Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease.

Dysfunction of the endosomal-lysosomal network is a notable feature of Alzheimer's disease (AD) pathology. Dysfunctional endo-lysosomal vacuoles accumulate in dystrophic neurites surrounding amyloid ß (Aß) plaques and may be involved in the pathogenesis and progression of Aß aggregates. Trafficking and thus maturation of these dysfunctional vacuoles is disrupted in the vicinity of Aß plaques. Transmembrane protein 55B (TMEM55B), also known as phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1 (PIP4P1) is an endo-lysosomal membrane protein that is necessary for appropriate trafficking of endo-lysosomes. The present study tested whether overexpression of TMEM55B in the hippocampus could prevent plaque-associated axonal accumulation of dysfunctional endo-lysosomes, reduce Aß plaque load, and prevent hippocampal-dependent learning and memory deficits in the 5XFAD mouse models of Aß plaque pathology. Immunohistochemical analyses revealed a modest but significant reduction in the accumulation of endo-lysosomes in dystrophic neurites surrounding Aß plaques, but there was no change in hippocampal-dependent memory or plaque load. Overall, these data indicate a potential role for TMEM55B in reducing endo-lysosomal dysfunction during AD-like Aß pathology.

Mixture effects of prenatal exposure to polybrominated diphenyl ethers on urinary oxidative stress biomarkers in the Chemicals in Our Bodies Cohort.

Polybrominated diphenyl ethers (PBDEs) exposure is associated with preterm birth. Laboratory studies suggest that PBDEs lead to elevated oxidative stress, a known contributor to preterm birth in epidemiologic studies. We hypothesized that elevated levels of PBDEs would be associated with increased oxidative stress during human pregnancy. Participants in this analysis were enrolled in the Chemicals in Our Bodies cohort and resided in the San Francisco Bay Area (N=201). Four PBDEs (BDE-47, -99, -100, -153) were measured in second trimester serum. Urinary oxidative stress biomarkers were measured at two timepoints (second and third trimester) and included 8-isoprostane-prostaglandin-F2α [8-iso-PGF2α], 2,3-dinor-5,6-dihydro-8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and prostaglandin-F2α [PGF2α]. Associations between individual PBDEs and oxidative stress biomarkers (averaged and trimester specific) were examined using linear regression. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess cumulative effects of PBDEs. Quantile g-computation showed that higher concentrations of PBDEs were associated with increasing 8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and PGF2α. Associations were greatest in magnitude for second trimester levels of 2,3-dinor-8-iso-PGF2α (mean change per quartile increase=0.25, 95% confidence interval=0.09, 0.41). Associations were similar using BKMR and linear regression. Our findings suggest that oxidative stress may be a plausible biological pathway by which PBDE exposure might lead to preterm birth.

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Associations of per- and polyfluoroalkyl substances with maternal metabolic and inflammatory biomarkers in early-to-mid-pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. METHODS: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. RESULTS: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. IMPLICATIONS: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings.

Evaluation of RETRO-Mapping for electrophysiological features including direction of plane activity during atrial fibrillation using multipolar catheters in humans.

INTRODUCTION: A quantifiable, automated standard of analyzing heart rhythm has long eluded cardiologists due, in part, to the limitations in technology and the ability to analyze large electrogram datasets. In this proof-of-concept study, we propose new measures to quantify plane activity in atrial fibrillation (AF) using our Representation of Electrical Tracking of Origin (RETRO)-Mapping software. METHODS: We recorded 30 s segments of electrograms at the lower posterior wall of the left atrium using a 20-pole double loop catheter (AFocusII). The data were analyzed with the custom RETRO-Mapping algorithm in MATLAB. Thirty second segments were analyzed for number of activation edges, conduction velocity (CV), cycle length (CL), activation edge direction, and wavefront direction. These features were compared across 34 613 plane edges in three types of AF: persistent AF treated with amiodarone (11 906 wavefronts), persistent AF without amiodarone (14 959 wavefronts), and paroxysmal AF (7748 wavefronts). Change in activation edge direction between subsequent frames and change in overall wavefront direction between subsequent wavefronts were analyzed. RESULTS: All activation edge directions were represented across the lower posterior wall. The median change in activation edge direction followed a linear pattern for all three types of AF with R2 = 0.932 for persistent AF treated without amiodarone, R2 = 0.942 for paroxysmal AF, and R2 = 0.958 for persistent AF treated with amiodarone. All medians and the standard deviation error bars remained below 45° (suggesting all activation edges were traveling within a 90° sector, a criterion for plane activity). The directions of approximately half of all wavefronts (56.1% for persistent without amiodarone, 51.8% for paroxysmal, 48.8% for persistent with amiodarone) were predictive of the directions of the subsequent wavefront. CONCLUSION: RETRO-Mapping can measure electrophysiological features of activation activity and this proof-of-concept study suggests that this can be extended to the detection of plane activity in three types of AF. Wavefront direction may have a role in future work for predicting plane activity. For this study, we focused more on the ability of the algorithm to detect plane activity and less the differences between the types of AF. Future work should be in validating these results with a larger data set and comparing with other types of activation such as rotational, collision, and focal. Ultimately, this work can be implemented in real-time for prediction of wavefronts during ablation procedures.

Implementation and Evolution of Mitigation Measures, Testing, and Contact Tracing in the National Football League, August 9-November 21, 2020.

The National Football League (NFL) and the NFL Players Association (NFLPA) began the 2020 football season in July, implementing extensive mitigation and surveillance measures in facilities and during travel and gameplay. Mitigation protocols* were evaluated and modified based on data from routine reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19); proximity tracking devices; and detailed interviews. Midseason, transmission was observed in persons who had cumulative interactions of <15 minutes' duration, leading to a revised definition of high-risk contacts that required consideration of mask use, setting and room ventilation in addition to proximity and duration of interaction. The NFL also developed an intensive protocol that imposed stricter infection prevention precautions when a case was identified at an NFL club. The intensive protocol effectively prevented the occurrence of high-risk interactions, with no high-risk contacts identified for 71% of traced cases at clubs under the intensive protocol. The incorporation of the nature and location of the interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to proximity and duration, likely improved identification of exposed persons at higher risk for SARS-CoV-2 infection. Quarantine of these persons, along with testing and intensive protocols, can reduce spread of infection.

Mixture effects of prenatal exposure to per- and polyfluoroalkyl substances and polybrominated diphenyl ethers on maternal and newborn telomere length.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures. METHODS: Study participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes. RESULTS: T/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal-fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples. CONCLUSIONS: Our findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

Associations between prenatal maternal exposure to per- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) and birth outcomes among pregnant women in San Francisco.

BACKGROUND: Perfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores. METHODS: Women included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted ß coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models. RESULTS: The highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (ß = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (ß = - 0.26, 95% CI = -0.48, - 0.04; ß = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores. DISCUSSION: Among a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.

Association of polybrominated diphenyl ether (PBDE) levels with biomarkers of placental development and disease during mid-gestation.

BACKGROUND: Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function. METHODS: To evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods. RESULTS: PBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive). CONCLUSIONS: We found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

Changes in Perception of Various Telehealth Topics Before and After a Patient-Centered Outcomes Research Institute Telehealth Research Dissemination Conference.

Background: The Telehealth Dissemination Forum brought together a cross section of telehealth providers and constituents to review the latest telehealth research funded by Patient-Centered Outcomes Research Institute (PCORI) and to ascertain whether there were known gaps in the research. Methods: A pre- and postsurvey was conducted before and after the general overview of the market and research presentations. Using elements of human-centered design, participants were exposed to alternative problem solving and program design methods with the goal of translating the research into practice. Participants were stratified into four groups each with a moderator. Designers instructed the group throughout the design session. Results: A debrief was conducted at the end of the day to determine the value of the session as written evaluations were often not completed or less constructive. Postmeeting surveys were analyzed. Conclusions: We determined that the dissemination was effective; knowledge, attitudes, practices, and beliefs changed based on how this information was presented. The forum had an impact on participants as they left with design tools to assist with complex problem solving.

The cystathionine-ß-synthase domains on the guanosine 5''-monophosphate reductase and inosine 5'-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels.

The Leishmania guanosine 5'-monophosphate reductase (GMPR) and inosine 5'-monophosphate dehydrogenase (IMPDH) are purine metabolic enzymes that function maintaining the cellular adenylate and guanylate nucleotide. Interestingly, both enzymes contain a cystathionine-ß-synthase domain (CBS). To investigate this metabolic regulation, the Leishmania GMPR was cloned and shown to be sufficient to complement the guaC (GMPR), but not the guaB (IMPDH), mutation in Escherichia coli. Kinetic studies confirmed that the Leishmania GMPR catalyzed a strict NADPH-dependent reductive deamination of GMP to produce IMP. Addition of GTP or high levels of GMP induced a marked increase in activity without altering the Km values for the substrates. In contrast, the binding of ATP decreased the GMPR activity and increased the GMP Km value 10-fold. These kinetic changes were correlated with changes in the GMPR quaternary structure, induced by the binding of GMP, GTP, or ATP to the GMPR CBS domain. The capacity of these CBS domains to mediate the catalytic activity of the IMPDH and GMPR provides a regulatory mechanism for balancing the intracellular adenylate and guanylate pools.

Concentrations of Persistent Organic Pollutants in California Children's Whole Blood and Residential Dust.

We evaluated relationships between persistent organic pollutant (POP) levels in the blood of children with leukemia and POP levels in dust from their household vacuum cleaners. Blood and dust were collected from participants of the California Childhood Leukemia Study at various intervals from 1999 to 2007 and analyzed for two polybrominated diphenyl ethers (PBDEs), two polychlorinated biphenyls (PCBs), and two organochlorine pesticides using gas chromatography-mass spectrometry. Due to small blood sample volumes (100 µL), dichlorodiphenyldichloroethylene (DDE) and BDE-153 were the only analytes with detection frequencies above 70%. For each analyte, depending on its detection frequency, a multivariable linear or logistic regression model was used to evaluate the relationship between POP levels in blood and dust, adjusting for child's age, ethnicity, and breastfeeding duration; mother's country of origin; household annual income; and blood sampling date. In linear regression, concentrations of BDE-153 in blood and dust were positively associated; whereas, DDE concentrations in blood were positively associated with breastfeeding, maternal birth outside the U.S., and Hispanic ethnicity, but not with corresponding dust-DDE concentrations. The probability of PCB-153 detection in a child's blood was marginally associated with dust-PCB-153 concentrations (p = 0.08) in logistic regression and significantly associated with breastfeeding. Our findings suggest that dust ingestion is a source of children's exposure to certain POPs.

Concentrations of persistent organic pollutants in California women's serum and residential dust.

BACKGROUND: Humans are exposed to persistent organic pollutants (POPs) through various routes, including consumption of contaminated food and accidental ingestion of settled dust. OBJECTIVES: We aimed to identify key routes of exposure to organochlorine pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in California women of reproductive age. METHODS: Blood was collected from 48 mothers participating in the California Childhood Leukemia Study from 2006 to 2007 and analyzed for POPs using gas chromatography-mass spectrometry. Multivariable linear regression models of natural-log transformed serum concentrations were used to identify determinants of exposure from available questionnaire information on dietary habits, reproductive history, and demographic characteristics, as well as vacuum cleaner dust-POP levels. RESULTS: After adjusting for blood lipid levels, age, body mass index, cumulative lactation, and sampling date, serum concentrations of multiple major PCBs were positively associated with fish consumption, but not dust-PCB levels. After adjusting for blood lipid levels, Hispanic ethnicity, country of origin, and household annual income, serum concentrations of multiple major PBDEs were positively associated with dust-PBDE levels. CONCLUSIONS: Our findings suggest that the relative contribution of specific exposure routes to total POP intake varies by chemical class, with dust being a relatively important source of PBDEs and diet being a relatively important source of PCBs.

Idiopathic Hypereosinophilic Syndrome With Cutaneous Manifestations and Flame Figures: A Spectrum of Eosinophilic Dermatoses Whose Features Overlap With Wells' Syndrome.

IMPORTANCE: Wells syndrome (WS) (eosinophilic cellulitis) is an uncommon eosinophilic dermatitis that has been rarely described in association with, but distinct from, hypereosinophilic syndrome (HES). OBSERVATIONS: We report a case of an eosinophilic dermatosis with flame figures in association with idiopathic HES, manifested by inflammatory myocarditis, asthma, and peripheral blood eosinophilia. CONCLUSIONS AND RELEVANCE: The diagnoses of WS and HES, rather than being distinct findings, may represent 2 entities on a spectrum of hypereosinophilic diseases. The diagnosis of WS should be made with caution and should prompt a thorough investigation that includes a work-up for a systemic eosinophilic disorder.

Pediatric intracerebral hemorrhage score: a simple grading scale for intracerebral hemorrhage in children.

BACKGROUND AND PURPOSE: The intracerebral hemorrhage (ICH) score is the most commonly used clinical grading scale for outcome prediction after adult ICH. We created a similar scale in children to inform clinical care and assist in clinical research. METHODS: Children, full-term newborns to 18 years, with spontaneous ICH were prospectively enrolled from 2007 to 2012 at 3 centers. The pediatric ICH score was created by identifying factors associated with poor outcome. The score's ability to detect moderate disability or worse and severe disability or death was examined with sensitivity, specificity, and area under the receiver operating characteristic curve. RESULTS: The pediatric ICH score components include ICH volume>2% to 3.99% of total brain volume (TBV): 1 point; ICH volume≥4% TBV: 2 points; acute hydrocephalus: 1 point; herniation: 1 point; and infratentorial location: 1 point. The score ranges from 0 to 5. At 3-month follow-up of 60 children, 10 were severely disabled or dead, 30 had moderate disability, and 20 had good recovery. A pediatric ICH score≥1 predicted moderate disability or worse with a sensitivity of 75% (95% confidence interval [CI], 59% to 87%) and a specificity of 70% (95% CI, 46% to 88%). A pediatric ICH score≥2 predicted severe disability or death with a sensitivity and specificity of 90% (95% CI, 55% to 99%) and 68% (95% CI, 53% to 80%), respectively. The area under the receiver operating characteristic curve for classifying outcome as severe disability or death was 0.88 (95% CI, 0.78-0.97). CONCLUSIONS: The pediatric ICH score is a simple clinical grading scale that may ultimately be used for risk stratification, clinical care, and research.

18F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals derived from a single-institution 18F-FDG-directed surgery experience: feasibility and quantification of 18F-FDG accumulation within 18F-FDG-avid lesions and background tissues.

BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a well-established imaging modality for a wide variety of solid malignancies. Currently, only limited data exists regarding the utility of PET/CT imaging at very extended injection-to-scan acquisition times. The current retrospective data analysis assessed the feasibility and quantification of diagnostic (18)F-FDG PET/CT oncologic imaging at extended injection-to-scan acquisition time intervals. METHODS: (18)F-FDG-avid lesions (not surgically manipulated or altered during (18)F-FDG-directed surgery, and visualized both on preoperative and postoperative (18)F-FDG PET/CT imaging) and corresponding background tissues were assessed for (18)F-FDG accumulation on same-day preoperative and postoperative (18)F-FDG PET/CT imaging. Multiple patient variables and (18)F-FDG-avid lesion variables were examined. RESULTS: For the 32 (18)F-FDG-avid lesions making up the final (18)F-FDG-avid lesion data set (from among 7 patients), the mean injection-to-scan times of the preoperative and postoperative (18)F-FDG PET/CT scans were 73 (± 3, 70-78) and 530 (± 79, 413-739) minutes, respectively (P < 0.001). The preoperative and postoperative mean (18)F-FDG-avid lesion SUV(max) values were 7.7 (± 4.0, 3.6-19.5) and 11.3 (± 6.0, 4.1-29.2), respectively (P < 0.001). The preoperative and postoperative mean background SUV(max) values were 2.3 (± 0.6, 1.0-3.2) and 2.1 (± 0.6, 1.0-3.3), respectively (P = 0.017). The preoperative and postoperative mean lesion-to-background SUV(max) ratios were 3.7 (± 2.3, 1.5-9.8) and 5.8 (± 3.6, 1.6-16.2), respectively, (P < 0.001). CONCLUSIONS: (18)F-FDG PET/CT oncologic imaging can be successfully performed at extended injection-to-scan acquisition time intervals of up to approximately 5 half-lives for (18)F-FDG while maintaining good/adequate diagnostic image quality. The resultant increase in the (18)F-FDG-avid lesion SUV(max) values, decreased background SUV(max) values, and increased lesion-to-background SUV(max) ratios seen from preoperative to postoperative (18)F-FDG PET/CT imaging have great potential for allowing for the integrated, real-time use of (18)F-FDG PET/CT imaging in conjunction with (18)F-FDG-directed interventional radiology biopsy and ablation procedures and (18)F-FDG-directed surgical procedures, as well as have far-reaching impact on potentially re-shaping future thinking regarding the "most optimal" injection-to-scan acquisition time interval for all routine diagnostic (18)F-FDG PET/CT oncologic imaging.

Associations of per- and polyfluoroalkyl substances with maternal early second trimester sex-steroid hormones.

BACKGROUND/AIMS: Pregnant women are exposed to persistent environmental contaminants, including per- and polyfluoroalkyl substances (PFAS) that disrupt thyroid function. However, it is unclear if PFAS alter maternal sex-steroid hormone levels, which support pregnancy health and fetal development. METHODS: In Illinois women with relatively high socioeconomic status (n = 460), we quantified perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid, perfluorohexanesulphonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid concentrations in fasting serum samples at median 17 weeks gestation, along with plasma progesterone, testosterone, and estradiol. We evaluated covariate-adjusted associations of ln-transformed hormones with each ln-transformed PFAS individually using linear regression and with the PFAS mixture using quantile-based g-computation (QGComp). RESULTS: Interquartile range (IQR) increases in PFOS were associated with higher progesterone (%Δ 3.0; 95%CI: -0.6, 6.6) and estradiol (%Δ: 8.1; 95%CI: 2.2, 14.4) levels. Additionally, PFHxS was positively associated with testosterone (%Δ: 10.2; 95%CI: 4.0, 16.7), whereas both PFDeA and PFUdA were inversely associated with testosterone (%Δ: -5.7; 95%CI: -10.3, -0.8, and %Δ: -4.1; 95%CI: -7.6, -0.4, respectively). The IQR-standardized PFAS mixture was not associated with progesterone (%Δ: 1.6; 95%CI: -5.8, 9.2), due equal partial positive (%Δ: 9.2; driven by PFOA) and negative (%Δ: -7.4; driven by PFOS) mixture associations. Similarly, the mixture was not associated with testosterone (%Δ: 5.3; 95%CI: -9.0, 20.1), due to similar partial positive (%Δ: 23.6; driven by PFHxS) and negative (%Δ: -17.4; driven by PFDeA) mixture associations. However, we observed a slightly stronger partial positive (%Δ: 25.6; driven by PFOS and PFUdA) than negative (%Δ: -16.3; driven by PFOA) association resulting in an overall non-significant positive trend between the mixture and estradiol (%Δ: 8.5; 95%CI: -3.7, 20.9). CONCLUSION: PFAS mixture modeled using QGComp was not associated with maternal sex-steroid hormones due to potential opposing effects of certain PFAS. Additional prospective studies could corroborate these findings.

Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association.

BACKGROUND: The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population. METHODS AND RESULTS: A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD. CONCLUSIONS: Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation throughout childhood may enhance identification of significant deficits, allowing for appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning.

The 5XFAD mouse model of Alzheimer's disease displays age-dependent deficits in habituation to a novel environment.

Habituation is a form of learning characterized by a decrement in responsiveness to a stimulus that is repeated or prolonged. In rodents, habituation to a novel environment is characterized by a decrease in locomotion over time spent in a novel environment. Habituation to a novel environment is dependent on hippocampal function, suggesting that habituation behavior may be a relevant readout for hippocampal-dependent memory deficits that are characteristic of Alzheimer's disease (AD). Current assays that measure hippocampal-dependent memory in preclinical animal models of AD have not accurately predicted the cognitive protection of novel interventions in human trials. Here, we tested whether a behavioral habituation paradigm could detect age-associated changes in a common preclinical mouse model of AD-like amyloid pathology, the 5XFAD mouse. We exposed 5XFAD mice and age-matched wild-type (WT) littermates at 3, 6, and 9 months of age to a novel environment over two sessions separated by 24 h and measured their locomotion. WT mice habituated to the novel environment over time, while 5XFAD mice displayed age-dependent deficits in behavioral habituation. We replicated our results using publicly available open field data from 5XFAD and late-onset AD mouse models with TREM2*R47H and APOE4 mutations. Overall, we present behavioral habituation as a potentially sensitive task to assess age-associated behavioral deficits in 5XFAD mice and other mouse models of AD that could be used to test the preclinical efficacy of novel AD therapeutics.

COVID-19 Vaccine Equity and Access: Case Study for Health Care Chatbots.

BACKGROUND: Disparities in COVID-19 information and vaccine access have emerged during the pandemic. Individuals from historically excluded communities (eg, Black and Latin American) experience disproportionately negative health outcomes related to COVID-19. Community gaps in COVID-19 education, social, and health care services (including vaccines) should be prioritized as a critical effort to end the pandemic. Misinformation created by the politicization of COVID-19 and related public health measures has magnified the pandemic's challenges, including access to health care, vaccination and testing efforts, as well as personal protective equipment. Information and Communication Technology (ICT) has been demonstrated to reduce the gaps of marginalization in education and access among communities. Chatbots are an increasingly present example of ICTs, particularly in health care and in relation to the COVID-19 pandemic. OBJECTIVE: This project aimed to (1) follow an inclusive and theoretically driven design process to develop and test a COVID-19 information ICT bilingual (English and Spanish) chatbot tool named "Ana" and (2) characterize and evaluate user experiences of these innovative technologies. METHODS: Ana was developed following a multitheoretical framework, and the project team was comprised of public health experts, behavioral scientists, community members, and medical team. A total of 7 iterations of ß chatbots were tested, and a total of 22 ß testers participated in this process. Content was curated primarily to provide users with factual answers to common questions about COVID-19. To ensure relevance of the content, topics were driven by community concerns and questions, as ascertained through research. Ana's repository of educational content was based on national and international organizations as well as interdisciplinary experts. In the context of this development and pilot project, we identified an evaluation framework to explore reach, engagement, and satisfaction. RESULTS: A total of 626 community members used Ana from August 2021 to March 2022. Among those participants, 346 used the English version, with an average of 43 users per month; and 280 participants used the Spanish version, with an average of 40 users monthly. Across all users, 63.87% (n=221) of English users and 22.14% (n=62) of Spanish users returned to use Ana at least once; 18.49% (n=64) among the English version users and 18.57% (n=52) among the Spanish version users reported their ranking. Positive ranking comprised the "smiley" and "loved" emojis, and negative ranking comprised the "neutral," "sad," and "mad" emojis. When comparing negative and positive experiences, the latter was higher across Ana's platforms (English: n=41, 64.06%; Spanish: n=41, 77.35%) versus the former (English: n=23, 35.93%; Spanish: n=12, 22.64%). CONCLUSIONS: This pilot project demonstrated the feasibility and capacity of an innovative ICT to share COVID-19 information within diverse communities. Creating a chatbot like Ana with bilingual content contributed to an equitable approach to address the lack of accessible COVID-19-related information.