Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD.

Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children's Hospital from 2005-2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery-Buktenica Developmental Test of Visual-Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((ß, 95% CI) 0.0977, 0.0382-0.1571; p = 0.0022) and white matter (0.0023, 0.0001-0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157-0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011-0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality's contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical-cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.

Quantitative Magnetic Resonance Cerebral Spinal Fluid Flow Properties and Executive Function Cognitive Outcomes in Congenital Heart Disease.

Cerebrospinal fluid (CSF) circulation has recently been shown to be important in nutrient distribution, waste removal, and neurogenesis. Increased CSF volumes are frequently observed in congenital heart disease (CHD) and are associated with neurodevelopmental deficits. This suggests prolonged perturbation to the CSF system and possible interference to its homeostatic function, which may contribute to the neurodevelopmental deficits in CHD. CSF flow has yet to be studied in CHD patients, but the pulsatile flow of CSF throughout the brain is driven mainly by cardiopulmonary circulation. Given the underlying heart defects in CHD, the cardiopulmonary circulatory mechanisms in CHD might be impaired with resultant perturbation on the CSF circulation. In this study, we determine whether CSF flow, using MRI measurements of static and dynamic pulsatile flow, is abnormal in youths with CHD compared to healthy controls in relation to executive cognitive function. CSF flow measurements were obtained on a total of 58 child and young adult participants (CHD=20, healthy controls = 38). The CSF flow was measured across the lumen of the Aqueduct of Sylvius using cardiac-gated phase-contrast MRI at 3.0T. Static pulsatility was characterized as anterograde and retrograde peak velocities, mean velocity, velocity variance measurements, and dynamic pulsatility calculated as each participant's CSF flow deviation from the study cohort's consensus flow measured with root mean squared deviation (RMSD) were obtained. The participants had neurocognitive assessments for executive function with focus on inhibition, cognitive flexibility, and working memory domains. The CHD group demonstrated greater dynamic pulsatility (higher overall flow RMSD over the entire CSF flow cycle) compared to controls (p=0.0353), with no difference detected in static pulsatility measures. However, lower static CSF flow pulsatility (anterograde peak velocity: p=0.0323) and lower dynamic CSF flow pulsatility (RMSD: p=0.0181) predicted poor inhibitory executive function outcome. Taken together, while the whole CHD group exhibited higher dynamic CSF flow pulsatility compared to controls, the subset of CHD subjects with relatively reduced static and dynamic CSF flow pulsatility had the worst executive functioning, specifically the inhibition domain. These findings suggest that altered CSF flow pulsatility may be central to not only brain compensatory mechanisms but can also drive cognitive impairment in CHD. Further studies are needed to investigate possible mechanistic etiologies of aberrant CSF pulsatility (i.e. primary cardiac hemodynamic disturbances, intrinsic brain vascular stiffness, altered visco-elastic properties of tissue, or glial-lymphatic disturbances), which can result in acquired small vessel brain injury (including microbleeds and white matter hyperintensities).

Functional network organization is locally atypical in children and adolescents with congenital heart disease.

Children and adolescents with congenital heart disease (CHD) frequently experience neurodevelopmental impairments that can impact academic performance, memory, attention, and behavioral function, ultimately affecting overall quality of life. This study aims to investigate the impact of CHD on functional brain network connectivity and cognitive function. Using resting-state fMRI data, we examined several network metrics across various brain regions utilizing weighted networks and binarized networks with both absolute and proportional thresholds. Regression models were fitted to patient neurocognitive exam scores using various metrics obtained from all three methods. Our results unveil significant differences in network connectivity patterns, particularly in temporal, occipital, and subcortical regions, across both weighted and binarized networks. Furthermore, we identified distinct correlations between network metrics and cognitive performance, suggesting potential compensatory mechanisms within specific brain regions.

Mitotic Block and Epigenetic Repression Underlie Neurodevelopmental Defects and Neurobehavioral Deficits in Congenital Heart Disease.

Poor neurodevelopment is often observed with congenital heart disease (CHD), especially with mutations in chromatin modifiers. Here analysis of mice with hypoplastic left heart syndrome (HLHS) arising from mutations in Sin3A associated chromatin modifier Sap130 , and adhesion protein Pcdha9, revealed neurodevelopmental and neurobehavioral deficits reminiscent of those in HLHS patients. Microcephaly was associated with impaired cortical neurogenesis, mitotic block, and increased apoptosis. Transcriptional profiling indicated dysregulated neurogenesis by REST, altered CREB signaling regulating memory and synaptic plasticity, and impaired neurovascular coupling modulating cerebral blood flow. Many neurodevelopmental/neurobehavioral disease pathways were recovered, including autism and cognitive impairment. These same pathways emerged from genome-wide DNA methylation and Sap130 chromatin immunoprecipitation sequencing analyses, suggesting epigenetic perturbation. Mice with Pcdha9 mutation or forebrain-specific Sap130 deletion without CHD showed learning/memory deficits and autism-like behavior. These novel findings provide mechanistic insights indicating the adverse neurodevelopment in HLHS may involve cell autonomous/nonautonomous defects and epigenetic dysregulation and suggest new avenues for therapy.

Predicting Ion Sequestration in Charged Polymers with the Steepest-Entropy-Ascent Quantum Thermodynamic Framework.

The steepest-entropy-ascent quantum thermodynamic framework is used to investigate the effectiveness of multi-chain polyethyleneimine-methylenephosphonic acid in sequestering rare-earth ions (Eu3+) from aqueous solutions. The framework applies a thermodynamic equation of motion to a discrete energy eigenstructure to model the binding kinetics of europium ions to reactive sites of the polymer chains. The energy eigenstructure is generated using a non-Markovian Monte Carlo model that estimates energy level degeneracies. The equation of motion is used to determine the occupation probability of each energy level, describing the unique path through thermodynamic state space by which the polymer system sequesters rare-earth ions from solution. A second Monte Carlo simulation is conducted to relate the kinetic path in state space to physical descriptors associated with the polymer, including the radius of gyration, tortuosity, and Eu-neighbor distribution functions. These descriptors are used to visualize the evolution of the polymer during the sequestration process. The fraction of sequestered Eu3+ ions depends upon the total energy of the system, with lower energy resulting in greater sequestration. The kinetics of the overall sequestration are dependent on the steepest-entropy-ascent principle used by the equation of motion to generate a unique kinetic path from an initial non-equilibrium state.

Predicting Polymer Brush Behavior in Solvents Using the Steepest-Entropy-Ascent Quantum Thermodynamic Framework.

The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework is utilized to study the effects of temperature on polymer brushes. The brushes are represented by a discrete energy spectrum, and energy degeneracies obtained through the replica-exchange Wang-Landau algorithm. The SEAQT equation of motion is applied to the density of states to establish a unique kinetic path from an initial thermodynamic state to a stable equilibrium state. The kinetic path describes the brush's evolution in state space, as it interacts with a thermal reservoir. The predicted occupation probabilities along the kinetic path are used to determine the expected thermodynamic and structural properties. The polymer density profile of a polystyrene brush in cyclohexane solvent is predicted using the equation of motion, and it agrees qualitatively with the experimental density profiles. The Flory-Huggins parameter chosen to describe brush-solvent interactions affects the solvent distribution in the brush but has a minimal impact on the polymer density profile. Three types of nonequilibrium kinetic paths with differing amounts of entropy production are considered: a heating path, a cooling path, and a heating-cooling path. Properties such as tortuosity, radius of gyration, brush density, solvent density, and brush chain conformations are calculated for each path.

MOF-based heterogeneous catalysis in continuous flow via incorporation onto polymer-based spherical activated carbon supports.

We present an approach to harnessing the tuneable catalytic properties of complex nanomaterials for continuous flow heterogeneous catalysis by combining them with the scalable and industrially implementable properties of carbon pelleted supports. This approach, in turn, will enable these catalytic materials, which largely currently exist in forms unsuitable for this application (e.g. powders), to be fully integrated into large scale, chemical processes. A composite heterogeneous catalyst consisting of a metal-organic framework-based Lewis acid, MIL-100(Sc), immobilised onto polymer-based spherical activated carbon (PBSAC) support has been developed. The material was characterised by focused ion beam-scanning electron microscopy-energy dispersive X-ray analysis, powder X-ray diffraction, N2 adsorption, thermogravimetric analysis, atomic absorption spectroscopy, light scattering and crush testing with the catalytic activity studied in continuous flow. The mechanically robust spherical geometry makes the composite material ideal for application in packed-bed reactors. The catalyst was observed to operate without any loss in activity at steady state for 9 hours when utilised as a Lewis acid catalyst for the intramolecular cyclisation of (±)-citronellal as a model reaction. This work paves the way for further development into the exploitation of MOF-based continuous flow heterogeneous catalysis.

Recurrent urinary tract infection management and prevention techniques among a population-based cohort of women.

INTRODUCTION: Recurrent urinary tract infection (rUTI), defined as three or more UTIs in 12 months, has psychological, physical, and financial burden. Many women with rUTI are not satisfied with care and report only starting preventative measures after several infections. The goal of this study is to elucidate current UTI management trends and the implementation of UTI prevention strategies. METHODS: A web-based study was sent to a national sample of adult women enrolled in ResearchMatch.org. Women were recruited to participate if they had a self-reported UTI in the past 12 months. RESULTS: Of the 755 subjects, nearly 30% reported rUTI. Among women with rUTI, more than 50% reported being peri- or postmenopausal, and two-thirds reported vaginal symptoms. 15.8% of women with rUTI reported dissatisfaction with care versus 7.9% of women without rUTI. Most women see their primary care physician for UTI management and only 26% of women with rUTI follow with a urologist. More than 65% of women increase their fluid intake, wipe from front to back, and urinate after sexual activity to prevent UTIs. Significantly more women with rUTI use transvaginal estrogen, cranberry extract, and low-dose prophylactic antibiotics. These interventions appear to be driven by urologists. CONCLUSION: Most women who have had a UTI in the last 12 months implement lifestyle changes to prevent future infections. Most women see their PCP for UTI management and women with rUTI are twice as likely to report dissatisfaction with care. Despite urologists optimizing medical rUTI prevention, they appear to be underutilized.

Graphene oxide-coated Ag-TiO2 hybrid nanocomposites for superior photocatalytic activity.

Graphene oxide (GO) has now emerged as one of the most promising materials in different areas such as photocatalysis, adsorption, and energy storage due to its high surface area, unique layered structure, etc. Among various types of precursors, anthracite coal has attracted a lot of attention nowadays as it affords GO a high concentration of sp2 carbons resulting in high conductivity and superior absorbance in the visible region. In this report, we have prepared GO-TiO2 nanocomposites as it is supposed to possess high photocatalytic activity owing to facile electron transmission from the conduction band of TiO2 to the GO surface resulting in a much lower degree of electron-hole pair recombination. To boost the photocatalytic activity further, TiO2 was coated with Ag nanoparticles as well. These hybrid structures were characterized by different analytical techniques, for example, XRD, HR-TEM, SEM, and Raman spectroscopy. The XRD pattern of these composites consists of characteristic peaks corresponding to GO, TiO2, and Ag. The HR-TEM studies confirm the presence of GO layers, cube-shaped TiO2, and spherical Ag nanoparticles. Phenol and 4-nitrophenol have been used as model pollutants to evaluate the photooxidation efficiencies under both UV and visible light irradiation. Under UV irradiation, the GO/Ag-TiO2 ternary nanocomposite shows better photooxidation efficiency (62%) compared to Ag-TiO2 (38%), GO-TiO2 (9%), GO (17%), and TiO2 (8%) toward phenol degradation. The GO/Ag-TiO2 is also having the highest photocatalytic activity toward the removal of phenol under visible light irradiation (34%). The ternary heterostructure (85%) also possesses superior photooxidation activity compared to Ag-TiO2 (44%) and GO-TiO2 (71%) toward the degradation of p-nitrophenol under UV light radiation for 60 min. The above observation reveals that the cooperative effect of Ag, TiO2, and GO is playing a crucial role to result in the high photooxidation activity of the GO/Ag-TiO2 hetero-nanocomposites.

Perezone and its phenyl glycine derivative induce cytotoxicity via caspases on human glial cancer cells.

The new phenyl glycine derivative of perezone was obtained in a single reaction step in ca. 80% yield which showed remarkable cytotoxic activity against the astrocytoma U-251 cell line. After 24 h of exposure, both perezone (IC50 = 6.83 ± 1.64 µM) and its phenyl glycine derivative (2.60 ± 1.69 µM) showed cytotoxic effect on U-251 cells but were five times less cytotoxic on the non-tumoral SVGp12 cell line (IC50 = 28.54 ± 1.59 and 31.87 ± 1.54 µM respectively). Both compounds induced cellular morphological changes (pyknosis or cytoplasmic vacuolization) and increased the expression of caspases 3, 8, and 9 genes related to apoptosis. In the acute toxicity study, phenyl glycine perezone (DL50 = 2000 mg/Kg) demonstrated to be less toxic than perezone (DL50 = 500 mg/Kg). Phenylglycine-perezone can envisage a beneficial therapeutic potential.

Predicting non-equilibrium folding behavior of polymer chains using the steepest-entropy-ascent quantum thermodynamic framework.

The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework is used to explore the influence of heating and cooling on polymer chain folding kinetics. The framework predicts how a chain moves from an initial non-equilibrium state to stable equilibrium along a unique thermodynamic path. The thermodynamic state is expressed by occupation probabilities corresponding to the levels of a discrete energy landscape. The landscape is generated using the Replica Exchange Wang-Landau method applied to a polymer chain represented by a sequence of hydrophobic and polar monomers with a simple hydrophobic-polar amino acid model. The chain conformation evolves as energy shifts among the levels of the energy landscape according to the principle of steepest entropy ascent. This principle is implemented via the SEAQT equation of motion. The SEAQT framework has the benefit of providing insight into structural properties under non-equilibrium conditions. Chain conformations during heating and cooling change continuously without sharp transitions in morphology. The changes are more drastic along non-equilibrium paths than along quasi-equilibrium paths. The SEAQT-predicted kinetics are fitted to rates associated with the experimental intensity profiles of cytochrome c protein folding with Rouse dynamics.

The biopsychosocial impacts of anxiety on overactive bladder in women.

AIMS: Links between emotional state and the bladder have long been recognized, as psychological comorbidity is a common feature of overactive bladder (OAB). However, how psychological factors might contribute to the development and severity of OAB remains unclear. Therefore, we sought to examine the effect of anxiety on OAB with a specific focus on bladder hypersensitivity. METHODS: In a sample of 120 adult women with OAB, we compared those with at least mild anxiety (PROMIS Anxiety score ≥55) to those with lower anxiety. Analyses focused on patient-reported questionnaires assessing urinary symptom severity and quality of life, psychological stress symptoms, general somatic symptoms, and results of quantitative sensory testing (QST), including temporal summation to heat pain (TSP). TSP was used to index elevated C-fiber responsiveness (i.e., central sensitization). RESULTS: Thirty-six (30%) women had at least mild anxiety. While there were no group differences for urinary symptom severity, more anxious women reported worse OAB-specific quality of life, greater psychological stress burden, higher stress reactivity, and greater somatic symptoms. On QST, there were no differences between anxiety groups for pain threshold (43.6 ± 3.1°C vs. 44.0 ± 3.1°C, p = 0.6) and tolerance (47.3 ± 1.5°C vs. 47.4 ± 1.6°C, p = 0.7). However, those with anxiety had significantly higher TSP than those without anxiety (6.0 ± 4.8 vs. 3.7 ± 3.9, p = 0.006), indicating greater central sensitization. CONCLUSIONS: Women with OAB and at least mild anxiety symptoms reported greater psychosocial burdens (i.e., psychological stress, stress reactivity, OAB-specific QOL) and somatic symptom severity and demonstrated greater central sensitization on QST than those without anxiety. These findings support the hypothesis that anxiety and psychological stress impact hypersensitivity mechanisms that may underlie and contribute to OAB, although further research is needed to better understand how and to what extent.

Compensatory coping and depression in women with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Women with genitourinary pain, a hallmark symptom of interstitial cystitis/bladder pain syndrome (IC/BPS), are at a two- to four-fold risk for depression as compared to women without genitourinary pain. Despite the pervasive impact of IC/BPS on psychological health, there is a paucity of empirical research on understanding the relation between IC/BPS and psychological distress. It has been previously reported that women with overactive bladder use increased compensatory coping and these behaviors are associated with heightened anxiety and stress. However, it is unknown whether a similar pattern emerges in IC/BPS populations, as ICBPS and OAB share many similar urinary symptoms. The current study examined the relationship between compensatory coping behaviors and symptoms of psychological distress in a sample of women with IC/BPS to inform understanding of risk and potential mechanisms for intervention. METHOD: This was a secondary analysis of an observational cohort of women with bladder symptoms. Fifty-five adult women with IC/BPS completed validated assessments of genitourinary symptoms, emotional distress, and bladder coping behaviors. Five compensatory coping behaviors were summed to create a total Bladder Coping Score. Linear regression examined associations between individual coping behaviors, total compensatory coping scores, and other risk variables. RESULTS: Most (93%) participants reported use of at least one compensatory coping behavior. Age, education level, history of vaginal birth, and symptom severity were all associated with greater compensatory coping scores, and anxiety was not. Beyond the influence of symptom severity, higher levels of depression were significantly associated with higher compensatory coping scores. DISCUSSION: Greater compensatory coping was associated with increased depression but not anxiety, suggesting different profiles of coping and psychological distress may exist among different types of bladder dysfunction.

Associations between Maternal Risk Factors and Intrinsic Placental and Fetal Brain Functional Properties in Congenital Heart Disease.

The relationship between maternal risk factors (MRFs) (particularly pre-gravid obesity, diabetes, and hypertension) and congenital heart disease (CHD) to placental and fetal brain outcomes is poorly understood. Here, we tested the hypothesis that MRF and CHD would be associated with reduced intrinsic placental and fetal brain function using a novel non-invasive technique. Pregnant participants with and without MRF and fetal CHD were prospectively recruited and underwent feto-placental MRI. Using intrinsic properties of blood oxygen level dependent imaging (BOLD) we quantified spatiotemporal variance of placenta and fetal brain. MRFs and CHD were correlated with functional characteristics of the placenta and fetal brain. Co-morbid MRF (hypertension, diabetes, and obesity) reduced spatiotemporal functional variance of placenta and fetal brain (p < 0.05). CHD predicted reduced fetal brain temporal variance compared to non-CHD (p < 0.05). The presence of both MRF and CHD was associated with reduced intrinsic pBOLD temporal variance (p = 0.047). There were no significant interactions of MRFs and CHD status on either temporal or spatial variance of intrinsic brain BOLD. MRF and CHD reduced functional characteristic of placenta and brain in fetuses. MRF modification and management during pregnancy may have the potential to not only provide additional risk stratification but may also improve neurodevelopmental outcomes.

Clinical factors associated with microstructural connectome related brain dysmaturation in term neonates with congenital heart disease.

Objective: Term congenital heart disease (CHD) neonates display abnormalities of brain structure and maturation, which are possibly related to underlying patient factors, abnormal physiology and perioperative insults. Our primary goal was to delineate associations between clinical factors and postnatal brain microstructure in term CHD neonates using diffusion tensor imaging (DTI) magnetic resonance (MR) acquisition combined with complementary data-driven connectome and seed-based tractography quantitative analyses. Our secondary goal was to delineate associations between mild dysplastic structural brain abnormalities and connectome and seed-base tractography quantitative analyses. These mild dysplastic structural abnormalities have been derived from prior human infant CHD MR studies and neonatal mouse models of CHD that were collectively used to calculate to calculate a brain dysplasia score (BDS) that included assessment of subcortical structures including the olfactory bulb, the cerebellum and the hippocampus. Methods: Neonates undergoing cardiac surgery for CHD were prospectively recruited from two large centers. Both pre- and postoperative MR brain scans were obtained. DTI in 42 directions was segmented into 90 regions using a neonatal brain template and three weighted methods. Clinical data collection included 18 patient-specific and 9 preoperative variables associated with preoperative scan and 6 intraoperative (e.g., cardiopulmonary bypass and deep hypothermic circulatory arrest times) and 12 postoperative variables associated with postoperative scan. We compared patient specific and preoperative clinical factors to network topology and tractography alterations on a preoperative neonatal brain MRI, and intra and postoperative clinical factors to network topology alterations on postoperative neonatal brain MRI. A composite BDS was created to score abnormal findings involving the cerebellar hemispheres and vermis, supratentorial extra-axial fluid, olfactory bulbs and sulci, hippocampus, choroid plexus, corpus callosum, and brainstem. The neuroimaging outcomes of this study included (1) connectome metrics: cost (number of connections) and global/nodal efficiency (network integration); (2) seed based tractography methods of fractional anisotropy (FA), radial diffusivity, and axial diffusivity. Statistics consisted of multiple regression with false discovery rate correction (FDR) comparing the clinical risk factors and BDS (including subcortical components) as predictors/exposures and the global connectome metrics, nodal efficiency, and seed based- tractography (FA, radial diffusivity, and axial diffusivity) as neuroimaging outcome measures. Results: A total of 133 term neonates with complex CHD were prospectively enrolled and 110 had analyzable DTI. Multiple patient-specific factors including d-transposition of the great arteries (d-TGA) physiology and severity of impairment of fetal cerebral substrate delivery (i.e., how much the CHD lesion alters typical fetal circulation such that the highest oxygen and nutrient rich blood from the placenta are not directed toward the fetal brain) were predictive of preoperative reduced cost (p < 0.0073) and reduced global/nodal efficiency (p < 0.03). Cardiopulmonary bypass time predicted postoperative reduced cost (p < 0.04) and multiple postoperative factors [extracorporeal membrane oxygenation (ECMO), seizures and cardiopulmonary resuscitation (CPR)] were predictive of postoperative reduced cost and reduced global/nodal efficiency (p < 0.05). Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. Total BDS was not predictive of brain network topology. However, key subcortical components of the BDS score did predict key global and nodal network topology: abnormalities of the cerebellum predicted reduced cost (p < 0.0417) and of the hippocampus predicted reduced global efficiency (p < 0.0126). All three subcortical structures predicted unique alterations of nodal efficiency (p < 0.05), including hippocampal abnormalities predicting widespread reduced nodal efficiency in all lobes of the brain, cerebellar abnormalities predicting increased prefrontal nodal efficiency, and olfactory bulb abnormalities predicting posterior parietal-occipital nodal efficiency. Conclusion: Patient-specific (d-TGA anatomy, preoperative impairment of fetal cerebral substrate delivery) and postoperative (e.g., seizures, need for ECMO, or CPR) clinical factors were most predictive of diffuse postnatal microstructural dysmaturation in term CHD neonates. Anthropometric measurements (weight, length, and head size) predicted tractography outcomes. In contrast, subcortical components (cerebellum, hippocampus, olfactory) of a structurally based BDS (derived from CHD mouse mutants), predicted more localized and regional postnatal microstructural differences. Collectively, these findings suggest that brain DTI connectome and seed-based tractography are complementary techniques which may facilitate deciphering the mechanistic relative contribution of clinical and genetic risk factors related to poor neurodevelopmental outcomes in CHD.

Impact of COVID-19 related maternal stress on fetal brain development: A Multimodal MRI study.

Background: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Methods: Pregnant participants with healthy pregnancies were prospectively recruited in 2020-2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using ltivariate models. Results: Fetal brain stem volume increased with increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). Conclusions: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic.

Predicting defect stability and annealing kinetics in two-dimensional PtSe2using steepest entropy ascent quantum thermodynamics.

The steepest-entropy-ascent quantum thermodynamic (SEAQT) framework was used to calculate the stability of a collection of point defects in 2D PtSe2and predict the kinetics with which defects rearrange during thermal annealing. The framework provides a non-equilibrium, ensemble-based framework with a self-consistent link between mechanics (both quantum and classical) and thermodynamics. It employs an equation of motion derived from the principle of steepest entropy ascent (maximum entropy production) to predict the time evolution of a set of occupation probabilities that define the states of a system undergoing a non-equilibrium process. The system is described by a degenerate energy landscape of eigenvalues, and the entropy is found from the occupation probabilities and the eigenlevel degeneracies. Scanning tunneling microscopy was used to identify the structure and distribution of point defects observed experimentally in a 2D PtSe2film. A catalog of observed defects includes six unique point defects (vacancies and anti-site defects on Pt and Se sublattices) and twenty combinations of multiple point defects in close proximity. The defect energies were estimated with density functional theory, while the degeneracies, or density of states, for the 2D film with all possible combinations or arrangements of cataloged defects was constructed using a non-Markovian Monte-Carlo approach (i.e. the Replica-Exchange-Wang-Landau algorithm (Vogelet al2013Phys. Rev. Lett.110210603)) with a q-state Potts model. The energy landscape and associated degeneracies were determined for a 2D PtSe2film two molecules thick and30×30unit cells in area (total of 5400 atoms). The SEAQT equation of motion was applied to the energy landscape to determine how an arbitrary density and arrangement of the six defect types evolve during annealing. Two annealing processes were modeled: heating from 77 K (-196 ∘C) to 523 K (250 ∘C) and isothermal annealing at 523 K. The SEAQT framework predicted defect configurations, which were consistent with experimental STM images.

Impact of COVID-19 Related Maternal Stress on Fetal Brain Development: A Multimodal MRI Study.

BACKGROUND: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neurostructural differences have been re-ported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. METHODS: Pregnant participants with healthy pregnancies were prospectively recruited in 2020-2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. RESULTS: Increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). CONCLUSIONS: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic.

United Kingdom Early Detection Initiative (UK-EDI): protocol for establishing a national multicentre cohort of individuals with new-onset diabetes for early detection of pancreatic cancer.

INTRODUCTION: Pancreatic cancer is a leading cause of cancer deaths worldwide. Screening for this disease has potential to improve survival. It is not feasible, with current screening modalities, to screen the asymptomatic adult population. However, screening of individuals in high-risk groups is recommended. Our study aims to provide resources and data that will inform strategies to screen individuals with new-onset diabetes (NOD) for pancreatic cancer. METHODS AND ANALYSIS: The United Kingdom Early Detection Initiative (UK-EDI) for pancreatic cancer is a national, prospective, observational cohort study that aims to recruit 2500 individuals with NOD (<6 months postdiagnosis) aged 50 years and over, with follow-up every 6 months, over a 3-year period. For study eligibility, diagnosis of diabetes is considered to be clinical measurement of haemoglobin A1c ≥48 mmol/mol. Detailed clinical information and biospecimens will be collected at baseline and follow-up to support the development of molecular, epidemiological and demographic biomarkers for earlier detection of pancreatic cancer in the high-risk NOD group. Socioeconomic impacts and cost-effectiveness of earlier detection of pancreatic cancer in individuals with NOD will be evaluated. The UK-EDI NOD cohort will provide a bioresource for future early detection research to be conducted. ETHICS AND DISSEMINATION: The UK-EDI study has been reviewed and approved by the London-West London and GTAC Research Ethics Committee (Ref 20/LO/0058). Study results will be disseminated through presentations at national and international symposia and publication in peer-reviewed, Open Access journals.