Nutrigenetics—Personalized Nutrition in the Genetic Age

Diet is an important modifiable determinant of disease, and it is becoming clear that diet and genetic risk factors are interactive in determining risk for diseases such as cardiovascular disease, diabetes and cancers. Advances in technology have improved our understanding of gene-nutrient interactions, and lead to the development of nutrigenetics, personalized nutrition based on genetics. While evidence is strong for some associations, others remain unclear. As such, the implementation of nutrigenetics remains controversial. While some argue it is not ready for clinical use, it has also been argued that nutrigenetics is unfairly held to a higher standard than traditional nutrition research. Despite the future promise of nutrigenetic testing for improving health outcomes, several barriers in science, technology, acceptance and ethics exist to its implementation. Gene-nutrient associations have been identified in a number of lifestyle-associated diseases, and better understanding of these relationships may lead to improved health outcomes. However, the success of nutrigenetics is not only dependent on the strength of the science, but in consumer acceptance and uptake. This narrative review provides an overview of the current landscape for nutrigenetics in relation to key disease states, and addresses the potential barriers to implementation

Dynamics of precipitation pattern formation at geothermal hot springs

We formulate and model the dynamics of spatial patterns arising during the precipitation of calcium carbonate from a supersaturated shallow water flow. The model describes the formation of travertine deposits at geothermal hot springs and rimstone dams of calcite in caves. We find explicit solutions for travertine domes at low flow rates, identify the linear instabilities which generate dam and pond formation on sloped substrates, and present simulations of statistical landscape evolution

Simple Viscous Flows: from Boundary Layers to the Renormalization Group

The seemingly simple problem of determining the drag on a body moving through a very viscous fluid has, for over 150 years, been a source of theoretical confusion, mathematical paradoxes, and experimental artifacts, primarily arising from the complex boundary layer structure of the flow near the body and at infinity. We review the extensive experimental and theoretical literature on this problem, with special emphasis on the logical relationship between different approaches. The survey begins with the developments of matched asymptotic expansions, and concludes with a discussion of perturbative renormalization group techniques, adapted from quantum field theory to differential equations. The renormalization group calculations lead to a new prediction for the drag coefficient, one which can both reproduce and surpass the results of matched asymptotics

Pulmonary Deposition of Radionucleotide-Labeled Palivizumab: Proof-of-Concept Study

Objective: Current prevention and/or treatment options for respiratory syncytial virus (RSV) infections are limited as no vaccine is available. Prophylaxis with palivizumab is very expensive and requires multiple intramuscular injections over the RSV season. Here we present proof-of-concept data using nebulized palivizumab delivery as a promising new approach for the prevention or treatment of severe RSV infections, documenting both aerosol characteristics and pulmonary deposition patterns in the lungs of lambs. Design: Prospective animal study. Setting: Biosecurity Control Level 2-designated large animal research facility at the Murdoch Children’s Research Institute, Melbourne, Australia. Subjects: Four weaned Border-Leicester/Suffolk lambs at 5 months of age. Interventions: Four lambs were administered aerosolized palivizumab conjugated to Tc-99m, under gaseous anesthesia, using either the commercially available AeroNeb Go® or the investigational HYDRA device, placed in-line with the inspiratory limb of a breathing circuit. Lambs were scanned in a single-photon emission computed tomography (SPECT/CT) scanner in the supine position during the administration procedure. Measurements and Main Results: Both the HYDRA and AeroNeb Go® produced palivizumab aerosols in the 1–5 µm range with similar median (geometric standard deviation and range) aerosol droplet diameters for the HYDRA device (1.84 ± 1.40 μm, range = 0.54–5.41μm) and the AeroNeb Go® (3.07 ± 1.56 μm, range = 0.86–10 μm). Aerosolized palivizumab was delivered to the lungs at 88.79–94.13% of the total aerosolized amount for all lambs, with a small proportion localized to either the trachea or stomach. No difference between devices were found. Pulmonary deposition ranged from 6.57 to 9.25% of the total dose of palivizumab loaded in the devices, mostly in the central right lung. Conclusions: Aerosolized palivizumab deposition patterns were similar in all lambs, suggesting a promising approach in the control of severe RSV lung infections

Integrated assessment of global climate, air pollution, and dietary, malnutrition and obesity health impacts of food production and consumption between 2014 and 2018

Agriculture accounts for approximately 10% of global greenhouse gas emissions and is simultaneously associated with impacts on human health through food consumption, and agricultural air pollutant emissions. These impacts are often quantified separately, and there is a lack of modelling tools to facilitate integrated assessments. This work presents a new model that integrates assessment of agricultural systems on (i) human health indirectly through dietary, obesity and malnutrition health risks from food consumption, (ii) human health directly through exposure to air pollutants from agricultural emissions, and (iii) greenhouse gas emissions. In the model, national food demand is the starting point from which the livestock and crop production systems that meet this are represented. The model is applied for 2014–2018 to assess the robustness of the GHG emissions and health burden results that this integrated modelling framework produces compared to previous studies that have quantified these variables independently. Methane and nitrous oxide emissions globally in 2018 were estimated to be 129 and 4.4 million tonnes, respectively, consistent with previous estimates. Agricultural systems were also estimated to emit 44 million tonnes of ammonia. An estimated 4.1 million deaths were associated with dietary health risks, 6.0 million with overweight/obesity, and 730 thousand infant deaths from malnutrition, consistent with previous studies. Agricultural air pollutant emissions were estimated to be associated with 537 thousand premature deaths attributable to fine particulate matter (PM2.5) exposure, and 184 thousand premature deaths from methane-induced ground-level ozone. These health impacts provide substantial opportunities to design integrated strategies that mitigate climate change, and improve human health, and also highlight possible trade-offs that the expansion of agricultural production could have due to increased emissions. The model presented here provides for the consistent evaluation of the implications of different agricultural strategies to meet food demand while minimising human health and climate change impacts

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Exotic fish in exotic plantations: a multi-scale approach to understand amphibian occurrence in the mediterranean region

Globally, amphibian populations are threatened by a diverse range of factors including habitat destruction and alteration. Forestry practices have been linked with low diversity and abundance of amphibians. The effect of exotic Eucalyptus spp. plantations on amphibian communities has been studied in a number of biodiversity hotspots, but little is known of its impact in the Mediterranean region. Here, we identify the environmental factors influencing the presence of six species of amphibians (the Caudata Pleurodeles waltl, Salamandra salamandra, Lissotriton boscai, Triturus marmoratus and the anurans Pelobates cultripes and Hyla arborea/meridionalis) occupying 88 ponds. The study was conducted in a Mediterranean landscape dominated by eucalypt plantations alternated with traditional use (agricultural, montados and native forest) at three different scales: local (pond), intermediate (400 metres radius buffer) and broad (1000 metres radius buffer). Using the Akaike Information Criterion for small samples (AICc), we selected the top-ranked models for estimating the probability of occurrence of each species at each spatial scale separately and across all three spatial scales, using a combination of covariates from the different magnitudes. Models with a combination of covariates at the different spatial scales had a stronger support than those at individual scales. The presence of predatory fish in a pond had a strong effect on Caudata presence. Permanent ponds were selected by Hyla arborea/meridionalis over temporary ponds. Species occurrence was not increased by a higher density of streams, but the density of ponds impacted negatively on Lissotriton boscai. The proximity of ponds occupied by their conspecifics had a positive effect on the occurrence of Lissotriton boscai and Pleurodeles waltl. Eucalypt plantations had a negative effect on the occurrence of the newt Lissotriton boscai and anurans Hyla arborea/meridionalis, but had a positive effect on the presence of Salamandra salamandra, while no effect on any of the other species was detected. In conclusion, eucalypts had limited effects on the amphibian community at the intermediate and broad scales, but predatory fish had a major impact when considering all the scales combined. The over-riding importance of introduced fish as a negative impact suggests that forest managers should prevent new fish introductions and eradicate fish from already-occupied ponds whenever possible

Anuran responses to spatial patterns of agricultural landscapes in Argentina

Context: Amphibians are declining worldwide and land use change to agriculture is recognized as a leading cause. Argentina is undergoing an agriculturalization process with rapid changes in landscape structure. Objectives: We evaluated anuran response to landscape composition and configuration in two landscapes of east-central Argentina with different degrees of agriculturalization. We identified sensitive species and evaluated landscape influence on communities and individual species at two spatial scales. Methods: We compared anuran richness, frequency of occurrence, and activity between landscapes using call surveys data from 120 sampling points from 2007 to 2009. We evaluated anuran responses to landscape structure variables estimated within 250 and 500-m radius buffers using canonical correspondence analysis and multimodel inference from a set of candidate models. Results: Anuran richness was lower in the landscape with greater level of agriculturalization with reduced amount of forest cover and stream length. This pattern was driven by the lower occurrence and calling activity of seven out of the sixteen recorded species. Four species responded positively to the amount of forest cover and stream habitat. Three species responded positively to forest cohesion and negatively to rural housing. Two responded negatively to crop area and diversity of cover classes. Conclusions: Anurans within agricultural landscapes of east-central Argentina are responding to landscape structure. Responses varied depending on species and study scale. Life-history traits contribute to responses differences. Our study offers a better understanding of landscape effects on anurans and can be used for land management in other areas experiencing a similar agriculturalization process.Facultad de Ciencias ExactasCentro de Investigaciones del Medioambient