers’ behaviors and choices regarding formal service use, suggesting that investigators should pay more attention to cultural influences in future caregiving research.

To investigate the clinical and magnetic resonance imaging (MRI) characteristics of patients with varicella zoster virus (VZV) reactivation involving the cranial nerves and central nervous system (CNS).This is a retrospective, multi-center case-series of 37 patients with VZV infection affecting the cranial nerves and CNS.The median age was 71 years [IQR 51.5-76]; 21 (57%) were men. Cerebrospinal fluid (CSF) was available in 24/37 (65%); median CSF white blood cell count was 11 [IQR 2-23] cells/μL and protein was 45.5 [IQR 34.5-75.5] mg/dL. VZV polymerase chain reaction (PCR) assays were positive in 6/21 (29%) CSF and 8/9 (89%) ocular samples. Clinical involvement included the optic nerve in 12 (32%), other cranial nerves in 20 (54%), brain parenchyma in 12 (32%) and spinal cord or nerve roots in 4 (11%). Twenty-seven/28 immunocompetent patients' MRIs were available for review (96%). Of the 27, 18 had T1 postcontrast fat saturated sequences without motion artifact to evaluate for cranial nerve enhancement and optic perineuritis (OPN). Eight/18 (44%) demonstrated OPN. All 8 experienced vision loss: 3 optic neuritis, 1 acute retinal necrosis, and 3 CNS vasculitis with 1 central and 1 branch retinal artery occlusion and 1 uveitis. Diplopic patients had cranial nerve and cavernous sinus enhancement. All immunosuppressed patients were imaged. Seven/9 (88%) had extensive neuraxis involvement, including encephalitis, vasculitis and transverse myelitis; one case had OPN.OPN is a frequent manifestation in VZV-associated vision loss among immunocompetent patients. Immunosuppressed patients had greater neuraxis involvement. Optimizing MRI protocols may improve early diagnosis in VZV reactivation.

Negative urgency – acting rashly in response to negative emotions – is a risk factor for central adiposity. We examine whether the relationship between negative urgency and waist-to-height ratio (WHtR) is mediated by eating behaviors (emotional eating, external eating, and cognitive restraint) and moderated by depressive symptom severity, factors that could be targeted to reduce risk associated with negative urgency. Using baseline data from the Nathan Kline Institute-Rockland Sample (N = 872; mean age = 42.4 years, SD = 15.3; 65% female; 27% non-White; mean body mass index = 27.9 kg/m(2), SD = 5.9), we conducted a series of mediation and moderated mediation analyses controlling for age, sex, race, and socioeconomic status. Overall, there was a positive association between negative urgency and WHtR. Emotional eating (ab = 0.02, SE = 0.003, 95% CI [0.02, 0.03]) and uncontrolled eating (ab = 0.008, SE = 0.002, 95% CI [0.004, 0.01]) were partial mediators of the relationship between negative urgency and WHtR, while cognitive restraint was not. In a parallel mediation model, emotional eating remained significant, while uncontrolled eating did not. Depressive symptom severity moderated the indirect effect of negative urgency on WHtR through emotional eating (b(int) = −0.08, p < .001) but not the direct effect of negative urgency on WHtR. Our results indicate that emotional eating is a viable potential mechanism explaining the relationship between negative urgency and WHtR, and the indirect effect of negative urgency on WHtR through emotional eating becomes stronger as depressive symptom severity decreases.

Purpose of review The COVID-19 public health emergency accelerated the adoption of telemedicine in neuro-ophthalmology. This review surveys the current telemedicine landscape and discusses associated limitations and opportunities. Recent findings Logistic considerations and regulatory changes related to the COVID-19 pandemic have spurred a proliferation of tele-neuro-ophthalmic practice. One significant benefit of telemedicine is increased access to the limited number of neuro-ophthalmologists in the country. Certain elements of the neuro-ophthalmic examination can be ascertained during a video visit or through the use of mobile applications. However, data quality can be limited and more direct evaluation of the fundus currently requires the implementation of imaging techniques, such as fundus photography and/or optical coherence tomography. For cases that require it, a 'hybrid' model can be adopted in which patients physically present to designated locations for testing and subsequently participate in televisit with the physician to discuss the assessment and plan. Summary Telemedicine provides an alternate pathway for patients to access the limited resource of neuro-ophthalmic care, and it will likely persist beyond the current COVID-19 pandemic. It has some limitations currently but continued progress in technologic, legal, and reimbursement strategies will hopefully facilitate further adoption.

Our previous finding that the BET inhibitor (BETi) JQ1 increases levels of the DNA damage marker γH2AX suggested that JQ1 might enhance the sensitivity of tumor cells to PARP inhibitors (PARPi), which are selectively toxic to cells that harbor relatively high levels of DNA damage. To address this hypothesis, we evaluated the effect of a BETi (JQ1 or I-BET762) combined with a PARPi (olaparib or veliparib) in KKU-055 and KKU-100 cholangiocarcinoma (CCA) cell lines and of JQ1 with olaparib in a xenograft model of CCA. Each combination was more effective than any of the four drugs as single agents. Combination indices ranged from 0.1 to 0.8 at the ED50 for all combinations, indicating synergy and demonstrating that synergy was not limited to a specific combination. Mechanistically, downregulation of BETi molecular targets BRD2 or BRD4 by shRNA sensitized CCA cells to BETi as single agents as well as to the combination of a BETi + a PARPi. Our data indicate that combinations of a BETi with a PARPi merit further evaluation as a promising strategy for CCA.

OBJECTIVE This study aims to summarize electronic waste (e-waste) worker health; examine associations between health and sociodemographic characteristics; and metal body burden. METHODS In 2016, 131 e-waste recycling workers were enrolled in the study, completed a questionnaire, and gave blood and urine samples for heavy metal concentration assessment (lead, cadmium, copper, zinc, nickel). The relationship between symptoms, general health, and metals is assessed via generalized estimating equation models (adjusted for age, education, sex, and village). RESULTS Cadmium in blood and copper in serum were most consistently associated with higher odds of poor health and prevalence of symptoms. We found inconsistent results between general health, symptom severity, and urinary nickel. Higher blood lead levels (BLL) were associated with fewer self-reported symptoms. CONCLUSIONS Exposure to certain metals in e-waste recycling communities may adversely impact health status.

The physiologic changes that accompany pregnancy can have important implications for neuro-ophthalmic disease. This article discusses pregnancy-related considerations for meningioma, pituitary disorders, demyelinating disease, myasthenia gravis, thyroid eye disease, idiopathic intracranial hypertension, cerebral venous sinus thrombosis, stroke, migraine, and cranial neuropathies. The article also details the potential neuro-ophthalmic complications of preeclampsia and eclampsia and reviews the use of common diagnostic studies during pregnancy.

SUMMARY Antibodies that target the glycan cap epitope on the ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization are not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures of diverse glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLDs) to the glycan cap, which we call the MLD anchor and cradle. Antibodies that bind to the MLD cradle share common features, including use of IGHV1–69 and IGHJ6 germline genes, which exploit hydrophobic residues and form β-hairpin structures to mimic the MLD anchor, disrupt MLD attachment, destabilize GP quaternary structure, and block cleavage events required for receptor binding. Our results provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies., In brief A rare subset of ebolavirus antibodies targeting the glycan cap are broadly neutralizing. Murin et al. report cryo-EM structures and custom in vitro assays identifying a conserved site of vulnerability in the glycan cap and detail mechanisms of action, including structural mimicry, trimer instability, and blocking cleavage., Graphical Abstract

ObjectiveTo describe the participation of minority women in clinical trials using immunologic agents for breast and gynecologic cancers.MethodsA retrospective review of completed clinical trials involving immunotherapy for breast and gynecologic cancers was performed. Completed trials were examined for data on race, tumor type, and start year. Minority enrollment was stratified by tumor site. Based on Center for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated and compared using Χ2 testing, p≤0.05.ResultsA total of 53 completed immunotherapy clinical trials involving 8820 patients were reviewed. Breast cancer trials were most common (n=24) and involved the most patients (n=6248, 71%). Racial breakdown was provided in 41 studies (77%) for a total of 7201 patients. Race reporting was lowest in uterine (n=4, 67%) and cervical cancer trials (n=6, 67%), and highest in ovarian cancer trials (n=12, 86%). White patients comprised 70% (n=5022) of all the patients included. Only 5% of patients involved were black (n=339), and 83% of these patients (n=282) were enrolled in breast cancer trials. Observed enrollment of black women was 32-fold lower for ovarian, 19-fold lower for cervical, 15-fold lower for uterine, and 11-fold lower for breast cancer than expected. While all trials reported race between 2013 and 2015, no consistent trend was seen towards increasing race reporting or in enrollment of black patients over time.ConclusionRacial disparities exist in clinical trials evaluating immunologic agents for breast and gynecologic cancers. Recruitment of black women is particularly low. In order to address inequity in outcomes for these cancers, it is crucial that significant attention be directed towards minority representation in immuno-oncologic clinical trials.

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n=34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures.

Socioeconomic factors appear to impact mental health conditions such as depression, but little is known about the relative and combined role of neighborhood and personal socioeconomic deprivation among Hispanics/Latinos. This study examined cross-sectional associations of neighborhood and personal socioeconomic deprivation with depression symptoms in a US Hispanic/Latino population from the San Diego Field Center of the Hispanic Community Health Study/Study of Latinos (n=3,851). Depression symptoms were assessed with the ten-item Centers for Epidemiological Studies in Depression Scale. Neighborhood socioeconomic deprivation was a composite of eleven variables (e.g., neighborhood income, education, employment, household crowding). Greater personal socioeconomic deprivation based on education, income, and employment was generally associated with higher depression symptoms, including after adjusting for neighborhood socioeconomic deprivation. Greater neighborhood socioeconomic deprivation was associated with higher depression symptoms in females but not males, but the association in females became non-significant when adjusting for personal socioeconomic deprivation. Neighborhood socioeconomic deprivation did not significantly interact with personal socioeconomic deprivation in relation to depression symptoms. The present findings support the association of personal socioeconomic status with mental health (indicated by depression symptoms) among Hispanic/Latino populations, whereas neighborhood socioeconomic deprivation did not relate to depression beyond the impact of personal indicators.

Blanketing is a highly debated practice utilized in the equine community as part of winter horse management. Despite this, little research is available on the prevalence, reasoning, and management decisions related to use of blankets for horses in North America. Therefore, the objective of this study was to develop an understanding of blanketing management practices and beliefs of North American horse owners. A 33-question, branched online survey was developed and available between December 1, 2020 and January 5, 2021 and advertised using social media and e-newsletters. The FREQ procedure for Chi-squared analysis in SAS was used when comparisons were made between participant-reported frequencies. There were 1,450 respondents from North America who completed the survey. Demographic information indicated the majority of respondents were from the Midwest region of the United States (68%); however, geographical region did not impact the frequency of blanket usage (P = .17, X

A consortium of laboratories established under the Children's Health Exposure Analysis Resource (CHEAR) used a multifaceted quality assurance program to promote measurement harmonization for trace organics analyses of human biospecimens that included: (1) participation in external quality assurance (EQA)/proficiency testing (PT) programs; (2) analyses of a urine-based CHEAR common quality control (QC) pool with each analytical batch across all participating laboratories; (3) method validation against NIST Standard Reference Materials® (SRMs); and (4) analyses of blinded duplicates and other project-specific QC samples. The capability of five CHEAR laboratories in organic chemical analysis increased across the 4-year period, and performance in the external PT program improved over time – recent challenges reporting >90% analytes with satisfactory performance. The CHEAR QC pools were analyzed for several classes of organic chemicals including phthalate metabolites and environmental phenols by the participating laboratories with every batch of project samples, which provided a rich source of measurement data for the assessment of intra- and inter-laboratory variance. Within-laboratory and overall variabilities in measurements across laboratories were calculated for target chemicals in urine QC pools; the coefficient of variation (CV) was generally below 25% across batches, studies and laboratories and indicated acceptable analytical imprecision. The suite of organic chemicals analyzed in the CHEAR QC pool was broader than those reported for commercially available reference materials. The accuracy of each of the laboratories' methods was verified through the analysis of several NIST SRMs and was, for example, 97 ± 5.2% for environmental phenols and 95 ± 11% for phthalates. Analysis of blinded duplicate samples showed excellent agreement and reliability of measurements. The intra-class correlation coefficients (ICC) for phthalate metabolites analyzed in various batches across three CHEAR laboratories showed excellent reliability (typically >0.90). Overall, the multifaceted quality assurance protocols followed among the CHEAR laboratories ensured reliable and reproducible data quality for several classes of organic chemicals. Increased participation in external PT programs through inclusion of additional target analytes will further enhance the confidence in data quality.

Harmonization and traceability are related metrological principles that are indispensable to assuring measurement comparability across different biomonitoring studies. The Children's Health Exposure Analysis Resource (CHEAR) was established in 2015 with six laboratories providing environmental exposure measurements on biospecimens. To ensure harmonization across studies for trace elements, CHEAR used a multi-faceted approach that included: 1) an initial interlaboratory validation exercise based on the analysis of certified blood and urine reference materials; 2) frequent participation in an established interlaboratory proficiency program for trace elements; and 3) analysis of a common pool of well-characterized biological reference materials with each analytical batch. Method accuracy and precision were established for each laboratory via analysis of NIST SRM 955c Toxic Elements in Caprine Blood, SRM 2668 Toxic Elements in Frozen Human Urine and SRM 3668 Mercury, Perchlorate, and Iodide in Frozen Human Urine. The differences among the six laboratories for As, Cd, Hg, and Mn in urine and Cd, Hg, and Pb in whole blood were judged to be fit-for-purpose. Interlaboratory performance over a 5-year period demonstrated an improvement in performance, such that for 2018–2019, >99% of challenges for urine As, Cd, Hg, and Mn, and 95% for whole blood Cd, Hg, Pb, and Mn, were found to be satisfactory. The CHEAR common reference materials were analyzed by at least 5 laboratories for 22 elements in urine and 13–14 elements in whole blood, thus providing a rich source of data to assess intra- and inter-run performance. The suite of trace elements with assigned values in both blood and urine matrices are more comprehensive than similar reference materials from other sources, and is reflective of the concentrations necessary to support biomonitoring studies. While some areas for future improvement were identified, significant progress was made to improve harmonization of trace element measurements in biological matrices among the CHEAR network labs.

Background Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. Methods All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. Results Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. Conclusions This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

Pancreatic cancer is a fatal disease. The five-year survival for patients with all stages of this tumor type is less than 10%, with a majority of patients dying from drug resistant, metastatic disease. Gemcitabine has been a standard of care for the treatment of pancreatic cancer for over 20 years, but as a single agent gemcitabine is not curative. Since the only therapeutic option for the over 80 percent of pancreatic cancer patients ineligible for surgical resection is chemotherapy with or without radiation, the last few decades have seen a significant effort to develop effective therapy for this disease. This review addresses preclinical and clinical efforts to identify agents that target molecular characteristics common to pancreatic tumors and to develop mechanism-based combination approaches to therapy. Some of the most promising combinations include agents that inhibit transcription dependent on BET proteins (BET bromodomain inhibitors) or that inhibit DNA repair mediated by PARP (PARP inhibitors).

SUMMARY Synthetically engineered DNA-encoded monoclonal antibodies (DMAbs) are an in vivo platform for evaluation and delivery of human mAb to control against infectious disease. Here, we engineer DMAbs encoding potent anti-Zaire ebolavirus (EBOV) glycoprotein (GP) mAbs isolated from Ebola virus disease survivors. We demonstrate the development of a human IgG1 DMAb platform for in vivo EBOV-GP mAb delivery and evaluation in a mouse model. Using this approach, we show that DMAb-11 and DMAb-34 exhibit functional and molecular profiles comparable to recombinant mAb, have a wide window of expression, and provide rapid protection against lethal mouse-adapted EBOV challenge. The DMAb platform represents a simple, rapid, and reproducible approach for evaluating the activity of mAb during clinical development. DMAbs have the potential to be a mAb delivery system, which may be advantageous for protection against highly pathogenic infectious diseases, like EBOV, in resource-limited and other challenging settings., Graphical Abstract, In Brief Monoclonal antibodies are an important approach for emerging infectious disease prevention. Patel et al. demonstrate engineering and in vivo delivery of DNA-encoded monoclonal antibodies (DMAbs) targeting the Zaire ebolavirus (EBOV) glycoprotein. DMAbs protect against lethal mouse-adapted EBOV and are useful for rapid evaluation of fully human mAbs in live animal models.

Little is known about the role of low health literacy (LHL) among breast surgical oncology patients. We initiated a prospective health literacy assessment to determine the relationship between health literacy and surgical treatment. Among 512 patients, univariate analysis revealed no statistical significance in the relationship of health literacy to breast surgery type, contralateral prophylactic mastectomy, or reconstruction following mastectomy. In a multivariate analysis, women with LHL were less likely to undergo reconstruction (aOR 0.81, 95% CI 0.69-0.94, P value = .006). Tailored interventions are needed to combat disparities in cancer treatment associated with LHL, with focus on reconstruction following mastectomy.

We analyzed clinical and histopathologic data of 97 pediatric patients who underwent excision of dermoid cysts. On review, 16.5% of the sample population demonstrated localized chronic inflammatory changes, including the presence of giant cells and epithelial disruption. These features were considered indicative of prior cyst rupture. Age at time of initial presentation was significantly older and cyst size was significantly larger in patients with histopathologic signs of previous rupture. Longer time to presentation and time to excision were associated with increased odds of spontaneous rupture.

Recent evidence suggests that atypical major depressive disorder (MDD) – whose key features include the reversed somatic symptoms of hyperphagia (increased appetite) and hypersomnia (increased sleep) – is a stronger predictor of future obesity than other MDD subtypes. The mechanisms underlying this relationship are unclear. The present study sought to elucidate whether the individual symptoms of hyperphagia, hypersomnia, poor appetite, and disturbed sleep have differential relationships with food attentional bias, emotional eating, external eating, and restrained eating. This cross-sectional laboratory study involved 103 young adults without obesity (mean age = 20 years, 79% female, 26% non-White, mean BMI = 23.4 kg/m2). We measured total depressive symptom severity and individual symptoms of hyperphagia, poor appetite, and disturbed sleep using the Hopkins Symptom Checklist-20 (SCL-20) and added an item to assess hypersomnia; food attentional bias using a Food Stroop task; and self-reported eating behaviors using the Dutch Eating Behavior Questionnaire. Hyperphagia was positively associated with emotional eating but negatively associated with food attentional bias. Hypersomnia was negatively associated with emotional eating. Poor appetite was negatively associated with emotional eating. Disturbed sleep was positively associated with food attentional bias and emotional eating. An aggregate of the remaining 15 depressive symptoms (SCL-15) was positively associated with emotional and restrained eating. Our findings highlight the importance of examining the direction of somatic depressive symptoms, and they set the stage for future research to identify subgroups of people with depression at greatest risk for obesity (e.g., those with hyperphagia and/or disturbed sleep) and the mechanisms responsible for this elevated risk (e.g., emotional eating).

Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of

Background Embolic events leading to retinal ischemia or cerebral ischemia share common risk factors; however, it has been well documented that the rate of concurrent cerebral infarction is higher in patients with a history of transient ischemic attack (TIA) than in those with monocular vision loss (MVL) due to retinal ischemia. Despite the fact that emboli to the ophthalmic artery (OA) and middle cerebral artery share the internal carotid artery (ICA) as a common origin or transit for emboli, the asymmetry in their final destination has not been fully explained. We hypothesize that the anatomic location of the OA takeoff from the ICA may contribute to the differential flow of small emboli to the retinal circulation vs the cerebral circulation. Methods We report a retrospective, comparative, case-control study on 28 patients with retinal ischemia and 26 patients with TIA or cerebral infarction caused by embolic events. All subjects underwent either computed tomography angiography or MRA. The location of the ipsilateral OA origin off the ICA was then graded in a blinded fashion and compared between cohorts. Vascular risk factors were collected for all patients, including age, sex, hypertension, hyperlipidemia, arrhythmia, diabetes, coronary artery disease, and smoking. Results We find that in patients with retinal ischemia of embolic etiology, the ipsilateral OA takeoff from the ICA is more proximal than in patients with cerebral infarcts or TIA (P = 0.0002). We found no statistically significant differences in demographic, vascular, or systemic risk factors. Conclusions We find that the mean anatomical location of the OA takeoff from the ICA is significantly more proximal in patients with MVL due to retinal ischemia compared with patients with TIA or cerebral ischemia. This finding contributes significantly to our understanding of a long observed but poorly understood phenomenon that patients with MVL are less likely to have concurrent cerebral ischemia than are patients with TIA.

Various injuries to the neural tissues can cause irreversible damage to multiple functions of the nervous system ranging from motor control to cognitive function. The limited treatment options available for patients have led to extensive interest in studying the mechanisms of neuronal regeneration and recovery from injury. Since many neurons are terminally differentiated, by increasing cell survival following injury it may be possible to minimize the impact of these injuries and provide translational potential for treatment of neuronal diseases. While several cell types are known to survive injury through plasma membrane repair mechanisms, there has been little investigation of membrane repair in neurons and even fewer efforts to target membrane repair as a therapy in neurons. Studies from our laboratory group and others demonstrated that mitsugumin 53 (MG53), a muscle-enriched tripartite motif (TRIM) family protein also known as TRIM72, is an essential component of the cell membrane repair machinery in skeletal muscle. Interestingly, recombinant human MG53 (rhMG53) can be applied exogenously to increase membrane repair capacity both in vitro and in vivo. Increasing the membrane repair capacity of neurons could potentially minimize the death of these cells and affect the progression of various neuronal diseases. In this study we assess the therapeutic potential of rhMG53 to increase membrane repair in cultured neurons and in an in vivo mouse model of neurotrauma. We found that a robust repair response exists in various neuronal cells and that rhMG53 can increase neuronal membrane repair both in vitro and in vivo. These findings provide direct evidence of conserved membrane repair responses in neurons and that these repair mechanisms can be targeted as a potential therapeutic approach for neuronal injury.

ObjectiveMyelin oligodendrocyte glycoprotein–immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in patients with MOGAD, we conducted a multicenter retrospective study to determine the rate of relapses on various treatments.MethodsWe determined the frequency of relapses in patients receiving various forms of long-term immunotherapy for MOGAD. Inclusion criteria were history of ≥1 CNS demyelinating attacks, MOG-IgG seropositivity, and immunotherapy for ≥6 months. Patients were reviewed for CNS demyelinating attacks before and during long-term immunotherapy.ResultsSeventy patients were included. The median age at initial CNS demyelinating attack was 29 years (range 3–61 years; 33% ConclusionThis large retrospective multicenter study of patients with MOGAD suggests that maintenance immunotherapy reduces recurrent CNS demyelinating attacks, with the lowest ARR being associated with maintenance IVIG therapy. Traditional MS disease-modifying agents appear to be ineffective. Prospective randomized controlled studies are required to validate these conclusions.

BACKGROUND Patients receiving long-term parenteral nutrition (PN) treatment are at risk of developing metabolic bone diseases (MBDs). The bone compartment serves as a repository for a range of metal(loid)s that are administered intravenously to patients via PN solutions. Thus, the mineral composition of patient bones may be linked to the development of MBDs in this group. METHODS We measured 12 elements in bone samples obtained post mortem from 7 long-term (2-21 years) PN patients and 18 control bones obtained from hip/knee replacement surgery. The samples were cleaned, digested, and subsequently analyzed using a method based on inductively coupled plasma tandem mass spectrometry. RESULTS Compared with the control group, bones obtained from PN patients were significantly (P

The United States lacks a set of unified electronic waste recycling laws, contributing in part to the observed low rate of e-waste recycling behaviors among consumers. Individual factors of consumers contributing to the low recycling rates are not well understood. The objective of this study was to evaluate consumer behaviors, including barriers, surrounding e-waste recycling at a large Midwestern university in the United States. A survey was administered to faculty, graduate students, undergraduate students, and staff to determine their personal recycling habits, knowledge, and beliefs. The results indicate that free access to disposal, lack of consumer knowledge about products and disposal sites, and access to a recycling facility within a reasonable distance are all important factors in consumer decisions. Policy-makers and waste management professionals should focus on promotion of e-waste recycling behaviors through increased access to free or low-cost recycling as well as through the creation of recycling incentives.

Purpose of review To review the most recent literature on the relationship of spontaneous cerebrospinal fluid (CSF) leak with idiopathic intracranial hypertension (IIH) and considerations in management of these conditions. Recent findings A link has been proposed between spontaneous CSF leak and IIH based on similar demographics, radiologic, and clinical findings in these patients, and on a plausible mechanism of skull base erosion in the setting of high CSF pressure over time. IIH patients with CSF leak may not present with classic IIH signs and symptoms as the leak can alleviate excess pressure; however, they may develop these after a leak is repaired. There may also be a higher risk of leak recurrence if intracranial hypertension is not treated postoperatively. Summary A growing body of evidence supports an association between IIH and spontaneous CSF leak. However, this relationship is still not fully elucidated, and there is no current agreement on how to incorporate screening, management, or counseling guidelines for CSF leak into the care of IIH patients. There are also no specific guidelines for evaluation/management of IIH in patients with spontaneous CSF leak. Further interdisciplinary research is needed to explore this connection and to establish screening, evaluation, and management guidelines.

Social media are an ever-present part of daily life and for researchers and may be a useful platform to increase potential participant pools for Web-based surveys. Although survey usage to evaluate practices in the equine community is not new, the use of social media to advertise and enhance the usage of Web-based surveys is novel. In 2018, the University of Minnesota (UMN) equine Extension program developed and administered two Web-based surveys through the UMN equine Extension Facebook page and monthly e-newsletter. Surveys focused on industry practices and motivating factors behind the usage of hay nets and methods to provide water in the winter to horses. Two thousand eighty-eight participants started the hay net survey with a completion rate of 96%, whereas the winter water survey had a completion rate of 94%, with 930 participants starting the survey. Participant demographics aligned with previous survey populations and represented all regions of the United States. Both surveys revealed information, which described current industry practices as well as future research needs. In addition, participants were asked if scientific research would impact future decision-making in regards to equine management. When exploring hay net practices, most participants responded “maybe” (48%, n = 527), whereas for the winter water survey, the majority responded “yes” (68%, n = 877). Web-based surveys administered through social media present multiple benefits, including savings of both cost and labor, compared with traditional mailed surveys. Despite the success observed with the present surveys, this methodology may not be suitable for organizations with limited social media followers.

Electronic waste recycling presents workers and communities with a potential for exposures to dangerous chemicals, including metals. This review examines studies that report on blood, hair, and urine biomarkers of communities and workers exposed to metals from e-waste. Our results from the evaluation of 19 publications found that there are consistently elevated levels of lead found in occupationally and non-occupationally exposed populations, in both the formal and the informal e-waste recycling sectors. Various other metals were found to be elevated in different exposure groups assessed using various types of biomarkers, but with less consistency than found in lead. Antimony and cadmium generally showed higher concentrations in exposed groups compared to reference group(s). Mercury and arsenic did not show a trend among exposure groups due to the dietary and environmental considerations. Observed variations in trends amongst exposure groups within studies using multiple biomarkers highlights the need to carefully select appropriate biomarkers. Our study concludes that there is a need for more rigorous research that moves past cross-sectional study designs, involves more thoughtful and methodical selection of biomarkers, and a systematic reporting standard for exposure studies to ensure that results can be compared across studies.

Recent studies from the Madre de Dios region of Peru report elevated mercury exposure among the general population. Our objective was to assess mercury exposure, risk factors, risk perceptions, and knowledge among women of childbearing age, a population of concern due to risks to infant and fetal health. We collected hair samples and administered a survey among 200 women aged 18-49 years residing in Madre de Dios. Hair total mercury (THg) concentrations were analyzed in accordance with EPA Method 7473. Associations between exposures and potential risk factors were analyzed using generalized linear mixed models. Geometric mean hair THg concentration (±standard deviation) for all participants was 1.62 ± 2.54 μg/g (range: 0.01-30.12 μg/g), and 67 participants (33.5%) had concentrations above the 2.2 μg/g reference dose established by the World Health Organization (WHO). Higher exposure was significantly associated with higher fish consumption (p = 0.03) and less mercury knowledge (p 0.0001), but not with age or educational attainment. Most participants (86.2%) expressed concern about mercury contamination, but few (26.2%) had knowledge of the health risks associated with exposure. Many residents consumed fish species previously found to have low mercury concentrations, but more than 25% of participants reported consuming fish species with high mercury concentrations. We did not observe cross-sectional differences in fish intake among women who were pregnant or breastfeeding at the time of data collection.

Pediatric anxiety disorders are highly prevalent, but tend to go undetected as pediatricians often lack relevant training. We developed a brief, video-based training program for pediatric residents aimed at improving early identification of child anxiety disorders. The novel training was completed in a group-based format or via an online, asynchronous training program. Pediatric residents from 2 residency programs (n = 63) participated and completed pre- and posttraining surveys evaluating attitudes about previous training, knowledge about child anxiety, perceived evaluation skills, and responses to clinical vignettes. Most residents (81%) reported they did not receive enough prior training in the presentation of anxiety disorders in young children. Residents’ knowledge and perceived evaluation skills increased posttraining. On the vignette-based assessment, residents demonstrated increased sensitivity with regard to interference, diagnosis, and referral urgency. Despite some challenges with participation, results provide preliminary evidence that brief training programs could be an effective way to improve resident education.

Youth with a history of adverse childhood experiences (ACEs) are more likely to develop risky health behaviors. With the increase of media use in the general population, it is likely that these high-risk youth are developing maladaptive behaviors associated with media use (i.e., problematic media use). The goals of this article are (1) to describe symptoms of problematic media use in high-risk youth and (2) to determine whether ACEs are related to problematic media use in this population. Data were collected through online questionnaires from 348 parents or legal guardians of children ages 5 to 18 years, the majority of whom had been adopted. Parents and guardians reported on the child’s history of ACEs and completed the Problematic Media Use Measure-Short Form (PMUM-SF). Almost half of the participants reported that their child had a history of four or more ACEs (48.9%). Caregivers of foster or adopted children reported more symptoms of problematic media use than those reporting on their biological children. After adjusting for covariates, the number of ACEs predicted problematic media use above and beyond variance explained by demographic factors or screen time amount. Children with a history of ACEs had higher problematic media use compared to children without ACEs.

Ensuring harmonization of (ultra-)trace element measurements in non-traditional matrices is a particular analytical challenge that is highlighted in this work for seminal plasma as part of the developmental core at the Wadsworth Center Human Health Exposure Analysis Resource Targeted Laboratory. Seminal plasma was collected from 39 male partners of women undergoing in vitro fertilization and analyzed by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) following deproteinization with concentrated HNO3. Validation was accomplished using: 1) two aqueous NIST SRMs; 2) a seminal plasma QC pool, characterized via standard additions; 3) standard additions on a subset of samples; and 4) sample duplicates. Agreement with NIST certified or reference values were obtained to within ±15% for the SRMs, and agreement between aqueous calibration values and standard additions values agreed to within ±10-20% for all elements. Standard additions of seminal plasma samples revealed varying matrix effects for Cu and Cr that were not found for the pooled samples. Duplicate analyses agreed to within ±10-30% depending on element. A potential source of contamination in colloidal silica used for processing seminal plasma was identified that requires further study. Comparisons with literature indicate lack of consensus for As, Cd, Cr, Mn, Pb, and V content in seminal plasma. Further work is needed to improve harmonization of future studies.

Purpose of review Papilledema associated with idiopathic intracranial hypertension (IIH) may result in irreversible, progressive visual loss. The development of tools for the evaluation of pediatric patients with IIH is particularly relevant as many patients may not be able to comply with the detailed clinical evaluation utilized in adults for the treatment and management of this disease. The purpose of this review is to summarize relevant articles on the diagnostic tools used in evaluation and management of pediatric IIH. Recent findings Studies suggest that characteristic pediatric IIH MRI findings include empty sella turcica, decreased pituitary gland size, optic nerve tortuosity, perioptic subarachnoid space enlargement, posterior globe flattering, and intraocular protrusion of the optic nerve head. On optical coherence tomography (OCT), increased retinal nerve fiber layer and macular thickness may be observed in children with IIH compared with controls. The retinal nerve fiber layer thickness seems to coincide with the severity of papilledema and may be more sensitive than funduscopy for detecting optic nerve head elevation. Research on ultrasound of the optic nerve shows increased size of the optic nerve sheath diameter in pediatric IIH patients, and this may correlate with increased opening pressure on lumbar puncture. Summary There appears to be characteristic findings on MRI, OCT, and ultrasound studies in pediatric IIH patients. Although ultrasound is rarely used for monitoring these patients nowadays, MRI and OCT can be useful in the evaluation and management of these individuals.

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary “patterns” of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: −2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF.

A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. This adaptation is mediated by a transition in nutrient sensitivity of the mTORC1 pathway, which leads to intermittent mTORC1 activity. Disrupting nutrient sensitivity of mTORC1 in mature β cells reverts insulin secretion to a functionally immature state. Finally, manipulating nutrient sensitivity of mTORC1 in stem cell-derived β cells in vitro strongly enhances their glucose-responsive insulin secretion. These results reveal a mechanism by which nutrients regulate β cell function, thereby enabling a metabolic adaptation for the newborn.