Optimizing Epicardial Restraint and Reinforcement Following Myocardial Infarction: Moving Towards Localized, Biomimetic, and Multitherapeutic Options

The mechanical reinforcement of the ventricular wall after a myocardial infarction has been shown to modulate and attenuate negative remodeling that can lead to heart failure. Strategies include wraps, meshes, cardiac patches, or fluid-filled bladders. Here, we review the literature describing these strategies in the two broad categories of global restraint and local reinforcement. We further subdivide the global restraint category into biventricular and univentricular support. We discuss efforts to optimize devices in each of these categories, particularly in the last five years. These include adding functionality, biomimicry, and adjustability. We also discuss computational models of these strategies, and how they can be used to predict the reduction of stresses in the heart muscle wall. We discuss the range of timing of intervention that has been reported. Finally, we give a perspective on how novel fabrication technologies, imaging techniques, and computational models could potentially enhance these therapeutic strategies. Keywords: ventricular restraint; infarct reinforcement; biomimetic

Evaluating Split Nitrogen Applications and In-Season Tests for Organic Winter Bread Wheat

Achieving high grain yields and crude protein (CP) standards in organic winter wheat (Triticum aestivum L.) is challenging because ensuring that adequate nitrogen (N) is available at key periods of wheat growth is difficult in organic systems. Split application regimes and in-season N management tests may improve organic production. In field trials conducted over four site-years in Maine and Vermont, USA, N application regimes were analyzed for their effects on organic winter wheat, N uptake, grain yield, and CP. Tiller density and tissue N tests were evaluated as in-season decision tools. Eight treatments arranged in a non-factorial design differed in terms of N application timing (pre-plant (PP), topdress at tillering (T1), and topdress at pre-stem extension (T2)) and N rate. Treatments were: (1) an untreated check, (2) pre-plant N at a low rate of 78 kg N ha−1(PPL), (3) pre-plant N at a high rate of 117 or 157 kg N ha−1 (PPH), (4) T178, (5) PPL + T139, (6) PPL + T239, (7) PPH + T239, and (8) PPL + T139 +T239. Responses to N treatments were variable among site-years, however some common results were identified. The PP-only treatments increased grain yields more than they increased CP. The T178 and PPH + T239 treatments were the most effective at increasing yield and CP, compared with the PP-only treatments. Tiller density and tissue N tests were good predictors of grain yield (r = 0.52, p < and CP (r = 0.75, p < 0.001) respectively. Future work should test in-season decision tools using a wider range of tiller densities, and topdress N rates against tissue N measurements

Using Farmer Storytelling to Build Understanding of Our New Weather Reality

A storytelling session was successful in raising awareness and understanding of the types of changes in weather patterns farmers are experiencing in Maine, what impacts those changes are having on their operations, and the changes farmers are making in response. Using an outreach approach rooted in farmer stories allowed us to bypass the controversy that often surrounds topics related to climate change. Likewise, focusing on the farmers\u27 experiences and avoiding corrective statements during this introductory session resulted in productive dialogue. We recommend replicating this approach within different agricultural sectors to increase understanding of sector-specific risks and strategies for adaptation

A prospective, population-based study of the role of visual impairment in motor vehicle crashes among older drivers: the SEE study.

PURPOSE: To determine the role of vision and visual attention factors in automobile crash involvement. METHODS: Drivers aged 65 to 84 years were identified during the baseline interview (1993-1995) of the Salisbury Eye Evaluation (SEE) Study. Crash involvement through December 1997 was determined from Maryland State motor vehicle records. Vision tests at baseline included distance acuity at normal and low luminance, contrast sensitivity, glare sensitivity, stereoacuity, and visual fields. Visual attention was evaluated with the Useful Field of View Test (UFOV; Visual Awareness, Chicago, IL). Survival analysis was used to determine the relative risk of a crash as a function of demographic variables, miles driven, vision, and visual attention. RESULTS: One hundred twenty (6.7%) of the 1801 drivers were involved in a crash during the observation interval. Glare sensitivity and binocular field loss were significant predictors of crash involvement (P < 0.05). For those with moderate or better vision (<3 letters for glare sensitivity and <20 points missed for binocular visual fields) increased glare sensitivity or reduced visual fields were, paradoxically, associated with a reduction in crash risk, whereas for those with poorer levels of vision, increased glare sensitivity or reduced visual fields were associated with increased crash risk. Worse UFOV score was associated with increased crash risk. CONCLUSIONS: Glare sensitivity, visual field loss, and UFOV were significant predictors of crash involvement. Acuity, contrast sensitivity, and stereoacuity were not associated with crashes. These results suggest that current vision screening for drivers' licensure, based primarily on visual acuity, may miss important aspects of visual impairment

A Soft Robotic Actuator System for in vivo Modeling of Normal Pressure Hydrocephalus

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: In vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus

Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models

Regenerative medicine approaches, specifically stem cell technologies, have demonstrated significant potential to treat a diverse array of pathologies. However, such approaches have resulted in a modest clinical benefit, which may be attributed to poor cell retention/survival at the disease site. A delivery system that facilitates regional and repeated delivery to target tissues can provide enhanced clinical efficacy of cell therapies when localized delivery of high doses of cells is required. In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation to target tissue, and filling/refilling with a therapeutic cargo, and is demonstrated in an array of clinical applications that are easily translated to human studies. Regenervoir consists of a porous reservoir fabricated from a single material, a flexible thermoplastic polymer, capable of delivering cargo via fill lines to target tissues. A radiopaque shear thinning hydrogel can be delivered to the therapy reservoir and multiple fixation methods (laparoscopic tacks and cyanoacrylate bioadhesive) can be used to secure Regenervoir to target tissues through a minimally invasive approach.In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models that are easily translated to human studies, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation, and filling/refilling with a therapeutic cargo.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155890/1/adhm202000305.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155890/2/adhm202000305_am.pd

Low-grade inflammation, diet composition and health: current research evidence and its translation

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims

OBEDIS Core Variables Project : European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes.Peer reviewe