Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.

Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.

Drivers of natural disaster risk-reduction actions and their temporal dynamics: Insights from surveys during an imminent hurricane threat and its aftermath.

To improve preparedness for natural disasters, it is imperative to understand the factors that enable individual risk-reduction actions. This study offers such insights using innovative real-time (N = 871) and repeated (N = 255) surveys of a sample of coastal residents in Florida regarding flood preparations and their drivers during an imminent threat posed by Hurricane Dorian and its aftermath. Compared with commonly employed cross-sectional surveys, our methodology better represents relationships between preparedness actions undertaken during the disaster threat and their drivers derived from an extended version of Protection Motivation Theory (PMT).

Insights into the complementarity of natural disaster insurance purchases and risk reduction behavior.

While flooding is the costliest natural disaster risk, public-sector investments provide incomplete protection. Moreover, individuals are in general reluctant to voluntarily invest in measures which limit damage costs from natural disasters. The moral hazard hypothesis argues that insured individuals take fewer other preparedness measures based on their assumption that their losses will be covered anyway.

Evaluation of Human Performance Aiding Live Synthetically Engineered Bacteria in a Gut-on-a-Chip.

Synbiotics are a new class of live therapeutics employing engineered genetic circuits. The rapid adoption of genetic editing tools has catalyzed the expansion of possible synbiotics, exceeding traditional testing paradigms in terms of both throughput and model complexity. Herein, we present a simplistic gut-chip model using common Caco2 and HT-29 cell lines to establish a dynamic human screening platform for a cortisol sensing tryptamine producing synbiotic for cognitive performance sustainment.

Behavioral biases and heuristics in perceptions of COVID-19 risks and prevention decisions.

This study adds to an emerging literature on the factors associated with individual perceptions of COVID-19 risks and decision-making processes related to prevention behaviors. We conducted a survey in the Netherlands (N = 3600) in June-July 2020 when the first peak of COVID-19 infections, hospitalizations, and deaths had passed, and lockdown measures had been eased. Dutch policies relied heavily on individual prevention behaviors to mitigate a second infection wave.

Individual hurricane evacuation intentions during the COVID-19 pandemic: insights for risk communication and emergency management policies.

Unlabelled: The U.S. 2020 hurricane season was extraordinary because of a record number of named storms coinciding with the COVID-19 pandemic.

Characterization of an engineered live bacterial therapeutic for the treatment of phenylketonuria in a human gut-on-a-chip.

Engineered bacteria (synthetic biotics) represent a new class of therapeutics that leverage the tools of synthetic biology. Translational testing strategies are required to predict synthetic biotic function in the human body. Gut-on-a-chip microfluidics technology presents an opportunity to characterize strain function within a simulated human gastrointestinal tract.

Determinants of Probability Neglect and Risk Attitudes for Disaster Risk: An Online Experimental Study of Flood Insurance Demand among Homeowners.

Little is known about why individuals place either a high or a very low value on mitigating risks of disaster-type events, like floods. This study uses panel data methods to explore the psychological factors affecting probability neglect of flood risk relevant to the zero end-point of the probability weighting function in Prospect Theory, and willingness-to-pay for flood insurance. In particular, we focus on explanatory variables of anticipatory and anticipated emotions, as well as the threshold of concern.

Magnetic Control of MOF Crystal Orientation and Alignment.

Most metal-organic frameworks (MOFs) possess anisotropic properties, the full exploitation of which necessitates a general strategy for the controllable orientation of such MOF crystals. Current methods largely rely upon layer-by-layer MOF epitaxy or tuning of MOF crystal growth on appropriate substrates, yielding MOFs with fixed crystal orientations. Here, the dynamic magnetic alignment of different MOF crystals (NH -MIL-53(Al) and NU-1000) is shown.

Sudden cardiac death in adults with congenitally corrected transposition of the great arteries.

Background: Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart disease. There have been only few reports of sudden cardiac death (SCD) in patients with ccTGA and reasonable ventricular function.

Methods: A retrospective review of the medical records of all patients attending our adult congenital heart centre, with known ccTGA.

Right Ventricular Mass is Associated with Exercise Capacity in Adults with Repaired Tetralogy of Fallot.

The relationship between exercise capacity and right ventricular (RV) structure and function in adult repaired tetralogy of Fallot (TOF) is poorly understood. We therefore aimed to examine the relationships between cardiac MRI and cardiopulmonary exercise test variables in adult repaired TOF patients. In particular, we sought to determine the role of RV mass in determining exercise capacity.

Mechanisms of maintained exercise capacity in adults with repaired tetralogy of Fallot.

Background: The mechanisms whereby cardiac output is augmented with exercise in adult repaired tetralogy of Fallot (TOF) are poorly characterised.

Methods: 16 repaired TOF patients (25 ± 7 years of age) and 8 age and sex matched controls (25 ± 4 years of age) underwent cardiopulmonary exercise testing and then real-time cardiac MRI (1.5 T) at rest and whilst exercising within the scanner, aiming for 30% heart rate reserve (Level 1) and 60% heart rate reserve (Level 2), using a custom-built MRI compatible foot pedal device.

Potential new therapeutic modality revealed through agent-based modeling of the neuromuscular junction and acetylcholinesterase inhibition.

Background: One of the leading causes of death and illness within the agriculture industry is through unintentionally ingesting or inhaling organophosphate pesticides. OP intoxication directly inhibits acetylcholinesterase, resulting in an excitatory signaling cascade leading to fasciculation, loss of control of bodily fluids, and seizures.

Methods: Our model was developed using a discrete, rules-based modeling approach in NetLogo.

Predicting passive and active tissue:plasma partition coefficients: interindividual and interspecies variability.

A mechanistic tissue composition model incorporating passive and active transport for the prediction of steady-state tissue:plasma partition coefficients (K(t:pl)) of chemicals in multiple mammalian species was used to assess interindividual and interspecies variability. This approach predicts K(t:pl) using chemical lipophilicity, pKa, phospholipid membrane binding, and the unbound plasma fraction, together with tissue fractions of water, neutral lipids, neutral and acidic phospholipids, proteins, and pH. Active transport K(t:pl) is predicted using Michaelis-Menten transport parameters.

Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity.

Associations between ozone and morbidity using the Spatial Synoptic Classification system.

Background: Synoptic circulation patterns (large-scale tropospheric motion systems) affect air pollution and, potentially, air-pollution-morbidity associations. We evaluated the effect of synoptic circulation patterns (air masses) on the association between ozone and hospital admissions for asthma and myocardial infarction (MI) among adults in North Carolina.

Methods: Daily surface meteorology data (including precipitation, wind speed, and dew point) for five selected cities in North Carolina were obtained from the U.

Quantitative structure-activity relationships for organophosphates binding to trypsin and chymotrypsin.

Organophosphate (OP) nerve agents such as sarin, soman, tabun, and O-ethyl S-[2-(diisopropylamino) ethyl] methylphosphonothioate (VX) do not react solely with acetylcholinesterase (AChE). Evidence suggests that cholinergic-independent pathways over a wide range are also targeted, including serine proteases. These proteases comprise nearly one-third of all known proteases and play major roles in synaptic plasticity, learning, memory, neuroprotection, wound healing, cell signaling, inflammation, blood coagulation, and protein processing.

Use of respiratory function tests to predict survival in amyotrophic lateral sclerosis.

Respiratory function tests (RFTs) are commonly used as a measure of progression in ALS. This study assessed the ability of various RFTs to predict survival in ALS patients. Subjects with ALS had one or more measurements of seated and supine FVC, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP).

Perchlorate and radioiodide kinetics across life stages in the human: using PBPK models to predict dosimetry and thyroid inhibition and sensitive subpopulations based on developmental stage.

Perchlorate (ClO4(-)) is a drinking-water contaminant, known to disrupt thyroid hormone homeostasis in rats. This effect has only been seen in humans at high doses, yet the potential for long term effects from developmental endocrine disruption emphasizes the need for improved understanding of perchlorate's effect during the perinatal period. Physiologically based pharmacokinetic/dynamic (PBPK/PD) models for ClO4(-) and its effect on thyroid iodide uptake were constructed for human gestation and lactation data.

Abnormal right ventricular tissue velocities after repair of congenital heart disease--implications for late outcomes.

Background: Although repair of Tetralogy of Fallot (TOF) and transposition of the great arteries (TGA) has facilitated survival into adulthood, many survivors have residual haemodynamic abnormalities, including exercise intolerance and late right ventricular (RV) failure.

Methods: We studied 40 asymptomatic adult subjects (31.3+/-1.

Analysis of algorithms predicting blood:air and tissue:blood partition coefficients from solvent partition coefficients for prevalent components of JP-8 jet fuel.

Algorithms predicting tissue and blood partition coefficients (PCs) from solvent properties were compared to assess their usefulness in a petroleum mixture physiologically based pharmacokinetic/pharmacodynamic model. Measured blood:air and tissue:blood PCs for rat and human tissues were sought from literature resources for 14 prevalent jet fuel (JP-8) components. Average experimental PCs were compared with predicted PCs calculated using algorithms from 9 published sources.

PBPK model for radioactive iodide and perchlorate kinetics and perchlorate-induced inhibition of iodide uptake in humans.

Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures.

Evidence for competitive inhibition of iodide uptake by perchlorate and translocation of perchlorate into the thyroid.

Various published data sets that investigate the potential effect of exogenous perchlorate (ClO4-) on the uptake of iodide in the thyroid and subsequent changes in thyroid hormone levels are available. In order to best use the data towards the prediction of human health effects resulting from ClO4- exposure, the available literature data must be integrated into a self-consistent, coherent, and parsimonious quantitative model based on the most likely mode of action of perchlorate effect on thyroid function. We submit that the simplest mode of action for ClO4- in the thyroid that remains consistent with all available data involves competitive inhibition of iodide transport into the thyroid follicle, transport of perchlorate into the thyroid follicle against a concentration gradient, further transport into the thyroid lumen (where it may again interfere with iodide transport), and, finally, passive diffusion back into the blood.

Predicting fetal perchlorate dose and inhibition of iodide kinetics during gestation: a physiologically-based pharmacokinetic analysis of perchlorate and iodide kinetics in the rat.

Perchlorate (ClO4-) disrupts endocrine homeostasis by competitively inhibiting the transport of iodide (I-) into the thyroid. The potential for health effects from human exposure to ClO4- in drinking water is not known, but experimental animal studies are suggestive of developmental effects from ClO4- induced iodide deficiency during gestation. Normal hormone-dependent development relies, in part, on synthesis of hormones in the fetal thyroid from maternally supplied iodide.

PBPK predictions of perchlorate distribution and its effect on thyroid uptake of radioiodide in the male rat.

Due to perchlorate's (ClO4-) ability to competitively inhibit thyroid iodide (I-) uptake through the sodium-iodide symporter (NIS), potential human health risks exist from chronic exposure via drinking water. Such risks may include hypothyroidism, goiter, and mental retardation (if exposure occurs during critical periods in neurodevelopment). To aid in predicting perchlorate's effect on normal I- kinetics, we developed a physiologically-based pharmacokinetic (PBPK) model for the adult male rat.