Impact of Right Ventricular Surface Area-to-Volume Ratio on Ventricular Remodeling After Pulmonary Valve Replacement.

Optimal reverse remodeling of the right ventricle (RV), a sentinel goal of pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot, is not fully predicted by volume-based pre-PVR parameters. Our objectives were to characterize novel geometric RV parameters in patients receiving PVR and in controls, and to identify associations between these parameters and chamber remodeling post-PVR. Secondary analysis was performed on cardiac magnetic resonance (CMR) data from 60 patients enrolled in a randomized trial of PVR with and without surgical RV remodeling. 20 healthy age-matched subjects served as controls. The primary outcome was optimal post-PVR RV remodeling (end-diastolic volume index (EDVi) ≤ 114 ml/m2 and ejection fraction (EF) ≥ 48%) vs. suboptimal remodeling (EDVi ≥ 120 ml/m2 and EF ≤ 45%). RV geometry was markedly different at baseline in PVR patients compared with controls, with lower systolic surface area-to-volume ratio (SAVR) (1.16 ± 0.26 vs.1.44 ± 0.21 cm2/mL, p < 0.001) and lower systolic circumferential curvature (0.87 ± 0.27 vs. 1.07 ± 0.30 cm- 1, p = 0.007) but similar longitudinal curvature. In the PVR cohort, higher systolic SAVR was associated with higher RVEF both pre- and post-PVR (p < 0.001). Among PVR patients, 15 had optimal and 19 had suboptimal remodeling post-PVR. Multivariable modeling showed that among the geometric parameters, higher systolic SAVR (OR 1.68 per 0.1 cm2/mL increase; p = 0.049) and shorter systolic RV long-axis length (OR 0.92 per 0.1 cm increase; p = 0.035) were independently associated with optimal remodeling. Compared with controls, PVR patients have lower SAVR and lower circumferential but not longitudinal curvature. Higher pre-PVR systolic SAVR is associated with optimal remodeling post-PVR.

Surface area-to-volume ratio, not cellular viscoelasticity, is the major determinant of red blood cell traversal through small channels.

The remarkable deformability of red blood cells (RBCs) depends on the viscoelasticity of the plasma membrane and cell contents and the surface area to volume (SA:V) ratio; however, it remains unclear which of these factors is the key determinant for passage through small capillaries. We used a microfluidic device to examine the traversal of normal, stiffened, swollen, parasitised and immature RBCs. We show that dramatic stiffening of RBCs had no measurable effect on their ability to traverse small channels. By contrast, a moderate decrease in the SA:V ratio had a marked effect on the equivalent cylinder diameter that is traversable by RBCs of similar cellular viscoelasticity. We developed a finite element model that provides a coherent rationale for the experimental observations, based on the nonlinear mechanical behaviour of the RBC membrane skeleton. We conclude that the SA:V ratio should be given more prominence in studies of RBC pathologies.

Growth, nitrate uptake kinetics, and biofiltration potential of eucheumatoids with different thallus morphologies.

The declining production of commercially important eucheumatoids related to serious problems, like increasing susceptibility to ice-ice disease and epiphytism, may be ameliorated by nutrition. This ushered an increasing interest in incorporating seaweeds into an integrated multi-trophic aquaculture (IMTA) setup to take up excess inorganic nutrients produced by fish farms for their nourishment. In this regard, it is important to understand the nutrient uptake capacity of candidate seaweeds for incorporation into an IMTA system. Here, we examined the growth, nitrate ( NO3- ) uptake kinetics, and biofiltration potential of Eucheuma denticulatum and three strains of Kappaphycus alvarezii (G-O2, TR-C16, and SW-13) with distinct thallus morphologies. The NO3- uptake rates of the samples were determined under a range of NO3- concentrations (1-48 µM) and uptake rates were fitted to the Michaelis-Menten saturation equation. Among the examined eucheumatoids, only SW-13 had a linear response to NO3- concentration while other strains had uptake rates that followed the Michaelis-Menten saturation equation. Eucheuma denticulatum had the lowest Km (9.78 ± 1.48 µM) while G-O2 had the highest Vmax (307 ± 79.3 µmol · g-1 · min-1 ). The efficiency in NO3- uptake (highest Vmax /Km and α) was translated into the highest growth rate (3.41 ± 0.58% · d-1 ) measured in E. denticulatum. Our study provided evidence that eucheumatoids could potentially take up large amount of NO3- and fix CO2 when cultivated proximate to a fish farm as one component of an IMTA system. During a 45 -d cultivation period of eucheumatoids, as much as 370 g NO3- can be sequestered by every 1 kg initial biomass of E. denticulatum growing at 3% · d-1 . Furthermore, based on our unpublished photosynthetic measurements, the congeneric K. striatus can fix 27.5 g C · kg-1 DW during a 12 h daylight period.

A Proof of Concept for 3D Printing of Solid Lipid-Based Formulations of Poorly Water-Soluble Drugs to Control Formulation Dispersion Kinetics.

PURPOSE: The use of three-dimensional printing (3DP) in the development of pharmaceutical dosage forms is growing rapidly. However, the research is almost exclusively focussed on polymer-based systems with very little reported on 3D printing of lipid-based formulations. Thus, the aim of the work was to explore the feasibility of 3DP technology to prepare solid lipid-based formulations. Here, 3DP was applied for the preparation of solid self-microemulsifying drug delivery systems (S-SMEDDS) with defined surface area to volume (SA/V) ratios. METHODS: The S-SMEDDS formulations, comprised of Gelucire® 44/14, Gelucire® 48/16 and Kolliphor® P 188 were loaded with fenofibrate or cinnarizine as model drugs. The formulations were printed into four geometrical shapes - cylindrical, prism, cube and torus, and compared to a control cube manually prepared from bulk formulation. RESULTS: The printing process was not significantly affected by the presence of the model drugs. The as-printed S-SMEDDS formulations were characterised using differential scanning calorimetry and wide-angle X-ray scattering. The kinetics of dispersion depended on the SA/V ratio values. The digestion process was affected by the initial geometry of the dosage form by virtue of the kinetics of dispersion of the dosage forms into the digestion medium. CONCLUSIONS: This proof of concept study has demonstrated the potential of 3DP for the development of customised S-SMEDDS formulations without the need for an additional carrier or additive and with optimisation could elaborate a new class of dosage forms based on 3D printed lipids. Graphical abstract Lipid based formulations were 3D printed in various shapes to control the surface are to volume ratio and consequently the kinetics of dispersion.

Degradation of Tocopherol Molecules and Its Impact on the Polymerization of Triacylglycerols during Heat Treatment of Oil.

The aim of the study was to analyze the influence of the surface area to volume ratio of pressed and refined rapeseed oils on the changes in tocopherol content and polymerization of triacylglycerols during heating. In the study the pressed and refined rapeseed oil was heated at 170 °C, during 6, 12, and 18 h with three different surface area to volume (s/v) ratios (0.378, 0.189, and 0.126 cm-1). During heating, a decrease in tocopherols and increases in dimers, trimers, and oligomers of triacylglycerols were observed. However, the changes were dependent on the surface area to volume ratio used, type of oil and time of heating. The biggest changes were observed in oil with the biggest s/v ratio (0.378 cm-1), and the lowest when the s/v ratio was 0.126 cm-1. The pressed oil was characterized by faster degradation of tocopherols and slower increase of triacylglycerol polymer levels compared to refined oil.

Gas exchange characteristics of giant cacti species varying in stem morphology and life history strategy.

PREMISE OF THE STUDY: Giant cacti species possess long cylindrical stems that store massive amounts of water and other resources to draw on for photosynthesis, growth, and reproduction during hot and dry conditions. Across all giant cacti taxa, stem photosynthetic surface area to volume ratio (S:V) varies by several fold. This broad morphological diversity leads to the hypothesis that giant cacti function along a predictable resource use continuum from a "safe" strategy reflected in low S:V, low relative growth rates (RGR), and low net assimilation rates (Anet ) to a high-risk strategy that is reflected in high S:V, RGR, and Anet . METHODS: To test this hypothesis, whole-plant gas exchange, chlorophyll fluorescence, and whole-spine-tissue carbon isotope ratios (δ13 C) were measured in four giant cacti species varying in stem morphology and RGR. Measurements were conducted on five well-watered, potted plants per species. KEY RESULTS: Under conditions of mild diel temperatures and low atmospheric vapor pressure deficit, Anet , transpiration (E), and stomatal conductance (Gs ) were significantly higher, and water-use efficiency (Anet : Gs ) was lower in fast-growing, multi-stemmed species compared to the slower growing, single-stemmed species. However, under warmer, less optimal conditions, gas exchange converged between stem types, and neither δ13 C nor chlorophyll fluorescence varied among species. CONCLUSIONS: The results add to a growing body of evidence that succulent-stemmed plants function along a similar economic spectrum as leaf-bearing plants such that functional traits including stem RGR, longevity, morphology, and gas exchange are correlated across species with varying life-history strategies.

Body size and body composition effects on heat loss from the hands during severe cold exposure.

OBJECTIVES: This study investigated the influence of body size and composition on maintaining hand temperature during severe cold exposure. The hand's high surface area-to-volume ratio predisposes the hand to heat loss, increasing the risk of cold injury and even hypothermia, which are major selective pressures in cold environments. While vasoregulation may reduce heat loss from the hand, the effect of body form, tissue thermogenesis, and body insulation on heat loss is unknown. MATERIALS AND METHODS: Thermal imaging was used to determine heat loss during a 3-min ice-water hand immersion test carried out on 114 volunteers (female = 63, male = 51). Established anthropometric measures were used to quantify body size, and bioelectrical impedance analysis determined skeletal muscle and fat mass. RESULTS: Skeletal muscle mass relative to body mass was a highly significant predictor of heat loss, while body mass, fat mass, and stature were not. Body composition and body size had little to no significant influence during rewarming after immersion. DISCUSSION: The thermogenic properties of muscle mass support maintenance of hand temperature during severe cold exposure. The findings here suggest that muscular individuals are less susceptible to heat loss and cold injury, and may be better at manual tasks in cold conditions than nonmuscular individuals.

Quantification of human lung structure and physiology using hyperpolarized 129Xe.

PURPOSE: To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality. METHODS: Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model. RESULTS: The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm(-1) ; total septal wall thickness = 9.2 ± 6.5 µm; blood-air barrier thickness = 1.0 ± 0.3 µm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text. CONCLUSION: The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases.

Constant surface area-to-volume ratio during cell growth as a design principle in mammalian cells.

All cells are subject to geometric constraints, such as surface area-to-volume (SA/V) ratio, that impact cell functions and force biological adaptations. Like the SA/V ratio of a sphere, it is generally assumed that the SA/V ratio of cells decreases as cell size increases. Here, we investigate this in near-spherical mammalian cells using single-cell measurements of cell mass and surface proteins, as well as imaging of plasma membrane morphology. We find that the SA/V ratio remains surprisingly constant as cells grow larger. This observation is largely independent of the cell cycle and the amount of cell growth. Consequently, cell growth results in increased plasma membrane folding, which simplifies cellular design by ensuring sufficient membrane area for cell division, nutrient uptake and deformation at all cell sizes.

A novel model-based equation for size dependent mean recovery coefficients for spheres and other shapes.

BACKGROUND: In NM-imaging, theoretical curves for the recovery coefficient (RC) of the signal maximum and mean are known for spheres and cubes, if a 3D Gaussian PSF is assumed. The RC of the maximum is also known for cylinders. For these and other shapes empirical equations with one or two fit-parameters have been utilized. METHODS: An equation for the RC for large objects of arbitrary shape is derived and generalized into an empirical equation for smaller objects, which is verified by numerical simulations. The proposed equation is compared to published results on SPECT kidney phantom measurements and to PET measurements on the NEMA IEC PET body phantom with six spheres. RESULTS: The signal loss (1-RC) for large spheres is inversely proportional to the radius, where the slope is proportional to the FWHM of the spatial resolution. For non-spherical shapes the generalized instead of the volume equivalent radius should be utilized. For smaller objects, an equation with one added empirical fit-parameter is presented. It is demonstrated that the EANM-guidelines' two-parameter logistic function results in a poor fit if the theoretical slope and inverse proportionality are forced and it gives a suboptimal fit when both parameters are fitted. CONCLUSIONS: A novel model-based equation for the mean RC-curve is derived. It can be used for arbitrary shapes as long as the sphericity is taken into account and it is accurate down to RC = 10 %. One parameter is directly related to the spatial resolution, while the other is a shape depending fit-parameter.

The Surface Area to Volume Ratio Changes the Pharmacokinetic and Pharmacodynamic Parameters in the Subcutaneous Tissue Cage Model: As Illustrated by Carprofen in Sheep.

Introduction: Pharmacokinetic and pharmacodynamic models can be powerful tools for predicting outcomes. Many models are based on repetitive sampling of the vascular space, due to the simplicity of obtaining samples. As many drugs do not exert their effect in the vasculature, models have been developed to sample tissues outside the bloodstream. Tissue cages are hollow devices implanted subcutaneously, or elsewhere, that are filled with fluid allowing repetitive sampling to occur. The physical dimensions of the cage, namely, the diffusible surface area to volume ratio, would be expected to change the rate of drug movement into and out of tissue cages. Methods: Seven sheep were implanted with five pairs of tissue cages, subcutaneously. Each pair of cages had a different length but a fixed diffusible surface area, so the surface area to volume ratio differed. Carrageenan was injected into half of the cages in each animal during one sampling period in a cross-over design. Samples from each cage and the bloodstream were obtained at 14-time points during two sampling periods. The concentration of carprofen was measured using LC-MS/MS and the results were modeled using nonlinear mixed-effects techniques. Prostaglandin metabolites were also measured and the change over time was analyzed using linear mixed effect modeling. Results: The presence of carrageenan within an animal changed the systemic pharmacokinetics of carprofen. The rate of drug movement into and out of the tissue cages varied with the surface area to volume ratio. The concentration time curve for prostaglandin metabolites changed with cage size. Conclusion: The surface area volume ratio of tissue cages will influence the calculated pharmacokinetic parameters and may affect calculated pharmacodynamics, thus, it is an important factor to consider when using tissue cage data for dosing regimes.

Physiological functional traits explain morphological variation of Ulva prolifera during the drifting of green tides.

Ulva prolifera green tides, one of the greatest marine ecological disasters, originate in the southern Yellow Sea of China and obtain the highest biomass in Haizhou Bay (latitude around 35° N) during northward drift. U. prolifera shows different morphologies from southern Haizhou Bay (SH) to northern Haizhou Bay (NH). Owing to the distinct nutrient environments between SH and NH, we hypothesized that thalli in NH with poor nutrients increased the surface area to volume ratio (SA:VOL) to better absorb nutrients. Here, we tested this hypothesis by comparing the SA:VOL of thalli in SH and NH. The results showed that the thalli in NH had a lower SA:VOL than those in SH, and SA:VOL had positive relationships with temperature and nutrients, contrary to the general hypothesis. The novel results suggested that morphological differences of U. prolifera were the result of developmental state rather than environmental acclimation. Indicators of reproduction (reproductive allocation ratio) were negatively related to variation in tissue contents of C, N, P, and crude protein, whereas indicators of growth (tissue contents of C, N, P, and crude protein) showed significant positive influences on SA:VOL. The results indicated that a trade-off relationship between reproduction and growth existed in the northward drift. All the results suggested that physiological functional traits affected morphological variation of U. prolifera in different environmental conditions during the drifting of green tides. This study presents new insights into the opportunist species nature of U. prolifera through morphological variation and associated functional consequences.

Macroevolution of desiccation-related morphology in plethodontid salamanders as inferred from a novel surface area to volume ratio estimation approach.

Evolutionary biologists have long been interested in the macroevolutionary consequences of various selection pressures, yet physiological responses to selection across deep time are not well understood. In this paper, we investigate how a physiologically relevant morphological trait, surface area to volume ratio (SA:V) of lungless salamanders, has evolved across broad regional and climatic variation. SA:V directly impacts an organisms' ability to retain water, leading to the expectation that smaller SA:Vs would be advantageous in arid, water-limited environments. To explore the macroevolutionary patterns of SA:V, we first develop an accurate method for estimating SA:V from linear measurements. Next, we investigate the macroevolutionary patterns of SA:V across 257 salamander species, revealing that higher SA:Vs phylogenetically correlate with warmer, wetter climates. We also observe higher SA:V disparity and rate of evolution in tropical species, mirrored by higher climatic disparity in available and occupied tropical habitats. Taken together, these results suggest that the tropics have provided a wider range of warmer, wetter climates for salamanders to exploit, thereby relaxing desiccation pressures on SA:V. Overall, this paper provides an accurate, efficient method for quantifying salamander SA:V, allowing us to demonstrate the power of physiological selection pressures in influencing the macroevolution of morphology.

Design and Characterization of Sheet-Based Gyroid Porous Structures with Bioinspired Functional Gradients.

A new type of sheet porous structures with functionally gradients based on triply periodic minimal surfaces (TPMS) is proposed for designing bone scaffolds. The graded structures were generated by constructing branched features with different number of sheets. The design of the structure was formulated mathematically and five types of porous structure with different structural features were used for investigation. The relative density (RD) and surface area to volume (SA/V) ratio of the samples were analyzed using a slice-based approach to confirm their relationships with design parameters. All samples were additively manufactured using selective laser melting (SLM), and their physical morphologies were observed and compared with the designed models. Compression tests were adopted to study the mechanical properties of the proposed structure from the obtained stress-strain curves. The results reveal that the proposed branched-sheet structures could enhance and diversify the physical and mechanical properties, indicating that it is a potential method to tune the biomechanical properties of porous scaffolds for bone tissue engineering (TE).

Exploring tablet design options for tailoring drug release and dose via fused deposition modeling (FDM) 3D printing.

The aim of this paper was to explore tablet design options for FDM 3D printing for simultaneous tailoring of drug release and dose. The drug, griseofulvin (GF), the polymer, hydroxypropyl cellulose (HPC), and processing temperatures were selected to avoid confounding effects arising from drug-polymer interactions. Filaments containing 0-30 wt% GF were prepared using a twin-screw extruder. Five tablet designs were printed using combinations of fixed or varying drug-concentration filaments, fixed or varying tablet sizes, or placebo and drug-rich regions. Two of five options met the main objective; varying drug-concentration filaments for fixed tablet size or printing fixed size duo-tablet having internal placebo regions of varying sizes. Analysis of the drug dissolution profiles revealed that the tablet surface area to volume (SA/V) ratio was the dominant factor, a higher SA/V ratio resulted in a faster release rate, mostly independent of the drug amount or its placement within the tablet. Use of HPC led to near zero-order release for most cases. For duo-tablets, long lag times proportional to placebo shell-thickness were observed. These results suggest that design options other than varying the tablet size would be needed to achieve desired drug release from FDM-based 3D printed personalized dosages.

Distortions of perceived volume and length of body parts.

We experience our body as a 3D, volumetric object in the world. Measures of our conscious body image, in contrast, have investigated the perception of body size along one or two dimensions at a time. There is, thus, a discrepancy between existing methods for measuring body image and our subjective experience of having 3D body. Here we assessed in a sample of healthy adults the perception of body size in terms of its 1D length and 3D volume. Participants were randomly assigned to two groups using different measuring units (other body part and non-body object). They estimated how many units would fit in a perceived size of body segments and the whole body. The patterns of length and volume misperception across judged segments were determined as their perceived size proportional to their actual size. The pattern of volume misperception paints the representation of 3D body proportions resembling those of a somatosensory homunculus. The body parts with a smaller actual surface area relative to their volume were underestimated more. There was a tendency for body parts underestimated in volume to be overestimated in length. Perceived body proportions thus changed as a function of judgement type while showing a similarity in magnitude of the absolute estimation error, be it an underestimation of volume or overestimation of length. The main contribution of this study is assessing the body image as a 3D body representation, and thus extending beyond the conventional 'allocentric' focus to include the body on the inside. Our findings highlight the value of studying the perceptual distortions "at the baseline", i.e., in healthy population, so as to advance the understanding of the nature of perceptual distortions in clinical conditions.

Effects of surface area to volume ratio of PLGA scaffolds with different architectures on scaffold degradation characteristics and drug release kinetics.

In this work, PLGA scaffolds with different architectures were fabricated to investigate the effects of surface area to volume ratio (SVR) (which resulted from the different architectures) on scaffold degradation characteristics and drug release kinetics with minocycline as the model drug. It was hypothesized that the thin strand scaffolds, which had the highest SVR, would degrade faster than the thick strand and globular scaffolds as the increase in surface area will allow more contact between water molecules and degradable ester groups in the polymer. However, it was found that globular scaffolds, which had the lowest SVR, resulted in the fastest degradation which demonstrated that the amount of degradation of the scaffolds does not only depend on the SVR but also on other factors such as the retention of acidic degradation byproducts in the scaffold and scaffold porosity. PLGA 50 : 50 globular scaffolds resulted in a biphasic release profile, with a burst release in the beginning and the middle of the release study which may be beneficial for some drug delivery applications. A clear correlation between SVR and release rates was not observed, indicating that besides the availability of more surface area for drug to diffuse out of the polymer matrix, other factors such as amount of scaffold degradation and scaffold porosity may play a role in determining drug release kinetics. Further studies, such as scanning electron microscopy, need to be performed in the future to further evaluate the porosity, morphology and structure of the scaffolds.

EFFECT OF ZINC AVAILABILITY ON GROWTH, MORPHOLOGY, AND NUTRIENT INCORPORATION IN A COASTAL AND AN OCEANIC DIATOM(1).

We investigated the effect of Zn availability on growth rate (µ), cell morphology, and elemental stoichiometry and incorporation rate in two marine diatoms. For the coastal diatom Skeletonema costatum (Grev.) Cleve, the half-saturation constant (KS ) for growth was 4.1 pM Zn(2+) , and growth ceased at ≤ 2.6 pM Zn(2+) , whereas for the oceanic diatom Thalassiosira oceanica Hasle, KS was 0.5 pM Zn(2+) , and µ remained at ∼40%µmax even at 0.3 pM Zn(2+) . Under Zn-limiting (Zn-L) conditions, S. costatum decreased cell size significantly, leading to an 80% increase in surface area to volume ratio (SA/V) at Zn(2+) of 3.5 pM compared to Zn-replete (Zn-R) conditions (at Zn(2+) of 13.2 pM), whereas T. oceanica's morphology did not change appreciably. Cell quotas of C, N, P, Si, and chl a significantly decreased under Zn limitation in S. costatum (at Zn(2+) of 3.5 pM), whereas Zn limitation in T. oceanica (at Zn(2+) of 0.3 pM) had little effect on quotas. Elemental stoichiometry was ∼85C:10N:9Si:1P and 81C:9N:5Si:1P for S. costatum, and 66C:5N:2Si:1P and 52C:6N:2Si:1P for T. oceanica, under Zn-R and Zn-L conditions, respectively. Incorporation rates of all elements were significantly reduced under Zn limitation for both diatoms, but particularly for Si in S. costatum, and for C in T. oceanica, despite its apparent tolerance of low Zn conditions. With [Zn(2+) ] in some parts of the ocean being of the same order (∼0.2 to 2 pM) as our low Zn conditions for T. oceanica, our results support the hypothesis that in situ growth and C acquisition may be limited by Zn in some oceanic species.