Effects of dietary camelina, flaxseed, and canola oil supplementation on plasma fatty acid concentrations and health parameters in horses.

Camelina (Camelina sativa) is a hardy, low-input oilseed crop that provides a rich source of the n-3 fatty acid, α-linolenic acid (ALA). The primary purpose of the present study was to assess the effects of dietary camelina oil (CAM) consumption on various health parameters, as compared to horses fed canola oil (OLA) or flax oil (FLX). Secondly, to determine how dietary CAM, FLX, and OLA alter circulating plasma total lipids across time. Thirty horses, from three separate herds, were used for this study [14.9 years ± 5.3 years; 544 ± 66 kg calculated BW (mean ± SD)]. After a 4-week gradual acclimation period using sunflower oil mixed with soaked hay cubes, horses were balanced by location, age, sex, weight, and breed and randomly allocated to one of three treatment oils (CAM, OLA, or FLX) at an inclusion of 370 mg of oil/kg BW/day. Horses had ad libitum access to hay and/or pasture for the duration of the study. Body condition score (BCS), BW, oil intake, complete blood counts, plasma biochemical profiles, and plasma total lipids were measured on weeks 0, 2, 4, 8, and 16 throughout the 16-week treatment period. BW, BCS, and oil intake were analyzed using an ANOVA using PROC GLIMMIX in SAS Studio. Complete blood counts and biochemical profiles were analyzed using an ANCOVA, and fatty acids were analyzed using an ANOVA in PROC MIXED in SAS Studio. No differences were observed among treatment groups for BW, BCS, oil intake, complete blood counts, and biochemical parameters. Individual fatty acids that differed among treatments and/or across time were largely reflective of the different FA profiles of the oils provided. Most notably, plasma ALA was greater for FLX than OLA, but neither differed from CAM (P = 0.01). Linoleic acid did not differ among treatments or over time (P > 0.05). The n-6:n-3 ratio decreased over time for both CAM and FLX, and ratios were lower for FLX than OLA at week 16, but not different from CAM (P = 0.02). These results suggest that dietary CAM had no adverse effects on health parameters and that daily supplementation of CAM and FLX at 370 mg of oil/kg BW/day induces positive changes (a decrease) in the n-6:n-3 status of the horse. Consequently, CAM may be considered as an alternative oil to FLX in equine diets.

Morphogens enable interacting supracellular phases that generate organ architecture.

During vertebrate organogenesis, increases in morphological complexity are tightly coupled to morphogen expression. In this work, we studied how morphogens influence self-organizing processes at the collective or "supra"-cellular scale in avian skin. We made physical measurements across length scales, which revealed morphogen-enabled material property differences that were amplified at supracellular scales in comparison to cellular scales. At the supracellular scale, we found that fibroblast growth factor (FGF) promoted "solidification" of tissues, whereas bone morphogenetic protein (BMP) promoted fluidity and enhanced mechanical activity. Together, these effects created basement membrane-less compartments within mesenchymal tissue that were mechanically primed to drive avian skin tissue budding. Understanding this multiscale process requires the ability to distinguish between proximal effects of morphogens that occur at the cellular scale and their functional effects, which emerge at the supracellular scale.

Development shapes the evolutionary diversification of rodent stripe patterns.

Vertebrate groups have evolved strikingly diverse color patterns. However, it remains unknown to what extent the diversification of such patterns has been shaped by the proximate, developmental mechanisms that regulate their formation. While these developmental mechanisms have long been inaccessible empirically, here we take advantage of recent insights into rodent pattern formation to investigate the role of development in shaping pattern diversification across rodents. Based on a broad survey of museum specimens, we first establish that various rodents have independently evolved diverse patterns consisting of longitudinal stripes, varying across species in number, color, and relative positioning. We then interrogate this diversity using a simple model that incorporates recent molecular and developmental insights into stripe formation in African striped mice. Our results suggest that, on the one hand, development has facilitated pattern diversification: The diversity of patterns seen across species can be generated by a single developmental process, and small changes in this process suffice to recapitulate observed evolutionary changes in pattern organization. On the other hand, development has constrained diversification: Constraints on stripe positioning limit the scope of evolvable patterns, and although pattern organization appears at first glance phylogenetically unconstrained, development turns out to impose a cryptic constraint. Altogether, this work reveals that pattern diversification in rodents can in part be explained by the underlying development and illustrates how pattern formation models can be leveraged to interpret pattern evolution.

Effects of Presbyphagia on Oropharyngeal Swallowing Observed during Modified Barium Swallow Studies.

OBJECTIVES: Understanding how aging impacts swallowing can help differentiate typical from atypical behaviors. This study aimed to quantify age-related swallowing alterations observed during a modified barium swallow study. DESIGN: Cross-sectional study. SETTING: Adult fluoroscopy suite in a metropolitan hospital at an academic center. PARTICIPANTS: 195 healthy adults distributed across 3 age categories: 21-39; 40-59; 60+ years. MEASUREMENTS: 17 physiologic components of swallowing across three functional domains (oral, pharyngeal, esophageal), including summed composite scores (Oral Total [OT] and Pharyngeal Total [PT]), from the validated and standardized Modified Barium Swallow Impairment Profile. RESULTS: Most components (65%) demonstrated no impairment (scores of "0"). The odds of a worse (higher) score increased significantly with age for: Tongue Control during Bolus Hold, Hyolaryngeal Movement, Laryngeal Closure, Pharyngeal Contraction, and Pharyngoesophageal Segment Opening. OT and PT scores for 40-59-year-olds were worse than the youngest group (p=.01 and p <.001, respectively). Adults 60+ years had significantly worse PT scores among all groups (p-values <.01). CONCLUSION: Oropharyngeal swallowing physiology evolves as healthy adults age and should be considered during clinical decision-making.

Forced and spontaneous symmetry breaking in cell polarization.

How does breaking the symmetry of an equation alter the symmetry of its solutions? Here, we systematically examine how reducing underlying symmetries from spherical to axisymmetric influences the dynamics of an archetypal model of cell polarization, a key process of biological spatial self-organization. Cell polarization is characterized by nonlinear and non-local dynamics, but we overcome the theory challenges these traits pose by introducing a broadly applicable numerical scheme allowing us to efficiently study continuum models in a wide range of geometries. Guided by numerical results, we discover a dynamical hierarchy of timescales that allows us to reduce relaxation to a purely geometric problem of area-preserving geodesic curvature flow. Through application of variational results, we analytically construct steady states on a number of biologically relevant shapes. In doing so, we reveal non-trivial solutions for symmetry breaking.

Topological braiding and virtual particles on the cell membrane.

Braiding of topological structures in complex matter fields provides a robust framework for encoding and processing information, and it has been extensively studied in the context of topological quantum computation. In living systems, topological defects are crucial for the localization and organization of biochemical signaling waves, but their braiding dynamics remain unexplored. Here, we show that the spiral wave cores, which organize the Rho-GTP protein signaling dynamics and force generation on the membrane of starfish egg cells, undergo spontaneous braiding dynamics. Experimentally measured world line braiding exponents and topological entropy correlate with cellular activity and agree with predictions from a generic field theory. Our analysis further reveals the creation and annihilation of virtual quasi-particle excitations during defect scattering events, suggesting phenomenological parallels between quantum and living matter.

Treatment Preferences for Cardiac Procedures of Patients With Chronic Kidney Disease in Acute Coronary Syndrome: Design and Pilot Testing of a Discrete Choice Experiment.

BACKGROUND: Chronic kidney disease is associated with a high incidence of acute coronary syndrome and related morbidity and mortality. Treatment choices for patients with chronic kidney disease involve trade-offs in the potential benefits and harms of invasive management options. OBJECTIVE: The objective was to quantify preferences of patients with chronic kidney disease toward invasive heart procedures. DESIGN: Design and pilot a discrete choice experiment. SETTING: We piloted the discrete choice experiment in 2 multidisciplinary chronic kidney disease clinics in Calgary, Alberta, using an 8-question survey. PATIENTS: Eligible patients included those aged 18 years and older, an estimated glomerular filtration rate < 45 mL/min/1.73 m2, not currently receiving dialysis, and able to communicate in English. MEASUREMENTS: Quantification of the average importances of key attributes of invasive heart procedures. METHODS: We identified attributes most important to patients and physicians concerning invasive versus conservative management for acute coronary syndrome, using semi-structured qualitative interviews. Levels for each attribute were derived from analysis of early invasive versus conservative acute coronary syndrome management clinical trials and cohort studies, where subgroups of patients with chronic kidney disease were reported. We designed the pilot study with patient partners with relevant lived experience and considered statistical efficiency to estimate main effects and interactions, as well as response efficiency. Hierarchical Bayesian estimation was used to quantify average importances of attributes. RESULTS: We recruited 43 patients with chronic kidney disease, mean (SD) age 67 (14) years, 67% male, and 35% with a history of cardiovascular disease, of whom 39 completed the survey within 2 weeks of enrollment. The results of the pilot revealed acute kidney injury requiring dialysis and permanent kidney replacement therapy, as well as death within 1 year were the most important attributes. Measures of internal validity for the pilot discrete choice experiment were comparable to those for other published discrete choice experiments. LIMITATIONS: Discrete choice experiments are complex instruments and often cognitively demanding for patients. This survey included multiple risk attributes which may have been challenging for some patients to understand. CONCLUSIONS: This pilot study demonstrates the feasibility of a discrete choice experiment to quantify preferences of patients with chronic kidney disease toward the benefits and trade-offs related to invasive versus conservative management for acute coronary syndrome. These preliminary findings suggest that patients with chronic kidney disease may be on average similarly risk averse toward kidney replacement therapy and death. This pilot information will be used to inform a larger discrete choice experiment that will refine these estimates of patient preferences and characterize subgroups with distinct treatment preferences, which should provide new knowledge that can facilitate shared decision-making between patients with chronic kidney disease and their care providers in the setting of acute coronary syndrome.

CONTEXTE: L'insuffisance rénale chronique (IRC) est associée à une forte incidence du syndrome coronarien aigu, de même qu'à la morbidité et à la mortalité qui y sont liées. Les options de traitement pour les patients atteints d'IRC impliquent de faire des compromis sur les avantages et inconvénients des options invasives. OBJECTIF: Quantifier les préférences des patients atteints d'IRC quant aux procédures cardiaques invasives. CONCEPTION: Concevoir et piloter une expérience avec choix discrets. CADRE: Nous avons mené cette expérience avec choix discrets dans deux cliniques multidisciplinaires de néphropathie chronique de Calgary (Alberta) à l'aide d'un sondage en huit questions. SUJETS: Les patients admissibles étaient des adultes avec un débit de filtration glomérulaire estimé (DFGe) inférieur à 45 mL/min/1,73 m 2 et ne suivant pas de traitements de dialyse. Les patients inclus devaient être capables de communiquer en anglais. MESURES: Quantification de l'importance moyenne des principaux attributs des procédures cardiaques effractives. MÉTHODOLOGIE: Les attributs les plus importants pour les patients et les médecins concernant une gestion invasive par rapport à une gestion conservatrice du syndrome coronarien aigu ont été déterminés à l'aide d'interviews qualitatives semi-structurées. L'analyse d'essais cliniques et d'études de cohorte ayant inclus des sous-groupes de patients atteints d'IRC et portant sur la gestion invasive précoce du syndrome coronarien aigu par opposition à une gestion conservatrice a permis de dériver les le degré d'importance pour chaque attribut. Nous avons conçu l'étude pilote en compagnie de patients partenaires ayant une expérience vécue pertinente et nous avons tenu compte de l'efficacité statistique pour estimer les principaux effets et interactions, de même que l'efficacité de la réponse. Une estimation hiérarchique bayésienne a été employée pour quantifier l'importance moyenne des attributs. RÉSULTATS: Nous avons recruté 43 patients atteints d'IRC dont l'âge moyen (É-T) était de 67 ans (14). La cohorte était constituée à 67 % d'hommes et 35 % des sujets avaient des antécédents de maladies cardiovasculaires. L'étude porte sur les 39 patients ayant rempli le questionnaire dans les deux semaines suivant le recrutement. Les résultats de l'étude pilote ont révélé que la mortalité dans la première année et l'insuffisance rénale aiguë (IRA) nécessitant la dialyse et une thérapie de remplacement rénal permanente étaient les attributs les plus importants. Les mesures des intervalles de validité de cette expérience pilote avec choix discrets étaient similaires à ceux des autres expériences publiées du même type. LIMITES: Les expériences avec choix discrets sont des outils complexes et souvent exigeants pour les patients sur le plan cognitif. Ce questionnaire comportait plusieurs attributs de risque qui ont peut-être été difficiles à comprendre pour certains patients. CONCLUSION: Cette étude pilote démontre la faisabilité d'une expérience avec choix discrets pour qualifier les préférences des patients atteints d'IRC en ce qui concerne les avantages et les compromis liés à une gestion invasive ou conservatrice du syndrome coronarien aigu. Ces résultats préliminaires semblent indiquer que les patients atteints d'IRC seraient en moyenne tout aussi réticents envers le risque de thérapie de remplacement rénal qu'envers le risque de décès. Les informations tirées de ce pilote serviront à orienter une plus vaste expérience avec choix discrets qui raffinera ces estimations des préférences des patients et caractérisera les sous-groupes ayant des préférences de traitements distinctes. Ceci fournira de nouvelles connaissances susceptibles de faciliter la prise de décision partagée entre les patients atteints d'IRC et leurs fournisseurs de soins dans le contexte du syndrome coronarien aigu.

Gait-optimized locomotion of wave-driven soft sheets.

Inspired by the robust locomotion of limbless animals in a range of environments, the development of soft robots capable of moving by localized swelling, bending, and other forms of differential growth has become a target for soft matter research over the last decade. Engineered soft robots exhibit a wide range of morphologies, but theoretical investigations of soft robot locomotion have largely been limited to slender bodied or one-dimensional examples. Here, we demonstrate design principles regarding the locomotion of two-dimensional soft materials driven by morphoelastic waves along a dry substrate. Focusing on the essential common aspects of many natural and man-made soft actuators, a continuum model is developed which links the deformation of a thin elastic sheet to surface-bound excitation waves. Through a combination of analytic and numerical methods, we investigate the relationship between induced active stress and self-propulsion performance of self-propelling sheets driven by FitzHugh-Nagumo type chemical waves. Examining the role of both sheet geometry and terrain geography on locomotion, our results can provide guidance for the design of more efficient soft crawling devices.

Structural Redundancy in Supracellular Actomyosin Networks Enables Robust Tissue Folding.

Tissue morphogenesis is strikingly robust. Yet, how tissues are sculpted under challenging conditions is unknown. Here, we combined network analysis, experimental perturbations, and computational modeling to determine how network connectivity between hundreds of contractile cells on the ventral side of the Drosophila embryo ensures robust tissue folding. We identified two network properties that mechanically promote robustness. First, redundant supracellular cytoskeletal network paths ensure global connectivity, even with network degradation. By forming many more connections than are required, morphogenesis is not disrupted by local network damage, analogous to the way redundancy guarantees the large-scale function of vasculature and transportation networks. Second, directional stiffening of edges oriented orthogonal to the folding axis promotes furrow formation at lower contractility levels. Structural redundancy and directional network stiffening ensure robust tissue folding with proper orientation.

Time-resolved imaging of bound and dissociating nuclear wave packets in strong-field ionized iodomethane.

We report the results of a time-resolved coincident ion momentum imaging experiment probing nuclear wave packet dynamics in the strong-field ionization and dissociation of iodomethane (CH3I), a prototypical polyatomic system for photochemistry and ultrafast laser science. By measuring yields, kinetic energies, and angular distributions of CH3+ + I+ and CH3+ + I++ ion pairs as a function of the delay between two 25 fs, 790 nm pump and probe pulses, we map both, bound and dissociating nuclear wave packets in intermediate cationic states, thereby tracking different ionization and dissociation pathways. In both channels, we find oscillatory features with a 130 fs periodicity resulting from vibrational motion (C-I symmetric stretch mode) in the first electronically excited state of CH3I+. This vibrational wave packet dephases within 1 ps, in good agreement with a simple wave packet propagation model. Our results indicate that the first excited cationic state plays a key role in the dissociative ionization of CH3I and that it represents an important intermediate in the sequential double and multiple ionization at moderate intensities.

Geometry of Wave Propagation on Active Deformable Surfaces.

Fundamental biological and biomimetic processes, from tissue morphogenesis to soft robotics, rely on the propagation of chemical and mechanical surface waves to signal and coordinate active force generation. The complex interplay between surface geometry and contraction wave dynamics remains poorly understood, but it will be essential for the future design of chemically driven soft robots and active materials. Here, we couple prototypical chemical wave and reaction-diffusion models to non-Euclidean shell mechanics to identify and characterize generic features of chemomechanical wave propagation on active deformable surfaces. Our theoretical framework is validated against recent data from contractile wave measurements on ascidian and starfish oocytes, producing good quantitative agreement in both cases. The theory is then applied to illustrate how geometry and preexisting discrete symmetries can be utilized to focus active elastic surface waves. We highlight the practical potential of chemomechanical coupling by demonstrating spontaneous wave-induced locomotion of elastic shells of various geometries. Altogether, our results show how geometry, elasticity, and chemical signaling can be harnessed to construct dynamically adaptable, autonomously moving mechanical surface waveguides.

Exploring relationships between body condition score, body fat, activity level and inflammatory biomarkers.

Obesity is associated with inflammatory disorders in humans, including degenerative joint disease. While obesity is endemic in horses, its relationship to equine degenerative joint disease has not been explored. The current study sought to describe relationships between: body weight (BW), body condition score (BCS), lameness grade (AAEP), total body fat mass (kg; FM) and fat per cent (FP) [multifrequency bioelectrical impedance analysis (mfBIA)], age, gender, activity level (AL), synovial fluid (SF) and plasma (PL) PGE2 and glycosaminoglycan (GAG) in horses. During this field investigation, the BCS (of nine) of 54 horses at multiple farms in southern Ontario, Canada, was determined. Horses were categorized as thin (BCS=3/9; n = 6), moderate (BCS=4 or 5/9; n = 18), overweight (BCS=6 or 7/9; n = 19) or obese (BCS=8 or 9/9; n = 11). Total fat mass (kg) and body fat% was measured using mfBIA, lameness was assessed (AAEP lameness scale) and synovial fluid was collected via aseptic arthrocentesis from the left intercarpal joint for assessment of inflammatory biomarkers (PGE2 , GAG). Means were compared with a one-way ANOVA; correlation coefficients were calculated using a Spearman Rank Order Correlation to reveal correlations between variables. BCS was positively correlated with BW, FM, FP, AL and PL-PGE2 . BW was also significantly positively correlated with PL-PGE2 . It is concluded that BCS is significantly correlated with PL-PGE2 , due in part to the combined effect of AL and body condition. Net inflammatory effects of body fat on risk for joint disease require further study.

Actomyosin-based tissue folding requires a multicellular myosin gradient.

Tissue folding promotes three-dimensional (3D) form during development. In many cases, folding is associated with myosin accumulation at the apical surface of epithelial cells, as seen in the vertebrate neural tube and the Drosophila ventral furrow. This type of folding is characterized by constriction of apical cell surfaces, and the resulting cell shape change is thought to cause tissue folding. Here, we use quantitative microscopy to measure the pattern of transcription, signaling, myosin activation and cell shape in the Drosophila mesoderm. We found that cells within the ventral domain accumulate different amounts of active apical non-muscle myosin 2 depending on the distance from the ventral midline. This gradient in active myosin depends on a newly quantified gradient in upstream signaling proteins. A 3D continuum model of the embryo with induced contractility demonstrates that contractility gradients, but not contractility per se, promote changes to surface curvature and folding. As predicted by the model, experimental broadening of the myosin domain in vivo disrupts tissue curvature where myosin is uniform. Our data argue that apical contractility gradients are important for tissue folding.

Infrared multiple photon dissociation spectrum of protonated bis(2-methoxyethyl) ether obtained with a tunable CO2 laser.

A moderate-resolution infrared multiple photon dissociation (IRMPD) spectrum of protonated bis(2-methoxyethyl) ether (diglyme) was obtained using a grating-tuned CO2 laser. The experimental spectrum compares well with one calculated theoretically at the MP2 level and exhibits defined peaks over the span of the CO2 laser output lines as opposed to a relatively featureless spectrum over this wavelength range obtained using free electron laser infrared radiation. The lowest energy structure corresponding to the calculated vibrational spectrum is consistent with structures previously calculated at the same level of theory. Alternative structures were calculated at lower levels of theory for comparison and investigation of the energetics of proton-heteroatom interactions. Broadening of the IRMPD action spectrum due to energetic phenomena characteristic of proton bridges was not observed and thus did not obscure the correlation between theoretical calculations and experimentally determined spectra as it may have in previous studies.

Impact fragmentation of model flocks.

Predicting the bulk material properties of active matter is challenging since these materials are far from equilibrium and standard statistical-mechanics approaches may fail. We report a computational study of the surface properties of a well known active matter system: aggregations of self-propelled particles that are coupled via an orientational interaction and that resemble bird flocks. By simulating the impact of these models flocks on an impermeable surface, we find that they fragment into subflocks with power-law mass distributions, similar to shattering brittle solids but not to splashing liquid drops. Thus, we find that despite the interparticle interactions, these model flocks do not possess an emergent surface tension.

Detection, isolation and characterisation of cyclolinopeptides J and K in ageing flax.

Methionine sulfone containing peptides CLs J (11) and K (12) may be produced from their reduced forms by oxidation but it is not known if these compounds occur in foods that contain flax. These compounds have been reported to possess greater immunosuppressive activity than their reduced methionine sulfoxide peptide forms 4 and 6, respectively. Since 11 and 12 have not been detected in commercial flax oil and milled flax seed, we tested for their presence in flax food products. Here we report that 11 and 12 accumulate in ground flaxseed that is exposed to air and heat (100°C) for more than 4h. Standards of 11 and 12 were prepared, isolated and extensively characterised using HPLC-MS/MS, 1D and 2D NMR methods. We also report the excellent thermal and oxidative stability of these peptides. Due to the harsh conditions required to produce 11 and 12, it is expected that their levels in flax based foods would be low and therefore their presence could serve as an indicative measure of severe oxidation of a food product.

Oral rosmarinic acid-enhanced Mentha spicata modulates synovial fluid biomarkers of inflammation in horses challenged with intra-articular LPS.

A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 ± 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal joint. Synovial fluid (SF) samples were taken on postinjection day (PID)-21 (i.e. prior to commencement of supplementation), PID0, PID0.25, PID0.5, PID1 and PID3 and analysed for PGE(2), GAG, NO, protein and total nucleated cells counts. Blood biochemistry and haematology screens were conducted at PID-21, PID0, PID1 and PID3. There was a significant reduction in LPS-induced PGE(2) and GAG in SF in horses supplemented with HRAM compared with controls and a tendency to increase complement recognition protein accumulation in synovial fluid of HRAM horses. Plasma from HRAM horses had reduced total white blood cells, segmented neutrophils (compared with baseline concentrations) and lymphocytes (compared with controls), and increased SF nucleated cell count (compared with baseline concentrations and controls). It is concluded that HRAM offered as part of the feed alter biomarkers of inflammation in SF of LPS-challenged horses. Larger studies that seek to clarify effects of HRAM on synovial fluid cell counts and possible role of HRAM-induced interference with complement signalling are warranted.