Harmonizing the assessment of allostatic load across cycles of the Canadian Health Measures Survey: Variable selection and calculation method.

Background: The availability of measures to operationalize allostatic load - the cumulative toll on the body of responding to stressor demands - in population health surveys may differ across years or surveys, hampering analyses on the entire sampled population. Here, impacts of variable selection and calculation method were evaluated to generate an allostatic load index applicable across all cycles of the Canadian Health Measures Survey (CHMS). Methods: Data from CHMS cycles 1 to 4 were used to compare allostatic load scores when replacing the most prevalent risk factor, waist-to-hip ratio - available in cycles 1 to 4 but not 5 and 6 - with body mass index (BMI), waist circumference, waist circumference within BMI groups (classified as normal, overweight, or obese), or waist-to-height ratio. Indexes were generated using clinical or sex-specific empirically defined risk thresholds and as count-based or continuous scores. Logistic regression models that included age and sex were used to relate each potential index to socioeconomic indicators (educational attainment, household income). Results: Of the variables assessed, waist-to-height ratio and waist circumference were closest to waist-to-hip ratio according to an individual's percentile ranking and in classifying "at risk" using either clinical or empirically defined cut-offs. Allostatic load profiles generated using waist-to-height ratios most closely resembled profiles constructed using waist-to-hip ratios. Sex-dependent associations with educational attainment and household income were maintained across constructs whether indexes were count-based or continuous. Interpretation: Allostatic load profiles and associations with socioeconomic indicators were robust to variable substitution and method of calculation, supporting the use of a harmonized index across survey cycles to assess the cumulative toll on health of stressor exposure.

Hexagonal Boron Nitride Self-Launches Hyperbolic Phonon Polaritons.

Hexagonal boron nitride (hBN) is a 2D material that supports traveling waves composed of material vibrations and light, and is attractive for nanoscale optical devices that function in the infrared. However, the only current method of launching these traveling waves requires the use of a metal nanostructure. Here, we show that the polaritonic waves can be launched into the 2D structure by folds within hBN, alone, taking advantage of the intrinsic material properties. Our findings suggest that structural continuity between the fold and hBN crystal is crucial for creating self-launched waves with a constant phase front. This approach offers a single material system to excite the polaritonic modes, and the approach is applicable to a broad range of 2D crystals and thus could be useful in future characterization.

Phospholipid Bilayers: Stability and Encapsulation of Nanoparticles.

Nanoparticles are widely studied for their potential medical uses in diagnostics and therapeutics. The interface between a nanoparticle and its target has been a focus of research, both to guide the nanoparticle and to prevent it from deactivating. Given nature's frequent use of phospholipid vesicles as carriers, much attention has been paid to phospholipids as a vehicle for drug delivery. The physical chemistry of bilayer formation and nanoparticle encapsulation is complex, touching on fundamental properties of hydrophobicity. Understanding the design rules for particle synthesis and encapsulation is an active area of research. The aim of this review is to provide a perspective on what preparative guideposts have been empirically discovered and how these are related to theoretical understanding. In addition, we aim to summarize how modern theory is beginning to help guide the design of functional particles that can effectively cross biological membranes.

How osmolytes influence hydrophobic polymer conformations: A unified view from experiment and theory.

It is currently the consensus belief that protective osmolytes such as trimethylamine N-oxide (TMAO) favor protein folding by being excluded from the vicinity of a protein, whereas denaturing osmolytes such as urea lead to protein unfolding by strongly binding to the surface. Despite there being consensus on how TMAO and urea affect proteins as a whole, very little is known as to their effects on the individual mechanisms responsible for protein structure formation, especially hydrophobic association. In the present study, we use single-molecule atomic force microscopy and molecular dynamics simulations to investigate the effects of TMAO and urea on the unfolding of the hydrophobic homopolymer polystyrene. Incorporated with interfacial energy measurements, our results show that TMAO and urea act on polystyrene as a protectant and a denaturant, respectively, while complying with Tanford-Wyman preferential binding theory. We provide a molecular explanation suggesting that TMAO molecules have a greater thermodynamic binding affinity with the collapsed conformation of polystyrene than with the extended conformation, while the reverse is true for urea molecules. Results presented here from both experiment and simulation are in line with earlier predictions on a model Lennard-Jones polymer while also demonstrating the distinction in the mechanism of osmolyte action between protein and hydrophobic polymer. This marks, to our knowledge, the first experimental observation of TMAO-induced hydrophobic collapse in a ternary aqueous system.

A microgroove patterned multiwell cell culture plate for high-throughput studies of cell alignment.

Grooved substrates are commonly used to guide cell alignment and produce in vitro tissues that mimic certain aspects of in vivo cellular organization. These more sophisticated tissues provide valuable in vitro models for testing drugs and for dissecting out molecular mechanisms that direct tissue organization. To increase the accessibility of these tissue models we describe a simple and yet reproducible strategy to produce 1 µm-spaced grooved well plates suitable for conducting automated analysis of cellular responses. We characterize the alignment of four human cell types: retinal epithelial cells, umbilical vein endothelial cells, foreskin fibroblasts, and human pluripotent stem-cell-derived cardiac cells on grooves. We find all cells align along the grooves to differing extents at both sparse and confluent densities. To increase the sophistication of in vitro tissue organization possible, we also created hybrid substrates with controlled patterns of microgrooved and flat regions that can be identified in real-time using optical microscopy. Using our hybrid patterned surfaces we explore: (i) the ability of neighboring cells to provide a template to organize surrounding cells that are not directly exposed to grooved topographic cues, and (ii) the distance over which this template effect can operate in confluent cell sheets. We find that in fibroblast sheets, but not epithelial sheets, cells aligned on grooves can direct alignment of neighboring cells in flat regions over a limited distance of approximately 200 µm. Our hybrid surface plate provides a novel tool for studying the collective response of groups of cells exposed to differential topographical cues.