Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.

The role of IL-2 cytokine family in asthma.

BACKGROUND: The interleukin-2 (IL-2) family of cytokines, including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, are pivotal regulators of the immune response, impacting both innate and adaptive immunity. Understanding their molecular characteristics, receptor interactions, and signalling pathways is essential for elucidating their roles in health and disease. OBJECTIVES: This review provides a comprehensive overview of the IL-2 family of cytokines, highlighting their molecular biology, receptor interactions, and signalling mechanisms. Furthermore, it explores the involvement of IL-2 family cytokines in the pathogenesis of chronic respiratory diseases, with a specific focus on chronic obstructive pulmonary disease (COPD) and asthma. METHODS: A thorough literature review was conducted to gather insights into the molecular biology, receptor interactions, and signalling pathways of IL-2 family cytokines. Additionally, studies investigating the roles of these cytokines in chronic respiratory diseases, particularly COPD and asthma, were analysed to discern their implications in wider pathophysiology of disease. RESULTS: IL-2 family cytokines exert pleiotropic effects on immune cells, modulating cellular proliferation, differentiation, and survival. Dysregulation of IL-2 family cytokines has been implicated in the pathogenesis of chronic respiratory illnesses, including COPD and asthma. Elevated levels of IL-2 and IL-9 have been associated with disease severity in COPD, while IL-4 and IL-9 play crucial roles in asthma pathogenesis by promoting airway inflammation and remodelling. CONCLUSION: Understanding the intricate roles of IL-2 family cytokines in chronic respiratory diseases provides valuable insights into potential therapeutic targets for these conditions. Targeting specific cytokines or their receptors may offer novel treatment modalities to attenuate disease progression and improve clinical outcomes in patients with COPD and asthma.

Maternal selenium deficiency during pregnancy in association with autism and ADHD traits in children: The Odense Child Cohort.

BACKGROUND: Selenoproteins regulate pathways controlling neurodevelopment, e.g., redox signaling and thyroid hormone metabolism. However, studies investigating maternal selenium in relation to child neurodevelopmental disorders are scarce. METHODS: 719 mother-child pairs from the prospective population-based Odense Child Cohort study in Denmark were included. Three selenium biomarkers, i.e. concentrations of serum selenium, selenoprotein P (SELENOP), and activity of glutathione peroxidase 3 (GPX3), along with serum copper, zinc and iron were measured in early third trimester (at 28.9+/-0.8 weeks of pregnancy). ADHD and ASD traits in children were assessed systematically using the established Child Behaviour Checklist at 5 years of age, based on a Danish reference cohort with cut-off at 90th percentile. Multivariable regression models adjusted for biologically relevant confounders were applied. RESULTS: 155 of 719 (21.6 %) children had ASD traits and 59 of 719 (8.2 %) children had traits of ADHD at 5 years of age. In crude and adjusted models, all three selenium biomarkers associated inversely with ADHD traits. For ADHD, fully adjusted OR for 10 µg/L increment in selenium was 0.76 (95 % CI 0.60, 0.94), for one mg/L increment in SELENOP was 0.73 (0.56, 0.95), and for 10 U/L increment in GPx3 was 0.93 (0.87,1.00). Maternal total selenium was inversely associated with child ASD traits, OR per 10 µg/L increment was 0.85 (0.74, 0,98). SELENOP and GPx3 were not associated with ASD traits. The associations were specific to selenium, as other trace elements such as copper, zinc, or iron were not associated with the outcomes. CONCLUSIONS: The results provide coherent evidence for selenium deficiency as a risk factor for ADHD and ASD traits in an environment with borderline supply, the causality of which should be elucidated in a randomized controlled trial.

Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features.

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.e., higher family history density (FHD) scores). The AUD dataset included a group of 30 adult males (mean age = 41.25 years) with a lifetime diagnosis of AUD and currently abstinent and a group of 30 male controls (mean age = 27.24 years) without any history of AUD. A second dataset of young adults who were categorized based on their FHD scores comprised a group of 40 individuals (20 males) with high FHD of AUD (mean age = 25.33 years) and a group of 31 individuals (18 males) with low FHD (mean age = 25.47 years). Brain age was predicted using 187 brain morphological features of cortical thickness and brain volume in an XGBoost regression model; a bias-correction procedure was applied to the predicted brain age. Results showed that both AUD and high FHD individuals showed an increase of 1.70 and 0.09 years (1.08 months), respectively, in their brain age relative to their chronological age, suggesting accelerated brain aging in AUD and risk for AUD. Increased brain age was associated with poor performance on neurocognitive tests of executive functioning in both AUD and high FHD individuals, indicating that brain age can also serve as a proxy for cognitive functioning and brain health. These findings on brain aging in these groups may have important implications for the prevention and treatment of AUD and ensuing cognitive decline.

Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort.

BACKGROUND: Diet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. OBJECTIVES: The aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. METHODS: This study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. RESULTS: Se and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006). CONCLUSIONS: Low serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.

Immunologic response and seroconversion following third-dose COVID-19 vaccination in solid organ transplant recipients: A meta-analysis.

INTRODUCTION: The immunogenicity and efficacy of COVID-19 vaccination varied by demographic, including solid organ transplant recipients on immunosuppressive therapy. AIM: This purpose of this study is to assess seropositivity and seroconversion in solid-organ transplant recipients before and after third-dose COVID-19 vaccination. METHODS: This study is a systematic review and meta-analysis performed using PRISMA guidelines. To analyze clinical and cohort studies reporting immunologic response and seroconversion third-dose vaccination, a systematic search was performed using electronic databases (PubMed, Scopus, Cochrane, Directory of Open Access Journal (DOAJ), and Clinicaltrials.gov). RESULT: There were 18 full-text papers that could be analyzed qualitatively and quantitatively. After the third vaccination, the pooled rate seropositivity was 67.00% (95% CI 59.511; 74.047, I2 = 93.82%), and the pooled rate seroconversion was 52.51% (95% CI 44.03; 60.91, I2 = 92.15%). The pooled rate of seroconversion after the mRNA-based booster was 52.380% (95% CI 40.988; 63.649, I2 = 94.35%), and after the viral-vector-based booster was 42.478% (95% CI 35.222; 49.900, I2 = 0.00%). CONCLUSION: Based on the analysis of immunologic responses and seroconversion findings, the third-dose vaccination of solid organ transplant recipients is an effective method in establishing better immunity against COVID-19.

Maternal cortisol in 3rd trimester is associated with traits of neurodevelopmental disorder in offspring. Odense Child Cohort.

BACKGROUND: Prenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). AIM: To investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD. MATERIAL AND METHODS: Mother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27-30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex. RESULTS: Maternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m2 (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits. CONCLUSION: Higher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Higher Maternal Cortisol Associated With Lower Blood Pressure in Offspring From 3 Months to 5 Years of Age in the Odense Child Cohort.

BACKGROUND: Synthetic glucocorticoid exposure in late pregnancy may be associated with higher blood pressure in offspring. We hypothesized that endogenous cortisol in pregnancy relates to offspring blood pressure (OBP). OBJECTIVE: To investigate associations between maternal cortisol status in third trimester pregnancy and OBP. METHODS: We included 1317 mother-child pairs from Odense Child Cohort, an observational prospective cohort. Serum (s-) cortisol and 24-hour urine (u-) cortisol and cortisone were assessed in gestational week 28. Offspring systolic blood pressure and diastolic blood pressure were measured at age 3, 18 months, and 3 and 5 years. Associations between maternal cortisol and OBP were examined by mixed effects linear models. RESULTS: All significant associations between maternal cortisol and OBP were negative. In boys in pooled analyses, 1 nmol/L increase in maternal s-cortisol was associated with average decrease in systolic blood pressure (ß=-0.003 mmHg [95% CI, -0.005 to -0.0003]) and diastolic blood pressure (ß=-0.002 mmHg [95% CI, -0.004 to -0.0004]) after adjusting for confounders. At 3 months of age, higher maternal s-cortisol was significantly associated with lower systolic blood pressure (ß=-0.01 mmHg [95% CI, -0.01 to -0.004]) and diastolic blood pressure (ß=-0.010 mmHg [95% CI, -0.012 to -0.011]) in boys after adjusting for confounders, which remained significant after adjusting for potential intermediate factors. CONCLUSIONS: We found temporal sex dimorphic negative associations between maternal s-cortisol levels and OBP, with significant findings in boys. We conclude that physiological maternal cortisol is not a risk factor for higher blood pressure in offspring up to 5 years of age.

Higher free thyroxine associated with PFAS exposure in first trimester. The Odense Child Cohort.

BACKGROUND: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings. OBJECTIVES: To investigate associations between serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH). METHODS: In the Odense Child Cohort, a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status. RESULTS: A doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses. CONCLUSION: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified.

Intermittent brain network reconfigurations and the resistance to social media influence.

Since its development, social media has grown as a source of information and has a significant impact on opinion formation. Individuals interact with others and content via social media platforms in a variety of ways, but it remains unclear how decision-making and associated neural processes are impacted by the online sharing of informational content, from factual to fabricated. Here, we use EEG to estimate dynamic reconfigurations of brain networks and probe the neural changes underlying opinion change (or formation) within individuals interacting with a simulated social media platform. Our findings indicate that the individuals who changed their opinions are characterized by less frequent network reconfigurations while those who did not change their opinions tend to have more flexible brain networks with frequent reconfigurations. The nature of these frequent network configurations suggests a fundamentally different thought process between intervals in which individuals are easily influenced by social media and those in which they are not. We also show that these reconfigurations are distinct to the brain dynamics during an in-person discussion with strangers on the same content. Together, these findings suggest that brain network reconfigurations may not only be diagnostic to the informational context but also the underlying opinion formation.

Pregnancy Exposure to Perfluoroalkyl Substances and Associations With Prolactin Concentrations and Breastfeeding in the Odense Child Cohort.

CONTEXT: Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown. OBJECTIVE: To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy. MATERIALS AND METHODS: Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations. RESULTS: Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations. CONCLUSIONS: These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences.

Quantification of three-dimensional morphology of craniofacial mineralized tissue defects in Tgfbr2/Osx-Cre mice.

Craniofacial morphology is affected by the growth, development, and three-dimensional (3D) relationship of mineralized structures including the skull, jaws, and teeth. Despite fulfilling different purposes within this region, cranial bones and tooth dentin are derived from mesenchymal cells that are affected by perturbations within the TGF-ß signaling pathway. TGFBR2 encodes a transmembrane receptor that is part of the canonical, SMAD-dependent TGF-ß signaling pathway and mutations within this gene are associated with Loeys-Dietz syndrome, a condition which often presents with craniofacial signs including craniosynostosis and cleft palate. To investigate the role of Tgfbr2 in immature, but committed, mineralized tissue forming cells, we analyzed postnatal craniofacial morphology in mice with conditional Tgfbr2 deletion in Osx-expressing cells. Novel application of a 3D shape-based comparative technique revealed that Tgfbr2 in Osx-expressing cells results in impaired postnatal molar root and anterior cranial growth. These findings support those from studies using similar Tgfbr2 conditional knockout models, highlight the anomalous facial and dental regions/structures using tomographic imaging-based techniques, and provide insight into the role of Tgfbr2 during postnatal craniofacial development.

Alterations in Electroencephalography Theta as Candidate Biomarkers of Acute Cannabis Intoxication.

The trend toward cannabis legalization in the United States over the past two decades has unsurprisingly been accompanied by an increase in the number of cannabis users and use patterns that potentially pose wider risks to the public like driving under the influence. As such, it is becoming increasingly important to develop methods to accurately quantify cannabis intoxication and its associated impairments on cognitive and motor function. Electroencephalography (EEG) offers a non-invasive method for quantitatively assessing neurophysiological biomarkers of intoxication and impairment with a high degree of temporal resolution. Twelve healthy, young recreational cannabis users completed a series of neurocognitive tasks with concurrent EEG acquisition using the ABM STAT X24 EEG headset in a within-subject counterbalanced design. The 1-h testbed consisted of resting state tasks and tests of attention and memory. Spectral densities were computed for resting state tasks, and event-related potentials (ERPs) were obtained for the attention and memory tasks. Theta band power (3-5 Hz) was decreased during cannabis intoxication compared to placebo during resting state tasks, as were average P400 and late positive potential (LPP) amplitudes during attention and memory tasks. Cannabis intoxication was also associated with elevated frontal coherence and diminished anterior-posterior coherence in the Theta frequency band. This work highlights the utility of EEG to identify and quantify neurophysiological biomarkers from recordings obtained during a short neurocognitive testbed as a method for profiling cannabis intoxication. These biomarkers may prove efficacious in distinguishing intoxicated from non-intoxicated individuals in lab and real-world settings.

Elevated Inter-Brain Coherence Between Subjects With Concordant Stances During Discussion of Social Issues.

Social media platforms offer convenient, instantaneous social sharing on a mass scale with tremendous impact on public perceptions, opinions, and behavior. There is a need to understand why information spreads including the human motivations, cognitive processes, and neural dynamics of large-scale sharing. This study introduces a novel approach for investigating the effect social media messaging and in-person discussion has on the inter-brain dynamics within small groups of participants. The psychophysiological impact of information campaigns and narrative messaging within a closed social media environment was assessed using 24-channel wireless EEG. Data were acquired from three- or four-person groups while subjects debated contemporary social issues framed by four scenarios of varying controversy: (a) investing in ethical vs. unethical corporations, (b) selecting travel destination based on social awareness, (c) determining verdict in a murder trial and the punishment of life in prison or death penalty, and (d) decision to vaccinate. Pre-/post-scenario questionnaires assess the effects of the social media information. Inter-brain coherence between subject pairs on each social issue discussed by subjects was analyzed by concordance, agreement vs. disagreement, and by group unanimity, unanimous vs. not unanimous. Subject pairs that agreed on the social issues raised in the scenarios had significantly greater inter-brain coherence in gamma frequency range than disagreeing pairs over cortical regions known to be involved in social interactions. These effects were magnified when comparing groups where subject pairs were unanimous in their stance on the social issues for some but not all scenarios. While there was considerable overlap between scenarios in what EEG channels were significant, there was enough variability to indicate the possibility of scenario-specific effects on inter-brain coherence.

Extracorporeal membrane oxygenation network organisation and clinical outcomes during the COVID-19 pandemic in Greater Paris, France: a multicentre cohort study.

BACKGROUND: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic. METHODS: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO. FINDINGS: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm H2O (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation. INTERPRETATION: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources. FUNDING: None.

Adapting fasting plasma glucose threshold for GDM diagnosis according to the population distribution - An approach to the Danish paradox.

AIMS: To examine third trimester fasting venous plasma glucose (FVPG) according to the distribution of a Danish population of pregnant women and identify potential local FVPG thresholds for GDM diagnosis related to risks of adverse pregnancy outcomes. METHODS: In the observational Odense Child Cohort (OCC) study, 1516 women had FVPG measured at 27-28 weeks' gestation and were considered normal by Danish criteria and remained untreated. Maternal FVPG from OCC were standardized according to the local FVPG mean and standard deviation calibrated to data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. Associations between maternal FVPG and clinical and anthropometric outcomes were analysed. Potential FVPG cut points were identified. RESULTS: Unadjusted areas under the ROC curve for FVPG to discriminate for large for gestational age (LGA) and hypertensive disorders of pregnancy were 0.61 (95% CI 0.56, 0.67) and 0.57 (95% CI 0.52, 0.63), respectively. The Youden FVPG cut point for LGA was 5.5 mmol/L and 5.0 mmol/L for hypertensive disorders of pregnancy. CONCLUSIONS: This study identified a potential locally appropriate third trimester FVPG cut point between 5.5 and 5.7 mmol/L based on LGA risk in pregnancy. This cut point should be validated prospectively in other Danish cohorts.

Prenatal exposure to bisphenol A and autistic- and ADHD-related symptoms in children aged 2 and5 years from the Odense Child Cohort.

BACKGROUND: Bisphenol A (BPA) is a non-persistent chemical with endocrine disrupting abilities used in a variety of consumer products. Fetal exposure to BPA is of concern due to the elevated sensitivity, which particularly relates to the developing brain. Several epidemiological studies have investigated the association between prenatal BPA exposure and neurodevelopment, but the results have been inconclusive. OBJECTIVE: To assess the association between in utero exposure to BPA and Attention Deficit/Hyperactivity Disorder (ADHD-) symptoms and symptoms of Autism Spectrum Disorder (ASD) in 2 and 5-year old Danish children. METHOD: In the prospective Odense Child Cohort, BPA was measured in urine samples collected in gestational week 28 and adjusted for osmolality. ADHD and ASD symptoms were assessed with the use of the ADHD scale and ASD scale, respectively, derived from the Child Behaviour Checklist preschool version (CBCL/1½-5) at ages 2 and 5 years. Negative binomial and multiple logistic regression analyses were performed to investigate the association between maternal BPA exposure (continuous ln-transformed or divided into tertiles) and the relative differences in ADHD and ASD problem scores and the odds (OR) of an ADHD and autism score above the 75th percentile adjusting for maternal educational level, maternal age, pre-pregnancy BMI, parity and child age at evaluation in 658 mother-child pairs at 2 years of age for ASD-score, and 427 mother-child pairs at 5 years of age for ADHD and ASD-score. RESULTS: BPA was detected in 85.3% of maternal urine samples even though the exposure level was low (median 1.2 ng/mL). No associations between maternal BPA exposure and ASD at age 2 years or ADHD at age 5 years were found. Trends of elevated Odds Ratios (ORs) were seen among 5 year old children within the 3rd tertile of BPA exposure with an ASD-score above the 75th percentile (OR = 1.80, 95% CI 0.97,3.32), being stronger for girls (OR = 3.17, 95% CI 1.85,9.28). A dose-response relationship was observed between BPA exposure and ASD-score at 5 years of age (p-trend 0.06) in both boys and girls, but only significant in girls (p-trend 0.03). CONCLUSION: Our findings suggest that prenatal BPA exposure even in low concentrations may increase the risk of ASD symptoms which may predict later social abilities. It is therefore important to follow-up these children at older ages, measure their own BPA exposure, and determine if the observed associations persist.

Resting state EEG biomarkers of cognitive decline associated with Alzheimer's disease and mild cognitive impairment.

In this paper, we explore the utility of resting-state EEG measures as potential biomarkers for the detection and assessment of cognitive decline in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Neurophysiological biomarkers of AD derived from EEG and FDG-PET, once characterized and validated, would expand the set of existing diagnostic molecular biomarkers of AD pathology with associated biomarkers of disease progression and neural dysfunction. Since symptoms of AD often begin to appear later in life, successful identification of EEG-based biomarkers must account for age-related neurophysiological changes that occur even in healthy individuals. To this end, we collected EEG data from individuals with AD (n = 26), MCI (n = 53), and cognitively normal healthy controls stratified by age into three groups: 18-40 (n = 129), 40-60 (n = 62) and 60-90 (= 55) years old. For each participant, we computed power spectral density at each channel and spectral coherence between pairs of channels. Compared to age matched controls, in the AD group, we found increases in both spectral power and coherence at the slower frequencies (Delta, Theta). A smaller but significant increase in power of slow frequencies was observed for the MCI group, localized to temporal areas. These effects on slow frequency spectral power opposed that of normal aging observed by a decrease in the power of slow frequencies in our control groups. The AD group showed a significant decrease in the spectral power and coherence in the Alpha band consistent with the same effect in normal aging. However, the MCI group did not show any significant change in the Alpha band. Overall, Theta to Alpha ratio (TAR) provided the largest and most significant differences between the AD group and controls. However, differences in the MCI group remained small and localized. We proposed a novel method to quantify these small differences between Theta and Alpha bands' power using empirically derived distributions of spectral power across the time domain as opposed to averaging power across time. We defined Power Distribution Distance Measure (PDDM) as a distance measure between probability distribution functions (pdf) of Theta and Alpha power. Compared to average TAR, using PDDF enhanced the statistical significance, the effect size, and the spatial distribution of significant effects in the MCI group. We designed classifiers for differentiating individual MCI and AD participants from age-matched controls. The classification performance measured by the area under ROC curve after cross-validation were AUC = 0.85 and AUC = 0.6, for AD and MCI classifiers, respectively. Posterior probability of AD, TAR, and the proposed PDDM measure were all significantly correlated with MMSE score and neuropsychological tests in the AD group.